997: Competitive Victimhood

Adam Curry & John C. Dvorak

2h 53m
January 7th, 2018
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Executive Producers: Sir Atomic Rod Adams Baron of the Suncoast, Dame Francine Hardaway

Associate Executive Producers: Sir Nick of the SouthSide, Michael Peters

Cover Artist: Scuba Steve

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Mixed Reality - BOOM! Surface Phone
Windows Mixed Reality Ultimate Guide | VRHeads
Sun, 07 Jan 2018 04:45
Looking for some help? Accessories? Games? Ideas on what to do in Windows Mixed Reality? Our ultimate guide has everything you're looking for.
Windows Mixed Reality (WMR) has entered the VR arena, offering a varied selection of headsets and motion controllers from a variety of manufacturers. The platform's integration with SteamVR has only expanded the selection of games, apps, and experiences already found in the Microsoft Store, offering up an overall impressive library. Whether you recently got your hands on a WMR headset or you already have some experience under your belt, this guide aims to provide you with recommendations, suggestions, and help with the emerging VR platform.
See at Microsoft Store
Meet Windows Mixed RealityComing out of the gate with five different headsets from five different manufacturers, including Acer, Dell, HP, Lenovo, and Samsung, WMR is available at a few different price points. If you're thinking that it might be for you, check out these articles to help you get to know the platform.
Powering Windows Mixed Reality
Compared to the Oculus Rift and HTC Vive, WMR doesn't require nearly as much PC power to get it off the ground, though some games do need a fair amount of power to run properly. These articles will help you get acquainted with what's required to run regular WMR and WMR Ultra, as well as some pre-built PC options that make it easy to get going.
How to get everything set up for Windows Mixed Reality
Now that you have a WMR headset and a PC to run it, it's time to get started! Use these links to get everything set up quickly and properly.
Safety and comfortGames, apps, and experiences for Windows Mixed Reality
There are plenty of games and experiences available already in the Microsoft Store with more on the way every day. Don't forget about Steam's enormous library of VR content! We're here to help you sort the great from the not-so-great content.
Troubleshooting Windows Mixed Reality
Even the best systems experience issues, and WMR is no different. Luckily, most issues can be taken care of quickly and easily. If you're experiencing problems with WMR, be sure to check out these links for help.
Updated December 20, 2017: We've refreshed this guide to ensure you're still getting information on everything Windows Mixed Reality has to offer.
Navigating the Windows Mixed Reality home
Sun, 07 Jan 2018 03:51
Just like the Windows PC experience starts with the desktop, Windows Mixed Reality starts with the home. The Windows Mixed Reality home leverages our innate ability to understand and navigate 3D places. With HoloLens, your home is your physical space. With immersive headsets, your home is a virtual place.
Your home is also where you'll use the Start menu to open and place apps and content. You can fill your home with mixed reality content and multitask by using multiple apps at the same time. The things you place in your home stay there, even if you restart your device.
The Start menu consists of:
System information (network status, battery status, current time, and volume)Cortana (on immersive headsets, a Start tile; on HoloLens, at the top of Start)Pinned appsThe All apps button (plus sign)Photo and video buttons for mixed reality captureSwitch between the pinned apps and All apps views by selecting the plus or minus buttons. To open the Start menu on HoloLens, use the bloom gesture. On an immersive headset, press the Windows button on your controller.
Launching apps To launch an app, select it on Start. The Start menu will disappear, and the app will open in placement mode, as either a 2D window or a 3D model.
To run the app, you'll need to then place it in your home:
Use your gaze or controller to position the app where you want it. It will automatically adjust (in size and position) to conform to the space where you place it.Place the app using air-tap (HoloLens) or the Select button (immersive headsets). To cancel and bring back the Start menu, use the bloom gesture or the Windows button.2D apps, created for desktop, mobile, or Xbox can be modified to run as mixed reality immersive apps using the HolographicSpace API. An immersive app takes the user out of the home and into an immersive experience. Users can return home with the bloom gesture (HoloLens) or by pressing the Windows button on their controller (immersive headsets).
Apps can also be launched via an app-to-app API or via Cortana.
Moving and adjusting apps Select Adjust on the app bar to reveal controls that move, scale, and rotate mixed reality content. When you're finished, select Done.
Different apps may have additional options on the app bar. For example, Microsoft Edge has Scroll, Drag, and Zoom choices.
The Back button navigates back to previously viewed screens in the app. It will stop when you reach the beginning of the experiences that have been shown in the app, and will not navigate to other apps.
Getting around your home With HoloLens, you move through physical space to move around your home.
With immersive headsets, you can similarly get up and walk around in your playspace to move within a similar area in the virtual world. To move across longer distances, you can use the thumbstick on your controller to virtually "walk," or you can use teleportation to immediately jump longer distances.
To teleport:
Bring up the teleportation reticle.Using motion controllers: press the thumbstick forward and hold it in that position.Using an Xbox controller: press the left thumbstick forward and hold it in that position.Using a mouse: hold down the right-click mouse button (and use the scroll wheel to rotate the direction you want to face when you teleport).Place the reticle where you want to teleport.Using motion controllers: tilt the controller (on which you're holding the thumbstick forward) to move the reticle.Using an Xbox controller: use your gaze to move the reticle.Using a mouse: move your mouse to move the reticle.Release the button to teleport where the reticle was placed.To virtually "walk:"
Using motion controllers: click down on the thumbstick and hold, then move the thumbstick in the direction you want to "walk."Using an Xbox controller: click down on the left thumbstick and hold, then move the thumbstick in the direction you want to "walk."Immersive headset input support Windows Mixed Reality immersive headsets support multiple input types for navigating the Windows Mixed Reality home. HoloLens does not support accessory inputs for navigation, because you physically walk around and see your environment. However, HoloLens does support inputs for interacting with apps.
Motion controllers The best Windows Mixed Reality experience will be with Windows Mixed Reality motion controllers that support 6 degrees-of-freedom tracking using just the sensors in your headset - no external cameras or markers required!
Navigation commands coming soon.
Gamepad Left thumbstick:Press and hold the left thumbstick forward to bring up the teleportation reticle.Tap the thumbstick left, right, or back to move left, right, or back in small increments.Click down on the left thumbstick and hold, then move the thumbstick in the direction you want to virtually "walk."Tap the right thumbstick left or right to rotate the direction you're facing by 45 degrees.Pressing the A button performs a select and acts like the air tap gesture.Pressing the Guide button brings up the Start menu and acts like the bloom gesture.Pressing the left and right triggers lets you zoom in and out of a 2D desktop app you're interacting with in the home.Keyboard and mouse Note: Use Windows Key + Y to switch the mouse between controlling your PC's desktop and the Windows Mixed Reality home.
Within the Windows Mixed Reality home:
Pressing the left-click mouse button performs a select and acts like the air tap gesture.Holding the right-click mouse button brings up the teleportation reticle.Pressing the Windows key on the keyboard brings up the Start Menu and acts like the bloom gesture.When gazing at a 2D desktop app, you can left-click to select, right-click to bring up context menus, and use the scroll wheel to scroll (just like on your PC's desktop).Cortana Cortana is your personal assistant in Windows Mixed Reality, just like on PC and phone. HoloLens has a built-in microphone, but immersive headsets may require additional hardware. Use Cortana to open apps, restart your device, look things up online, and more. Developers may also choose to integrate Cortana into their experiences.
You can also use voice commands to get around your home. For example, point at a button (using gaze or a controller, depending on the device) and say ''Select.'' Other voice commands include ''Go home,'' ''Bigger,'' ''Smaller,'' ''Close,'' and ''Face me.''
Store, Settings, and system apps Windows Mixed Reality has a number of built-in apps, such as:
Windows Store to get apps and gamesWindows Feedback to submit feedback about the system and system appsSettings to configure system settings (including networking and system updates)Microsoft Edge to browse websitesPhotos to view and share photos and videosCalibration (HoloLens only) for adjusting the HoloLens experience to the current userLearn Gestures (HoloLens) or Learn Mixed Reality (immersive headsets) to learn about using your deviceHolograms to decorate your world with mixed reality contentMixed Reality Portal (desktop) for setting up and managing your immersive headset and streaming a live preview of your view in the headset for others to see.Desktop (immersive headsets) for viewing your desktop monitor while in an immersive headsetSee also
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Intel Armageddon
From Trey, explanation of the bug
I’m just starting Thursday’s show, and heard you asking John
about the flaw. I’m sure you’ve had it explained by now, but just in case I
figured I would send you this.
Modern processors get some of their go-fast juice by trying
to guess what you’re going to ask it to do next. It predicts that you’re going
to want the CPU to do XYZ, and gets started on it. It’s actually pretty damn
good, so by the time you ask it to do the work it’s either already done or
close to done.
The flaw is that researchers figured out how anyone can ask
the processor what it has guessed you will want to do. This means that an
attacker can read things in the computer’s memory that they’re not supposed to
have access to. This is especially bad in places like Amazon’s EC2 or Microsoft’s
Azure where they run virtual servers for many different customers on the same
physical hardware.
The only fix for this is to disable this prediction ability.
Doing so, however, means you don’t get the speed boost from it. That’s why the
fix slows computers down by 12-30%
——
I do IT Security for Cisco. Specifically I get paid to
understand these vulnerabilities and explain them to less technical
folks.
Trey
Meltdown, Spectre: The password theft bugs at the heart of Intel CPUs ' The Register
Thu, 04 Jan 2018 22:58
Summary The severe design flaw in Intel microprocessors that allows sensitive data, such as passwords and crypto-keys, to be stolen from memory is real '' and its details have been revealed.
On Tuesday, we warned that a blueprint blunder in Intel's CPUs could allow applications, malware, and JavaScript running in web browsers, to obtain information they should not be allowed to access: the contents of the operating system kernel's private memory areas. These zones often contain files cached from disk, a view onto the machine's entire physical memory, and other secrets. This should be invisible to normal programs.
Thanks to Intel's cockup '' now codenamed Meltdown '' that data is potentially accessible, meaning bad websites and malware can attempt to rifle through the computer's memory looking for credentials, RNG seeds, personal information, and more.
Here's a video demonstrating a Meltdown attack:
On a shared system, such as a public cloud server, it is possible, depending on the configuration, for software in a guest virtual machine to drill down into the host machine's physical memory and steal data from other customers' virtual machines. See below for details on Xen and VMware hypervisor updates.
Intel is not the only one affected. Arm and AMD processors are as well '' to varying degrees. AMD insisted there is a "near-zero" risk its chips can be attacked in some scenarios, but its CPUs are vulnerable in others. The chip designer has put up a basic page that attempts to play down the impact of the bugs on its hardware.
Arm has produced a list of its affected cores, which are typically found in smartphones, tablets and similar handheld gadgets. That list also links to workaround patches for Linux-based systems. Nothing useful from Intel so far.
This is, essentially, a mega-gaffe by the semiconductor industry. As they souped up their CPUs to race them against each other, they left behind one thing in the dust. Security.
One way rival processors differentiate themselves, and perform faster than their competitors, is to rely on speculative execution. In order to keep their internal pipelines primed with computer code to obey, they do their best to guess which instructions will be executed next, fetch those from memory, and carry them out. If the CPU guesses wrong, it has to undo the speculatively executed code, and run the actual stuff required.
Unfortunately, the chips in our desktop PCs, laptops, phones, fondleslabs, and backend servers do not completely walk back every step taken when they realize they've gone down the wrong path of code. That means remnants of data they shouldn't have been allowed to fetch remain in their temporary caches, and can be accessed later.
The trick is to line up instructions in a normal user process that cause the processor to speculatively fetch data from protected kernel memory before performing any security checks. The crucial Meltdown-exploiting x86-64 code can be as simple as...
; rcx = kernel address; rbx = probe arrayretry: mov al, byte [rcx] shl rax, 0xc jz retry mov rbx, qword [rbx + rax]Trying to fetch a byte from the kernel address as a user process triggers an exception '' but the subsequent instructions have already been speculatively executed out of order, and touch a cache line based on the content of that fetched byte.
An exception is raised, and handled non-fatally elsewhere, while the out-of-order instructions have already acted on the content of the byte. Doing some Flush+Reload magic on the cache reveals which cache line was touched and thus the content of the kernel memory byte. Repeat this over and over, and eventually you dump the contents of kernel memory.
On Wednesday, following research by a sizable collection of boffins, details of three closely related vulnerabilities involving the abuse of speculative execution in modern CPUs were made public:
CVE-2017-5753: Known as Variant 1, a bounds check bypassCVE-2017-5715: Known as Variant 2, branch target injectionCVE-2017-5754: Known as Variant 3, rogue data cache loadThese have been helpfully grouped into two logo'd and branded vulnerabilities: Meltdown (Variant 3), and Spectre (Variants 1 and 2). Both links go to a website with the full technical papers detailing the attacks if you want to see in gory detail how they work.
There is also a Google Project Zero blog post going over the finer points. Finally, here's some proof-of-concept exploit code that runs on Windows.
Here's a summary of the two branded bugs:
MeltdownThis is the big bug reported on Tuesday.It can be exploited by normal programs to read the contents of private kernel memory.It affects potentially all out-of-order execution Intel processors since 1995, except Itanium and pre-2013 Atoms. It definitely affects out-of-order x86-64 Intel CPUs since 2011. There are workaround patches to kill off this vulnerability available now for Windows, and for Linux. Apple's macOS has been patched since version 10.13.2. Installing and enabling the latest updates for your OS should bring in the fixes. You should go for it. If you're a Windows Insider user, you're likely already patched. Windows Server admins must enable the kernel-user space splitting feature once it is installed; it's not on by default.Amazon has updated its AWS Linux guest kernels to protect customers against Meltdown. Google recommends its cloud users apply necessary patches and reboot their virtual machines. Microsoft is deploying fixes to Azure. If you're using a public cloud provider, check them out for security updates.The workarounds move the operating system kernel into a separate virtual memory space. On Linux, this is known as Kernel Page Table Isolation, or KPTI, and it can be enabled or disabled during boot up. You may experience a performance hit, depending on your processor model and the type of software you are running. If you are a casual desktop user or gamer, you shouldn't notice. If you are hitting storage, slamming the network, or just making a lot of rapid-fire kernel system calls, you will notice a slowdown. Your mileage may vary.It also affects Arm Cortex-A75 cores, which aren't available yet. Qualcomm's upcoming Snapdragon 845 is an example part that uses the A75. There are Linux kernel KPTI patches available to mitigate this. The performance hit isn't known, but expected to be minimal.Additionally, Cortex-A15, Cortex-A57 and Cortex-A72 cores suffer from a variant of Meltdown: protected system registers can be accessed, rather than kernel memory, by user processes. Arm has a detailed white paper and product table, here, describing all its vulnerable cores, the risks, and mitigations.Meltdown does not affect any AMD processors.Googlers confirmed an Intel Haswell Xeon CPU would allow a normal user program to read kernel memory.It was discovered and reported by three independent teams: Jann Horn (Google Project Zero); Werner Haas, Thomas Prescher (Cyberus Technology); and Daniel Gruss, Moritz Lipp, Stefan Mangard, Michael Schwarz (Graz University of Technology).SpectreSpectre allows, among other things, user-mode applications to extract information from other processes running on the same system. Alternatively, it can be used by code to extract information from its own process. Imagine malicious JavaScript in a webpage churning away using Spectre bugs to extract login cookies for other sites from the browser's memory.It is a very messy vulnerability that is hard to patch, but is also tricky to exploit. It's hard to patch because just installing the aforementioned KPTI features is pointless on most platforms '' you must recompile your software with countermeasures to avoid it being attacked by other programs, or wait for a chipset microcode upgrade. There are no solid Spectre fixes available yet for Intel and AMD parts.In terms of Intel, Googlers have found that Haswell Xeon CPUs allow user processes to access arbitrary memory; the proof-of-concept worked just within one process, though. More importantly, the Haswell Xeon also allowed a user-mode program to read kernel memory within a 4GB range on a standard Linux install.This is where it gets really icky. It is possible for an administrative user within a guest virtual machine on KVM to read the host server's kernel memory in certain conditions. According to Google:AMD insists its processors are practically immune to Variant 2 Spectre attacks. As for Variant 1, you'll have to wait for microcode updates or recompile your software with forthcoming countermeasures described in the technical paper on the Spectre website.The researchers say AMD's Ryzen family is affected by Spectre. Googlers have confirmed AMD FX and AMD Pro cores can allow arbitrary data to be obtained by a user process; the proof-of-concept worked just within one process, though. An AMD Pro running Linux in a non-default configuration '' the BPF JIT is enabled '' also lets a normal user process read from 4GB of kernel virtual memory.For Arm, Cortex-R7, Cortex-R8, Cortex-A8, Cortex-A9, Cortex-A15, Cortex-A17, Cortex-A57, Cortex-A72, Cortex-A73, and Cortex-A75 cores are affected by Spectre. Bear in mind Cortex-R series cores are for very specific and tightly controlled embedded environments, and are super unlikely to run untrusted code. To patch for Arm, apply the aforementioned KPTI fixes to your kernel, and/or recompile your code with new defenses described in the above-linked white paper.Googlers were able to test that an Arm Cortex-A57 was able to be exploited to read arbitrary data from memory via cache sniffing; the proof-of-concept worked just within one process, though. Google is confident ARM-powered Android devices running the latest security updates are protected due to measures to thwart exploitation attempts '' specifically, access to high-precision timers needed in attacks is restricted. Further security patches, mitigations and updates for Google's products '' including Chrome and ChromeOS '' are listed here.Discovered and reported by these separate teams: Jann Horn (Google Project Zero); and Paul Kocher in collaboration with, in alphabetical order, Daniel Genkin (University of Pennsylvania and University of Maryland), Mike Hamburg (Rambus), Moritz Lipp (Graz University of Technology), and Yuval Yarom (University of Adelaide and Data61).We're told Intel, AMD and Arm were warned of these security holes back in June last year. Our advice is to sit tight, install OS and firmware security updates as soon as you can, don't run untrusted code, and consider turning on site isolation in your browser (Chrome, Firefox) to thwart malicious webpages trying to leverage these design flaws to steal session cookies from the browser process.
If you are using the Xen hypervisor, you should grab security patches when they become available. Intel and AMD processors are affected, and they're still checking whether Arm is.
"Xen guests may be able to infer the contents of arbitrary host memory, including memory assigned to other guests," due to these processor security holes, according to the hypervisor project team. If you've experienced a mass reboot '' or are scheduled for one '' by your public cloud provider, this may be why.
Meanwhile, VMware's ESXi, Workstation and Fusion hypervisors need patching to counteract the underlying hardware design flaws.
Finally, if you are of the opinion that us media types are being hysterical about this design blunder, check this out: CERT recommends throwing away your CPU and buying an non-vulnerable one to truly fix the issue. ®
Google Online Security Blog: More details about mitigations for the CPU Speculative Execution issue
Fri, 05 Jan 2018 11:19
Posted by Matt Linton, Senior Security Engineer and Pat Parseghian, Technical Program Manager Yesterday, Google's Project Zero team posted detailed technical information on three variants of a new security issue involving speculative execution on many modern CPUs. Today, we'd like to share some more information about our mitigations and performance.
In response to the vulnerabilities that were discovered we developed a novel mitigation called ''Retpoline'' -- a binary modification technique that protects against ''branch target injection'' attacks. We shared Retpoline with our industry partners and have deployed it on Google's systems, where we have observed negligible impact on performance.
In addition, we have deployed Kernel Page Table Isolation (KPTI) -- a general purpose technique for better protecting sensitive information in memory from other software running on a machine -- to the entire fleet of Google Linux production servers that support all of our products, including Search, Gmail, YouTube, and Google Cloud Platform.
There has been speculation that the deployment of KPTI causes significant performance slowdowns. Performance can vary, as the impact of the KPTI mitigations depends on the rate of system calls made by an application. On most of our workloads, including our cloud infrastructure, we see negligible impact on performance.
In our own testing, we have found that microbenchmarks can show an exaggerated impact. Of course, Google recommends thorough testing in your environment before deployment; we cannot guarantee any particular performance or operational impact.
Speculative Execution and the Three Methods of Attack
In addition, to follow up on yesterday's post, today we're providing a summary of speculative execution and how each of the three variants work.
In order to improve performance, many CPUs may choose to speculatively execute instructions based on assumptions that are considered likely to be true. During speculative execution, the processor is verifying these assumptions; if they are valid, then the execution continues. If they are invalid, then the execution is unwound, and the correct execution path can be started based on the actual conditions. It is possible for this speculative execution to have side effects which are not restored when the CPU state is unwound, and can lead to information disclosure.
Project Zero discussed three variants of speculative execution attack. There is no single fix for all three attack variants; each requires protection independently.
Variant 1 (CVE-2017-5753), ''bounds check bypass.'' This vulnerability affects specific sequences within compiled applications, which must be addressed on a per-binary basis.Variant 2 (CVE-2017-5715), ''branch target injection''. This variant may either be fixed by a CPU microcode update from the CPU vendor, or by applying a software mitigation technique called ''Retpoline'' to binaries where concern about information leakage is present. This mitigation may be applied to the operating system kernel, system programs and libraries, and individual software programs, as needed.Variant 3 (CVE-2017-5754), ''rogue data cache load.'' This may require patching the system's operating system. For Linux there is a patchset called KPTI (Kernel Page Table Isolation) that helps mitigate Variant 3. Other operating systems may implement similar protections - check with your vendor for specifics.This attack variant allows malicious code to circumvent bounds checking features built into most binaries. Even though the bounds checks will still fail, the CPU will speculatively execute instructions after the bounds checks, which can access memory that the code could not normally access. When the CPU determines the bounds check has failed, it discards any work that was done speculatively; however, some changes to the system can be still observed (in particular, changes to the state of the CPU caches). The malicious code can detect these changes and read the data that was speculatively accessed. The primary ramification of Variant 1 is that it is difficult for a system to run untrusted code within a process and restrict what memory within the process the untrusted code can access. In the kernel, this has implications for systems such as the extended Berkeley Packet Filter (eBPF) that takes packet filterers from user space code, just-in-time (JIT) compiles the packet filter code, and runs the packet filter within the context of kernel. The JIT compiler uses bounds checking to limit the memory the packet filter can access, however, Variant 1 allows an attacker to use speculation to circumvent these limitations. Mitigation requires analysis and recompilation so that vulnerable binary code is not emitted. Examples of targets which may require patching include the operating system and applications which execute untrusted code. This attack variant uses the ability of one process to influence the speculative execution behavior of code in another security context (i.e., guest/host mode, CPU ring, or process) running on the same physical CPU core. Modern processors predict the destination for indirect jumps and calls that a program may take and start speculatively executing code at the predicted location. The tables used to drive prediction are shared between processes running on a physical CPU core, and it is possible for one process to pollute the branch prediction tables to influence the branch prediction of another process or kernel code. In this way, an attacker can cause speculative execution of any mapped code in another process, in the hypervisor, or in the kernel, and potentially read data from the other protection domain using techniques like Variant 1. This variant is difficult to use, but has great potential power as it crosses arbitrary protection domains. Mitigating this attack variant requires either installing and enabling a CPU microcode update from the CPU vendor (e.g., Intel's IBRS microcode), or applying a software mitigation (e.g., Google's Retpoline) to the hypervisor, operating system kernel, system programs and libraries, and user applications. This attack variant allows a user mode process to access virtual memory as if the process was in kernel mode. On some processors, the speculative execution of code can access memory that is not typically visible to the current execution mode of the processor; i.e., a user mode program may speculatively access memory as if it were running in kernel mode. Using the techniques of Variant 1, a process can observe the memory that was accessed speculatively. On most operating systems today, the page table that a process uses includes access to most physical memory on the system, however access to such memory is limited to when the process is running in kernel mode. Variant 3 enables access to such memory even in user mode, violating the protections of the hardware. Mitigating this attack variant requires patching the operating system. For Linux, the patchset that mitigates Variant 3 is called Kernel Page Table Isolation (KPTI). Other operating systems/providers should implement similar mitigations. Mitigations for Google products You can learn more about mitigations that have been applied to Google's infrastructure, products, and services here.
Intel CEO's massive stock dump raises eyebrows - Jan. 4, 2018
Fri, 05 Jan 2018 11:14
Krzanich now holds only the minimum number of shares he's required to own.
Intel says there's nothing to see here: Krzanich remains confident about the company's future, and his massive stock sale was unrelated to the security issue that sent shares down about 6% over the past two days.
"Brian's sale is unrelated," the company said in a statement. "It was made pursuant to a pre-arranged stock sale plan ... with an automated sale schedule. He continues to hold shares in-line with corporate guidelines."
Related or not, it doesn't exactly give investors the warm fuzzies about Intel's stock prospects.
"He's an engineer; he can do math," said Stacy Rasgon, an Intel analyst at Sanford Bernstein. "This is not an incredibly bullish statement regardless of the security stuff."
The funny thing is Intel (INTC ) seemed to be in the middle of a turnaround. The company had a wildly successful 2017. The stock soared 27% after a solid summer quarter. Analysts are bullish: More than half call Intel a "buy," and just one in eight holds a negative outlook for the stock.
Brian KrzanichKrzanich himself was optimistic in his year-end message to employees. He said 2017 would be a record year and 2018 would mark the year Intel put the slumping PC market in the rearview mirror, according to Intel spokeswoman Cara Walker.
Yet on October 30, just three days before Intel's stock reached its 2017 peak, Krzanich announced a plan to sell 245,000 of his own shares by November 29. That left him with just 250,000 -- the fewest he's allowed to hold under his contract with Intel.
Krzanich had been selling stock all year. Bit by bit, he sold shares 21 times during 2017, but his largest sale by far was his last, when he dumped $50 million worth of stock: $28 million in just-vested options plus $22 million worth of Intel shares he had previously owned.
CEOs sell stock for all kinds of reasons: diversification, liquidity, financing a big purchase. But that's a massive amount of stock that Krzanich dumped, and holding the minimum isn't a great look.
"In all the years I've been at this and of all the companies I've covered, I can't recall another single massive sale on this scale," Rasgon said.
Krzanich sold stock 18 times in 2016, but none of those sales approached the size of his 2017 year-end cash-out. He ended 2016 with 18,000 more shares than he started.
The timing of the November sale doesn't look great either.
Related: Update your software today. Seriously.
Intel's Walker confirmed that security analysts informed the company in June of the security holes in its PC and phone microchips. (Intel made the public aware on Wednesday.) It's not clear how severe the problem will ultimately be for Intel -- it may have to pay to replace some customers' chips, but that's far from certain.
Walker says the company doesn't expect the security flaw will cost a lot of money to fix, and it is already taking steps to solve the problem.
But the CEO's stock sale still violates rule No. 1 for CEOs: Don't do anything that gives you front-page headlines for the wrong reasons.
CNNMoney (New York) First published January 4, 2018: 3:44 PM ET
An Update on AMD Processor Security | AMD
Fri, 05 Jan 2018 12:04
Information Security is a Priority at AMD
There has been recent press coverage regarding a potential security issue related to modern microprocessors and speculative execution. Information security is a priority at AMD, and our security architects follow the technology ecosystem closely for new threats.
It is important to understand how the speculative execution vulnerability described in the research relates to AMD products, but please keep in mind the following:
The research described was performed in a controlled, dedicated lab environment by a highly knowledgeable team with detailed, non-public information about the processors targeted.The described threat has not been seen in the public domain.When AMD learned that researchers had discovered a new CPU attack targeting the speculative execution functionality used by multiple chip companies' products, we immediately engaged across the ecosystem to address the teams' findings.
The research team identified three variants within the speculative execution research. The below grid details the specific variants detailed in the research and the AMD response details.
Variant / AMD Response Matrix Google Project Zero (GPZ) Research TitleDetailsVariant OneBounds Check BypassResolved by software / OS updates to be made available by system vendors and manufacturers. Negligible performance impact expected.Variant TwoBranch Target InjectionDifferences in AMD architecture mean there is a near zero risk of exploitation of this variant. Vulnerability to Variant 2 has not been demonstrated on AMD processors to date.Variant ThreeRogue Data Cache LoadZero AMD vulnerability due to AMD architecture differences.As the security landscape continues to evolve, a collaborative effort of information sharing in the industry represents the strongest defense.
Total protection from all possible attacks remains an elusive goal and this latest example shows how effective industry collaboration can be.
As always, AMD strongly encourages its customers to consistently undertake safe computing practices, examples of which include: not clicking on unrecognized hyperlinks, following strong password protocols, using secure networks, and accepting regular software updates.
Intel hit with three lawsuits over chip security
Fri, 05 Jan 2018 19:07

Intel, which has lost billions of dollars in market value this week after revelations of chip vulnerabilities that have opened up most of the world's computing devices to the risk of hacking, is now facing at least three related lawsuits '-- one of which estimates damages of more than $15 billion.
One of the lawsuits, filed Wednesday in the U.S. District Court in San Jose, seeks class-action status on behalf of all Intel customers who bought a defective CPU. The suit claims that patches being released by Intel and others are inadequate because security researchers have said the fixes will slow down computers.
''In essence, Intel x86-64x CPU owners are left with the unappealing choice of either purchasing a new processor or computer containing a CPU that does not contain the Defect, or continuing to use a computer with massive security vulnerabilities or one with significant performance degradation,'' the lawsuit says.
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Intel disputed that point in a news release this week, saying ''Apple, Amazon, Google and Microsoft are among those reporting that they are seeing little to no performance impact.'' The companies have reportedly been working on fixes for the flaws, dubbed Meltdown and Spectre, for months.
Thursday, the Santa Clara chip giant said it ''continues to believe that the performance impact of these updates is highly workload-dependent and, for the average computer user, should not be significant and will be mitigated over time.''
Tech news site the Register was the first to report Tuesday about the security flaws. Meltdown is specific to Intel chips and could allow hackers to access a computer's memory. Spectre, which affects Intel, AMD and ARM chips, could let hackers trick applications into handing over computer users' information.
The other lawsuits were filed in Oregon and Indiana and are also seeking class-action status. All three lawsuits accuse Intel of knowingly selling core processors with security defects.
''Every aggrieved consumer misled by Intel's intentional failure to disclose the material defect in its microchips as alleged in this complaint suffered an actual ascertainable loss of the purchase price they paid for their microchip,'' says the suit filed Thursday in Oregon, which seeks national class-action status.
That lawsuit says ''the amount in controversy exceeds $15 billion, based on $200 statutory damages per consumer and Intel's estimated 2017 fourth quarter sales revenue of $16.3 billion.''
Intel shares are up about 1.2 percent Friday, to $44.96, after falling as much as nearly 7 percent this week after the Register report and the subsequent follow-up by security researchers. AMD shares, which rose about 10 percent over the past few days, are down about 2.5 percent Friday to $11.82.
Photo: Intel headquarters in Santa Clara. (Mercury News archives)
Tags:chips, Intel, Lawsuits, Meltdown, Security, Spectre
Intel Security Risk Is Much Worse Than Management Commentary Indicates - Intel Corporation (NASDAQ:INTC) | Seeking Alpha
Fri, 05 Jan 2018 15:50
As security concerns about its processors mounted, Intel (INTC) responded to the developments and followed it up with a conference call further alleviate investor concerns.
As we demonstrate below, Intel's narrative on the subject is not fully credible.
To begin with, investors need to familiarize themselves with the problem. The security issue appears to have been first notified to Intel on 6/1/2017 by Google Project Zero team. (The Google (GOOG) (GOOGL) link may be hard to understand and non-technically inclined investors may find the explanation of Meltdown and Spectre much more comprehensible).
In short, the problem is about malicious code having access to unauthorized information on the system. Information such as passwords, personal data, and critical documents. The security concerns are severe. Per standard industry practices, Intel, and several industry players including Advanced Micro Devices (AMD), ARM, Microsoft (MSFT), several software and security companies, have been working on understanding the scope of the problem and identifying fixes to mitigate the problem.
The status of affairs now is that Meltdown, something that seems to be impacting mainly Intel processors, is an immediate challenge that needs to be mitigated. Spectre, on the other hand, is a tougher exploit that affects all modern microprocessors but is not an immediate concern. Spectre is being seen as a likely long-term problem for the industry.
Information that has become available over the last few days indicates that some of the fixes for Meltdown require extensive changes to operating systems such as Linux and Windows and have severe performance implications. While some consumer benchmarks have barely shown any deterioration, some database and cloud-related benchmarks have shown 5% to 30% performance impact. Some benchmarks have shown even more severe performance degradation close to 50%.
AMD is on the record that the Meltdown-related fixes do not apply to its processor architecture and there is no need for performance-crippling patches for its products.
With this backdrop, how does Intel address the issue?
Abysmally.
For example, Intel says in its press release and subsequent presentation that:
''Intel believes these exploits do not have the potential to corrupt, modify or delete data.''
Note that the security issue is not about corrupting, modifying, or deleting data. It is about unauthorized access to critical data. Intel is certainly not addressing the root cause of concern here.
Intel may also not be telling the whole truth when it says:
''Recent reports that these exploits are caused by a ''bug'' or a ''flaw'' and are unique to Intel products are incorrect. Based on the analysis to date, many types of computing devices '-- with many different vendors' processors and operating systems '-- are susceptible to these exploits.''
While this is technically true, the real problem at hand, severe performance degradation, seems to not apply to AMD but only to Intel.
Intel goes a step further and throws mud in the discussion by saying:
''Intel is committed to product and customer security and is working closely with many other technology companies, including AMD, ARM Holdings and several operating system vendors, to develop an industry-wide approach to resolve this issue promptly and constructively.''
This sentence seems to implicate AMD and ARM without quite saying that they too may have problems. Intel continues the obfuscation with the following statement:
''Intel has begun providing software and firmware updates to mitigate these exploits. Contrary to some reports, any performance impacts are workload-dependent, and, for the average computer user, should not be significant and will be mitigated over time.''
While it is true that Intel is providing software and firmware, as they should, saying that performance impact to the ''average computer user'' is insignificant is an incomplete statement. The security issues, especially from Meltdown, appear to be big challenges for not ''average computer users'' but for server and data center deployments.
Intel caps off its response with what we deem to be an incredulous statement:
''Intel believes its products are the most secure in the world and that, with the support of its partners, the current solutions to this issue provide the best possible security for its customers.''
How Intel can claim that its products are most secure when its products have found to be lacking is beyond us.
Intel's dancing around the issue and evading specifics got worse in the subsequent conference call.
During the call, Intel acknowledged that it has seen no degradation in some applications and up to 30% degradation in some applications. Intel did not want to get into details on the impact on desktop or laptop PC users and server or cloud users but there is abundant information in the public domain that indicates that the server and cloud applications are likely the most impacted.
Intel claimed that these security issues have no financial impact on Intel. We are extremely skeptical about this claim because the performance impact of the fixes can be high. A hypothetical 10% performance hit from the bug fixes would mean that server cloud customers would have to add 10% more in CPU resources to mitigate the performance problem. This can be a big cost hit for today's data centers. It is difficult to see server and cloud customers giving Intel a free pass on this one.
Considering the scope of the problem and given that all Intel processors on the field are impacted, and AMD processors are not impacted, it is easy to visualize multi-billion recall situations for Intel.
Intel also skipped answering questions about competitive impact. With AMD's EPYC chip already being a strong server contender even before this security issue surfaced, it is easy to see that Intel will be in a worse competitive position. With some benchmarks seeing 30% impact, it will become much easier for AMD to win server and cloud sockets. And, AMD will have a stronger security story to the boot.
What is even worse is that Intel now has the need to delay future product releases to incorporate the fixes for this security problem. We expect a minimum 6-month delay to allow for design and validation of most future product releases (especially the Xeon family). This will make Intel's product roadmap that much less competitive with AMD.
AMD has already come up with a counter to Intel since Intel's initial claims which indicate that AMD products do not have the same susceptibilities.
In our view, the security problem is a much bigger problem than Intel is acknowledging, and Intel investors will be in for a very rough ride for the next couple of years. While Intel may not have much of a problem on the consumer side from this security issue, in our view, Intel's data center business is at a serious risk.
Furthermore, the PR effort is in such a poor form, it makes Intel looks bad. Note what Linus Torvalds, creator of Linux, has to say on the subject (image below)
SummaryIn spite of Intel's claims otherwise, this security problem is a big deal and this also piles up on Intel's deteriorating competitive position.
Given that Intel's products have the problem and AMD products do not, in effect, AMD solutions are incrementally better by up to 30% and have superior security in our opinion. This makes Intel's server and data center prospects very cloudy.
With a whole host of product, process, and security-related problems, the time has now come for investors to sell Intel short.
Our view of Intel: Sell Short
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Amazon: Intel Meltdown patch will slow down your AWS EC2 server ' The Register
Sat, 06 Jan 2018 05:56
Some Amazon AWS customers have complained of noticeable slowdowns on their cloud server instances '' following the deployment of a security patch to counter the Intel processor design flaw dubbed Meltdown.
Punters said that, since AWS shored up its infrastructure, and began rolling out its Meltdown-patched Linux in December, they have noticed an increase in CPU utilization by their EC2 virtual machines. The solution is to either optimize application code running on the VMs, or move to a more powerful and expensive virtual machine to take the extra load.
Amazon has said it will help those suffering slower-than-expected performance.
To be clear, your humble vultures here at El Reg highly recommend you apply the Meltdown patches on your Intel-powered systems: the processor bug allows user processes to read passwords, keys and other sensitive data out of the kernel's protected memory area.
The software fixes '' which are available for Linux, Windows, and macOS on Intel CPUs '' move the operating system kernel into its own separate virtual memory space, protecting it from Meltdown exploits. The downside is that this introduces extra overhead, potentially slowing down the system.
The performance hit varies wildly depending on the type of applications you're running. Casual desktop users and gamers applying Meltdown mitigations on their computers shouldn't notice any slowdowns. Light installations, such as simple web servers, will be mildly affected. Machines hammering disk storage, slamming the network, or otherwise making lots of system calls, may experience up to 30 per cent reduction in performance. Your mileage may vary.
AMD processors are not affected by this particular design cockup.
A discussion thread in the AWS support forums details dips in performance that occur after rebooting Linux virtual machines with the Meltdown workaround '' dubbed Kernel Page Table Isolation, or KPTI, on Linux '' installed.
"Immediately following the reboot my server running on this instance started to suffer from CPU stress," one admin noted after enabling the patch.
"Looking at CPU stats there was a very clear change in daily CPU usage pattern, despite continuing normal traffic to my server. I performed extensive review of what might have changed on my server configuration but drew a complete blank - configuration of the server did not change."
Another added: "This just happened to us today on a c3.large. The cost to us to move the platform to new hardware and the lost confidence from our customers is huge."
Developer Tim Gostony was also able to record how defending against Chipzilla's design blunder impacted the performance of two of his Intel-powered EC2 Linux instances.
AWS confirmed that the potentially-performance-limiting update the users spoke of was its fix for the kernel memory bug that afflicts the Intel CPUs it uses for the EC2 service. This low-level hardware vulnerability was discovered by researchers who privately alerted Intel in June 2017. Operating system-level workarounds were quietly developed, and rolled out on AWS from December. On Tuesday this week, word of Intel's insecure speculative execution engine, at the heart of the security flaw, emerged.
On Wednesday, a collective of researchers went public with details of Meltdown, plus a related set of processor security holes dubbed Spectre '' which also hits Intel chips, plus some AMD and Arm cores.
A drop in CPU performance is particularly troublesome for cloud compute subscribers where providers bill by the hour or second. When workloads take longer to run, customers end up paying more over the long run.
AWS told El Reg it will be reaching out to customers who notice a slowdown to help get performance back up to pre-patch levels.
"We don't expect meaningful performance impact for most customer workloads," the cloud giant said. "There may end up being cases that are workload or OS specific that experience more of a performance impact. In those isolated cases, we will work with customers to mitigate any impact."
Meanwhile, Microsoft Azure is deploying Meltdown defenses, and Google's Compute Engine is secured. Check with your cloud provider for the latest on its response to Intel's engineering gaffe. The slowdown problem is not limited to AWS: you may experience a performance hit on other clouds. If so, this is why. ®
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Hate trumps Love
Michael Wolff Did What Every Other White House Reporter Is too Cowardly to Do
Sat, 06 Jan 2018 05:27
I'm gonna begin this post with the same disclaimer that needs to come with every post about Michael Wolff, which is that Wolff is fartsniffer whose credibility is often suspect and who represents the absolute worst of New York media cocktail circuit inbreeding. But in a way, it's fitting that our least reliable president could finally find himself undone at the hands of one of our least reliable journalists.
All of the Wolff's excerpts from Fire & Fury so far (the book was rushed into stores today) read like jayvee fan fiction. They read like a pilot that Steve Bannon himself wrote, pitched to Hollywood, and had rejected 17 times over. They read, in short, like bullshit. And yet'... Wolff has audio. He's got hours upon hours of audio. Not only that, but the book has already caused legitimate upheaval in the administration, opened a permanent rift between President Trump and Bannon, AND it confirms what we have all always known to be true: that the president severely lacks the cognitive ability to do this job, and that he is surrounded at all times by a cadre of enablers, dunces, and outright thieves. As much as I wanna discredit Wolff, he got receipts and, more important, he used them. Wolff got it all. Wolff nailed them.
And look how he did it. He did it by sleazily ingratiating himself with the White House, gaining access, hosting weird private dinners, and then taking full advantage of the administration's basic lack of knowledge about how reporting works. Some of the officials Wolff got on tape claim to be unaware that they were on the record. Wolff denies this, but he's very much upfront in the book's intro about the fact that he was able to take full advantage of the incredible "lack of experience" on display here. In other words, Wolff got his book by taking advantage of a bunch of naive dopes.
Thank God for that. Wolff has spent this week thoroughly exploiting Trump and his minions the same way they've exploited the cluelessness of others. And he pulled it off because, at long last, there was a reporter out there willing to toss decorum aside and burn bridges the same way Trump does.
Everyone around Donald Trump is too polite to Donald Trump. Democrats, foreign dignitaries, underlings'... all of them. And the White House press is perhaps the worst offender. From the media pool playing along with Sarah Sanders during press conferences'--conferences where Sanders openly lies and pisses on democracy'--to access merchants like Maggie Haberman doling out Trump gossip like so many bread crumbs, too many reporters have been far too deferential to an administration that is brazenly racist, dysfunctional, and corrupt. And for what purpose? It's clear to me that Haberman and the like aren't saving up their chits for just the EXACT right time to bring this Administration down. No, the only end goal of their access is continued access, to preserve it indefinitely so that the copy spigot never gets shut off. They are abiding by traditional wink-wink understandings that have long existed between the government and the press covering it.
But Wolff didn't do that. He did not engage in some endless bullshit access tango. No, Wolff actually USED his access, and extended zero courtesy to Trump on the process, and it's going to pay off for him not just from a book sales standpoint, but from a real journalistic impact. I am utterly sick to death of hearing anonymous reports about people inside the White House ''concerned'' about the madman currently in charge of everything. These people don't deserve the courtesy of discretion. They don't deserve to dictate the terms of coverage to people. They deserve to be torched.
Trump ascended into power in part because he relied on other people being too nice. It's fun to rampage through china shop when the china shop owner is standing over there being like, ''SIR, that is not how we do things here!'' If Trump refuses to abide by the standard (and now useless) ''norms'' of the presidency'--shit, if he doesn't even KNOW them'--why should ANYONE in the press adhere to needless norms of their own? They shouldn't, and it appears that Michael Wolff was one of the few people to instinctively grasp that, and I hope more White House insiders follow his lead. Sometimes you need a rat to catch a rat.
Scripting News: Michael Wolff's book
Fri, 05 Jan 2018 11:37

I ordered a copy, of course. # I've read the New York excerpt and the Hollywood Reporter piece, and have so many things to say. Let's start with two.# We knew the Trump White House is a chaotic planless place, a random Ouija board, manipulated by rich donors to drain the Treasury, quickly, and to service their pet projects. But with Wolff's writing we have stories to go with this, until now we could only imagine. We had a spy in there the whole time. We didn't even know. What a gift. # And with a clear picture of how much a fool Trump is we know there is nothing more to him than what he appears to be, a well-compensated money-laundering self-promoting agent for Russian oligarchs. That's all Trump is. # (C) 1994-2017 Dave Winer.
Last update: Thursday January 4, 2018; 11:01 AM EST.
ABC News' mistake-prone Brian Ross doesn't return from suspension as planned after botching report on Trump, Russia | Fox News
Thu, 04 Jan 2018 22:23
ABC News' embattled chief investigative correspondent, Brian Ross, has not returned to work as scheduled Thursday, despite the end of his suspension for botching an ''exclusive'' report on Donald Trump and Russia.
Ross was placed on a four-week, unpaid suspension after he reported incorrectly on live television that fired National Security Adviser Michael Flynn would testify that Trump had ordered him to make contact with Russians about foreign policy while Trump was still a candidate. The report raised the specter of Trump's impeachment and sent the stock market plummeting.
After ABC was forced to retract the report, ABC News President James Goldston said on a staff conference call that he'd never felt more ''rage, disappointment and frustration'' in his entire career, and that Ross would never cover Trump again.
Today, an ABC News spokesperson declined to comment on whether Ross will ever be returning to work at all.
''Sounds like separation negotiations,'' an industry insider told Fox News.
Just after Ross was suspended, President Trump told a crowd in Florida that Ross should have been fired.
''They took this fraudster from ABC,'' Trump said. ''They suspended him for a month. They should have fired him for what he wrote. He drove the stock market down 350 points in minutes, which by the way, tells you they really like me, right? When you think of it, and you know what he cost people? And I said to everybody get yourself a lawyer and sue ABC News, sue them.''
(Copyright 2017 The Associated Press. All rights reserved.)
For his part, Ross wrote on Twitter that his job ''is to hold people accountable'' and noted, ''That's why I agree with being held accountable myself.''
Ross' gaffe was the latest in a series of black marks for the multi-award winning reporter, who has been at ABC News since 1994 after spending nearly two decades at NBC. He has not been sanctioned for past errors.
In 2001, Ross incorrectly reported that Saddam Hussein's Iraqi dictatorship may have been responsible for anthrax attacks that terrorized the United States in the months after 9/11. Then-White House press secretary Ari Fleischer tweeted last month that he ''explicitly told ABC News not to go with the anthrax story because it was wrong. Brian Ross went with it anyway - and one week later issued a murky, hard to understand correction.''
ABC News Chief Foreign Correspondent Terry Moran, who was the network's chief White House correspondent at the time, then slammed his own colleague with a terse tweet saying, of Fleischer's tweet, ''This is correct.''
In 2006, Ross reported that then-House Speaker Dennis Hastert was a target of a federal corruption probe involving former lobbyist Jack Abramoff. Despite the Justice Department's denial, Ross insisted that Hastert was ''very much in the mix'' of the investigation. Hastert was never approached by prosecutors.
In 2010, Ross fronted a report called ''Taking on Toyota,'' which claimed that some of the Japanese automaker's cars contained a defect that caused ''unintended acceleration.'' The report included footage of a tachometer shooting from 1,000 to 6,200 RPM in seconds while Ross sat behind the wheel. However, the same footage showed that the car Ross was inside was parked with the doors open at the time.
In a letter to ABC News at the time, Toyota complained that the work by a key expert Ross cited in his report was funded by ''a paid advocate for trial lawyers involved in litigation against Toyota.'' The carmaker added that the expert's demonstrations were carried out ''under conditions that are virtually impossible to occur in real-world conditions.''
Perhaps most infamously, Ross reported in 2012 that Colorado movie theater shooter James Holmes may have had ties to the Tea Party movement.
''There is a Jim Holmes of Aurora, Colorado, page on the Colorado Tea Party site as well, talking about him joining the tea party last year,'' Ross reported on ''Good Morning America.'' ''Now, we don't know if this is the same Jim Holmes '' but this is Jim Holmes of Aurora, Colorado.''
Ross later apologized for the report, but received withering criticism '-- including being dubbed ''America's Wrongest Reporter'' by the now-defunct Gawker website.
''When there's breaking news, especially about terrorism and national security, ABC News' Brian Ross is there,'' John Cook wrote in a post on the gossip blog, before adding, ''And under no circumstances should you listen to anything he says.''
ABC's beleaguered investigative operation also took another hit last month when it acknowledged ''reprimanding'' its top investigative producer for leaking embargoed polling information to President Trump's campaign on Election Day.
ABC News, part of the reliably liberal Disney ABC Television Group, has been quietly undergoing a series of layoffs and demotions as it cuts costs amid perennially poor performance by the overall TV division. The possible exit of Ross, who is believed to make more than $1,000,000 a year, would help the struggling news division save money, both by eliminating his salary cost and also the cost of his producers and expensive productions.
Also adding to cost savings: ABC announced last month the planned departure of anchor Elizabeth Vargas, who draws a seven-figure income. More departures by high-paid talent and executives are expected to follow.
Frank Miles contributed to this report.
Michael Wolff note says he doesn't know if Trump book is all true - Business Insider
Sun, 07 Jan 2018 14:54
Michael Wolff, the author of "Fire and Fury: Inside the Trump White House." AP Photo/Carolyn Kaster
"Fire and Fury: Inside the Trump White House" has set the political world ablaze.It contains vivid, detailed, and embarrassing accounts of President Donald Trump and those around him.But the book's author, Michael Wolff, says he can't be sure that all of it is true.The author of the explosive new book about Donald Trump's presidency acknowledged in an author's note that he wasn't certain all of its content was true.
Michael Wolff, the author of "Fire and Fury: Inside the Trump White House," included a note at the start that casts significant doubt on the reliability of the specifics contained in the rest of its pages.
Several of his sources, he says, were definitely lying to him, while some offered accounts that flatly contradicted those of others.
But some were nonetheless included in the vivid account of the West Wing's workings, in a process Wolff describes as "allowing the reader to judge" whether the sources' claims are true.
Donald Trump, seen at a meeting in the White House the day after elements of Wolff's book began to be reported. AP
In other cases, the media columnist said, he did use his journalistic judgment and research to arrive at what he describes "a version of events I believe to be true."
Here is the relevant part of the note, from the 10th page of the book's prologue:
"Many of the accounts of what has happened in the Trump White House are in conflict with one another; many, in Trumpian fashion, are baldly untrue. These conflicts, and that looseness with the truth, if not with reality itself, are an elemental thread of the book.
"Sometimes I have let the players offer their versions, in turn allowing the reader to judge them. In other instances I have, through a consistency in the accounts and through sources I have come to trust, settled on a version of events I believe to be true."
The book itself, reviewed by Business Insider from a copy acquired prior to its Friday publication, is not always clear about what level of confidence the author has in any particular assertion.
Lengthy, private conversations are reported verbatim, as are difficult-to-ascertain details like what somebody was thinking or how the person felt.
Wolff attributes his book to "more than two hundred interviews" with people including Trump and "most members of his senior staff." According to the news website Axios, Wolff has dozens of hours of tapes to back up what he said.
Claims contained in the book have been widely reported by the media in the US and further afield.
They include assertions that Trump never wanted to be president, that all of his senior staff considered him an idiot, that he tried to lock the Secret Service out of his room, and that he ate at McDonald's to avoid being poisoned.
Business Insider rounded up some more of the most eye-catching claims in this article.
Trump, who sought to block publication of the book but was too late, tweeted Thursday that it was "full of lies, misrepresentations and sources that don't exist."
The White House press secretary, Sarah Huckabee Sanders, described the book as "complete fantasy."
Asked to rebut specific points, she said: "I'm not going to waste my time or the country's time going page by page and talking about a book that is complete fantasy and just full of tabloid gossip."
Other people mentioned in the book have also disputed claims made about them.
Former British Prime Minister Tony Blair, who the book said warned Trump that he may be under surveillance from British spies, issued a statement describing the claim as "categorically absurd" and "simply untrue."
Anna Wintour, the longtime Vogue editor, also dismissed the claim that she lobbied Trump to be his ambassador to the UK as "laughably preposterous."
Other journalists have also urged caution. Some cited Wolff's track record '-- questions were raised about his 2008 book on Rupert Murdoch '-- and others compared his claims with their own knowledge of the Trump White House.
On Friday morning, Wolff responded to claims about the accuracy of his book in an interivew with NBC's "Today" show.
Host Savannah Guthrie asked him: "You stand by everything in the book? Nothing made up?"
He responded: "Absolutely everything in the book."
Shortly after, he expanded, saying: "I am certainly and absolutely, in every way, comfortable with everything I've reported in this book."
This isn't necessarily at odds with what he said in the author's note, as it allows for the possibility that he was told something untrue and repeated it without realising, or reached a wrong conclusion when presenting a version of contested events.
Scoop: Wolff taped interviews with Bannon, top officials - Axios
Sun, 07 Jan 2018 14:54
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Remember Who Michael Wolff Is
Sun, 07 Jan 2018 15:15
GettyA March Madness-style bracket to find the most loathed man in media might include Rupert Murdoch biographer, movie theater scofflaw, and resident killjoy Michael Wolff as its No. 1 overall seed. The ornery press critic is, as Fox News' Howard Kurtz once said with understatement, ''rarely impressed by anyone other than himself.'' And immediate reactions to the rollout of a new, likely overwritten book about the first year in Donald Trump's White House are likely already feeding Wolff's Vanity Fair-sized ego.
Fire and Fury: Inside the Trump White House will probably sell bigly. But I implore you all, before latching onto the sort of two-scoops-of-ice-cream anecdotes that have inspired many a tweeted screenshot, to consider the source: the same Trumpian gremlin who's often been admonished for the very same brand of writing over the past two decades.
The PR tour for Wolff's book, out Jan. 9, began in earnest on Wednesday. The Guardian, which got a copy ''ahead of publication from a bookseller in New England,'' wrote up Steve Bannon's reaction to a Trump Tower meeting between Donald Trump Jr. and a group of Russians in 2016 contained in the book: ''treasonous, or unpatriotic, or bad shit.'' Hours later, New York magazine reportedly pushed up its pre-planned publication of an excerpt that would be widely shared by political media types for its intimate retellings of Donald Trump's cluelessness during the transition'--Who's John Boehner?'--his apparent inability to make it to the Fourth Amendment during a lesson about the Constitution, and his reprimanding the White House's housekeeping staff for picking his shirts up off the floor apparently against his wishes.
''Few people who knew Trump had illusions about him,'' Wolff breathlessly writes. ''That was his appeal: He was what he was. Twinkle in his eye, larceny in his soul.''
It's hard to imagine what exactly that means. But it sounds fun and breezy while appearing to take no prisoners'--classic Wolff fare. The published selections portray Trump as stupid and vindictive, his aides as basically good-faith underlings struggling to manage a walking, talking national security threat. And New York included a lengthy editor's note on how The Hollywood Reporter contributing editor landed such fly-on-the-wall accounts, which included extensive direct quotations:
Shortly after Trump's inauguration, Wolff says, he was able to take up ''something like a semi-permanent seat on a couch in the West Wing'''--an idea encouraged by the president himself. Because no one was in a position to either officially approve or formally deny such access, Wolff became ''more a constant interloper than an invited guest.'' There were no ground rules placed on his access, and he was required to make no promises about how he would report on what he witnessed.
Since then, he conducted more than 200 interviews. In true Trumpian fashion, the administration's lack of experience and disdain for political norms made for a hodgepodge of journalistic challenges. Information would be provided off-the-record or on deep background, then casually put on the record. Sources would fail to set any parameters on the use of a conversation, or would provide accounts in confidence, only to subsequently share their views widely. And the president's own views, private as well as public, were constantly shared by others.
These are the type of lax ground rules that allow writers plenty of wiggle room'--the type of which Wolff has long been known to take full advantage, at times with questionably accurate results. The difference is that the people in Trump's orbit are likely even less reliable sources than many of his past subjects.
Wolff's 1998 book about pursuing digital riches, Burn Rate, was met by largely positive reviews in the midst of the dot-com bubble. But longtime press critic Jack Shafer'--perhaps as close to a defender as Wolff has'--also wondered in his take for Slate whether Wolff's nitty-gritty details could be trusted:
Wolff exploits the human tendency to confuse frankness and cruelty with truth-telling. And by repeatedly reminding the reader of what a dishonest, scheming little shit he is, he seeks to inflate his credibility. A real liar wouldn't tell you that he's a liar as Wolff does, would he? The wealth of verbatim quotations'--constituting a good third of this book'--also enhances Burn Rate's verisimilitude. But should it? Wolff writes that he jotted down bits of dialogue on his legal pads during meetings while others composed to-do lists. Not to accuse anyone of Stephen Glassism, but I'd love to see Wolff post those copious notes on his promotional Web site, www.burnrate.com.
Michelle Cottle made similar observations in a 2004 profile for the New Republic, published when Wolff was a media writer at Vanity Fair, tut-tutting him as ''neither as insightful nor as entertaining when dissecting politics.'' She continued:
Much to the annoyance of Wolff's critics, the scenes in his columns aren't recreated so much as created'--springing from Wolff's imagination rather than from actual knowledge of events. Even Wolff acknowledges that conventional reporting isn't his bag. Rather, he absorbs the atmosphere and gossip swirling around him at cocktail parties, on the street, and especially during those long lunches at Michael's....''His great gift is the appearance of intimate access,'' says an editor who has worked with Wolff. ''He is adroit at making the reader think that he has spent hours and days with his subject, when in fact he may have spent no time at all.''
Even the late David Carr, would-be reverend of the media class from his New York Times pulpit, wrote that ''Wolff has never distinguished himself as a reporter'' when reviewing his 2008 Murdoch biography, The Man Who Owns The News. ''Over the years, Carr wrote, ''he has succeeded in cutting through the clutter by being far less circumspect'--and sometimes more vicious'--than other journalists, whom he views as archaic losers about to go the way of the Walkman.'' Factual errors be damned, Carr added with a begrudging thumbs-up, for ''Wolff prefers the purity of his constructs.''
That approach would seem to be even more dangerous with a book sold as an ''inside story'' of a White House that has proven atrocious at narrating its own story with any grasp of the truth. Since the selections of Wolff's book have dropped, administration officials trotted out the usual cries of false anecdotes and fake sources'--usually a good sign for those in search of the facts. But journalists have already started poking holes in some of the juicier aspects of Wolff's account. Just one example: a simple Google search proves Trump has previously spokenabout Boehner at length, making the notion that he would respond ''Who?'' to a mention of the former House Speaker feel dubious at best. But such details are what gets shared or aggregated, often uncritically.
None of that is to say that Fire and Fury won't be an entertaining read. Wolff has been a frequent critic of the media's Trump coverage, lambasting the press earlier this year for portraying Trump as ''an inept and craven sociopath.'' He's also spoken in favor of journalists acting only as stenographers. Those may have been sly plays to get greater access to the Trump Administration before biting its hand en route to a bestseller.
But if these early excerpts are any indication, Wolff's turn at stenography led to the same basic observations as everybody else'--that the administration is chock full of back-stabbing, out-of-their-depth staffers washed up from a campaign that no one, even the man who's now president, expected to win. The fact that the internet has latched onto so many of these colorful'--if only ''notionally accurate'''--anecdotes may say less about Wolff, that much-hated media man, than it does about the rest of us.
Trump Rotation
Trump rejects author's accusations, calls self 'stable genius'
Sun, 07 Jan 2018 13:55

WASHINGTON (Reuters) - U.S. President Donald Trump on Saturday rejected an author's accusations that he is mentally unfit for office and said his business career and election victory showed he is ''a very stable genius.''
Michael Wolff, who was granted unusually wide access to the White House during much of Trump's first year, has said in promoting his book that Trump is unfit for the presidency. He told BBC Radio in an interview broadcast on Saturday that his book is creating ''the perception and the understanding that will finally end ... this presidency.''
Trump battled back in a series of extraordinary morning posts on Twitter, which appeared to catch some in his inner circle off guard.
Trump said Democratic critics and the U.S. news media were bringing up the ''old Ronald Reagan playbook and screaming mental stability and intelligence'' since they have not been able to bring him down in other ways.
Reagan, a Republican who was the U.S. president from 1981-1989, was diagnosed with Alzheimer's disease in 1994 and died in 2004.
''Actually, throughout my life, my two greatest assets have been mental stability and being, like, really smart,'' said Trump, a former reality TV star and developer.
''I went from VERY successful businessman, to top T.V. Star ... to President of the United States (on my first try). I think that would qualify as not smart, but genius ... and a very stable genius at that!''
Trump, 71, sent the tweets from the presidential retreat at Camp David, Maryland, where he discussed a legislative agenda for the year with Republican congressional leaders and many Cabinet secretaries.
Wolff's book, ''Fire and Fury - Inside the Trump White House,'' portrays Trump as unfocused, unprepared and petty while presiding over a chaotic White House.
Trump, answering questions from reporters at Camp David after the meeting, called Wolff a ''fraud'' and said the book is ''a complete work of fiction.''
''I think it's a disgrace,'' he said.
U.S. President Donald Trump departs for Camp David from the White House in Washington, U.S., January 5, 2018. REUTERS/Kevin Lamarque ACCESS QUESTIONTrump said he never granted Wolff an interview for the book and blamed former adviser Steve Bannon, who he called ''Sloppy Steve,'' for granting Wolff access at the White House. Wolff has said he spoke to Trump but that the president may not have known he was being interviewed.
The tweets were another sign of Trump's frustration at what he views as unfair treatment by the news media of his presidency amid a federal investigation into whether he or his campaign aides colluded with Russia during the 2016 presidential campaign, in which he defeated Democrat Hillary Clinton.
White House Chief of Staff John Kelly told reporters at Camp David that he had not been aware of Trump's morning tweets. Kelly said Trump did not seem angry and on Friday night had watched a new movie, ''The Greatest Showman'' about legendary circus promoter P.T. Barnum, with the lawmakers.
An employee of Book Culture book store unloads copies of "Fire and Fury: Inside the Trump White House" by author Michael Wolff inside the store in New York, U.S. January 5, 2018. REUTERS/Shannon Stapleton Trump, asked about a New York Times report that his aides had pressured Attorney General Jeff Sessions not to recuse himself from the Russia investigation, said: ''Everything I've done has been 100 percent proper.''
Trump, who has often criticized Sessions of his performance as attorney general, said he nonetheless supports him. Sessions had not been invited to the weekend retreat.
Wolff's book has proved to be another shock to the system for Trump and his top aides, coming just as he starts his second year in office.
Wolff told NBC News on Friday that White House staff treated Trump like a child.
''The one description that everyone gave, everyone has in common '-- they all say he is like a child,'' Wolff said. ''And what they mean by that, he has a need for immediate gratification. It's all about him.
''This man does not read, does not listen. He's like a pinball, just shooting off the sides.''
Trump is to undergo the first physical examination of his presidency on Jan. 12. The exam was announced on Dec. 7 after questions arose about Trump's health when he slurred part of a speech announcing that the United States recognized Jerusalem as the capital of Israel.
White House officials and Trump's high-profile supporters have launched an effort to raise doubts about Wolff's credibility. White House spokesman Sarah Sanders said earlier in the week that the book includes ''mistake after mistake after mistake.''
Additional reporting by James Oliphant in Camp David, Maryland; Editing by Lisa Von Ahn and Bill Trott
Is President Trump Mentally Ill? It Doesn't Matter '' Talking Points Memo
Sun, 07 Jan 2018 13:55
We are now back on to the feverish debate about whether or not Donald Trump is mentally ill or suffering from the onset of dementia. The most important thing to know about this debate is that it simply doesn't matter. Diagnoses are something for trained professionals and even they are challenged to make them without a proper in-person examination. But again, it doesn't matter.
For public purposes, clinical diagnoses are only relevant as predictors of behavior. If the President has a cognitive deficiency or mental illness that might cause him to act in unpredictable or dangerous ways or simply be unable to do the job, we need to know. But My God, we do know! We see him acting in these ways every day '' and not just in multiple news reports from an abundance of different news organizations. We see it with our own eyes: in his public actions, his public statements, his tweets. All the diagnosis of a mental illness could tell us is that Trump might be prone to act in ways that we literally see him acting in every day: impulsive, erratic, driven by petty aggressions and paranoia, showing poor impulsive control, an inability to moderate self-destructive behavior. He is frequently either frighteningly out of touch with reality or sufficiently pathological in his lying that it is impossible to tell. Both are very bad.
It is now widely believed that President Reagan showed early signs of his later Alzheimers diagnosis during the latter part of his presidency. How much or whether it affected his ability to carry out his duties is less clear. But that is a very different case. The kinds of subtle lapses in memory or cognition that might hint at such an affliction would be very difficult for the public to be aware of, especially if his staff is making efforts to conceal them. We don't have that problem here.
It is also important to understand the nature of mental health diagnoses. Neurological disorders and lapses of cognitive function are different and something I know less about. But a key element of most DSM-V diagnoses is the degree to which the behavior or affect impairs normal life functions. Can you hold down a job? Can you carry on healthy or functional relationships with other people? Can you sleep and take basic care of your health? This fact is important for a number of reasons. But it highlights an important fact: the nature of clinical diagnoses of mental illness are heavily informed by the need for and potential efficacy of treatment. The framework of these clinical definitions simply don't line up well with the issues that are important to ask about public officials, which are more or less entirely about behavior.
One of the diagnoses you often hear tossed around, rightly or wrongly, is Narcissistic Personality Disorder (NPD), a Class B personality disorder. I think most psychologists and psychiatrists would tell you, privately if not publicly, that a number of Trump's behaviors could (I stress, ''could'') be explained by NPD. But that doesn't tell us that much. Lots of symptoms and behaviors can be explained by many different diseases and disorders. Or no disorder or problem at all. That's why you need a proper examination. (This applies of course to both somatic and mental illnesses.) Some shrinks may say they've seen enough to know; others would say, no, never without a full examination. Again, for our purposes, it doesn't matter. If the entire psychiatric profession got together and examined Trump and pronounced him entirely free of any mental illness, his behavior wouldn't be any less whacked or dangerous in a President.
That brings us back to the point. It's really only the behavior that matters to us as citizens. A diagnosis would only be helpful to learn about behavior we don't know about or predict future endangering behavior. Since we know about the behavior we're talking about, none of that matters or applies. In common sense, every day rather than clinical language Trump is clearly unstable, erratic, impulsive. In a word, he's nuts and not well. As citizens, we are entirely able and entitled to make these determinations. They are ordinary English language descriptors that the psychiatric profession doesn't control and shouldn't want to control. The entire debate over whether Trump is ''mentally ill'' is simply a diversion, premised on the idea that we need either permission or dictation to say he is not able to safely or competently fulfill the job of President. We don't. The observed behavior is really all that is necessary and all that matters. It's very clear.
Trump is now dangerous '' that makes his mental health a matter of public interest | Bandy Lee | Opinion | The Guardian
Sun, 07 Jan 2018 13:51
The man in the Oval Office of the White House. Photograph: Saul Loeb/AFP/Getty Images
E ight months ago, a group of us put our concerns into a book, The Dangerous Case of Donald Trump: 27 Psychiatrists and Mental Health Experts Assess a President. It became an instant bestseller, depleting bookstores within days. We thus discovered that our endeavours resonated with the public.
While we keep within the letter of the Goldwater rule '' which prohibits psychiatrists from diagnosing public figures without a personal examination and without consent '' there is still a lot that mental health professionals can tell before the public reaches awareness. These come from observations of a person's patterns of responses, of media appearances over time, and from reports of those close to him. Indeed, we know far more about Trump in this regard than many, if not most, of our patients. Nevertheless, the personal health of a public figure is her private affair '' until, that is, it becomes a threat to public health.
To make a diagnosis one needs all the relevant information '' including, I believe, a personal interview. But to assess dangerousness, one only needs enough information to raise alarms. It is about the situation rather than the person. The same person may not be a danger in a different situation, while a diagnosis stays with the person.
It is Trump in the office of the presidency that poses a danger. Why? Past violence is the best predictor of future violence, and he has shown: verbal aggressiveness, boasting about sexual assaults, inciting violence in others, an attraction to violence and powerful weapons and the continual taunting of a hostile nation with nuclear power. Specific traits that are highly associated with violence include: impulsivity, recklessness, paranoia, a loose grip on reality with a poor understanding of consequences, rage reactions, a lack of empathy, belligerence towards others and a constant need to demonstrate power.
There is another pattern by which he is dangerous. His cognitive function, or his ability to process knowledge and thoughts, has begun to be widely questioned. Many have noted a distinct decline in his outward ability to form complete sentences, to stay with a thought, to use complex words and not to make loose associations. This is dangerous because of the critical importance of decision-making capacity in the office that he holds. Cognitive decline can result from any number of causes '' psychiatric, neurological, medical, or medication-induced '' and therefore needs to be investigated. Likewise, we do not know whether psychiatric symptoms are due to a mental disorder, medication, or a physical condition, which only a thorough examination can reveal.
A diagnosis in itself, as much as it helps define the course, prognosis, and treatment, is Trump's private business, but what is our affair is whether the president and commander-in-chief has the capacity to function in his office. Mental illness, or even physical disability, does not necessarily impair a president from performing his function. Rather, questions about this capacity mobilised us to speak out about our concerns, with the intent to warn and to educate the public, so that we can help protect its own safety and wellbeing.
At no other time has a group of mental health professionals been so concerned about a sitting president's dangerousness
Indeed, at no other time in US history has a group of mental health professionals been so collectively concerned about a sitting president's dangerousness. This is not because he is an unusual person '' many of his symptoms are very common '' but it is highly unusual to find a person with such signs of danger in the office of presidency. For the US, it may be unprecedented; for parts of the world where this has happened before, the outcome has been uniformly devastating.
Pathology does not feel right to the healthy. It repels, but it also exhausts and confuses. There is a reason why staying in close quarters with a person suffering from mental illness usually induces what is called a ''shared psychosis''. Vulnerable or weakened individuals are more likely to succumb, and when their own mental health is compromised, they may develop an irresistible attraction to pathology. No matter the attraction, unlike healthy decisions that are life-affirming, choices that arise out of pathology lead to damage, destruction, and death. This is the definition of disease, and how we tell it apart from health.
Politics require that we allow everyone an equal chance; medicine requires that we treat everyone equally in protecting them from disease. That is why a liberal health professional would not ignore signs of appendicitis in a patient just because he is a Republican. Similarly, health professionals would not call pancreatic cancer something else because it is afflicting the president. When signs of illness become apparent, it is natural for the physician to recommend an examination. But when the disorder goes so far as to affect an individual's ability to perform her function, and in some cases risks harm to the public as a result, then the health professional has a duty to sound the alarm.
The progress of the special counsel Robert Mueller's investigations was worrisome to us for the effects it would have on the president's stability. We predicted that Trump, who has shown marked signs of psychological fragility under ordinary circumstances, barely able to cope with basic criticism or unflattering news, would begin to unravel with the encroaching indictments. And if his mental stability suffered, then so would public safety and international security.
Kim Jong-un's new year speech increased tensions about who had the biggest nuclear button. Photograph: Jung Yeon-Je/AFP/Getty ImagesIndeed, that is what began to unfold: Trump became more paranoid, espousing once again conspiracy theories that he had let go of for a while. He seemed further to lose his grip on reality by denying his own voice on the Access Hollywood tapes. Also, the sheer frequency of his tweets seemed to reflect an agitated state of mind, and his retweeting some violent anti-Muslim videos showed his tendency to resort to violence when under pressure.
Trump views violence as a solution when he is stressed and desires to re-establish his power. Paranoia and overwhelming feelings of weakness and inadequacy make violence very attractive, and powerful weapons very tempting to use '' all the more so for their power. His contest with the North Korean leader about the size of their nuclear buttons is an example of that and points to the possibility of great danger by virtue of the power of his position.
It does not take a mental health professional to see that a person of Trump's impairments, in the office of the presidency, is a danger to us all. What mental health experts can offer is affirmation that these signs are real, that they may be worse than the untrained person suspects, and that there are more productive ways of handling them than deflection or denial.
Screening for risk of harm is a routine part of mental health practice, and there are steps that we follow when someone poses a risk of danger: containment, removal from access to weapons and an urgent evaluation. When danger is involved, it is an emergency, where an established patient-provider relationship is not necessary, nor is consent; our ethical code mandates that we treat the person as our patient.
In medicine, mental impairment is considered as serious as physical impairment: it is just as debilitating, just as objectively observable and established just as reliably through standardised assessments. Mental health experts routinely perform capacity or fitness for duty examinations for courts and other legal bodies, and offer their recommendations. This is what we are calling for, urgently, in doing our part as medical professionals. The rest of the decision is up to the courts or, in this case, up to the body politic.
Shut Up Slave!
France's Macron Says He Wants Law To Combat Fake News : The Two-Way : NPR
Thu, 04 Jan 2018 22:56
French President Emmanuel Macron delivers his New Year wishes to the news media at the Elysee Palace in Paris, on Wednesday. Ludovic Marin/AFP/Getty Imageshide caption
toggle captionLudovic Marin/AFP/Getty Images French President Emmanuel Macron delivers his New Year wishes to the news media at the Elysee Palace in Paris, on Wednesday.
Ludovic Marin/AFP/Getty Images French President Emmanuel Macron says he will push a new law aimed at clamping down on fake news, saying he hopes to have it in place by the end of the year.
Speaking at a news conference at the Elysee Palace in Paris on Wednesday, Macron said such a law was essential, especially during elections.
"The freedom of the press is not a special freedom, it is the highest expression of freedom," Macron said. "If we want to protect liberal democracies, we have to be strong and have clear rules." Adding that, "A law will follow in due course."
Among other things, Macron said the law should require websites to disclose their source of funding and have a cap on the amount of money they receive from sponsored content.
During an election, the government would be authorized to block a website to suppress fake news, he said. He insisted that press freedom could be preserved under such a law.
Months after the U.S. election, which top American intelligence officials agree was manipulated by Russia, accusations began to surface that Moscow was trying to influence France's presidential election.
In February, Macron '-- then beginning a surge in the polls against his pro-Russian ultra-nationalist opponent Marine Le Pen'-- said his campaign was being targeted by Kremlin-supported media and hackers.
The Washington Post notes that "On the eve of the vote, Macron's campaign suffered a massive cyberattack that it compared to the hacking of Hillary Clinton's presidential campaign last year. U.S. intelligence agencies have blamed that operation on the Russian government."
We Stand With Dreamers
Sat, 06 Jan 2018 14:43
In June 2013, the Senate passed comprehensive, bipartisan immigration reform. A brave group of Republican and Democrats defied pessimists and proved there was a chance for common ground, even on difficult issues.
While the grand immigration compromise eventually stalled in the House of Representatives, four and a half years later, there is still reason to hope that Washington can again defy the skeptics and pass a bipartisan DREAM Act.
There are nearly 800,000 young people whose lives hang in the balance. Dreamers were brought to the U.S. as children, built their lives here, and were finally given a chance to come out of the shadows. Pulling the rug from under these immigrants would cost the economy billions, break up families, and disrupt the promising futures of hard-working young people. It's fundamentally unfair and un-American.
Americans across the political spectrum support legal status for Dreamers. Some 88% of Americans and more than 78% of Republicans want legislation to protect Dreamers. Here on Twitter, the conversation has been active, with 16.4 million Tweets just since August, with 3.5 million of those Tweets happening in just the three days around President Trump's September 5 announcement.
Twitter has also supported Dreamers, joining more than 100 companies in filing an amicus brief in the Northern District of California that argues there is ample constitutional and statutory authority to support Deferred Action for Childhood Arrivals (DACA). We've trained immigrant rights groups on how to use our platform, and our executives have stood up to push Congress to act.
The good news is that bipartisan agreement is again within reach. As Congress debates a long-term continuing resolution to keep the government open past December 22, politicians on both of the aisle say the time is right to address this issue. Just last week, 34 Republican Members of Congress signed a letter to Speaker Paul Ryan urging him to get behind a deal this month. ''We must pass legislation that protects DACA recipients from deportation and gives them the opportunity to apply for a more secured status in our country as soon as possible,'' the lawmakers wrote. ''Reaching across the aisle to protect DACA recipients before the holidays is the right thing to do.''
It is important to add to the conversation: Tweet using the hashtag #DreamActNow, and consider reaching out to your congressional delegation. We've never had a better opportunity to do right by our Dreamers.
World Leaders on Twitter
Sat, 06 Jan 2018 14:41
There's been a lot of discussion about political figures and world leaders on Twitter, and we want to share our stance.
Twitter is here to serve and help advance the global, public conversation. Elected world leaders play a critical role in that conversation because of their outsized impact on our society.
Blocking a world leader from Twitter or removing their controversial Tweets would hide important information people should be able to see and debate. It would also not silence that leader, but it would certainly hamper necessary discussion around their words and actions.
We review Tweets by leaders within the political context that defines them, and enforce our rules accordingly. No one person's account drives Twitter's growth, or influences these decisions. We work hard to remain unbiased with the public interest in mind.
We are working to make Twitter the best place to see and freely discuss everything that matters. We believe that's the best way to help our society make progress.
Door flexwerken worden werknemers als informatieverwerkende eenheden behandeld - Mode & Mooi - Voor nieuws, achtergronden en columns
Sat, 06 Jan 2018 18:49
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Dimension B
Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression
Sun, 07 Jan 2018 14:22
Highlights'Psilocybin with psychological support was used successfully to treat depression.
'Amygdala responses to fearful faces were increased one day after psilocybin session.
'Increased amygdala responses predicted positive clinical outcomes.
'Psilocybin assisted therapy treats depression by reviving emotional responsiveness.
AbstractRecent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions.
Trial registrationISRCTN, number ISRCTN14426797.
KeywordsPsilocybin ;Psychedelics ;Depression ;Amygdala ;fMRI ;Emotional processing 1. IntroductionPsychedelic therapy is a re-emerging paradigm in psychiatry (dos Santos et al., 2016 ; Mithoefer et al., 2016). Unlike other psychopharmacological treatment models that seek to medicate patients on a chronic basis, the psychedelic model seeks to treat core psychological issues via a small number of profound and potentially transformative psychological experiences (Pahnke et al., 1970 ; Watts et al., 2017). Our recent open-label study of psilocybin with psychological support for treatment-resistant depression (TRD) yielded promising results, with all patients showing some reduction in depressive symptoms at 1 week and half meeting criteria for remission at 3 weeks (Carhart-Harris et al., 2017 ). Furthermore, other clinical studies with psilocybin have found reductions in anxiety and depressive symptoms after psilocybin with psychological support (Griffiths et al., 2016 ; Ross et al., 2016).
Psilocybin, a classic psychedelic and non-selective serotonin 2A receptor (5-HT2AR) agonist, was discovered and marketed in the 1950s and 60s (Hofmann et al., 1958 ). After much early enthusiasm about the therapeutic potential of psychedelics (Grinspoon and Bakalar, 1979 ; Rucker et al., 2016), a politically-led about-turn in the mid-1960s and early 1970s effectively ended all research with these drugs, and it has only been in the last 10''15 years that clinical researchers have begun to work with them again. During this renascent period, impressive results have been found for the treatment of depression (Carhart-Harris et al., 2016 ; Os"rio et al., 2015), end of life anxiety (Gasser et al., 2014a; Griffiths et al., 2016; Grob et al., 2011 ; Ross et al., 2016), obsessive compulsive disorder (Moreno et al., 2006 ) and addiction (Bogenschutz and Johnson, 2016 ).
The amygdala has previously been implicated in the pathophysiology of depression (Drevets et al., 1992 ) as well as the action of some antidepressants (Ma, 2015 ) and psychedelics (Kraehenmann et al., 2015 ; Spain et al., 2015). The amygdala is a complex subcortical structure that is sensitive to emotional stimuli (Janak and Tye, 2015 ; Sergerie et al., 2008). Functional MRI studies of untreated clinically depressed patients have found amygdala hyper-sensitivity to negative emotional stimuli (Drevets et al., 1992 ; Ma, 2015), and treatment with SSRIs has been found to attenuate this; both with chronic SSRI-use as well as early in treatment, prior to the appearance of clinical improvements (Godlewska et al., 2012 ).
Here, we sought to explore the antidepressant action of psilocybin on amygdala responses to emotional faces using a functional magnetic resonance imaging (fMRI) paradigm that has been well-validated in the context of SSRI-based treatments for depression (Ma, 2015 ). Patients underwent balanced versions of an emotional faces paradigm before and one-day after treatment with psilocybin. Psilocybin has been found to be associated with improved mood in the sub-acute period days after exposure (Majić et al., 2015 ). We therefore predicted that amygdala responses to emotional faces would be altered post-treatment and that this might relate to changes in depression severity. We were particularly interested in the fearful versus neutral faces contrast, due to previous findings of reduced amygdala responses to negative emotional stimuli with SSRIs (Ma, 2015 ). We also predicted that the nature of the acute psychological experience under psilocybin would relate to the post-treatment changes in amygdala responses.
2. Material and methodsThis trial received a favourable opinion from the National Research Ethics Service London'--West London, was sponsored and approved by Imperial College London and by the UK MHRA. All participants provided written informed consent.
Psilocybin - Wikipedia
Sun, 07 Jan 2018 14:22

PsilocybinNamesIUPAC name[3-(2-Dimethylaminoethyl)-1H-indol-4-yl] dihydrogen phosphate
Identifiers273158ChEBIChemSpiderECHA InfoCard 100.007.542EC Number 208-294-4KEGGMeSHPsilocybine RTECS numberNM3150000InChI=1S/C12H17N2O4P/c1-14(2)7-6-9-8-13-10-4-3-5-11(12(9)10)18-19(15,16)17/h3-5,8,13H,6-7H2,1-2H3,(H2,15,16,17) Y Key: QVDSEJDULKLHCG-UHFFFAOYSA-N Y InChI=1/C12H17N2O4P/c1-14(2)7-6-9-8-13-10-4-3-5-11(12(9)10)18-19(15,16)17/h3-5,8,13H,6-7H2,1-2H3,(H2,15,16,17)
CN(C)CCC1=CNC2=C1C(=CC=C2)OP(=O)(O)O
PharmacologyLowOral, intravenousPharmacokinetics:Hepaticoral: 163±64 minintravenous: 74.1±19.6 min[1]
RenalLegal statusPropertiesC 12H 17N 2O 4P Molar mass284.25 g·mol''1Melting point220''228 °C (428''442 °F)[2]solubleSolubilitysoluble in methanolslightly soluble in ethanol
negligible in chloroform, benzene
HazardsLethal dose or concentration (LD, LC):285 mg/kg (mouse, i.v.)280 mg/kg (rat, i.v.)
12.5 mg/kg (rabbit, i.v.)[2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).Y verify (what is Y N ?)Infobox referencesPsilocybin[nb 1] ( sy-lÉ-SY -bin) is a naturally occurring psychedelicprodrug compound produced by more than 200 species of mushrooms, collectively known as psilocybin mushrooms. Psilocybin evolved in mushrooms from its ancestor, muscarine, some 20 million years ago.[4]
The most potent are members of the genus Psilocybe, such as P. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from about a dozen other genera. As a prodrug, psilocybin is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of LSD, mescaline, and DMT. In general, the effects include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and spiritual experiences, and can include possible adverse reactions such as nausea and panic attacks.
Imagery found on prehistoric murals and rock paintings of modern-day Spain and Algeria suggests that human usage of psilocybin mushrooms predates recorded history. In Mesoamerica, the mushrooms had long been consumed in spiritual and divinatory ceremonies before Spanish chroniclers first documented their use in the 16th century. In a 1957 Life magazine article, American banker and ethnomycologistR. Gordon Wasson described his experiences ingesting psilocybin-containing mushrooms during a traditional ceremony in Mexico, introducing the substance to popular culture. In 1959, the Swiss chemist Albert Hofmann isolated the active principle psilocybin from the mushroom Psilocybe mexicana. Hofmann's employer Sandoz marketed and sold pure psilocybin to physicians and clinicians worldwide for use in psychedelic psychotherapy. Although the increasingly restrictive drug laws of the late 1960s curbed scientific research into the effects of psilocybin and other hallucinogens, its popularity as an entheogen (spirituality-enhancing agent) grew in the next decade, owing largely to the increased availability of information on how to cultivate psilocybin mushrooms.
Some users of the drug consider it an entheogen and a tool to supplement practices for transcendence, including meditation and psychonautics. The intensity and duration of the effects of psilocybin are variable, depending on species or cultivar of mushrooms, dosage, individual physiology, and set and setting, as was shown in experiments led by Timothy Leary at Harvard University in the early 1960s. Once ingested, psilocybin is rapidly metabolized to psilocin, which then acts on serotonin receptors in the brain. The mind-altering effects of psilocybin typically last from two to six hours, although to individuals under the influence of psilocybin, the effects may seem to last much longer, since the drug can distort the perception of time. Psilocybin has a low toxicity and a relatively low harm potential, and reports of lethal doses of the drug are rare. Several modern bioanalytical methods have been adapted to rapidly and accurately screen the levels of psilocybin in mushroom samples and body fluids. Since the 1990s, there has been a renewal of scientific research into the potential medical and psychological therapeutic benefits of psilocybin for treating conditions including obsessive-compulsive disorder (OCD), post-traumatic stress disorder, social anxiety, treatment-resistant depression, cluster headaches, and anxiety related to terminal cancer.[5] Possession of psilocybin-containing mushrooms has been outlawed in most countries, and it has been classified as a scheduled drug by many national drug laws.
Effects [ edit] American psychologist and counterculture figure Timothy Leary conducted early experiments into the effects of psychedelic drugs, including psilocybin. (1989 photo)The effects of psilocybin are highly variable and depend on the mindset and environment in which the user has the experience, factors commonly referred to as set and setting. In the early 1960s, Timothy Leary and colleagues at Harvard University investigated the role of set and setting on the effects of psilocybin. They administered the drug to 175 volunteers from various backgrounds in an environment intended to be similar to a comfortable living room. Ninety-eight of the subjects were given questionnaires to assess their experiences and the contribution of background and situational factors. Individuals who had experience with psilocybin prior to the study reported more pleasant experiences than those for whom the drug was novel. Group size, dosage, preparation, and expectancy were important determinants of the drug response. In general, those placed in groups of more than eight individuals felt that the groups were less supportive, and their experiences were less pleasant. Conversely, smaller groups (fewer than six individuals) were seen as more supportive. Participants also reported having more positive reactions to the drug in those groups. Leary and colleagues proposed that psilocybin heightens suggestibility, making an individual more receptive to interpersonal interactions and environmental stimuli.[6] These findings were affirmed in a later review by Jos ten Berge (1999), who concluded that dosage, set, and setting were fundamental factors in determining the outcome of experiments that tested the effects of psychedelic drugs on artists' creativity.[7]
After ingesting psilocybin, a wide range of subjective effects may be experienced: feelings of disorientation, lethargy, giddiness, euphoria, joy, and depression. About a third of users report feelings of anxiety or paranoia.[8] Low doses of the drug can induce hallucinatory effects. Closed-eye hallucinations may occur, in which the affected individual sees multicolored geometric shapes and vivid imaginative sequences.[9] Some individuals report experiencing synesthesia, such as tactile sensations when viewing colors.[10] At higher doses, psilocybin can lead to "Intensification of affective responses, enhanced ability for introspection, regression to primitive and childlike thinking, and activation of vivid memory traces with pronounced emotional undertones".[11] Open-eye visual hallucinations are common, and may be very detailed although rarely confused with reality.[9]
A 2011 prospective study by Roland R. Griffiths and colleagues suggests that a single high dosage of psilocybin can cause long-term changes in the personality of its users. About half of the study participants'--described as healthy, "spiritually active", and many possessing postgraduate degrees'--showed an increase in the personality dimension of openness (assessed using the Revised NEO Personality Inventory), and this positive effect was apparent more than a year after the psilocybin session. According to the study authors, the finding is significant because "no study has prospectively demonstrated personality change in healthy adults after an experimentally manipulated discrete event."[12] Although other researchers have described instances of psychedelic drug usage leading to new psychological understandings and personal insights,[13] it is not known whether these experimental results can be generalized to larger populations.[12]
Physical effects [ edit] Common responses include: pupil dilation (93%); changes in heart rate (100%), including increases (56%), decreases (13%), and variable responses (31%); changes in blood pressure (84%), including hypotension (34%), hypertension (28%), and general instability (22%); changes in stretch reflex (86%), including increases (80%) and decreases (6%); nausea (44%); tremor (25%); and dysmetria (16%) (inability to properly direct or limit motions).[nb 2] The temporary increases in blood pressure caused by the drug can be a risk factor for users with pre-existing hypertension.[9] These qualitative somatic effects caused by psilocybin have been corroborated by several early clinical studies.[15] A 2005 magazine survey of club goers in the UK found that nausea or vomiting was experienced by over a quarter of those who had used psilocybin mushrooms in the last year, although this effect is caused by the mushroom rather than psilocybin itself.[8] In one study, administration of gradually increasing dosages of psilocybin daily for 21 days had no measurable effect on electrolyte levels, blood sugar levels, or liver toxicity tests.[1]
Perceptual distortions [ edit] The ability of psilocybin to cause perceptual distortions is linked to its influence on the activity of the prefrontal cortex.Psilocybin is known to strongly influence the subjective experience of the passage of time.[16] Users often feel as if time is slowed down, resulting in the perception that "minutes appear to be hours" or "time is standing still".[17] Studies have demonstrated that psilocybin significantly impairs subjects' ability to gauge time intervals longer than 2.5 seconds, impairs their ability to synchronize to inter-beat intervals longer than 2 seconds, and reduces their preferred tapping rate.[17][18] These results are consistent with the drug's role in affecting prefrontal cortex activity,[19] and the role that the prefrontal cortex is known to play in time perception.[20] However, the neurochemical basis of psilocybin's effects on the perception of time are not known with certainty.[21]
Users having a pleasant experience can feel a sense of connection to others, nature, and the universe; other perceptions and emotions are also often intensified. Users having an unpleasant experience (a "bad trip") describe a reaction accompanied by fear, other unpleasant feelings, and occasionally by dangerous behavior. In general, the phrase "bad trip" is used to describe a reaction that is characterized primarily by fear or other unpleasant emotions, not just transitory experience of such feelings. A variety of factors may contribute to a psilocybin user experiencing a bad trip, including "tripping" during an emotional or physical low or in a non-supportive environment (see: set and setting). Ingesting psilocybin in combination with other drugs, including alcohol, can also increase the likelihood of a bad trip.[8][22] Other than the duration of the experience, the effects of psilocybin are similar to comparable dosages of LSD or mescaline. However, in the Psychedelics Encyclopedia, author Peter Stafford noted, "The psilocybin experience seems to be warmer, not as forceful and less isolating. It tends to build connections between people, who are generally much more in communication than when they use LSD."[23]
Spiritual [ edit] Psilocybin mushrooms have been and continue to be used in indigenous New World cultures in religious, divinatory, or spiritual contexts. Reflecting the meaning of the word entheogen ("the god within"), the mushrooms are revered as powerful spiritual sacraments that provide access to sacred worlds. Typically used in small group community settings, they enhance group cohesion and reaffirm traditional values.[24]Terence McKenna documented the worldwide practices of psilocybin mushroom usage as part of a cultural ethos relating to the Earth and mysteries of nature, and suggested that mushrooms enhanced self-awareness and a sense of contact with a "Transcendent Other"'--reflecting a deeper understanding of our connectedness with nature.[25]
Psychedelic drugs can induce states of consciousness that have lasting personal meaning and spiritual significance in individuals who are religious or spiritually inclined; these states are called mystical experiences. Some scholars have proposed that many of the qualities of a drug-induced mystical experience are indistinguishable from mystical experiences achieved through non-drug techniques, such as meditation or holotropic breathwork.[26][27] In the 1960s, Walter Pahnke and colleagues systematically evaluated mystical experiences (which they called "mystical consciousness") by categorizing their common features. These categories, according to Pahnke, "describe the core of a universal psychological experience, free from culturally determined philosophical or theological interpretations", and allow researchers to assess mystical experiences on a qualitative, numerical scale.[28]
In the 1962 Marsh Chapel Experiment, which was run by Pahnke at the Harvard Divinity School under the supervision of Timothy Leary,[29] almost all of the graduate degree divinity student volunteers who received psilocybin reported profound religious experiences.[30] One of the participants was religious scholar Huston Smith, author of several textbooks on comparative religion; he later described his experience as "the most powerful cosmic homecoming I have ever experienced."[31] In a 25-year followup to the experiment, all of the subjects given psilocybin described their experience as having elements of "a genuine mystical nature and characterized it as one of the high points of their spiritual life".[32] Psychedelic researcher Rick Doblin considered the study partially flawed due to incorrect implementation of the double-blind procedure, and several imprecise questions in the mystical experience questionnaire. Nevertheless, he said that the study cast "a considerable doubt on the assertion that mystical experiences catalyzed by drugs are in any way inferior to non-drug mystical experiences in both their immediate content and long-term effects".[33] This sentiment was echoed by psychiatrist William A. Richards, who in a 2007 review stated "[psychedelic] mushroom use may constitute one technology for evoking revelatory experiences that are similar, if not identical, to those that occur through so-called spontaneous alterations of brain chemistry."[34]
In their studies on the psilocybin experience, Johns Hopkins researchers use peaceful music and a comfortable room to help ensure a comfortable setting, and experienced guides to monitor and reassure the volunteers.A group of researchers from Johns Hopkins School of Medicine led by Griffiths conducted a study to assess the immediate and long-term psychological effects of the psilocybin experience, using a modified version of the mystical experience questionnaire and a rigorous double-blind procedure.[35] When asked in an interview about the similarity of his work with Leary's, Griffiths explained the difference: "We are conducting rigorous, systematic research with psilocybin under carefully monitored conditions, a route which Dr. Leary abandoned in the early 1960s."[36] The National Institute of Drug Abuse-funded study, published in 2006, has been praised by experts for the soundness of its experimental design.[nb 3] In the experiment, 36 volunteers without prior experience with hallucinogens were given psilocybin and methylphenidate (Ritalin) in separate sessions; the methylphenidate sessions served as a control and psychoactive placebo. The degree of mystical experience was measured using a questionnaire developed by Ralph W. Hood;[37] 61% of subjects reported a "complete mystical experience" after their psilocybin session, while only 13% reported such an outcome after their experience with methylphenidate. Two months after taking psilocybin, 79% of the participants reported moderately to greatly increased life satisfaction and sense of well-being. About 36% of participants also had a strong to extreme "experience of fear" or dysphoria (i.e., a "bad trip") at some point during the psilocybin session (which was not reported by any subject during the methylphenidate session); about one-third of these (13% of the total) reported that this dysphoria dominated the entire session. These negative effects were reported to be easily managed by the researchers and did not have a lasting negative effect on the subject's sense of well-being.[38]
A follow-up study conducted 14 months after the original psilocybin session confirmed that participants continued to attribute deep personal meaning to the experience. Almost one-third of the subjects reported that the experience was the single most meaningful or spiritually significant event of their lives, and over two-thirds reported it among their five most spiritually significant events. About two-thirds indicated that the experience increased their sense of well-being or life satisfaction.[30] Even after 14 months, those who reported mystical experiences scored on average 4 percentage points higher on the personality trait of Openness/Intellect; personality traits are normally stable across the lifespan for adults. Likewise, in a recent (2010) web-based questionnaire study designed to investigate user perceptions of the benefits and harms of hallucinogenic drug use, 60% of the 503 psilocybin users reported that their use of psilocybin had a long-term positive impact on their sense of well-being.[8][39]
In 2011, Griffiths and colleagues published the results of further studies designed to learn more about the optimum psilocybin doses needed for positive life-changing experiences, while minimizing the chance of negative reactions. In a 14-month followup, the researchers found that 94% of the volunteers rated their experiences with the drug as one of the top five most spiritually significant of their lives (44% said it was the single most significant). None of the 90 sessions that took place throughout the study were rated as decreasing well-being or life satisfaction. Moreover, 89% reported positive changes in their behaviors as a result of the experiences. The conditions of the experimental design included a single drug experience a month, on a couch, in a living-room-like setting, with eye shades and carefully chosen music (classical and world music). As an additional precaution to guide the experience, as with the 2006 study, the 2011 study included a "monitor" or "guide" whom the volunteers supposedly trusted. The monitors provided gentle reassurance when the volunteers experienced anxiety. The volunteers and monitors all remained blind to the exact dosages for the purpose of the experiment.[40]
Available forms [ edit] Although psilocybin may be prepared synthetically, outside of the research setting, it is not typically used in this form. The psilocybin present in certain species of mushrooms can be ingested in several ways: by consuming fresh or dried fruit bodies, by preparing a herbal tea, or by combining with other foods to mask the bitter taste.[41] In rare cases people have injected mushroom extracts intravenously.[8]
Adverse effects [ edit] Most of the comparatively few fatal incidents reported in the literature that are associated with psychedelic mushroom usage involve the simultaneous use of other drugs, especially alcohol. Probably the most common cause of hospital admissions resulting from psychedelic mushroom usage involve "bad trips" or panic reactions, in which affected individuals become extremely anxious, confused, agitated, or disoriented. Accidents, self-injury, or suicide attempts can result from serious cases of acute psychotic episodes.[8] Although no studies have linked psilocybin with birth defects,[42] it is recommended that pregnant women avoid its usage.[43]
Toxicity [ edit] Chart of dependence potential and effective dose/lethal dose ratio of several psychoactive drugs. Source:[44]The toxicity of psilocybin is low. In rats, the median lethal dose (LD50) when administered orally is 280 milligrams per kilogram (mg/kg), approximately one and a half times that of caffeine. When administered intravenously in rabbits, psilocybin's LD50 is approximately 12.5 mg/kg.[45] Psilocybin comprises approximately 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kilograms (3.7 lb) of dried mushrooms, or 17 kilograms (37 lb) of fresh mushrooms, would be required for a 60-kilogram (130 lb) person to reach the 280 mg/kg LD50 value of rats.[8] Based on the results of animal studies, the lethal dose of psilocybin has been extrapolated to be 6 grams, 1000 times greater than the effective dose of 6 milligrams.[46] The Registry of Toxic Effects of Chemical Substances assigns psilocybin a relatively high therapeutic index of 641 (higher values correspond to a better safety profile); for comparison, the therapeutic indices of aspirin and nicotine are 199 and 21, respectively.[47] The lethal dose from psilocybin toxicity alone is unknown at recreational or medicinal levels, and has rarely been documented'--as of 2011[update], only two cases attributed to overdosing on hallucinogenic mushrooms (without concurrent use of other drugs) have been reported in the scientific literature and may involve other factors aside from psilocybin.[8][nb 4]
Psychiatric [ edit] Panic reactions can occur after consumption of psilocybin-containing mushrooms, especially if the ingestion is accidental or otherwise unexpected. Reactions characterized by violent behavior, suicidal thoughts,[50] schizophrenia-like psychosis,[51][52] and convulsions[53] have been reported in the literature. A 2005 survey conducted in the United Kingdom found that almost a quarter of those who had used psilocybin mushrooms in the past year had experienced a panic attack.[8] Other adverse effects less frequently reported include paranoia, confusion, prolonged derealization (disconnection from reality), and mania.[39] Psilocybin usage can temporarily induce a state of depersonalization disorder.[54] Usage by those with schizophrenia can induce acute psychotic states requiring hospitalization.[8]
Recent evidence, however, has suggested against the contention that the use of psilocybin puts one at risk for developing long lasting mental disorders. An analysis of information from the National Survey on Drug Use and Health showed that the use of psychedelic drugs such as psilocybin is associated with significantly reduced odds of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt.[55]
The similarity of psilocybin-induced symptoms to those of schizophrenia has made the drug a useful research tool in behavioral and neuroimaging studies of this psychotic disorder.[56][57][58] In both cases, psychotic symptoms are thought to arise from a "deficient gating of sensory and cognitive information" in the brain that ultimately lead to "cognitive fragmentation and psychosis".[57]Flashbacks (spontaneous recurrences of a previous psilocybin experience) can occur long after having used psilocybin mushrooms. Hallucinogen persisting perception disorder (HPPD) is characterized by a continual presence of visual disturbances similar to those generated by psychedelic substances. Neither flashbacks nor HPPD are commonly associated with psilocybin usage,[8] and correlations between HPPD and psychedelics are further obscured by polydrug use and other variables.[59]
Tolerance and dependence [ edit] Tolerance to psilocybin builds and dissipates quickly; ingesting psilocybin more than about once a week can lead to diminished effects. Tolerance dissipates after a few days, so doses can be spaced several days apart to avoid the effect.[60] A cross-tolerance can develop between psilocybin and the pharmacologically similar LSD,[61] and between psilocybin and phenethylamines such as mescaline and DOM.[62]
Repeated use of psilocybin does not lead to physical dependence.[1] A 2008 study concluded that, based on US data from the period 2000''2002, adolescent-onset (defined here as ages 11''17) usage of hallucinogenic drugs (including psilocybin) did not increase the risk of drug dependence in adulthood; this was in contrast to adolescent usage of cannabis, cocaine, inhalants, anxiolytic medicines, and stimulants, all of which were associated with "an excess risk of developing clinical features associated with drug dependence".[63] Likewise, a 2010 Dutch study ranked the relative harm of psilocybin mushrooms compared to a selection of 19 recreational drugs, including alcohol, cannabis, cocaine, ecstasy, heroin, and tobacco. Psilocybin mushrooms were ranked as the illicit drug with the lowest harm,[64] corroborating conclusions reached earlier by expert groups in the United Kingdom.[65]
Interactions [ edit] Monoamine oxidase inhibitors (MAOI) have been known to prolong and enhance the effects of psilocybin.[66] Alcohol consumption may enhance the effects of psilocybin, because acetaldehyde, one of the primary breakdown metabolites of consumed alcohol, reacts with biogenic amines present in the body to produce MAOIs related to tetrahydroisoquinoline and β-carboline. Tobacco smokers may also experience more powerful effects with psilocybin,[8] because tobacco smoke exposure decreases the activity of MAO in the brain and peripheral organs.[67]
Pharmacology [ edit] Pharmacodynamics [ edit] The neurotransmitter serotonin is structurally similar to psilocybin.Psilocybin is rapidly dephosphorylated in the body to psilocin, which is a partial agonist for several serotonin receptors, which are also known as 5-hydroxytryptamine (5-HT) receptors. Psilocin has a high affinity for the 5-HT2B and 5-HT2C receptors in the human brain, and with a slightly lower affinity for the 5-HT2A receptor. Psilocin binds with low affinity to 5-HT1 receptors, including 5-HT1A and 5-HT1D.[1] Serotonin receptors are located in numerous parts of the brain, including the cerebral cortex, and are involved in a wide range of functions, including regulation of mood and motivation.[68] The psychotomimetic (psychosis-mimicking) effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT2Aantagonist drug ketanserin.[51] Various lines of evidence have shown that interactions with non-5-HT2 receptors also contribute to the subjective and behavioral effects of the drug.[62][nb 5] For example, psilocin indirectly increases the concentration of the neurotransmitter dopamine in the basal ganglia, and some psychotomimetic symptoms of psilocin are reduced by haloperidol, a non-selective dopamine receptor antagonist. Taken together, these suggest that there may be an indirect dopaminergic contribution to psilocin's psychotomimetic effects.[21] Unlike LSD, which binds to D2-like dopamine receptors in addition to having strong affinity for several 5-HT receptors, psilocybin and psilocin have no affinity for the dopamine D2 receptors.[1]
Pharmacokinetics [ edit] The effects of the drug begin 10''40 minutes after ingestion, and last 2''6 hours depending on dose, species, and individual metabolism.[70] The half life of psilocybin is 163 ± 64 minutes when taken orally, or 74.1 ± 19.6 minutes when injected intravenously.[1] A dosage of 4''10 mg, corresponding roughly to 50''300 micrograms per kilogram (µg/kg) of body weight, is required to induce psychedelic effects. A typical recreational dosage is 10''50 mg psilocybin, which is roughly equivalent to 10''50 grams of fresh mushrooms, or 1''5 grams of dried mushrooms.[8] A small number of people are unusually sensitive to psilocybin, such that a normally threshold-level dose of about 2 mg can result in effects usually associated with medium or high doses. In contrast, there are some who require relatively high doses to experience noticeable effects. Individual brain chemistry and metabolism play a large role in determining a person's response to psilocybin.[70]
Psilocybin is converted in the liver to the pharmacologically active psilocin, which is then either glucuronated to be excreted in the urine or further converted to various psilocin metabolites.Psilocybin is metabolized mostly in the liver. As it becomes converted to psilocin, it undergoes a first-pass effect, whereby its concentration is greatly reduced before it reaches the systemic circulation. Psilocin is broken down by the enzyme monoamine oxidase to produce several metabolites that can circulate in the blood plasma, including 4-hydroxyindole-3-acetaldehyde, 4-hydroxytryptophol, and 4-hydroxyindole-3-acetic acid.[1] Some psilocin is not broken down by enzymes and instead forms a glucuronide; this is a biochemical mechanism animals use to eliminate toxic substances by linking them with glucuronic acid, which can then be excreted in the urine.[71][72] Psilocin is glucuronated by the glucuronosyltransferase enzymes UGT1A9 in the liver, and by UGT1A10 in the small intestine.[73] Based on studies using animals, about 50% of ingested psilocybin is absorbed through the stomach and intestine. Within 24 hours, about 65% of the absorbed psilocybin is excreted into the urine, and a further 15''20% is excreted in the bile and feces. Although most of the remaining drug is eliminated in this way within 8 hours, it is still detectable in the urine after 7 days.[74] Clinical studies show that psilocin concentrations in the plasma of adults average about 8 µg/liter within 2 hours after ingestion of a single 15 mg oral psilocybin dose;[75] psychological effects occur with a blood plasma concentration of 4''6 µg/liter.[1] Psilocybin is about 100 times less potent than LSD on a weight per weight basis, and the physiological effects last about half as long.[76]
Chemistry and biosynthesis [ edit] Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine, 4-PO-Psilocin, or 4-PO-HO-DMT) is a prodrug that is converted into the pharmacologically active compound psilocin in the body by a dephosphorylation reaction. This chemical reaction takes place under strongly acidic conditions, or under physiological conditions in the body, through the action of enzymes called alkaline phosphatases.[77]
Psilocybin is a tryptamine compound with a chemical structure containing an indole ring linked to an ethylaminesubstituent. It is chemically related to the amino acidtryptophan, and is structurally similar to the neurotransmitterserotonin. Psilocybin is a member of the general class of tryptophan-based compounds that originally functioned as antioxidants in earlier life forms before assuming more complex functions in multicellular organisms, including humans.[78] Other related indole-containing psychedelic compounds include dimethyltryptamine, found in many plant species and in trace amounts in some mammals, and bufotenine, found in the skin of psychoactive toads.[79]
Psilocybin is an alkaloid that is soluble in water, methanol and aqueous ethanol, but insoluble in organic solvents like chloroform and petroleum ether.[80] Its pKa values are estimated to be 1.3 and 6.5 for the two successive phosphate OH groups and 10.4 for the dimethylamine nitrogen, so in general it exists as a zwitterionic structure.[81] Exposure to light is detrimental to the stability of aqueous solutions of psilocybin, and will cause it to rapidly oxidize'--an important consideration when using it as an analytical standard.[82] Osamu Shirota and colleagues reported a method for the large-scale synthesis of psilocybin without chromatographic purification in 2003.[83] Starting with 4-hydroxyindole, they generated psilocybin from psilocin in 85% yield, a marked improvement over yields reported from previous syntheses.[84][85][86] Purified psilocybin is a white, needle-like crystalline powder[83] with a melting point between 220''228 °C (428''442 °F),[45] and a slightly ammonia-like taste.[81]
Biosynthetically, the biochemical transformation from tryptophan to psilocybin involves several enzyme reactions: decarboxylation, methylation at the N9 position, 4-hydroxylation, and O-phosphorylation. Isotopic labeling experiments suggest that tryptophan decarboxylation is the initial biosynthetic step and that O-phosphorylation is the final step.[87][88]) The sequence of the intermediate enzymatic steps has been shown to involve 4 different enzymes (PsiD, PsiH, PsiK, and PsiM) in P. cubensis and P. cyanescens, although the biosynthetic pathway may differ between species.[89][90]
A possible biosynthetic route to psilocybin. Although the order of the first (decarboxylation) and last (phosphorylation) steps are known, the details of the hypothetical intracellular (de-) phosphorylation are speculative.[90]Analytical methods [ edit] Several relatively simple chemical tests '-- commercially available as reagent testing kits '-- can be used to assess the presence of psilocybin in extracts prepared from mushrooms. The drug reacts in the Marquis test to produce a yellow color, and a green color in the Mandelin test.[91] Neither of these tests, however, is specific for psilocybin; for example, the Marquis test will react with many classes of controlled drugs, such as those containing primary amino groups and unsubstituted benzene rings, including amphetamine and methamphetamine.[92]Ehrlich's reagent and DMACA reagent are used as chemical sprays to detect the drug after thin layer chromatography.[93] Many modern techniques of analytical chemistry have been used to quantify psilocybin levels in mushroom samples. Although the earliest methods commonly used gas chromatography, the high temperature required to vaporize the psilocybin sample prior to analysis causes it to spontaneously lose its phosphoryl group and become psilocin '-- making it difficult to chemically discriminate between the two drugs. In forensic toxicology, techniques involving gas chromatography coupled to mass spectrometry (GC''MS) are the most widely used due to their high sensitivity and ability to separate compounds in complex biological mixtures.[94] These techniques include ion mobility spectrometry,[95]capillary zone electrophoresis,[96]ultraviolet spectroscopy,[97] and infrared spectroscopy.[98]High performance liquid chromatography (HPLC) is used with ultraviolet,[82]fluorescence,[99]electrochemical,[100] and electrospray mass spectrometric detection methods.[101]
Various chromatographic methods have been developed to detect psilocin in body fluids: the rapid emergency drug identification system (REMEDi HS), a drug screening method based on HPLC;[102] HPLC with electrochemical detection;[100][103] GC''MS;[71][102] and liquid chromatography coupled to mass spectrometry.[104] Although the determination of psilocin levels in urine can be performed without sample clean-up (i.e., removing potential contaminants that make it difficult to accurately assess concentration), the analysis in plasma or serum requires a preliminary extraction, followed by derivatization of the extracts in the case of GC''MS. A specific immunoassay has also been developed to detect psilocin in whole blood samples.[105] A 2009 publication reported using HPLC to quickly separate forensically important illicit drugs including psilocybin and psilocin, which were identifiable within about half a minute of analysis time.[106] These analytical techniques to determine psilocybin concentrations in body fluids are, however, not routinely available, and not typically used in clinical settings.[22]
Natural occurrence [ edit] Psilocybin is present in varying concentrations in over 200 species of Basidiomycota mushrooms which evolved to produce the compound from muscarine some 20 million years ago.[4] In a 2000 review on the worldwide distribution of hallucinogenic mushrooms, Gast"n Guzmn and colleagues considered these to be distributed amongst the following genera: Psilocybe (116 species), Gymnopilus (14), Panaeolus (13), Copelandia (12), Hypholoma (6), Pluteus (6), Inocybe (6), Conocybe (4), Panaeolina (4), Gerronema (2) and Agrocybe, Galerina and Mycena (1 species each).[108] Guzmn increased his estimate of the number of psilocybin-containing Psilocybe to 144 species in a 2005 review. The majority of these are found in Mexico (53 species), with the remainder distributed in the US and Canada (22), Europe (16), Asia (15), Africa (4), and Australia and associated islands (19).[109] In general, psilocybin-containing species are dark-spored, gilled mushrooms that grow in meadows and woods of the subtropics and tropics, usually in soils rich in humus and plant debris.[110] Psilocybin mushrooms occur on all continents, but the majority of species are found in subtropical humid forests.[108]Psilocybe species commonly found in the tropics include P. cubensis and P. subcubensis. P. semilanceata '-- considered by Guzmn to be the world's most widely distributed psilocybin mushroom[111] '-- is found in Europe, North America, Asia, South America, Australia and New Zealand, but is entirely absent from Mexico.[109] Although the presence or absence of psilocybin is not of much use as a chemotaxonomical marker at the familial level or higher, it is used to classify taxa of lower taxonomic groups.[112]
Global distribution of over 100 psychoactive species of Psilocybe genus mushrooms.[113]Both the caps and the stems contain the psychoactive compounds, although the caps consistently contain more. The spores of these mushrooms do not contain psilocybin or psilocin.[95][114][115] The total potency varies greatly between species and even between specimens of a species collected or grown from the same strain.[116] Because most psilocybin biosynthesis occurs early in the formation of fruit bodies or sclerotia, younger, smaller mushrooms tend to have a higher concentration of the drug than larger, mature mushrooms.[117] In general, the psilocybin content of mushrooms is quite variable (ranging from almost nothing to 1.5% of the dry weight)[118] and depends on species, strain, growth and drying conditions, and mushroom size.[119] Cultivated mushrooms have less variability in psilocybin content than wild mushrooms.[120] The drug is more stable in dried than fresh mushrooms; dried mushrooms retain their potency for months or even years,[121] while mushrooms stored fresh for four weeks contain only traces of the original psilocybin.[8]
The psilocybin contents of dried herbarium specimens of Psilocybe semilanceata in one study were shown to decrease with the increasing age of the sample: collections dated 11, 33, or 118 years old contained 0.84%, 0.67%, and 0.014% (all dry weight), respectively.[122] Mature mycelia contain some psilocybin, while young mycelia (recently germinated from spores) lack appreciable amounts.[123] Many species of mushrooms containing psilocybin also contain lesser amounts of the analog compounds baeocystin and norbaeocystin,[124] chemicals thought to be biogenic precursors.[125] Although most species of psilocybin-containing mushrooms bruise blue when handled or damaged due to the oxidization of phenolic compounds, this reaction is not a definitive method of identification or determining a mushroom's potency.[116][126]
History [ edit] Early [ edit] There is evidence to suggest that psychoactive mushrooms have been used by humans in religious ceremonies for thousands of years. Murals dated 9000 to 7000 BCE found in the Sahara desert in southeast Algeria depict horned beings dressed as dancers, clothed in garb decorated with geometrical designs, and holding mushroom-like objects. Parallel lines extend from the mushroom shapes to the center of the dancers' heads.[127] 6,000-year-old pictographs discovered near the Spanish town of Villar del Humo illustrate several mushrooms that have been tentatively identified as Psilocybe hispanica, a hallucinogenic species native to the area.[128]
Archaeological artifacts from Mexico, as well as the so-called Mayan "mushroom stones" of Guatemala have also been interpreted by some scholars as evidence for ritual and ceremonial usage of psychoactive mushrooms in the Mayan and Aztec cultures of Mesoamerica.[129] In Nahuatl, the language of the Aztecs, the mushrooms were called teonancatl, or "God's flesh". Following the arrival of Spanish explorers to the New World in the 16th century, chroniclers reported the use of mushrooms by the natives for ceremonial and religious purposes. According to the Dominican friar Diego Durn in The History of the Indies of New Spain (published c. 1581), mushrooms were eaten in festivities conducted on the occasion of the accession to the throne of Aztec emperor Moctezuma II in 1502. The Franciscan friar Bernardino de Sahagºn wrote of witnessing mushroom usage in his Florentine Codex (published 1545''1590),[130] and described how some merchants would celebrate upon returning from a successful business trip by consuming mushrooms to evoke revelatory visions.[131] After the defeat of the Aztecs, the Spanish forbade traditional religious practices and rituals that they considered "pagan idolatry", including ceremonial mushroom use. For the next four centuries, the Indians of Mesoamerica hid their use of entheogens from the Spanish authorities.[132]
Although dozens of species of psychedelic mushrooms are found in Europe, there is little documented usage of these species in Old World history besides the use of Amanita muscaria among Siberian peoples.[133][134] The few existing historical accounts about psilocybin mushrooms typically lack sufficient information to allow species identification, and usually refer to the nature of their effects. For example, Flemish botanist Carolus Clusius (1526''1609) described the bolond gomba (crazy mushroom), used in rural Hungary to prepare love potions. English botanist John Parkinson included details about a "foolish mushroom" in his 1640 herbalTheatricum Botanicum.[135] The first reliably documented report of intoxication with Psilocybe semilanceata'--Europe's most common and widespread psychedelic mushroom'--involved a British family in 1799, who prepared a meal with mushrooms they had picked in London's Green Park.[136]
Modern [ edit] American banker and amateur ethnomycologistR. Gordon Wasson and his wife Valentina studied the ritual use of psychoactive mushrooms by the native population in the Mazatec village Huautla de Jim(C)nez. In 1957, Wasson described the psychedelic visions that he experienced during these rituals in "Seeking the Magic Mushroom", an article published in the popular American weekly Life magazine.[137] Later the same year they were accompanied on a follow-up expedition by French mycologist Roger Heim, who identified several of the mushrooms as Psilocybe species.[138] Heim cultivated the mushrooms in France, and sent samples for analysis to Albert Hofmann, a chemist employed by the Swiss multinational pharmaceutical company Sandoz (now Novartis). Hofmann, who had in 1938 created LSD, led a research group that isolated and identified the psychoactive compounds from Psilocybe mexicana.[139][140] Hofmann was aided in the discovery process by his willingness to ingest mushroom extracts to help verify the presence of the active compounds.[131] He and his colleagues later synthesized a number of compounds chemically related to the naturally occurring psilocybin, to see how structural changes would affect psychoactivity. The new molecules differed from psilocybin in the position of the phosphoryl or hydroxyl group at the top of the indole ring, and in the numbers of methyl groups (CH3) and other additional carbon chains.[141]
Albert Hofmann (shown here in 1993) purified psilocybin and psilocin from Psilocybe mexicana in the late 1950s.Two diethyl analogs (containing two ethyl groups in place of the two methyl groups) of psilocybin and psilocin were synthesized by Hofmann: 4-phosphoryloxy-N,N-diethyltryptamine, called CEY-19, and 4-hydroxy-N,N-diethyltryptamine, called CZ-74. Because their physiological effects last only about three and a half hours (about half as long as psilocybin), they proved more manageable in European clinics using "psycholytic therapy"'--a form of psychotherapy involving the controlled use of psychedelic drugs.[141] Sandoz marketed and sold pure psilocybin under the name Indocybin to physicians and clinicians worldwide.[142] There were no reports of serious complications when psilocybin was used in this way.[1]
In the early 1960s, Harvard University became a testing ground for psilocybin, through the efforts of Timothy Leary and his associates Ralph Metzner and Richard Alpert (who later changed his name to Ram Dass). Leary obtained synthesized psilocybin from Hofmann through Sandoz pharmaceutical. Some studies, such as the Concord Prison Experiment, suggested promising results using psilocybin in clinical psychiatry.[6][143] According to a 2008 review of safety guidelines in human hallucinogenic research, however, Leary and Alpert's well-publicized termination from Harvard and later advocacy of hallucinogen use "further undermined an objective scientific approach to studying these compounds".[144] In response to concerns about the increase in unauthorized use of psychedelic drugs by the general public, psilocybin and other hallucinogenic drugs suffered negative press and faced increasingly restrictive laws. In the United States, laws were passed in 1966 that prohibited the production, trade, or ingestion of hallucinogenic drugs; Sandoz stopped producing LSD and psilocybin the same year.[74] Further backlash against LSD usage swept psilocybin along with it into the Schedule I category of illicit drugs in 1970. Subsequent restrictions on the use of these drugs in human research made funding for such projects difficult to obtain, and scientists who worked with psychedelic drugs faced being "professionally marginalized".[145]
The increasing availability of information on growing techniques made it possible for amateurs to grow psilocybin mushrooms (Psilocybe cubensis pictured) without access to laboratory equipment.Despite the legal restrictions on psilocybin use, the 1970s witnessed the emergence of psilocybin as the "entheogen of choice".[146] This was due in large part to a wide dissemination of information on the topic, which included works such as those by author Carlos Castaneda, and several books that taught the technique of growing psilocybin mushrooms. One of the most popular of this latter group was published in 1976 under the pseudonyms O.T. Oss and O.N. Oeric by Jeremy Bigwood, Dennis J. McKenna, K. Harrison McKenna, and Terence McKenna, entitled Psilocybin: Magic Mushroom Grower's Guide. Over 100,000 copies were sold by 1981.[147] As ethnobiologist Jonathan Ott explains, "These authors adapted San Antonio's technique (for producing edible mushrooms by casing mycelial cultures on a rye grain substrate; San Antonio 1971) to the production of Psilocybe [Stropharia] cubensis. The new technique involved the use of ordinary kitchen implements, and for the first time the layperson was able to produce a potent entheogen in his own home, without access to sophisticated technology, equipment or chemical supplies."[148]
Because of a lack of clarity about laws about psilocybin mushrooms, retailers in the late 1990s and early 2000s (decade) commercialized and marketed them in smartshops in the Netherlands and the UK, and online. Several websites[nb 6] emerged that have contributed to the accessibility of information on description, use, effects and exchange of experiences among users. Since 2001, six EU countries have tightened their legislation on psilocybin mushrooms in response to concerns about their prevalence and increasing usage.[41] In the 1990s, hallucinogens and their effects on human consciousness were again the subject of scientific study, particularly in Europe. Advances in neuropharmacology and neuropsychology, and the availability of brain imaging techniques have provided impetus for using drugs like psilocybin to probe the "neural underpinnings of psychotic symptom formation including ego disorders and hallucinations".[11] Recent studies in the United States have attracted attention from the popular press and thrust psilocybin back into the limelight.[149][150]
Society and culture [ edit] Legal status [ edit] In the United States, psilocybin (and psilocin) were first subjected to federal regulation by the Drug Abuse Control Amendments of 1965, a product of a bill sponsored by Senator Thomas J. Dodd. The law'--passed in July 1965 and effected on February 1, 1966'--was an amendment to the federal Food, Drug and Cosmetic Act and was intended to regulate the unlicensed "possession, manufacture, or sale of depressant, stimulant and hallucinogenic drugs".[151] The statutes themselves, however, did not list the "hallucinogenic drugs" that were being regulated.[151] Instead, the term "hallucinogenic drugs" was meant to refer to those substances believed to have a "hallucinogenic effect on the central nervous system".[151]
Dried Psilocybe mushrooms showing the characteristic blue bruising on the stemsDespite the seemingly strict provisions of the law, many people were exempt from prosecution. The statutes "permit[ted] '... people to possess such drugs so long as they were for the personal use of the possessor, [for] a member of his household, or for administration to an animal".[151] The federal law that specifically banned psilocybin and psilocin was enacted on October 24, 1968. The substances were said to have "a high potential for abuse", "no currently accepted medical use," and "a lack of accepted safety".[152] On October 27, 1970, both psilocybin and psilocin became classified as Schedule I drugs and were simultaneously labeled "hallucinogens" under a section of the Comprehensive Drug Abuse Prevention and Control Act known as the Controlled Substances Act.[153] Schedule I drugs are illicit drugs that are claimed to have no known therapeutic benefit.
The United NationsConvention on Psychotropic Substances (adopted in 1971) requires its members to prohibit psilocybin, and parties to the treaty are required to restrict use of the drug to medical and scientific research under strictly controlled conditions. However, the mushrooms containing the drug were not specifically included in the convention, due largely to pressure from the Mexican government.[154]
Most national drug laws have been amended to reflect the terms of the convention; examples include the UK Misuse of Drugs Act 1971, the US Psychotropic Substances Act of 1978,[153] Australia Poisons Standard (October 2015),[155] the Canadian Controlled Drugs and Substances Act of 1997,[156] and the Japanese Narcotics and Psychotropics Control Law of 2002.[157] The possession and use of psilocybin is prohibited under almost all circumstances, and often carries severe legal penalties.[154]
Possession and use of psilocybin mushrooms, including the bluing species of Psilocybe, is therefore prohibited by extension. However, in many national, state, and provincial drug laws, there has been a great deal of ambiguity about the legal status of psilocybin mushrooms, as well as a strong element of selective enforcement in some places.[120][158] Most US state courts have considered the mushroom a 'container' of the illicit drugs, and therefore illegal. A loophole further complicates the legal situation'--the spores of psilocybin mushrooms do not contain the drugs, and are legal to possess in many areas. Jurisdictions that have specifically enacted or amended laws to criminalize the possession of psilocybin mushroom spores include Germany (since 1998),[157] and California, Georgia, and Idaho in the United States. As a consequence, there is an active underground economy involved in the sale of spores and cultivation materials, and an internet-based social network to support the illicit activity.[159]
Usage [ edit] A 2009 national survey of drug use by the US Department of Health and Human Services concluded that the number of first-time psilocybin mushroom users in the United States was roughly equivalent to the number of first-time users of cannabis.[154] In European countries, the lifetime prevalence estimates of psychedelic mushroom usage among young adults (15''34 years) range from 0.3% to 14.1%.[160]
In modern Mexico, traditional ceremonial use survives among several indigenous groups, including the Nahuas, the Matlatzinca, the Totonacs, the Mazatecs, Mixes, Zapotecs, and the Chatino. Although hallucinogenic Psilocybe species are abundant in low-lying areas of Mexico, most ceremonial use takes places in mountainous areas of elevations greater than 1,500 meters (4,900 ft). Guzmn suggests this is a vestige of Spanish colonial influence from several hundred years earlier, when mushroom use was persecuted by the Catholic Church.[161]
Research and potential for use in medicine [ edit] After a long interruption in the use of psilocybin in research, there has been a general shift in attitudes regarding research with hallucinogenic agents. Many countries are revising their positions and have started to approve studies to test the physiological and therapeutic effects of hallucinogens.[13]
Psilocybin has been a subject of medical research since the early 1960s, when Leary and Alpert ran the Harvard Psilocybin Project, in which they carried out a number of experiments to evaluate the therapeutic value of psilocybin in the treatment of personality disorders, or to augment psychological counseling.[162] In the 2000s (decade), there was a renewal of research concerning the use of psychedelic drugs for potential clinical applications, such as to address anxiety disorders, major depression, and various addictions.[163][164] In 2008, the Johns Hopkins research team published guidelines for responsibly conducting medical research trials with psilocybin and other hallucinogens in humans. These included recommendations on how to screen potential study volunteers to exclude those with personal or family psychiatric histories that suggest a risk of adverse reactions to hallucinogens.[144] A 2010 study on the short- and long-term subjective effects of psilocybin administration in clinical settings concluded that despite a small risk of acute reactions such as dysphoria, anxiety, or panic, "the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk"; the authors note, however, that the safety of the drug "cannot be generalized to situations in which psilocybin is used recreationally or administered under less controlled conditions."[11]
The first clinical study of psilocybin approved by the U.S. Food and Drug Administration (FDA) since 1970[165]'--led by Francisco Moreno at the University of Arizona and supported by the Heffter Research Institute and the Multidisciplinary Association for Psychedelic Studies'--studied the effects of psilocybin on patients with obsessive''compulsive disorder (OCD). The pilot study found that, when administered by trained professionals in a medical setting, the use of psilocybin was associated with substantial reductions in OCD symptoms in several of the patients.[166][167] This effect is caused largely by psilocybin's ability to reduce the levels of the 5-HT2A receptor, resulting in decreased responsiveness to serotonin.[62]
The chemical structures of psilocybin and related analogs have been used in computational biology to help model the structure, function, and ligand-binding properties of the 5-HT2CG-protein-coupled receptor.[168][169]
See also [ edit] ^ Synonyms and alternate spellings include: 4-PO-DMT (PO: phosphate; DMT: dimethyltryptamine), psilocybine, psilocibin, psilocybinum, psilotsibin, psilocin phosphate ester, and indocybin.[3] ^ Percentages are derived from a non-blind clinical study of 30 individuals who were given a dosage of 8''12 milligrams of psilocybin; from Passie (2002),[1] citing Quentin (1960).[14] ^ The academic communities' approval for the methodology employed is exemplified by the quartet of commentaries published in the journal Psychopharmacology titled "Commentary on: Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual experience by Griffiths et al.", by HD Kleber (pp. 291''2), DE Nichols (pp. 284''6), CR Schuster (pp. 289''90), and SH Snyder (pp. 287''8). ^ One of the reported fatalities, that of a 22-year-old French man who died in 1993,[48] was later challenged in the literature by Jochen Gartz and colleagues, who concluded "the few reported data concerning the victim are insufficient to exclude other possible causes of the fatality".[49] ^ Subjective effects are "feelings, perceptions, and moods personally experienced by an individual"; they are often assessed using methods of self-report, including questionnaires. Behavioral effects, in contrast, can be observed directly.[69] ^ The EMCDDA lists the general-purpose websites Erowid, Lycaeum, Mycotopia, The Shroomery, MushroomJohn and The Entheogen Review. Regional sites focusing on hallucinogenic mushrooms listed were Copenhagen Mushroom Link (Denmark), Champis (France), Daath (Hungary), Delysid (Spain), Enteogeneos (Portugal), Kouzeln(C) houbičky (Czech Republic), Norshroom (Norway), Planetahongo (Spain), Svampinfo (Sweden), and Taikasieniforum (Finland). It also listed Magic-Mushrooms.net. The report detailed several additional sites selling spore prints in 2006, but noted that many of these had ceased operation. References [ edit] ^ abcdefghij Passie T, Seifert J, Schneider U, Emrich HM (2002). "The pharmacology of psilocybin". Addiction Biology. 7 (4): 357''64. doi:10.1080/1355621021000005937. PMID 14578010. ^ ab Merck Index, 11th Edition, 7942 ^ "Psilocybine '' Compound Summary". PubChem. National Library of Medicine. 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Kennewick, Washington: Natural Products Company. ISBN 978-0-9614234-3-8. Stafford PJ. (1992). Psychedelics Encyclopedia (3rd ed.). Berkeley, California: Ronin Publishing. ISBN 0-914171-51-8. Stamets P. (1997). Psilocybin Mushrooms of the World: An Identification Guide. Berkeley, California: Ten Speed Press. ISBN 0-89815-839-7. Wurst M, Kysilka R, Flieger M (2002). "Psychoactive tryptamines from Basidiomycetes". Folia Microbiologica. 47 (1): 3''27. doi:10.1007/BF02818560. PMID 11980266. External links [ edit] Psychedelics(5-HT2A
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Others5-HT15-HT1AAgonists:8-OH-DPATAdatanserinAmphetamineAntidepressants (e.g., etoperidone, hydroxynefazodone, nefazodone, trazodone, triazoledione, vilazodone, vortioxetine)Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, lurasidone, quetiapine, ziprasidone)Azapirones (e.g., buspirone, eptapirone, gepirone, perospirone, tandospirone)Bay R 1531BefiradolBMY-14802CannabidiolDimemebfeDopamineEbalzotanEltoprazineEnciprazineErgolines (e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, lisuride, LSD, methylergometrine (methylergonovine), methysergide, pergolide)F-11461F-12826F-13714F-14679F-15063F-15599FlesinoxanFlibanserinFlumexadolLesopitronLY-293284LY-301317mCPPMKC-242NaluzotanNBUMPOsemozotanOxaflozanePardoprunoxPiclozotanRauwolscineRepinotanRoxindoleRU-24969S-14506S-14671S-15535SarizotanSerotonin (5-HT)SSR-181507SunepitronTryptamines (e.g., 5-CT, 5-MeO-DMT, 5-MT, bufotenin, DMT, indorenate, N-Me-5-HT, psilocin, psilocybin)TGBA01ADU-92016AUrapidilVilazodoneXaliprodenYohimbineAntagonists:Atypical antipsychotics (e.g., iloperidone, risperidone, sertindole)AV965Beta blockers (e.g., alprenolol, carteolol, cyanopindolol, iodocyanopindolol, isamoltane, oxprenolol, penbutolol, pindobind, pindolol, propranolol, tertatolol)BMY-7378CSP-2503DotarizineErgolines (e.g., metergoline)FlopropioneGR-46611IsamoltaneLecozotanMefwayMetitepine (methiothepin)MIN-117 (WF-516)MPPFNAN-190RobalzotanS-15535SB-649915SDZ 216-525SpiperoneSpiramideSpiroxatrineUH-301WAY-100135WAY-100635Xylamidine5-HT1BAgonists:CGS-12066ACP-93129CP-94253CP-122,288CP-135807EltoprazineErgolines (e.g., bromocriptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide)mCPPRU-24969Serotonin (5-HT)Triptans (e.g., avitriptan, donitriptan, eletriptan, sumatriptan, zolmitriptan)TFMPPTryptamines (e.g., 5-BT, 5-CT, 5-MT, DMT)Vortioxetine5-HT1DAgonists:CP-122,288CP-135807CP-286601Ergolines (e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, LSD, methysergide)GR-46611L-694247L-772405mCPPPNU-109291PNU-142633Serotonin (5-HT)TGBA01ADTriptans (e.g., almotriptan, avitriptan, donitriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan)Tryptamines (e.g., 5-BT, 5-CT, 5-Et-DMT, 5-MT, 5-(nonyloxy)tryptamine, DMT)5-HT1E5-HT1F5-HT25-HT2AAgonists: 25H/NB series (e.g., 25I-NBF, 25I-NBMD, 25I-NBOH, 25I-NBOMe, 25B-NBOMe, 25C-NBOMe, 25TFM-NBOMe, 2CBCB-NBOMe, 25CN-NBOH, 2CBFly-NBOMe)2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21)2C-B-FLY2CB-Ind5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT)α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT)AL-34662AL-37350ABromo-DragonFLYDimemebfeDMBMPPDOx (e.g., DOB, DOC, DOI, DOM)EfavirenzErgolines (e.g., 1P-LSD, ALD-52, bromocriptine, cabergoline, ergine (LSA), ergometrine (ergonovine), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, methylergometrine (methylergonovine), pergolide)FlumexadolJimscalineLorcaserinMDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA)O-4310OxaflozanePHA-57378PNU-22394PNU-181731RH-34Phenethylamines (e.g., lophophine, mescaline)Piperazines (e.g., BZP, quipazine, TFMPP)Serotonin (5-HT)TCB-2TFMFlyTryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)Antagonists:5-I-R911505-MeO-NBpBrTAC-90179AdatanserinAltanserinAntihistamines (e.g., cyproheptadine, hydroxyzine, ketotifen, perlapine)AMDAAtypical antipsychotics (e.g., amperozide, aripiprazole, asenapine, blonanserin, brexpiprazole, carpipramine, clocapramine, clorotepine, clozapine, fluperlapine, gevotroline, iloperidone, lurasidone, melperone, mosapramine, ocaperidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, zicronapine, ziprasidone, zotepine)CinanserinCSP-2503DeramciclaneDotarizineEplivanserinErgolines (e.g., amesergide, LY-53857, LY-215840, mesulergine, metergoline, methysergide, sergolexole)FananserinFlibanserinGlemanserinIrindaloneKetanserinKML-010LandipirdineLY-393558mCPPMedifoxamineMetitepine (methiothepin)MIN-101MIN-117 (WF-516)NaftidrofurylNantenineNelotanserinOpiranserin (VVZ-149)PelanserinPhenoxybenzaminePimavanserinPirenperonePizotifenPruvanserinRauwolscineRitanserinS-14671SarpogrelateSerotonin antagonists and reuptake inhibitors (e.g., etoperidone, hydroxynefazodone, lubazodone, mepiprazole, nefazodone, triazoledione, trazodone)SR-46349BTGBA01ADTeniloxazineTemanogrelTetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine)Tricyclic antidepressants (e.g., amitriptyline)Typical antipsychotics (e.g., chlorpromazine, fluphenazine, haloperidol, loxapine, perphenazine, pimozide, pipamperone, prochlorperazine, setoperone, spiperone, spiramide, thioridazine, thiothixene, trifluoperazine)VolinanserinXylamidineYohimbine5-HT2BAgonists:4-MethylaminorexAminorexAmphetamines (e.g., chlorphentermine, cloforex, dexfenfluramine, fenfluramine, levofenfluramine, norfenfluramine)BW-723C86DOx (e.g., DOB, DOC, DOI, DOM)Ergolines (e.g., cabergoline, dihydroergocryptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide)LorcaserinMDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, [MMDA (drug)Antagonists:AgomelatineAtypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, N-desalkylquetiapine (norquetiapine), N-desmethylclozapine (norclozapine), olanzapine, pipamperone, quetiapine, risperidone, ziprasidone)CyproheptadineEGIS-7625Ergolines (e.g., amesergide, bromocriptine, lisuride, LY-53857, LY-272015, mesulergine)KetanserinLY-393558mCPPMetadoxineMetitepine (methiothepin)PirenperonePizotifenPropranololPRX-08066RauwolscineRitanserinRS-127445SarpogrelateSB-200646SB-204741SB-206553SB-215505SB-221284SB-228357SDZ SER-082TegaserodTetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine)TrazodoneTypical antipsychotics (e.g., chlorpromazine)TIK-301Yohimbine5-HT2CAgonists:2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21)5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT)α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT)A-372159AL-38022AAlstonineCP-809101DimemebfeDOx (e.g., DOB, DOC, DOI, DOM)Ergolines (e.g., ALD-52, cabergoline, dihydroergotamine, ergine (LSA), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, pergolide)FlumexadolLorcaserinMDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA)MK-212Org 12962Org 37684OxaflozanePHA-57378Phenethylamines (e.g., lophophine, mescaline)Piperazines (e.g., aripiprazole, BZP, mCPP, quipazine, TFMPP)PNU-22394PNU-181731Ro60-0175Ro60-0213Serotonin (5-HT)Tryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)VabicaserinWAY-629WAY-161503YM-348Antagonists:AdatanserinAgomelatineAtypical antipsychotics (e.g., asenapine, clorotepine, clozapine, fluperlapine, iloperidone, melperone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, zotepine)CaptodiameCEPCCinanserinCyproheptadineDeramciclaneDesmetramadolDotarizineEltoprazineErgolines (e.g., amesergide, bromocriptine, LY-53857, LY-215840, mesulergine, metergoline, methysergide, sergolexole)EtoperidoneFluoxetineFR-260010IrindaloneKetanserinKetotifenLatrepirdine (dimebolin)MedifoxamineMetitepine (methiothepin)NefazodonePirenperonePizotifenPropranololRitanserinRS-102221S-14671SB-200646SB-206553SB-221284SB-228357SB-242084SB-243213SDZ SER-082TedatioxetineTetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine)TIK-301TramadolTrazodoneTricyclic antidepressants (e.g., amitriptyline, nortriptyline)Typical antipsychotics (e.g., chlorpromazine, loxapine, pimozide, pipamperone, thioridazine)Xylamidine5-HT3''75-HT3Agonists:Alcohols (e.g., butanol, ethanol (alcohol), trichloroethanol)m-CPBGPhenylbiguanidePiperazines (e.g., BZP, mCPP, quipazine)RS-56812Serotonin (5-HT)SR-57227SR-57227ATryptamines (e.g., 2-Me-5-HT, 5-CT, bufotenidine (5-HTQ))Volatiles/gases (e.g., halothane, isoflurane, toluene, trichloroethane)YM-31636Antagonists:AlosetronAS-8112Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine)AzasetronBatanoprideBemesetron (MDL-72222)BupropionCilansetronCSP-2503DazoprideDolasetronGalanolactoneGranisetronHydroxybupropionICS-205930LerisetronMemantineOndansetronPalonosetronRamosetronRenzaprideRicasetronTedatioxetineTetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine)ThujoneTropanserinTropisetronTypical antipsychotics (e.g., loxapine)Volatiles/gases (e.g., nitrous oxide, sevoflurane, xenon)VortioxetineZacoprideZatosetron5-HT45-HT5A5-HT6Agonists:Ergolines (e.g., dihydroergocryptine, dihydroergotamine, ergotamine, lisuride, LSD, mesulergine, metergoline, methysergide)Serotonin (5-HT)Tryptamines (e.g., 2-Me-5-HT, 5-BT, 5-CT, 5-MT, Bufotenin, E-6801, E-6837, EMD-386088, EMDT, LY-586713, N-Me-5-HT, tryptamine)WAY-181187WAY-208466Antagonists:ABT-354Atypical antipsychotics (e.g., aripiprazole, asenapine, clorotepine, clozapine, fluperlapine, iloperidone, olanzapine, tiospirone)AVN-101AVN-211AVN-322AVN-397BGC20-760BVT-5182BVT-74316CerlapirdineEGIS-12233GW-742457IdalopirdineKetanserinLandipirdineLatrepirdine (dimebolin)Metitepine (methiothepin)MS-245PRX-07034RitanserinRo 04-6790Ro 63-0563SB-258585SB-271046SB-357134SB-399885SB-742457Tetracyclic antidepressants (e.g., amoxapine, mianserin)Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, nortriptyline)Typical antipsychotics (e.g., chlorpromazine, loxapine)5-HT7Antagonists:Atypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, brexpiprazole, clorotepine, clozapine, fluperlapine, olanzapine, risperidone, sertindole, tiospirone, ziprasidone, zotepine)ButaclamolDR-4485EGIS-12233Ergolines (e.g., 2-Br-LSD (BOL-148), amesergide, bromocriptine, cabergoline, dihydroergotamine, ergotamine, LY-53857, LY-215840, mesulergine, metergoline, methysergide, sergolexole)JNJ-18038683KetanserinLY-215840Metitepine (methiothepin)RitanserinSB-258719SB-258741SB-269970SB-656104SB-656104ASB-691673SLV-313SLV-314SpiperoneSSR-181507Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine)Tricyclic antidepressants (e.g., amitriptyline, clomipramine, imipramine)Typical antipsychotics (e.g., acetophenazine, chlorpromazine, chlorprothixene, fluphenazine, loxapine, pimozide)Vortioxetine
Psilocybin - Wikipedia
Sun, 07 Jan 2018 14:22
PsilocybinNamesIUPAC name[3-(2-Dimethylaminoethyl)-1H-indol-4-yl] dihydrogen phosphate
Identifiers273158ChEBIChemSpiderECHA InfoCard 100.007.542EC Number 208-294-4KEGGMeSHPsilocybine RTECS numberNM3150000InChI=1S/C12H17N2O4P/c1-14(2)7-6-9-8-13-10-4-3-5-11(12(9)10)18-19(15,16)17/h3-5,8,13H,6-7H2,1-2H3,(H2,15,16,17) Y Key: QVDSEJDULKLHCG-UHFFFAOYSA-N Y InChI=1/C12H17N2O4P/c1-14(2)7-6-9-8-13-10-4-3-5-11(12(9)10)18-19(15,16)17/h3-5,8,13H,6-7H2,1-2H3,(H2,15,16,17)
CN(C)CCC1=CNC2=C1C(=CC=C2)OP(=O)(O)O
PharmacologyLowOral, intravenousPharmacokinetics:Hepaticoral: 163±64 minintravenous: 74.1±19.6 min[1]
RenalLegal statusPropertiesC 12H 17N 2O 4P Molar mass284.25 g·mol''1Melting point220''228 °C (428''442 °F)[2]solubleSolubilitysoluble in methanolslightly soluble in ethanol
negligible in chloroform, benzene
HazardsLethal dose or concentration (LD, LC):285 mg/kg (mouse, i.v.)280 mg/kg (rat, i.v.)
12.5 mg/kg (rabbit, i.v.)[2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).Y verify (what is Y N ?)Infobox referencesPsilocybin[nb 1] ( sy-lÉ-SY -bin) is a naturally occurring psychedelicprodrug compound produced by more than 200 species of mushrooms, collectively known as psilocybin mushrooms. Psilocybin evolved in mushrooms from its ancestor, muscarine, some 20 million years ago.[4]
The most potent are members of the genus Psilocybe, such as P. azurescens, P. semilanceata, and P. cyanescens, but psilocybin has also been isolated from about a dozen other genera. As a prodrug, psilocybin is quickly converted by the body to psilocin, which has mind-altering effects similar, in some aspects, to those of LSD, mescaline, and DMT. In general, the effects include euphoria, visual and mental hallucinations, changes in perception, a distorted sense of time, and spiritual experiences, and can include possible adverse reactions such as nausea and panic attacks.
Imagery found on prehistoric murals and rock paintings of modern-day Spain and Algeria suggests that human usage of psilocybin mushrooms predates recorded history. In Mesoamerica, the mushrooms had long been consumed in spiritual and divinatory ceremonies before Spanish chroniclers first documented their use in the 16th century. In a 1957 Life magazine article, American banker and ethnomycologistR. Gordon Wasson described his experiences ingesting psilocybin-containing mushrooms during a traditional ceremony in Mexico, introducing the substance to popular culture. In 1959, the Swiss chemist Albert Hofmann isolated the active principle psilocybin from the mushroom Psilocybe mexicana. Hofmann's employer Sandoz marketed and sold pure psilocybin to physicians and clinicians worldwide for use in psychedelic psychotherapy. Although the increasingly restrictive drug laws of the late 1960s curbed scientific research into the effects of psilocybin and other hallucinogens, its popularity as an entheogen (spirituality-enhancing agent) grew in the next decade, owing largely to the increased availability of information on how to cultivate psilocybin mushrooms.
Some users of the drug consider it an entheogen and a tool to supplement practices for transcendence, including meditation and psychonautics. The intensity and duration of the effects of psilocybin are variable, depending on species or cultivar of mushrooms, dosage, individual physiology, and set and setting, as was shown in experiments led by Timothy Leary at Harvard University in the early 1960s. Once ingested, psilocybin is rapidly metabolized to psilocin, which then acts on serotonin receptors in the brain. The mind-altering effects of psilocybin typically last from two to six hours, although to individuals under the influence of psilocybin, the effects may seem to last much longer, since the drug can distort the perception of time. Psilocybin has a low toxicity and a relatively low harm potential, and reports of lethal doses of the drug are rare. Several modern bioanalytical methods have been adapted to rapidly and accurately screen the levels of psilocybin in mushroom samples and body fluids. Since the 1990s, there has been a renewal of scientific research into the potential medical and psychological therapeutic benefits of psilocybin for treating conditions including obsessive-compulsive disorder (OCD), post-traumatic stress disorder, social anxiety, treatment-resistant depression, cluster headaches, and anxiety related to terminal cancer.[5] Possession of psilocybin-containing mushrooms has been outlawed in most countries, and it has been classified as a scheduled drug by many national drug laws.
Effects [ edit] American psychologist and counterculture figure Timothy Leary conducted early experiments into the effects of psychedelic drugs, including psilocybin. (1989 photo)The effects of psilocybin are highly variable and depend on the mindset and environment in which the user has the experience, factors commonly referred to as set and setting. In the early 1960s, Timothy Leary and colleagues at Harvard University investigated the role of set and setting on the effects of psilocybin. They administered the drug to 175 volunteers from various backgrounds in an environment intended to be similar to a comfortable living room. Ninety-eight of the subjects were given questionnaires to assess their experiences and the contribution of background and situational factors. Individuals who had experience with psilocybin prior to the study reported more pleasant experiences than those for whom the drug was novel. Group size, dosage, preparation, and expectancy were important determinants of the drug response. In general, those placed in groups of more than eight individuals felt that the groups were less supportive, and their experiences were less pleasant. Conversely, smaller groups (fewer than six individuals) were seen as more supportive. Participants also reported having more positive reactions to the drug in those groups. Leary and colleagues proposed that psilocybin heightens suggestibility, making an individual more receptive to interpersonal interactions and environmental stimuli.[6] These findings were affirmed in a later review by Jos ten Berge (1999), who concluded that dosage, set, and setting were fundamental factors in determining the outcome of experiments that tested the effects of psychedelic drugs on artists' creativity.[7]
After ingesting psilocybin, a wide range of subjective effects may be experienced: feelings of disorientation, lethargy, giddiness, euphoria, joy, and depression. About a third of users report feelings of anxiety or paranoia.[8] Low doses of the drug can induce hallucinatory effects. Closed-eye hallucinations may occur, in which the affected individual sees multicolored geometric shapes and vivid imaginative sequences.[9] Some individuals report experiencing synesthesia, such as tactile sensations when viewing colors.[10] At higher doses, psilocybin can lead to "Intensification of affective responses, enhanced ability for introspection, regression to primitive and childlike thinking, and activation of vivid memory traces with pronounced emotional undertones".[11] Open-eye visual hallucinations are common, and may be very detailed although rarely confused with reality.[9]
A 2011 prospective study by Roland R. Griffiths and colleagues suggests that a single high dosage of psilocybin can cause long-term changes in the personality of its users. About half of the study participants'--described as healthy, "spiritually active", and many possessing postgraduate degrees'--showed an increase in the personality dimension of openness (assessed using the Revised NEO Personality Inventory), and this positive effect was apparent more than a year after the psilocybin session. According to the study authors, the finding is significant because "no study has prospectively demonstrated personality change in healthy adults after an experimentally manipulated discrete event."[12] Although other researchers have described instances of psychedelic drug usage leading to new psychological understandings and personal insights,[13] it is not known whether these experimental results can be generalized to larger populations.[12]
Physical effects [ edit] Common responses include: pupil dilation (93%); changes in heart rate (100%), including increases (56%), decreases (13%), and variable responses (31%); changes in blood pressure (84%), including hypotension (34%), hypertension (28%), and general instability (22%); changes in stretch reflex (86%), including increases (80%) and decreases (6%); nausea (44%); tremor (25%); and dysmetria (16%) (inability to properly direct or limit motions).[nb 2] The temporary increases in blood pressure caused by the drug can be a risk factor for users with pre-existing hypertension.[9] These qualitative somatic effects caused by psilocybin have been corroborated by several early clinical studies.[15] A 2005 magazine survey of club goers in the UK found that nausea or vomiting was experienced by over a quarter of those who had used psilocybin mushrooms in the last year, although this effect is caused by the mushroom rather than psilocybin itself.[8] In one study, administration of gradually increasing dosages of psilocybin daily for 21 days had no measurable effect on electrolyte levels, blood sugar levels, or liver toxicity tests.[1]
Perceptual distortions [ edit] The ability of psilocybin to cause perceptual distortions is linked to its influence on the activity of the prefrontal cortex.Psilocybin is known to strongly influence the subjective experience of the passage of time.[16] Users often feel as if time is slowed down, resulting in the perception that "minutes appear to be hours" or "time is standing still".[17] Studies have demonstrated that psilocybin significantly impairs subjects' ability to gauge time intervals longer than 2.5 seconds, impairs their ability to synchronize to inter-beat intervals longer than 2 seconds, and reduces their preferred tapping rate.[17][18] These results are consistent with the drug's role in affecting prefrontal cortex activity,[19] and the role that the prefrontal cortex is known to play in time perception.[20] However, the neurochemical basis of psilocybin's effects on the perception of time are not known with certainty.[21]
Users having a pleasant experience can feel a sense of connection to others, nature, and the universe; other perceptions and emotions are also often intensified. Users having an unpleasant experience (a "bad trip") describe a reaction accompanied by fear, other unpleasant feelings, and occasionally by dangerous behavior. In general, the phrase "bad trip" is used to describe a reaction that is characterized primarily by fear or other unpleasant emotions, not just transitory experience of such feelings. A variety of factors may contribute to a psilocybin user experiencing a bad trip, including "tripping" during an emotional or physical low or in a non-supportive environment (see: set and setting). Ingesting psilocybin in combination with other drugs, including alcohol, can also increase the likelihood of a bad trip.[8][22] Other than the duration of the experience, the effects of psilocybin are similar to comparable dosages of LSD or mescaline. However, in the Psychedelics Encyclopedia, author Peter Stafford noted, "The psilocybin experience seems to be warmer, not as forceful and less isolating. It tends to build connections between people, who are generally much more in communication than when they use LSD."[23]
Spiritual [ edit] Psilocybin mushrooms have been and continue to be used in indigenous New World cultures in religious, divinatory, or spiritual contexts. Reflecting the meaning of the word entheogen ("the god within"), the mushrooms are revered as powerful spiritual sacraments that provide access to sacred worlds. Typically used in small group community settings, they enhance group cohesion and reaffirm traditional values.[24]Terence McKenna documented the worldwide practices of psilocybin mushroom usage as part of a cultural ethos relating to the Earth and mysteries of nature, and suggested that mushrooms enhanced self-awareness and a sense of contact with a "Transcendent Other"'--reflecting a deeper understanding of our connectedness with nature.[25]
Psychedelic drugs can induce states of consciousness that have lasting personal meaning and spiritual significance in individuals who are religious or spiritually inclined; these states are called mystical experiences. Some scholars have proposed that many of the qualities of a drug-induced mystical experience are indistinguishable from mystical experiences achieved through non-drug techniques, such as meditation or holotropic breathwork.[26][27] In the 1960s, Walter Pahnke and colleagues systematically evaluated mystical experiences (which they called "mystical consciousness") by categorizing their common features. These categories, according to Pahnke, "describe the core of a universal psychological experience, free from culturally determined philosophical or theological interpretations", and allow researchers to assess mystical experiences on a qualitative, numerical scale.[28]
In the 1962 Marsh Chapel Experiment, which was run by Pahnke at the Harvard Divinity School under the supervision of Timothy Leary,[29] almost all of the graduate degree divinity student volunteers who received psilocybin reported profound religious experiences.[30] One of the participants was religious scholar Huston Smith, author of several textbooks on comparative religion; he later described his experience as "the most powerful cosmic homecoming I have ever experienced."[31] In a 25-year followup to the experiment, all of the subjects given psilocybin described their experience as having elements of "a genuine mystical nature and characterized it as one of the high points of their spiritual life".[32] Psychedelic researcher Rick Doblin considered the study partially flawed due to incorrect implementation of the double-blind procedure, and several imprecise questions in the mystical experience questionnaire. Nevertheless, he said that the study cast "a considerable doubt on the assertion that mystical experiences catalyzed by drugs are in any way inferior to non-drug mystical experiences in both their immediate content and long-term effects".[33] This sentiment was echoed by psychiatrist William A. Richards, who in a 2007 review stated "[psychedelic] mushroom use may constitute one technology for evoking revelatory experiences that are similar, if not identical, to those that occur through so-called spontaneous alterations of brain chemistry."[34]
In their studies on the psilocybin experience, Johns Hopkins researchers use peaceful music and a comfortable room to help ensure a comfortable setting, and experienced guides to monitor and reassure the volunteers.A group of researchers from Johns Hopkins School of Medicine led by Griffiths conducted a study to assess the immediate and long-term psychological effects of the psilocybin experience, using a modified version of the mystical experience questionnaire and a rigorous double-blind procedure.[35] When asked in an interview about the similarity of his work with Leary's, Griffiths explained the difference: "We are conducting rigorous, systematic research with psilocybin under carefully monitored conditions, a route which Dr. Leary abandoned in the early 1960s."[36] The National Institute of Drug Abuse-funded study, published in 2006, has been praised by experts for the soundness of its experimental design.[nb 3] In the experiment, 36 volunteers without prior experience with hallucinogens were given psilocybin and methylphenidate (Ritalin) in separate sessions; the methylphenidate sessions served as a control and psychoactive placebo. The degree of mystical experience was measured using a questionnaire developed by Ralph W. Hood;[37] 61% of subjects reported a "complete mystical experience" after their psilocybin session, while only 13% reported such an outcome after their experience with methylphenidate. Two months after taking psilocybin, 79% of the participants reported moderately to greatly increased life satisfaction and sense of well-being. About 36% of participants also had a strong to extreme "experience of fear" or dysphoria (i.e., a "bad trip") at some point during the psilocybin session (which was not reported by any subject during the methylphenidate session); about one-third of these (13% of the total) reported that this dysphoria dominated the entire session. These negative effects were reported to be easily managed by the researchers and did not have a lasting negative effect on the subject's sense of well-being.[38]
A follow-up study conducted 14 months after the original psilocybin session confirmed that participants continued to attribute deep personal meaning to the experience. Almost one-third of the subjects reported that the experience was the single most meaningful or spiritually significant event of their lives, and over two-thirds reported it among their five most spiritually significant events. About two-thirds indicated that the experience increased their sense of well-being or life satisfaction.[30] Even after 14 months, those who reported mystical experiences scored on average 4 percentage points higher on the personality trait of Openness/Intellect; personality traits are normally stable across the lifespan for adults. Likewise, in a recent (2010) web-based questionnaire study designed to investigate user perceptions of the benefits and harms of hallucinogenic drug use, 60% of the 503 psilocybin users reported that their use of psilocybin had a long-term positive impact on their sense of well-being.[8][39]
In 2011, Griffiths and colleagues published the results of further studies designed to learn more about the optimum psilocybin doses needed for positive life-changing experiences, while minimizing the chance of negative reactions. In a 14-month followup, the researchers found that 94% of the volunteers rated their experiences with the drug as one of the top five most spiritually significant of their lives (44% said it was the single most significant). None of the 90 sessions that took place throughout the study were rated as decreasing well-being or life satisfaction. Moreover, 89% reported positive changes in their behaviors as a result of the experiences. The conditions of the experimental design included a single drug experience a month, on a couch, in a living-room-like setting, with eye shades and carefully chosen music (classical and world music). As an additional precaution to guide the experience, as with the 2006 study, the 2011 study included a "monitor" or "guide" whom the volunteers supposedly trusted. The monitors provided gentle reassurance when the volunteers experienced anxiety. The volunteers and monitors all remained blind to the exact dosages for the purpose of the experiment.[40]
Available forms [ edit] Although psilocybin may be prepared synthetically, outside of the research setting, it is not typically used in this form. The psilocybin present in certain species of mushrooms can be ingested in several ways: by consuming fresh or dried fruit bodies, by preparing a herbal tea, or by combining with other foods to mask the bitter taste.[41] In rare cases people have injected mushroom extracts intravenously.[8]
Adverse effects [ edit] Most of the comparatively few fatal incidents reported in the literature that are associated with psychedelic mushroom usage involve the simultaneous use of other drugs, especially alcohol. Probably the most common cause of hospital admissions resulting from psychedelic mushroom usage involve "bad trips" or panic reactions, in which affected individuals become extremely anxious, confused, agitated, or disoriented. Accidents, self-injury, or suicide attempts can result from serious cases of acute psychotic episodes.[8] Although no studies have linked psilocybin with birth defects,[42] it is recommended that pregnant women avoid its usage.[43]
Toxicity [ edit] Chart of dependence potential and effective dose/lethal dose ratio of several psychoactive drugs. Source:[44]The toxicity of psilocybin is low. In rats, the median lethal dose (LD50) when administered orally is 280 milligrams per kilogram (mg/kg), approximately one and a half times that of caffeine. When administered intravenously in rabbits, psilocybin's LD50 is approximately 12.5 mg/kg.[45] Psilocybin comprises approximately 1% of the weight of Psilocybe cubensis mushrooms, and so nearly 1.7 kilograms (3.7 lb) of dried mushrooms, or 17 kilograms (37 lb) of fresh mushrooms, would be required for a 60-kilogram (130 lb) person to reach the 280 mg/kg LD50 value of rats.[8] Based on the results of animal studies, the lethal dose of psilocybin has been extrapolated to be 6 grams, 1000 times greater than the effective dose of 6 milligrams.[46] The Registry of Toxic Effects of Chemical Substances assigns psilocybin a relatively high therapeutic index of 641 (higher values correspond to a better safety profile); for comparison, the therapeutic indices of aspirin and nicotine are 199 and 21, respectively.[47] The lethal dose from psilocybin toxicity alone is unknown at recreational or medicinal levels, and has rarely been documented'--as of 2011[update], only two cases attributed to overdosing on hallucinogenic mushrooms (without concurrent use of other drugs) have been reported in the scientific literature and may involve other factors aside from psilocybin.[8][nb 4]
Psychiatric [ edit] Panic reactions can occur after consumption of psilocybin-containing mushrooms, especially if the ingestion is accidental or otherwise unexpected. Reactions characterized by violent behavior, suicidal thoughts,[50] schizophrenia-like psychosis,[51][52] and convulsions[53] have been reported in the literature. A 2005 survey conducted in the United Kingdom found that almost a quarter of those who had used psilocybin mushrooms in the past year had experienced a panic attack.[8] Other adverse effects less frequently reported include paranoia, confusion, prolonged derealization (disconnection from reality), and mania.[39] Psilocybin usage can temporarily induce a state of depersonalization disorder.[54] Usage by those with schizophrenia can induce acute psychotic states requiring hospitalization.[8]
Recent evidence, however, has suggested against the contention that the use of psilocybin puts one at risk for developing long lasting mental disorders. An analysis of information from the National Survey on Drug Use and Health showed that the use of psychedelic drugs such as psilocybin is associated with significantly reduced odds of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt.[55]
The similarity of psilocybin-induced symptoms to those of schizophrenia has made the drug a useful research tool in behavioral and neuroimaging studies of this psychotic disorder.[56][57][58] In both cases, psychotic symptoms are thought to arise from a "deficient gating of sensory and cognitive information" in the brain that ultimately lead to "cognitive fragmentation and psychosis".[57]Flashbacks (spontaneous recurrences of a previous psilocybin experience) can occur long after having used psilocybin mushrooms. Hallucinogen persisting perception disorder (HPPD) is characterized by a continual presence of visual disturbances similar to those generated by psychedelic substances. Neither flashbacks nor HPPD are commonly associated with psilocybin usage,[8] and correlations between HPPD and psychedelics are further obscured by polydrug use and other variables.[59]
Tolerance and dependence [ edit] Tolerance to psilocybin builds and dissipates quickly; ingesting psilocybin more than about once a week can lead to diminished effects. Tolerance dissipates after a few days, so doses can be spaced several days apart to avoid the effect.[60] A cross-tolerance can develop between psilocybin and the pharmacologically similar LSD,[61] and between psilocybin and phenethylamines such as mescaline and DOM.[62]
Repeated use of psilocybin does not lead to physical dependence.[1] A 2008 study concluded that, based on US data from the period 2000''2002, adolescent-onset (defined here as ages 11''17) usage of hallucinogenic drugs (including psilocybin) did not increase the risk of drug dependence in adulthood; this was in contrast to adolescent usage of cannabis, cocaine, inhalants, anxiolytic medicines, and stimulants, all of which were associated with "an excess risk of developing clinical features associated with drug dependence".[63] Likewise, a 2010 Dutch study ranked the relative harm of psilocybin mushrooms compared to a selection of 19 recreational drugs, including alcohol, cannabis, cocaine, ecstasy, heroin, and tobacco. Psilocybin mushrooms were ranked as the illicit drug with the lowest harm,[64] corroborating conclusions reached earlier by expert groups in the United Kingdom.[65]
Interactions [ edit] Monoamine oxidase inhibitors (MAOI) have been known to prolong and enhance the effects of psilocybin.[66] Alcohol consumption may enhance the effects of psilocybin, because acetaldehyde, one of the primary breakdown metabolites of consumed alcohol, reacts with biogenic amines present in the body to produce MAOIs related to tetrahydroisoquinoline and β-carboline. Tobacco smokers may also experience more powerful effects with psilocybin,[8] because tobacco smoke exposure decreases the activity of MAO in the brain and peripheral organs.[67]
Pharmacology [ edit] Pharmacodynamics [ edit] The neurotransmitter serotonin is structurally similar to psilocybin.Psilocybin is rapidly dephosphorylated in the body to psilocin, which is a partial agonist for several serotonin receptors, which are also known as 5-hydroxytryptamine (5-HT) receptors. Psilocin has a high affinity for the 5-HT2B and 5-HT2C receptors in the human brain, and with a slightly lower affinity for the 5-HT2A receptor. Psilocin binds with low affinity to 5-HT1 receptors, including 5-HT1A and 5-HT1D.[1] Serotonin receptors are located in numerous parts of the brain, including the cerebral cortex, and are involved in a wide range of functions, including regulation of mood and motivation.[68] The psychotomimetic (psychosis-mimicking) effects of psilocin can be blocked in a dose-dependent fashion by the 5-HT2Aantagonist drug ketanserin.[51] Various lines of evidence have shown that interactions with non-5-HT2 receptors also contribute to the subjective and behavioral effects of the drug.[62][nb 5] For example, psilocin indirectly increases the concentration of the neurotransmitter dopamine in the basal ganglia, and some psychotomimetic symptoms of psilocin are reduced by haloperidol, a non-selective dopamine receptor antagonist. Taken together, these suggest that there may be an indirect dopaminergic contribution to psilocin's psychotomimetic effects.[21] Unlike LSD, which binds to D2-like dopamine receptors in addition to having strong affinity for several 5-HT receptors, psilocybin and psilocin have no affinity for the dopamine D2 receptors.[1]
Pharmacokinetics [ edit] The effects of the drug begin 10''40 minutes after ingestion, and last 2''6 hours depending on dose, species, and individual metabolism.[70] The half life of psilocybin is 163 ± 64 minutes when taken orally, or 74.1 ± 19.6 minutes when injected intravenously.[1] A dosage of 4''10 mg, corresponding roughly to 50''300 micrograms per kilogram (µg/kg) of body weight, is required to induce psychedelic effects. A typical recreational dosage is 10''50 mg psilocybin, which is roughly equivalent to 10''50 grams of fresh mushrooms, or 1''5 grams of dried mushrooms.[8] A small number of people are unusually sensitive to psilocybin, such that a normally threshold-level dose of about 2 mg can result in effects usually associated with medium or high doses. In contrast, there are some who require relatively high doses to experience noticeable effects. Individual brain chemistry and metabolism play a large role in determining a person's response to psilocybin.[70]
Psilocybin is converted in the liver to the pharmacologically active psilocin, which is then either glucuronated to be excreted in the urine or further converted to various psilocin metabolites.Psilocybin is metabolized mostly in the liver. As it becomes converted to psilocin, it undergoes a first-pass effect, whereby its concentration is greatly reduced before it reaches the systemic circulation. Psilocin is broken down by the enzyme monoamine oxidase to produce several metabolites that can circulate in the blood plasma, including 4-hydroxyindole-3-acetaldehyde, 4-hydroxytryptophol, and 4-hydroxyindole-3-acetic acid.[1] Some psilocin is not broken down by enzymes and instead forms a glucuronide; this is a biochemical mechanism animals use to eliminate toxic substances by linking them with glucuronic acid, which can then be excreted in the urine.[71][72] Psilocin is glucuronated by the glucuronosyltransferase enzymes UGT1A9 in the liver, and by UGT1A10 in the small intestine.[73] Based on studies using animals, about 50% of ingested psilocybin is absorbed through the stomach and intestine. Within 24 hours, about 65% of the absorbed psilocybin is excreted into the urine, and a further 15''20% is excreted in the bile and feces. Although most of the remaining drug is eliminated in this way within 8 hours, it is still detectable in the urine after 7 days.[74] Clinical studies show that psilocin concentrations in the plasma of adults average about 8 µg/liter within 2 hours after ingestion of a single 15 mg oral psilocybin dose;[75] psychological effects occur with a blood plasma concentration of 4''6 µg/liter.[1] Psilocybin is about 100 times less potent than LSD on a weight per weight basis, and the physiological effects last about half as long.[76]
Chemistry and biosynthesis [ edit] Psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine, 4-PO-Psilocin, or 4-PO-HO-DMT) is a prodrug that is converted into the pharmacologically active compound psilocin in the body by a dephosphorylation reaction. This chemical reaction takes place under strongly acidic conditions, or under physiological conditions in the body, through the action of enzymes called alkaline phosphatases.[77]
Psilocybin is a tryptamine compound with a chemical structure containing an indole ring linked to an ethylaminesubstituent. It is chemically related to the amino acidtryptophan, and is structurally similar to the neurotransmitterserotonin. Psilocybin is a member of the general class of tryptophan-based compounds that originally functioned as antioxidants in earlier life forms before assuming more complex functions in multicellular organisms, including humans.[78] Other related indole-containing psychedelic compounds include dimethyltryptamine, found in many plant species and in trace amounts in some mammals, and bufotenine, found in the skin of psychoactive toads.[79]
Psilocybin is an alkaloid that is soluble in water, methanol and aqueous ethanol, but insoluble in organic solvents like chloroform and petroleum ether.[80] Its pKa values are estimated to be 1.3 and 6.5 for the two successive phosphate OH groups and 10.4 for the dimethylamine nitrogen, so in general it exists as a zwitterionic structure.[81] Exposure to light is detrimental to the stability of aqueous solutions of psilocybin, and will cause it to rapidly oxidize'--an important consideration when using it as an analytical standard.[82] Osamu Shirota and colleagues reported a method for the large-scale synthesis of psilocybin without chromatographic purification in 2003.[83] Starting with 4-hydroxyindole, they generated psilocybin from psilocin in 85% yield, a marked improvement over yields reported from previous syntheses.[84][85][86] Purified psilocybin is a white, needle-like crystalline powder[83] with a melting point between 220''228 °C (428''442 °F),[45] and a slightly ammonia-like taste.[81]
Biosynthetically, the biochemical transformation from tryptophan to psilocybin involves several enzyme reactions: decarboxylation, methylation at the N9 position, 4-hydroxylation, and O-phosphorylation. Isotopic labeling experiments suggest that tryptophan decarboxylation is the initial biosynthetic step and that O-phosphorylation is the final step.[87][88]) The sequence of the intermediate enzymatic steps has been shown to involve 4 different enzymes (PsiD, PsiH, PsiK, and PsiM) in P. cubensis and P. cyanescens, although the biosynthetic pathway may differ between species.[89][90]
A possible biosynthetic route to psilocybin. Although the order of the first (decarboxylation) and last (phosphorylation) steps are known, the details of the hypothetical intracellular (de-) phosphorylation are speculative.[90]Analytical methods [ edit] Several relatively simple chemical tests '-- commercially available as reagent testing kits '-- can be used to assess the presence of psilocybin in extracts prepared from mushrooms. The drug reacts in the Marquis test to produce a yellow color, and a green color in the Mandelin test.[91] Neither of these tests, however, is specific for psilocybin; for example, the Marquis test will react with many classes of controlled drugs, such as those containing primary amino groups and unsubstituted benzene rings, including amphetamine and methamphetamine.[92]Ehrlich's reagent and DMACA reagent are used as chemical sprays to detect the drug after thin layer chromatography.[93] Many modern techniques of analytical chemistry have been used to quantify psilocybin levels in mushroom samples. Although the earliest methods commonly used gas chromatography, the high temperature required to vaporize the psilocybin sample prior to analysis causes it to spontaneously lose its phosphoryl group and become psilocin '-- making it difficult to chemically discriminate between the two drugs. In forensic toxicology, techniques involving gas chromatography coupled to mass spectrometry (GC''MS) are the most widely used due to their high sensitivity and ability to separate compounds in complex biological mixtures.[94] These techniques include ion mobility spectrometry,[95]capillary zone electrophoresis,[96]ultraviolet spectroscopy,[97] and infrared spectroscopy.[98]High performance liquid chromatography (HPLC) is used with ultraviolet,[82]fluorescence,[99]electrochemical,[100] and electrospray mass spectrometric detection methods.[101]
Various chromatographic methods have been developed to detect psilocin in body fluids: the rapid emergency drug identification system (REMEDi HS), a drug screening method based on HPLC;[102] HPLC with electrochemical detection;[100][103] GC''MS;[71][102] and liquid chromatography coupled to mass spectrometry.[104] Although the determination of psilocin levels in urine can be performed without sample clean-up (i.e., removing potential contaminants that make it difficult to accurately assess concentration), the analysis in plasma or serum requires a preliminary extraction, followed by derivatization of the extracts in the case of GC''MS. A specific immunoassay has also been developed to detect psilocin in whole blood samples.[105] A 2009 publication reported using HPLC to quickly separate forensically important illicit drugs including psilocybin and psilocin, which were identifiable within about half a minute of analysis time.[106] These analytical techniques to determine psilocybin concentrations in body fluids are, however, not routinely available, and not typically used in clinical settings.[22]
Natural occurrence [ edit] Psilocybin is present in varying concentrations in over 200 species of Basidiomycota mushrooms which evolved to produce the compound from muscarine some 20 million years ago.[4] In a 2000 review on the worldwide distribution of hallucinogenic mushrooms, Gast"n Guzmn and colleagues considered these to be distributed amongst the following genera: Psilocybe (116 species), Gymnopilus (14), Panaeolus (13), Copelandia (12), Hypholoma (6), Pluteus (6), Inocybe (6), Conocybe (4), Panaeolina (4), Gerronema (2) and Agrocybe, Galerina and Mycena (1 species each).[108] Guzmn increased his estimate of the number of psilocybin-containing Psilocybe to 144 species in a 2005 review. The majority of these are found in Mexico (53 species), with the remainder distributed in the US and Canada (22), Europe (16), Asia (15), Africa (4), and Australia and associated islands (19).[109] In general, psilocybin-containing species are dark-spored, gilled mushrooms that grow in meadows and woods of the subtropics and tropics, usually in soils rich in humus and plant debris.[110] Psilocybin mushrooms occur on all continents, but the majority of species are found in subtropical humid forests.[108]Psilocybe species commonly found in the tropics include P. cubensis and P. subcubensis. P. semilanceata '-- considered by Guzmn to be the world's most widely distributed psilocybin mushroom[111] '-- is found in Europe, North America, Asia, South America, Australia and New Zealand, but is entirely absent from Mexico.[109] Although the presence or absence of psilocybin is not of much use as a chemotaxonomical marker at the familial level or higher, it is used to classify taxa of lower taxonomic groups.[112]
Global distribution of over 100 psychoactive species of Psilocybe genus mushrooms.[113]Both the caps and the stems contain the psychoactive compounds, although the caps consistently contain more. The spores of these mushrooms do not contain psilocybin or psilocin.[95][114][115] The total potency varies greatly between species and even between specimens of a species collected or grown from the same strain.[116] Because most psilocybin biosynthesis occurs early in the formation of fruit bodies or sclerotia, younger, smaller mushrooms tend to have a higher concentration of the drug than larger, mature mushrooms.[117] In general, the psilocybin content of mushrooms is quite variable (ranging from almost nothing to 1.5% of the dry weight)[118] and depends on species, strain, growth and drying conditions, and mushroom size.[119] Cultivated mushrooms have less variability in psilocybin content than wild mushrooms.[120] The drug is more stable in dried than fresh mushrooms; dried mushrooms retain their potency for months or even years,[121] while mushrooms stored fresh for four weeks contain only traces of the original psilocybin.[8]
The psilocybin contents of dried herbarium specimens of Psilocybe semilanceata in one study were shown to decrease with the increasing age of the sample: collections dated 11, 33, or 118 years old contained 0.84%, 0.67%, and 0.014% (all dry weight), respectively.[122] Mature mycelia contain some psilocybin, while young mycelia (recently germinated from spores) lack appreciable amounts.[123] Many species of mushrooms containing psilocybin also contain lesser amounts of the analog compounds baeocystin and norbaeocystin,[124] chemicals thought to be biogenic precursors.[125] Although most species of psilocybin-containing mushrooms bruise blue when handled or damaged due to the oxidization of phenolic compounds, this reaction is not a definitive method of identification or determining a mushroom's potency.[116][126]
History [ edit] Early [ edit] There is evidence to suggest that psychoactive mushrooms have been used by humans in religious ceremonies for thousands of years. Murals dated 9000 to 7000 BCE found in the Sahara desert in southeast Algeria depict horned beings dressed as dancers, clothed in garb decorated with geometrical designs, and holding mushroom-like objects. Parallel lines extend from the mushroom shapes to the center of the dancers' heads.[127] 6,000-year-old pictographs discovered near the Spanish town of Villar del Humo illustrate several mushrooms that have been tentatively identified as Psilocybe hispanica, a hallucinogenic species native to the area.[128]
Archaeological artifacts from Mexico, as well as the so-called Mayan "mushroom stones" of Guatemala have also been interpreted by some scholars as evidence for ritual and ceremonial usage of psychoactive mushrooms in the Mayan and Aztec cultures of Mesoamerica.[129] In Nahuatl, the language of the Aztecs, the mushrooms were called teonancatl, or "God's flesh". Following the arrival of Spanish explorers to the New World in the 16th century, chroniclers reported the use of mushrooms by the natives for ceremonial and religious purposes. According to the Dominican friar Diego Durn in The History of the Indies of New Spain (published c. 1581), mushrooms were eaten in festivities conducted on the occasion of the accession to the throne of Aztec emperor Moctezuma II in 1502. The Franciscan friar Bernardino de Sahagºn wrote of witnessing mushroom usage in his Florentine Codex (published 1545''1590),[130] and described how some merchants would celebrate upon returning from a successful business trip by consuming mushrooms to evoke revelatory visions.[131] After the defeat of the Aztecs, the Spanish forbade traditional religious practices and rituals that they considered "pagan idolatry", including ceremonial mushroom use. For the next four centuries, the Indians of Mesoamerica hid their use of entheogens from the Spanish authorities.[132]
Although dozens of species of psychedelic mushrooms are found in Europe, there is little documented usage of these species in Old World history besides the use of Amanita muscaria among Siberian peoples.[133][134] The few existing historical accounts about psilocybin mushrooms typically lack sufficient information to allow species identification, and usually refer to the nature of their effects. For example, Flemish botanist Carolus Clusius (1526''1609) described the bolond gomba (crazy mushroom), used in rural Hungary to prepare love potions. English botanist John Parkinson included details about a "foolish mushroom" in his 1640 herbalTheatricum Botanicum.[135] The first reliably documented report of intoxication with Psilocybe semilanceata'--Europe's most common and widespread psychedelic mushroom'--involved a British family in 1799, who prepared a meal with mushrooms they had picked in London's Green Park.[136]
Modern [ edit] American banker and amateur ethnomycologistR. Gordon Wasson and his wife Valentina studied the ritual use of psychoactive mushrooms by the native population in the Mazatec village Huautla de Jim(C)nez. In 1957, Wasson described the psychedelic visions that he experienced during these rituals in "Seeking the Magic Mushroom", an article published in the popular American weekly Life magazine.[137] Later the same year they were accompanied on a follow-up expedition by French mycologist Roger Heim, who identified several of the mushrooms as Psilocybe species.[138] Heim cultivated the mushrooms in France, and sent samples for analysis to Albert Hofmann, a chemist employed by the Swiss multinational pharmaceutical company Sandoz (now Novartis). Hofmann, who had in 1938 created LSD, led a research group that isolated and identified the psychoactive compounds from Psilocybe mexicana.[139][140] Hofmann was aided in the discovery process by his willingness to ingest mushroom extracts to help verify the presence of the active compounds.[131] He and his colleagues later synthesized a number of compounds chemically related to the naturally occurring psilocybin, to see how structural changes would affect psychoactivity. The new molecules differed from psilocybin in the position of the phosphoryl or hydroxyl group at the top of the indole ring, and in the numbers of methyl groups (CH3) and other additional carbon chains.[141]
Albert Hofmann (shown here in 1993) purified psilocybin and psilocin from Psilocybe mexicana in the late 1950s.Two diethyl analogs (containing two ethyl groups in place of the two methyl groups) of psilocybin and psilocin were synthesized by Hofmann: 4-phosphoryloxy-N,N-diethyltryptamine, called CEY-19, and 4-hydroxy-N,N-diethyltryptamine, called CZ-74. Because their physiological effects last only about three and a half hours (about half as long as psilocybin), they proved more manageable in European clinics using "psycholytic therapy"'--a form of psychotherapy involving the controlled use of psychedelic drugs.[141] Sandoz marketed and sold pure psilocybin under the name Indocybin to physicians and clinicians worldwide.[142] There were no reports of serious complications when psilocybin was used in this way.[1]
In the early 1960s, Harvard University became a testing ground for psilocybin, through the efforts of Timothy Leary and his associates Ralph Metzner and Richard Alpert (who later changed his name to Ram Dass). Leary obtained synthesized psilocybin from Hofmann through Sandoz pharmaceutical. Some studies, such as the Concord Prison Experiment, suggested promising results using psilocybin in clinical psychiatry.[6][143] According to a 2008 review of safety guidelines in human hallucinogenic research, however, Leary and Alpert's well-publicized termination from Harvard and later advocacy of hallucinogen use "further undermined an objective scientific approach to studying these compounds".[144] In response to concerns about the increase in unauthorized use of psychedelic drugs by the general public, psilocybin and other hallucinogenic drugs suffered negative press and faced increasingly restrictive laws. In the United States, laws were passed in 1966 that prohibited the production, trade, or ingestion of hallucinogenic drugs; Sandoz stopped producing LSD and psilocybin the same year.[74] Further backlash against LSD usage swept psilocybin along with it into the Schedule I category of illicit drugs in 1970. Subsequent restrictions on the use of these drugs in human research made funding for such projects difficult to obtain, and scientists who worked with psychedelic drugs faced being "professionally marginalized".[145]
The increasing availability of information on growing techniques made it possible for amateurs to grow psilocybin mushrooms (Psilocybe cubensis pictured) without access to laboratory equipment.Despite the legal restrictions on psilocybin use, the 1970s witnessed the emergence of psilocybin as the "entheogen of choice".[146] This was due in large part to a wide dissemination of information on the topic, which included works such as those by author Carlos Castaneda, and several books that taught the technique of growing psilocybin mushrooms. One of the most popular of this latter group was published in 1976 under the pseudonyms O.T. Oss and O.N. Oeric by Jeremy Bigwood, Dennis J. McKenna, K. Harrison McKenna, and Terence McKenna, entitled Psilocybin: Magic Mushroom Grower's Guide. Over 100,000 copies were sold by 1981.[147] As ethnobiologist Jonathan Ott explains, "These authors adapted San Antonio's technique (for producing edible mushrooms by casing mycelial cultures on a rye grain substrate; San Antonio 1971) to the production of Psilocybe [Stropharia] cubensis. The new technique involved the use of ordinary kitchen implements, and for the first time the layperson was able to produce a potent entheogen in his own home, without access to sophisticated technology, equipment or chemical supplies."[148]
Because of a lack of clarity about laws about psilocybin mushrooms, retailers in the late 1990s and early 2000s (decade) commercialized and marketed them in smartshops in the Netherlands and the UK, and online. Several websites[nb 6] emerged that have contributed to the accessibility of information on description, use, effects and exchange of experiences among users. Since 2001, six EU countries have tightened their legislation on psilocybin mushrooms in response to concerns about their prevalence and increasing usage.[41] In the 1990s, hallucinogens and their effects on human consciousness were again the subject of scientific study, particularly in Europe. Advances in neuropharmacology and neuropsychology, and the availability of brain imaging techniques have provided impetus for using drugs like psilocybin to probe the "neural underpinnings of psychotic symptom formation including ego disorders and hallucinations".[11] Recent studies in the United States have attracted attention from the popular press and thrust psilocybin back into the limelight.[149][150]
Society and culture [ edit] Legal status [ edit] In the United States, psilocybin (and psilocin) were first subjected to federal regulation by the Drug Abuse Control Amendments of 1965, a product of a bill sponsored by Senator Thomas J. Dodd. The law'--passed in July 1965 and effected on February 1, 1966'--was an amendment to the federal Food, Drug and Cosmetic Act and was intended to regulate the unlicensed "possession, manufacture, or sale of depressant, stimulant and hallucinogenic drugs".[151] The statutes themselves, however, did not list the "hallucinogenic drugs" that were being regulated.[151] Instead, the term "hallucinogenic drugs" was meant to refer to those substances believed to have a "hallucinogenic effect on the central nervous system".[151]
Dried Psilocybe mushrooms showing the characteristic blue bruising on the stemsDespite the seemingly strict provisions of the law, many people were exempt from prosecution. The statutes "permit[ted] '... people to possess such drugs so long as they were for the personal use of the possessor, [for] a member of his household, or for administration to an animal".[151] The federal law that specifically banned psilocybin and psilocin was enacted on October 24, 1968. The substances were said to have "a high potential for abuse", "no currently accepted medical use," and "a lack of accepted safety".[152] On October 27, 1970, both psilocybin and psilocin became classified as Schedule I drugs and were simultaneously labeled "hallucinogens" under a section of the Comprehensive Drug Abuse Prevention and Control Act known as the Controlled Substances Act.[153] Schedule I drugs are illicit drugs that are claimed to have no known therapeutic benefit.
The United NationsConvention on Psychotropic Substances (adopted in 1971) requires its members to prohibit psilocybin, and parties to the treaty are required to restrict use of the drug to medical and scientific research under strictly controlled conditions. However, the mushrooms containing the drug were not specifically included in the convention, due largely to pressure from the Mexican government.[154]
Most national drug laws have been amended to reflect the terms of the convention; examples include the UK Misuse of Drugs Act 1971, the US Psychotropic Substances Act of 1978,[153] Australia Poisons Standard (October 2015),[155] the Canadian Controlled Drugs and Substances Act of 1997,[156] and the Japanese Narcotics and Psychotropics Control Law of 2002.[157] The possession and use of psilocybin is prohibited under almost all circumstances, and often carries severe legal penalties.[154]
Possession and use of psilocybin mushrooms, including the bluing species of Psilocybe, is therefore prohibited by extension. However, in many national, state, and provincial drug laws, there has been a great deal of ambiguity about the legal status of psilocybin mushrooms, as well as a strong element of selective enforcement in some places.[120][158] Most US state courts have considered the mushroom a 'container' of the illicit drugs, and therefore illegal. A loophole further complicates the legal situation'--the spores of psilocybin mushrooms do not contain the drugs, and are legal to possess in many areas. Jurisdictions that have specifically enacted or amended laws to criminalize the possession of psilocybin mushroom spores include Germany (since 1998),[157] and California, Georgia, and Idaho in the United States. As a consequence, there is an active underground economy involved in the sale of spores and cultivation materials, and an internet-based social network to support the illicit activity.[159]
Usage [ edit] A 2009 national survey of drug use by the US Department of Health and Human Services concluded that the number of first-time psilocybin mushroom users in the United States was roughly equivalent to the number of first-time users of cannabis.[154] In European countries, the lifetime prevalence estimates of psychedelic mushroom usage among young adults (15''34 years) range from 0.3% to 14.1%.[160]
In modern Mexico, traditional ceremonial use survives among several indigenous groups, including the Nahuas, the Matlatzinca, the Totonacs, the Mazatecs, Mixes, Zapotecs, and the Chatino. Although hallucinogenic Psilocybe species are abundant in low-lying areas of Mexico, most ceremonial use takes places in mountainous areas of elevations greater than 1,500 meters (4,900 ft). Guzmn suggests this is a vestige of Spanish colonial influence from several hundred years earlier, when mushroom use was persecuted by the Catholic Church.[161]
Research and potential for use in medicine [ edit] After a long interruption in the use of psilocybin in research, there has been a general shift in attitudes regarding research with hallucinogenic agents. Many countries are revising their positions and have started to approve studies to test the physiological and therapeutic effects of hallucinogens.[13]
Psilocybin has been a subject of medical research since the early 1960s, when Leary and Alpert ran the Harvard Psilocybin Project, in which they carried out a number of experiments to evaluate the therapeutic value of psilocybin in the treatment of personality disorders, or to augment psychological counseling.[162] In the 2000s (decade), there was a renewal of research concerning the use of psychedelic drugs for potential clinical applications, such as to address anxiety disorders, major depression, and various addictions.[163][164] In 2008, the Johns Hopkins research team published guidelines for responsibly conducting medical research trials with psilocybin and other hallucinogens in humans. These included recommendations on how to screen potential study volunteers to exclude those with personal or family psychiatric histories that suggest a risk of adverse reactions to hallucinogens.[144] A 2010 study on the short- and long-term subjective effects of psilocybin administration in clinical settings concluded that despite a small risk of acute reactions such as dysphoria, anxiety, or panic, "the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk"; the authors note, however, that the safety of the drug "cannot be generalized to situations in which psilocybin is used recreationally or administered under less controlled conditions."[11]
The first clinical study of psilocybin approved by the U.S. Food and Drug Administration (FDA) since 1970[165]'--led by Francisco Moreno at the University of Arizona and supported by the Heffter Research Institute and the Multidisciplinary Association for Psychedelic Studies'--studied the effects of psilocybin on patients with obsessive''compulsive disorder (OCD). The pilot study found that, when administered by trained professionals in a medical setting, the use of psilocybin was associated with substantial reductions in OCD symptoms in several of the patients.[166][167] This effect is caused largely by psilocybin's ability to reduce the levels of the 5-HT2A receptor, resulting in decreased responsiveness to serotonin.[62]
The chemical structures of psilocybin and related analogs have been used in computational biology to help model the structure, function, and ligand-binding properties of the 5-HT2CG-protein-coupled receptor.[168][169]
See also [ edit] ^ Synonyms and alternate spellings include: 4-PO-DMT (PO: phosphate; DMT: dimethyltryptamine), psilocybine, psilocibin, psilocybinum, psilotsibin, psilocin phosphate ester, and indocybin.[3] ^ Percentages are derived from a non-blind clinical study of 30 individuals who were given a dosage of 8''12 milligrams of psilocybin; from Passie (2002),[1] citing Quentin (1960).[14] ^ The academic communities' approval for the methodology employed is exemplified by the quartet of commentaries published in the journal Psychopharmacology titled "Commentary on: Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual experience by Griffiths et al.", by HD Kleber (pp. 291''2), DE Nichols (pp. 284''6), CR Schuster (pp. 289''90), and SH Snyder (pp. 287''8). ^ One of the reported fatalities, that of a 22-year-old French man who died in 1993,[48] was later challenged in the literature by Jochen Gartz and colleagues, who concluded "the few reported data concerning the victim are insufficient to exclude other possible causes of the fatality".[49] ^ Subjective effects are "feelings, perceptions, and moods personally experienced by an individual"; they are often assessed using methods of self-report, including questionnaires. Behavioral effects, in contrast, can be observed directly.[69] ^ The EMCDDA lists the general-purpose websites Erowid, Lycaeum, Mycotopia, The Shroomery, MushroomJohn and The Entheogen Review. Regional sites focusing on hallucinogenic mushrooms listed were Copenhagen Mushroom Link (Denmark), Champis (France), Daath (Hungary), Delysid (Spain), Enteogeneos (Portugal), Kouzeln(C) houbičky (Czech Republic), Norshroom (Norway), Planetahongo (Spain), Svampinfo (Sweden), and Taikasieniforum (Finland). It also listed Magic-Mushrooms.net. The report detailed several additional sites selling spore prints in 2006, but noted that many of these had ceased operation. References [ edit] ^ abcdefghij Passie T, Seifert J, Schneider U, Emrich HM (2002). "The pharmacology of psilocybin". Addiction Biology. 7 (4): 357''64. doi:10.1080/1355621021000005937. PMID 14578010. ^ ab Merck Index, 11th Edition, 7942 ^ "Psilocybine '' Compound Summary". PubChem. National Library of Medicine. 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Cited literature [ edit] Ballesteros S, Ram"n MF, Iturralde MJ, Mart­nez-Arrieta R (2006). "Natural sources of drugs of abuse: magic mushrooms". In Cole SM. New Research on Street Drugs. New York, New York: Nova Science Publishers. pp. 167''86. ISBN 978-1-59454-961-8. Boire RG. (2002). Sacred Mushrooms and the Law. Berkeley, California: Ronin Publishing. ISBN 978-1-57951-061-9. Doblin R. (1991). "Pahnke's "Good Friday Experiment": a long-term follow-up and methodological critique"(PDF) . Journal of Transpersonal Psychology. 23 (1): 1''25. Gartz J. (1997). Magic Mushrooms Around the World. Los Angeles, California: LIS Publications. ISBN 978-0-9653399-0-2. Marley G. (2010). "Psilocybin: gateway to the soul or just a good high?". Chanterelle Dreams, Amanita Nightmares: The Love, Lore, and Mystique of Mushrooms. White River Junction, Vermont: Chelsea Green Publishing. pp. 163''84. ISBN 1-60358-214-2. Ott J. (1993). Pharmacotheon: Entheogenic Drugs, their Plant Sources and History. Kennewick, Washington: Natural Products Company. ISBN 978-0-9614234-3-8. Stafford PJ. (1992). Psychedelics Encyclopedia (3rd ed.). Berkeley, California: Ronin Publishing. ISBN 0-914171-51-8. Stamets P. (1997). Psilocybin Mushrooms of the World: An Identification Guide. Berkeley, California: Ten Speed Press. ISBN 0-89815-839-7. Wurst M, Kysilka R, Flieger M (2002). "Psychoactive tryptamines from Basidiomycetes". Folia Microbiologica. 47 (1): 3''27. doi:10.1007/BF02818560. PMID 11980266. External links [ edit] Psychedelics(5-HT2A
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sergolexole)FananserinFlibanserinGlemanserinIrindaloneKetanserinKML-010LandipirdineLY-393558mCPPMedifoxamineMetitepine (methiothepin)MIN-101MIN-117 (WF-516)NaftidrofurylNantenineNelotanserinOpiranserin (VVZ-149)PelanserinPhenoxybenzaminePimavanserinPirenperonePizotifenPruvanserinRauwolscineRitanserinS-14671SarpogrelateSerotonin antagonists and reuptake inhibitors (e.g., etoperidone, hydroxynefazodone, lubazodone, mepiprazole, nefazodone, triazoledione, trazodone)SR-46349BTGBA01ADTeniloxazineTemanogrelTetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine)Tricyclic antidepressants (e.g., amitriptyline)Typical antipsychotics (e.g., chlorpromazine, fluphenazine, haloperidol, loxapine, perphenazine, pimozide, pipamperone, prochlorperazine, setoperone, spiperone, spiramide, thioridazine, thiothixene, trifluoperazine)VolinanserinXylamidineYohimbine5-HT2BAgonists:4-MethylaminorexAminorexAmphetamines (e.g., chlorphentermine, cloforex, dexfenfluramine, fenfluramine, levofenfluramine, norfenfluramine)BW-723C86DOx (e.g., DOB, DOC, DOI, DOM)Ergolines (e.g., cabergoline, dihydroergocryptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide)LorcaserinMDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, [MMDA (drug)Antagonists:AgomelatineAtypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, N-desalkylquetiapine (norquetiapine), N-desmethylclozapine (norclozapine), olanzapine, pipamperone, quetiapine, risperidone, ziprasidone)CyproheptadineEGIS-7625Ergolines (e.g., amesergide, bromocriptine, lisuride, LY-53857, LY-272015, mesulergine)KetanserinLY-393558mCPPMetadoxineMetitepine (methiothepin)PirenperonePizotifenPropranololPRX-08066RauwolscineRitanserinRS-127445SarpogrelateSB-200646SB-204741SB-206553SB-215505SB-221284SB-228357SDZ SER-082TegaserodTetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine)TrazodoneTypical antipsychotics (e.g., chlorpromazine)TIK-301Yohimbine5-HT2CAgonists:2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21)5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT)α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT)A-372159AL-38022AAlstonineCP-809101DimemebfeDOx (e.g., DOB, DOC, DOI, DOM)Ergolines (e.g., ALD-52, cabergoline, dihydroergotamine, ergine (LSA), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, pergolide)FlumexadolLorcaserinMDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA)MK-212Org 12962Org 37684OxaflozanePHA-57378Phenethylamines (e.g., lophophine, mescaline)Piperazines (e.g., aripiprazole, BZP, mCPP, quipazine, TFMPP)PNU-22394PNU-181731Ro60-0175Ro60-0213Serotonin (5-HT)Tryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)VabicaserinWAY-629WAY-161503YM-348Antagonists:AdatanserinAgomelatineAtypical antipsychotics (e.g., asenapine, clorotepine, clozapine, fluperlapine, iloperidone, melperone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, zotepine)CaptodiameCEPCCinanserinCyproheptadineDeramciclaneDesmetramadolDotarizineEltoprazineErgolines (e.g., amesergide, bromocriptine, LY-53857, LY-215840, mesulergine, metergoline, methysergide, sergolexole)EtoperidoneFluoxetineFR-260010IrindaloneKetanserinKetotifenLatrepirdine (dimebolin)MedifoxamineMetitepine (methiothepin)NefazodonePirenperonePizotifenPropranololRitanserinRS-102221S-14671SB-200646SB-206553SB-221284SB-228357SB-242084SB-243213SDZ SER-082TedatioxetineTetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine)TIK-301TramadolTrazodoneTricyclic antidepressants (e.g., amitriptyline, nortriptyline)Typical antipsychotics (e.g., chlorpromazine, loxapine, pimozide, pipamperone, thioridazine)Xylamidine5-HT3''75-HT3Agonists:Alcohols (e.g., butanol, ethanol (alcohol), trichloroethanol)m-CPBGPhenylbiguanidePiperazines (e.g., BZP, mCPP, quipazine)RS-56812Serotonin (5-HT)SR-57227SR-57227ATryptamines (e.g., 2-Me-5-HT, 5-CT, bufotenidine (5-HTQ))Volatiles/gases (e.g., halothane, isoflurane, toluene, trichloroethane)YM-31636Antagonists:AlosetronAS-8112Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine)AzasetronBatanoprideBemesetron (MDL-72222)BupropionCilansetronCSP-2503DazoprideDolasetronGalanolactoneGranisetronHydroxybupropionICS-205930LerisetronMemantineOndansetronPalonosetronRamosetronRenzaprideRicasetronTedatioxetineTetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine)ThujoneTropanserinTropisetronTypical antipsychotics (e.g., loxapine)Volatiles/gases (e.g., nitrous oxide, sevoflurane, xenon)VortioxetineZacoprideZatosetron5-HT45-HT5A5-HT6Agonists:Ergolines (e.g., dihydroergocryptine, dihydroergotamine, ergotamine, lisuride, LSD, mesulergine, metergoline, methysergide)Serotonin (5-HT)Tryptamines (e.g., 2-Me-5-HT, 5-BT, 5-CT, 5-MT, Bufotenin, E-6801, E-6837, EMD-386088, EMDT, LY-586713, N-Me-5-HT, tryptamine)WAY-181187WAY-208466Antagonists:ABT-354Atypical antipsychotics (e.g., aripiprazole, asenapine, clorotepine, clozapine, fluperlapine, iloperidone, olanzapine, tiospirone)AVN-101AVN-211AVN-322AVN-397BGC20-760BVT-5182BVT-74316CerlapirdineEGIS-12233GW-742457IdalopirdineKetanserinLandipirdineLatrepirdine (dimebolin)Metitepine (methiothepin)MS-245PRX-07034RitanserinRo 04-6790Ro 63-0563SB-258585SB-271046SB-357134SB-399885SB-742457Tetracyclic antidepressants (e.g., amoxapine, mianserin)Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, nortriptyline)Typical antipsychotics (e.g., chlorpromazine, loxapine)5-HT7Antagonists:Atypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, brexpiprazole, clorotepine, clozapine, fluperlapine, olanzapine, risperidone, sertindole, tiospirone, ziprasidone, zotepine)ButaclamolDR-4485EGIS-12233Ergolines (e.g., 2-Br-LSD (BOL-148), amesergide, bromocriptine, cabergoline, dihydroergotamine, ergotamine, LY-53857, LY-215840, mesulergine, metergoline, methysergide, sergolexole)JNJ-18038683KetanserinLY-215840Metitepine (methiothepin)RitanserinSB-258719SB-258741SB-269970SB-656104SB-656104ASB-691673SLV-313SLV-314SpiperoneSSR-181507Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine)Tricyclic antidepressants (e.g., amitriptyline, clomipramine, imipramine)Typical antipsychotics (e.g., acetophenazine, chlorpromazine, chlorprothixene, fluphenazine, loxapine, pimozide)Vortioxetine
Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression
Sun, 07 Jan 2018 14:22
Highlights'Psilocybin with psychological support was used successfully to treat depression.
'Amygdala responses to fearful faces were increased one day after psilocybin session.
'Increased amygdala responses predicted positive clinical outcomes.
'Psilocybin assisted therapy treats depression by reviving emotional responsiveness.
AbstractRecent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions.
Trial registrationISRCTN, number ISRCTN14426797.
KeywordsPsilocybin ;Psychedelics ;Depression ;Amygdala ;fMRI ;Emotional processing 1. IntroductionPsychedelic therapy is a re-emerging paradigm in psychiatry (dos Santos et al., 2016 ; Mithoefer et al., 2016). Unlike other psychopharmacological treatment models that seek to medicate patients on a chronic basis, the psychedelic model seeks to treat core psychological issues via a small number of profound and potentially transformative psychological experiences (Pahnke et al., 1970 ; Watts et al., 2017). Our recent open-label study of psilocybin with psychological support for treatment-resistant depression (TRD) yielded promising results, with all patients showing some reduction in depressive symptoms at 1 week and half meeting criteria for remission at 3 weeks (Carhart-Harris et al., 2017 ). Furthermore, other clinical studies with psilocybin have found reductions in anxiety and depressive symptoms after psilocybin with psychological support (Griffiths et al., 2016 ; Ross et al., 2016).
Psilocybin, a classic psychedelic and non-selective serotonin 2A receptor (5-HT2AR) agonist, was discovered and marketed in the 1950s and 60s (Hofmann et al., 1958 ). After much early enthusiasm about the therapeutic potential of psychedelics (Grinspoon and Bakalar, 1979 ; Rucker et al., 2016), a politically-led about-turn in the mid-1960s and early 1970s effectively ended all research with these drugs, and it has only been in the last 10''15 years that clinical researchers have begun to work with them again. During this renascent period, impressive results have been found for the treatment of depression (Carhart-Harris et al., 2016 ; Os"rio et al., 2015), end of life anxiety (Gasser et al., 2014a; Griffiths et al., 2016; Grob et al., 2011 ; Ross et al., 2016), obsessive compulsive disorder (Moreno et al., 2006 ) and addiction (Bogenschutz and Johnson, 2016 ).
The amygdala has previously been implicated in the pathophysiology of depression (Drevets et al., 1992 ) as well as the action of some antidepressants (Ma, 2015 ) and psychedelics (Kraehenmann et al., 2015 ; Spain et al., 2015). The amygdala is a complex subcortical structure that is sensitive to emotional stimuli (Janak and Tye, 2015 ; Sergerie et al., 2008). Functional MRI studies of untreated clinically depressed patients have found amygdala hyper-sensitivity to negative emotional stimuli (Drevets et al., 1992 ; Ma, 2015), and treatment with SSRIs has been found to attenuate this; both with chronic SSRI-use as well as early in treatment, prior to the appearance of clinical improvements (Godlewska et al., 2012 ).
Here, we sought to explore the antidepressant action of psilocybin on amygdala responses to emotional faces using a functional magnetic resonance imaging (fMRI) paradigm that has been well-validated in the context of SSRI-based treatments for depression (Ma, 2015 ). Patients underwent balanced versions of an emotional faces paradigm before and one-day after treatment with psilocybin. Psilocybin has been found to be associated with improved mood in the sub-acute period days after exposure (Majić et al., 2015 ). We therefore predicted that amygdala responses to emotional faces would be altered post-treatment and that this might relate to changes in depression severity. We were particularly interested in the fearful versus neutral faces contrast, due to previous findings of reduced amygdala responses to negative emotional stimuli with SSRIs (Ma, 2015 ). We also predicted that the nature of the acute psychological experience under psilocybin would relate to the post-treatment changes in amygdala responses.
2. Material and methodsThis trial received a favourable opinion from the National Research Ethics Service London'--West London, was sponsored and approved by Imperial College London and by the UK MHRA. All participants provided written informed consent.
F-Russia
BREAKING: District Court Judge Rules Fusion-GPS Must Turn Over Bank Records'... | The Last Refuge
Fri, 05 Jan 2018 11:39
U.S. District Judge Richard J Leon ruled today that Fusion-GPS must turn over their banking records as required under the existing congressional subpoena.
Fusion GPS had sought an injunction from the federal court blocking the U.S. House Intelligence Committee from forcing them to provide banking records related to their 2016 opposition research work on Russia related matters.
In a 26-page-ruling (full pdf below) Judge Leon rebuked each of the Fusion GPS reasons for the injunction and ruled the subpoena from the congressional committee was appropriate, proper and lawful.
This is critical and presents a joint approach toward the entire scheme. At the same time the Judicial Committees are focusing on the DOJ and FBI and how they used the FISA court, the House Intel Committee is focusing on the underlying documents, research and evidence behind the manipulated FISA warrant. Splendid.
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DPRK
Public Health Response to a Nuclear Detonation | Public Health Grand Rounds | CDC
Sun, 07 Jan 2018 15:06
January 16, 2018 at 1:00 p.m. (ET)
While a nuclear detonation is unlikely, it would have devastating results and there would be limited time to take critical protection steps. Despite the fear surrounding such an event, planning and preparation can lessen deaths and illness. For instance, most people don't realize that sheltering in place for at least 24 hours is crucial to saving lives and reducing exposure to radiation. While federal, state, and local agencies will lead the immediate response efforts, public health will play a key role in responding.
Join us for this session of Grand Rounds to learn what public health programs have done on a federal, state, and local level to prepare for a nuclear detonation. Learn how planning and preparation efforts for a nuclear detonation are similar and different from other emergency response planning efforts.
CDC's Public Health Grand Rounds Presents:
''Public Health Response to a Nuclear Detonation''
Tuesday, January 16, 2018
1:00 p.m. '' 2:00 p.m. (ET)
Global Communications Center (Building 19)
Alexander D. Langmuir Auditorium
Roybal Campus
Presented By:Dan Sosin, MD, MPH
Deputy Director and Chief Medical Officer
Office of Public Health Preparedness and Response
Centers for Disease Control and Prevention
''Public Health: Preparing for the Unthinkable''
CAPT Michael Noska, MS
Radiation Safety Officer and Senior Advisor for Health Physics
Chair, Advisory Team for Environment, Food and Health (A Team)
Office of the Commissioner
U.S. Food and Drug Administration
''Using Data and Decision Aids to Drive Response Efforts''
Robert Whitcomb, PhD
Chief, Radiation Studies Branch
Division of Environmental Hazards and Health Effects
National Center for Environmental Health
Centers for Disease Control and Prevention
''Public Health Resources to Meet Critical Components of Preparedness''
Betsy Kagey, PhD
Academic and Special Projects Liaison
Office of Emergency Preparedness and Response
Division of Health Protection
Georgia Department of Health
''Roadmap to Radiation Preparedness''
Facilitated By:John Iskander, MD, MPH,Scientific Director, Public Health Grand Rounds
Phoebe Thorpe, MD, MPH,Deputy Scientific Director, Public Health Grand Rounds
Susan Laird, MSN, RN,Communications Director, Public Health Grand Rounds
For non-CDC staff who want to attend in person:
Non-CDC staff must have prior security clearance. US citizens must submit a request to the Grand Rounds Team. A US state-issued photo ID (e.g., driver's license, US passport) is required.
Non-US citizens must submit their requests 20 days prior to the session to the Grand Rounds Team, and additional information will be required.
For individuals requiring reasonable accommodations:
It is the policy of CDC to provide reasonable accommodations (RA) for qualified individuals with disabilities to ensure their full inclusion in CDC-sponsored events. Employees are asked to submit RA requests at least 5 business days prior to the event. Please e-mail the request to grandrounds@cdc.gov.
For questions about this Grand Rounds topic:
Feel free to e-mail your questions before or during the session.
Grand Rounds is available for continuing education.
All continuing education credit for Public Health Grand Rounds (PHGR) is issued online through the CDC/ATSDR Training and Continuing Education Online system. If you have questions, you can email Learner Support or call them at 1-800-41-TRAIN (1-800-418-7246). Those who view PHGR and wish to receive continuing education must complete the online seminar evaluation. Continuing education will be available for up to 2 years and 1 month after the initial offering. The course code for all PHGR sessions is PHGR10.
Nothing to See Here
Fire breaks out near Hillary, Bill Clinton's home in New York - ABC15 Arizona
Sat, 06 Jan 2018 17:36
A small fire broke out in a US Secret Service facility on the property of the home of Bill and Hillary Clinton in Chappaqua, New York, on Wednesday.
The building was not connected to the home of the former US President and former US Secretary of State, and the Clintons were not there at the time of the fire, Hillary Clinton Communications Director Nick Merrill tweeted.
The fire was put out and nobody was injured, said Sgt. Arthur Mendoza of the New Castle Police Department.
The former first couple bought the home before Hillary Clinton's successful 2000 run for a US Senate seat. Chappaqua is about 40 miles north of New York City.
Deep State Meltdown
Ex-U.S. NSA contractor to plead guilty to massive theft of secret data
Thu, 04 Jan 2018 22:15
WASHINGTON (Reuters) - A former U.S. National Security Agency contractor has agreed to plead guilty to stealing classified information, according to court filings on Wednesday, in what may have been the largest heist of U.S. government secrets in history.
Harold Martin is scheduled to plead guilty to one count of willful retention of national defense information at a federal court in Baltimore on Jan. 22, according to the filings.
Prosecutors said Martin, who was indicted last February, spent up to 20 years stealing highly sensitive government material from the U.S. intelligence community related to national defense, collecting a trove of secrets he hoarded at his home in Glen Burnie, Maryland.
Authorities said they seized 50 terabytes of data from Martin's home, which officials said could be the biggest theft of classified information in U.S. history.
The government has not said what, if anything, Martin did with the stolen data.
He faces up to 10 years in prison on the single count. Martin has not struck a plea deal with prosecutors and could still be tried on the remaining 19 counts in the indictment, the court filings said.
A lawyer for Martin did not immediately respond to a request for comment.
The NSA has been hit by a series of damaging data breaches in recent years.
In December, former NSA employee Nghia Hoang Pho pleaded guilty to illegally taking classified information that an intelligence official said was later stolen from his home computer by Russian hackers.
Martin worked for Booz Allen Hamilton Holding Corp when he was taken into custody in August 2016.
Booz Allen also employed Edward Snowden, who leaked a trove of secret files to news organizations in 2013 that exposed vast domestic and international surveillance operations carried out by the NSA.
Martin was employed as a private contractor by at least seven companies, working for several government agencies beginning in 1993 after serving in the U.S. Navy for four years, according to the indictment.
His positions, which involved work on highly classified projects involving government computer systems, gave him various security clearances that routinely provided him access to top-secret information, it said.
The indictment also alleged that Martin stole documents from U.S. Cyber Command, the CIA and the National Reconnaissance Office.
Reporting by Eric Beech; Editing by Peter Cooney
NWO
Overstock Gets $100 Million from Soros Fund for Blockchain and More - CoinDesk
Sun, 07 Jan 2018 13:56
Overstock.com just got a hefty chunk of change from one of the biggest names in finance, and CEO Patrick Byrne says much of it will fund the company's blockchain work.
The company disclosed in a Securities and Exchange Commission (SEC) filing this week that the holder of a warrant had exercised its right to buy $100 million worth of shares. Although the filing did not identify this investor, Byrne told CoinDesk it was the Quantum Fund, managed by billionaire George Soros.
Of the $100 million Overstock received, Byrne said he anticipates $20 million will fund DeSoto Inc., the blockchain property rights joint venture he is working on in partnership with economist Hernando DeSoto.
As for the other $80 million, Byrne said he intends to invest the funds across Overstock's flagship e-commerce platform (which accepts bitcoin for payments) and the other blockchain ventures that are part of its Medici Ventures subsidiary.
Yet, Byrne indicated he sees those two businesses working more closely in the future.
"Maybe it's about time we stop seeing Overstock as two separate businesses," he said. "Our retail platform had 40 million unique people come to it last month. So as we're developing these blockchain applications, these blockchain companies, the retail business is an extremely valuable retail business to have in terms of bringing awareness and traffic to the blockchain properties that we anticipate developing."
Byrne continued, telling CoinDesk:
"By having the retail business involved, what we can really create is the wormhole between the two universes, the universe of conventional and the universe of crypto."
Quantum Fund did not respond to requests for comment by press time, but the Soros-controlled vehicle disclosed its purchase of a warrant to buy Overstock shares in November.
Byrne mentioned tZERO, Overstock's blockchain development platform for capital markets, as another area where some of the proceeds would be headed. But none of the Quantum investment will be used to purchase any of the crypto tokens issued in an initial coin offering (ICO) by tZERO in December.
Separately, however, Overstock itself is buying $30 million worth of tZERO tokens with other funds, Byrne told CoinDesk.
During the initial phase of its ongoing ICO, tZERO received $100 million in commitments from investors interested in purchasing the crypto tokens.
Generally speaking, Overstock will be hiring people "across Wall Street with expertise in risk management," Byrne said.
Boxes image via Overstock.com
The leader in blockchain news, CoinDesk is an independent media outlet that strives for the highest journalistic standards and abides by a strict set of editorial policies. Have breaking news or a story tip to send to our journalists? Contact us at news@coindesk.com.
Moral Self Licensing
Google's Latest Search: What Happened to Its Bikes? - WSJ
Sun, 07 Jan 2018 15:31
MOUNTAIN VIEW, Calif.'--Google has built a massive business organizing the world's information, but it's having a lot of trouble keeping track of its own bicycles.
Google maintains roughly 1,100 free, multicolored two-wheelers, known as Gbikes, for its employees to get around on its sprawling campus here. The program has inspired copycats across Silicon Valley and beyond.
But...
SJWBLMLGBBTQQIAAP
Apple Removes Where To Smoke From Its App Store | Cigar Aficionado
Sun, 07 Jan 2018 13:38
Apple Inc. has removed Cigar Aficionado's Where To Smoke app from its store. Despite the best efforts of Cigar Aficionado to change Apple's decision, the app is no longer available. Apple claimed Where To Smoke, which points users to cigar-friendly locations and does not sell cigars, was in violation of its policy.
''This is David versus Goliath, and it's a disgrace,'' said Marvin R. Shanken, editor and publisher of Cigar Aficionado magazine. ''Where To Smoke is a reader service, provided free of charge, to allow our fellow cigar lovers to find cigar-friendly locations. The fact that Apple banned it is an outrage. It's not only a disservice to our large readership, but an affront on free speech and the rights of Americans to enjoy a legal adult product.''
Apple continues to allow apps that promote, among other things, the procurement of marijuana. Weedmaps is described as ''the largest and most comprehensive marijuana directory and discovery resource on the planet,'' and Leafly claims to be ''the world's cannabis information resource,'' that allows users to ''explore thousands of marijuana strains and access the map to find a dispensary nearby that carries the cannabis strain for their medical needs.''
Apple said it made the move because Where To Smoke violated the rules of its App Store. ''We continue to find that your app promotes the use of tobacco or nicotine-related paraphernalia, including but not limited to cigars, cigarettes, pipes, hookahs, or e-cigarettes, which is not permitted on the App Store,'' a representative from Apple wrote in an email to M. Shanken Communications Inc., the owner of Cigar Aficionado and other magazines.
Cigar Aficionado fought the removal, but the argument failed to sway Apple. The app was removed on October 30.
Users who have already downloaded the app onto their iPhones can continue to use it, and they will continue to see new locations that Cigar Aficionado adds, although they will not get other updates, such as new designs or bug fixes.
While you can no longer get the app from Apple, you can still access Where To Smoke via other methods. Where To Smoke is available free of charge on our website. Simply go to wts.cigaraficionado.com and you can find more than 2,600 cigar-friendly locations near you. It works just like the app.
If you have an Android phone, you can get the Where To Smoke app in the Google Play Store. Again, it is free of charge.
This article first appeared in the November 7, 2017 issue of Cigar Insider.
#MeToo
Second Columbia Professor Resigns After Accusations of Sexual Misconduct
Thu, 04 Jan 2018 23:00
Columbia University lost its second professor this week to accusations of sexual misconduct by former students, in a wave of investigations into sexual harassment by university officials and faculty at American campuses.
Thomas Roma, director of Columbia's photography program since 1997, resigned effective immediately after five women came forward with allegations reported Wednesday in the New York Times. The university conducted internal investigations into the allegations when they were originally made over 15 years ago, and found in at least one case that both the alleged victim and Roma were responsible for the incident.
This comes after tenured history professor William Harris retired last month following accusations by an anonymous female graduate student that he had pursued nonconsensual sexual contact since 2012.
Meanwhile, Todd Heatherton abandoned his post as visiting scholar at New York University in November, when an investigation was opened into his alleged sexual misconduct as a psychology professor at Dartmouth College. He is among three Dartmouth faculty members who were placed on paid leave in October pending the results of inquiries into the claims.
Norman Pattiz, a long-time member of the University of California Board of Regents, announced last week that he would resign in mid-February, following sustained pressure over revelations in 2016 that he allegedly sexually harassed an employee at his radio company. UC students have since been demanding he step down, and called out UC President Janet Napolitano for her repeated statements about being devoted to combatting sexual misconduct'--even setting up a "student advisory board" on the issue'--while allowing Pattiz to remain.
At the University of Wisconsin-Milwaukee, 37 faculty and staff have been accused of sexual assault or harassment since 2013, according to a new report by the student paper, Media Milwaukee. Violations were found in 11 of those cases and two investigations are still pending, though it is unclear what action were taken by the administration when misconduct was discovered.
In a statement to a local new outlet, the university would only say "appropriate discipline was taken" when misconduct was found. "Most of the employees were terminated or had already left the university," added the university.
Media Milwaukee notes that the Office of Equity and Diversity Services, responsible for overseeing harassment reporting and investigations, has been "extremely understaffed for about 10 years," and seen frequent turnover, with four different interim directors since 2011.
A part-time chemistry professor at George Washington University has charged administrators subjected her to an "malicious" Title IX investigation into alleged sexual harassment of a student, and filed a lawsuit against the university and staff late last year.
Huffington Post Writer And Male Feminist Christian Chiakulas Was Charged With Domestic Abuse - One Angry Gamer
Sun, 07 Jan 2018 14:52
(Last Updated On: January 3, 2018) A Huffington Post contributor and self-proclaimed male-feminist and leftist, Christian Chiakulas, has a history of domestic abuse and physical violence carried out against his ex-wife, Amber Sweeney.
In a detailed expos(C) by the Gateway Pundit, it was revealed that the staunchly feminist Chiakulas is actually not against hitting on women who he feels disrespected him. The physical and emotional abuse had been going on for years, according to Sweeney, all while Chiakulas put on an act via his writing and online persona that he was all about third-wave feminism.
Sweeney told the Gateway Pundit'...
''He had punched me so hard I had a black eye. He has thrown me through a wall. Kicked me and beat me,'' ['...] ''He shoved me through the wall in front of our little one. She was a baby at the time.''
These aren't just baseless allegations and Sweeney didn't just vent through a hashtag, she went to the police about Chiakulas' violent outbursts and had domestic battery complaints filed against him. He was arrested on June 6th, 2016 and charged on two counts of bodily harm back on June 7th, 2016 according to police records obtained by the Gateway Pundit.
The misdemeanor wasn't enough to keep Chiakulas from further exacting carnage in Sweeney's life, he ended up filing for divorce and sought custody of their daughter. Sweeney attempted to raise money online since she couldn't afford to retain a lawyer at $1,500. She apparently was not able to get full custody due to a lack of being able to pay for proper legal representation.
Chiakulas had also managed to get into a fight with Sweeney's new boyfriend after she refused to talk to him, and so she filed two more charges of battery against him at the police station.
Leading up to the arrests Chiakulas had been making posts on Facebook claiming his ex-wife was a cheater and a compulsive liar and not to believe anything she says. On May 16th, 2016 he wrote'...
''Well, today I learned who my friends are. The answer is'... none of you motherfuckers. I'm not gonna be around for a while. Not that anyone cares.
''By the way, I hope you all are smart enough to know that my darling wife (who's been cheating on me since before we took our break and whose boyfriend just assaulted me) is a compulsive liar. Hope you all know not to believe the shit she says about me.
''Goodbye''
Chiakulas' comments about his ex-wife are in complete contradiction to his article on the Huffington Post, where he claims that men should believe women due to the rape culture prevalent in our society'...
''Rape culture is a part of patriarchy, and it involves the practice of shaming women for how they react to sexual assault, abuse, or harassment. One important way to counteract that, I would argue, is to support women, who are much more likely to become victims than men are.
''I did not support Graceanne Parks the way I should have. I am not saying that she is a victim of anything '' that is for her to decide. But she is a woman and if I consider myself principled and an ally of feminism and an enemy of patriarchy, then I should have supported her, even when it did not suit me personally.''
This message of support oddly enough coincided with his about-face turn that he posted on October 16th, 2017, where Chiakulas wrote a message on Facebook admitting to being an abuser'...
''Me too.
''No, I haven't been a victim. I've been an abuser. I've been a perpetrator. In big ways and little ways.
''Fellow men, and especially cis men, this is our responsibility. We are the ones overwhelmingly inflicting this pain. Don't you dare exempt yourself.
''I'm learning every day how to be better. I can never make up for all of the pain I've caused others in the past, but I can make sure that I never inflict that pain on anyone again, and that I hold other men accountable. That is what we all need to start doing, every day, in every situation, no matter what.''
Gateway Pundit makes the keen observation that on November 1st, 2017, Christian Chiakulas wrote an article for Patheos in support of the #MeToo campaign while excoriating Louis C.K., for the allegations that were raised against him.
When recently called out on his abuse in the public sphere, Chiakulas tried to redirect the conversation back to Jordan Chariton from The Young Turks, hoping to focus the conversation on him. This is despite the fact that the Huffington Post had to pull an article from Chiakulas that made baseless accusations against Chariton, which resulted in a legal situation where Chariton is suing for defamation.
After the article was pulled from the Huffington Post, Chiakulas attempted to continue to attack Chariton by posting the article on Medium. Chiakulas apparently hasn't been let go from the Huffington Post even after the media site had to pull down his article about Jordan Chariton.
Chiakulas' Twitter page is also filled with the typical talking points of feminism and Leftism.
Strangely enough Chiakulas had no run-ins with #GamerGate, despite being a rabid Leftist advocating for communism and being a militant feminist.
Related
Vice, Anti-GamerGate Website Suspends Andrew Creighton, Mike Germano For Sexual Misconduct - One Angry Gamer
Sun, 07 Jan 2018 14:52
(Last Updated On: January 4, 2018) Vice was one of the leading voices that falsely claimed that #GamerGate was about harassment, misogyny, and sending death and rape threats to female game developers. It turns out that after some of their outspoken anti-#GamerGate staff were fired for alleged sexual misconduct,sexual assault and rape, several more of their top executives are now being suspended for sexual misconduct following an investigation that spawned after an expos(C) by the New York Times was published back on December 23rd, 2017.
According to a report from the CBC that was published on January 2nd, 2018, Vice has suspended the company's president, Andrew Creighton, and the chief digital officer, Mike Germano.
Both executives were part of the New York Times expos(C), where it was revealed that in Creighton's case the company had paid out a hefty $135,000 settlement after an employee was allegedly fired for not reciprocating Creighton's sexual advances.
Germano had also allegedly pulled a woman onto his lap during a party and also made it known that there were certain women he didn't want to hire in order to have sex with them.
Following the New York Times piece, co-founders Suroosh Alvi and Shane Smith released a joint statement, apologizing for the inordinate amount of sexual misconduct and ''harassment'' culture cultivated at Vice, stating that they've been working to weed out ''misogynistic'' views from the media conglomerate'...
''Vice began 23 years ago as a punk magazine exploring the subversive counterculture that our writers, our readers and we were a part of. We were vehemently anti-censorship, anti-establishment and apolitical, and we wanted to build a company based on egalitarian principles.
''Ten years ago, we set out on a new journey, moving beyond covering just streetwear, drugs and sex, to news and social justice issues. Over the last decade, we have severed ties with colleagues who espoused misogynistic and extremist ideologies, and evolved Vice from a publication with a tiny staff to a media company employing thousands of the most talented creative minds all over the world.''
Vice was renown for publishing anti-#GamerGate articles during the early days of the consumer revolt. Gamers called out major news media organizations for their corrupt behavior and advocated for better ethics in media journalism. #GamerGate denizens took the fight to the doorstep of the FTC in order to encourage better disclosure practices among YouTubers and video game reviewers. After enough pressure, many enthusiast outlets did update their disclosure practices.
Despite publishing multiple lies and defamatory comments about #GamerGate, the consumer revolt has managed to stand tall in reputation above many of its detractors, who have fallen victim to the exact same kind of conduct for which they accused the gamers of #GamerGate.
(Thanks for the news tip Migi)
Related
No Belt 3 Roads
Cyprus set to come in from the cold and end energy isolation '' EURACTIV.com
Sun, 07 Jan 2018 14:56
Cyprus is due to end its energy isolation after it agreed with fellow EU member Greece to press on with an undersea electricity cable, which will also link the island to Israel in the hope of tapping into significant gas reserves in the eastern Mediterranean.
Cyprus is the only EU country that still lacks any electricity or gas interconnectors, a blemish on the EU's security of supply objectives and target of 10% interconnection between member states.
But that is set to change after Nicosia and Athens agreed on the cross-border cost allocation of the planned EuroAsia cable. According to one of the project's officials, Israel is expected to sign off on the plan next month.
The 1,520km-long undersea cable, which will link Israel and Cyprus's west and south coasts with Greece via the island of Crete, will have a capacity of 2,000MW and be able to transmit electricity in both directions.
If Israel approves the project as expected, work is expected to begin early next year and last until 2022. Costs for phase one are estimated at roughly '‚¬3.5 billion.
Commission funds France-Ireland power link that bypasses UKThe European Commission has allocated '‚¬4 million to a project that will link the French and Irish electricity grids via an undersea cable. Irish lawmakers have now touted the plan as an ''obvious solution'' to Ireland's energy reliance on a post-Brexit United Kingdom.
EuroAsia is one of the European Commission's Projects of Common Interest, intended to help the bloc meet its ambitious energy and climate goals by completing the internal market, increasing security of supply and unlocking the potential of renewable energy.
By linking Cyprus and Israel to the European mainland, the project aims to tap into the electricity-generating potential of gas reserves discovered in the Mediterranean off both countries' shores.
In April, Italy, Israel, Greece and Cyprus pledged to start work on the world's longest undersea gas pipeline, which also seeks to exploit the natural gas resources in the eastern Mediterranean.
But the costs of that ambitious project are estimated to be twice the EuroAsia cable's and the falling price of gas has cast doubt on its feasibility. The pipeline is not due to be completed until halfway through the next decade.
Ottoman Empire
Is ice finally thawing between EU, Turkey?
Fri, 05 Jan 2018 12:02
Is ice finally thawing between EU, Turkey?Semih Idiz January 4, 2018
Ending 2017 on a comparatively higher note, recent conversations and visits between officials from European countries and Turkey could help nudge both sides to better relations in 2018.
More:Is ice finally thawing between EU, Turkey?
Migrants
Czech President: Rise of Muslims led to a significant increase in crime and violence in Europe
Fri, 05 Jan 2018 12:34
In an interview with a Prague TV station, Czech president MiloÅ Zeman, warned about the dangers of immigration and Islam.
Zeman said, that the migration from African and Middle Eastern countries poses a serious threat for European culture. He wants the European Union to take action immediately:
''If the European Union does not reach the courage to strengthen its external borders, for which it constantly chatters but does nothing, we will have 10 million refugees (from Africa) in the course of the (coming) year'... The culture of these refugees is not compatible with European culture, which is what immigrants themselves understand.''
According to Zeman, the rise of Muslims in European countries has led to ''a significant increase in crime and an increase in the level of violence in the closed Muslim communities''.
Zeman has been criticising migration and especially Islam for a long time. In earlier interviews he said:
''If you want the unspoken truth, Islamic migration is not possible to integrate, and it is not capable of being assimilated into European culture.''
And:
''I think we can coexist with Buddhism, Hinduism, Shinto, Confucianism, but we cannot coexist with Islam. It has anchored in its sacred texts that it must rule the world and have unbelievers submit.''
Bookmakers see Zeman as a favourite to win the upcoming presidential elections, which will start next week. If elected, it would be his second term as president of the Czech Republic.
Immigratie in Amsterdam naar recordhoogte - Amsterdam - PAROOL
Sat, 06 Jan 2018 18:54
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BTC
Bitcoin exchange Coinbase just hired a VC and Hewlett-Packard veteran as president - Business Insider
Sat, 06 Jan 2018 17:35
Coinbase's newly appointed president Asiff Hirji stands with co-founder and CEO Brian Armstrong. Coinbase
The popular cryptocurrency exchange Coinbase just hired industry veteran Asiff Hirji as president and chief operating officer (COO). Hirji joins from the legendary VC firm Andreessen Horowitz '-- though he's also served executive roles at Hewlett-Packard and TP Ameritrade. The new hire come at a time of growing pains at the richly-valued company, whose popularity has outpaced its ability to expand. Tech veteran Asiff Hirji is joining the bitcoin exchange Coinbase as president and chief operating officer, the company announced Friday.
Hirji, a tech industry veteran, replaces Coinbase co-founder Fred Ehrsam, who served as president of the company until January. The leadership change comes as Coinbase, which has been valued by private investors at $1.6 billion, experiences growing pains.
With bitcoin's popularity and price surging, Coinbase's cryptocurrency exchanged has struggled to cope with a flood of novice traders.
The exchange has had several large-scale outages in the last few months, including this week, after bitcoin prices surged above $11,000 and then crashed back down around $9,000. On Wednesday, many Coinbase users found themselves locked out of their accounts and unable to trade.
The company has also faced challenges from the Internal Revenue Service (IRS), which on Wednesday won a year-long battle over its request for transaction information on more than 14,000 high-rolling Coinbase traders.
Hirji joins from the famed venture capital firm and Coinbase investor Andreessen Horowitz, where he was a partner. He also spent time in executive roles at Hewlett-Packard and the popular online stock trading platform TD Ameritrade.
Despite the challenges, Coinbase remains one of the more popular and mainstream exchanges for the digital currencies bitcoin, ether, and litecoin, at a time when both consumers and institutions like banks and governments are beginning to see value in cryptocurrencies.
The platform simplifies a trading process that many people find mystifying, and restricts its exchanges to established digital currencies that have shown stability, so as to not scare off new investors.
In September, the company put some of its a $100 million funding round toward growing its customer service department after some customers said they spent weeks trying to contact the company about issues like locked up funds.
Get the latest Bitcoin price here.>>
Just BingIt!
Chrome is turning into the new Internet Explorer 6 - The Verge
Fri, 05 Jan 2018 10:27
Chrome is now the most popular browser across all devices, thanks to Android's popularity and the rise of Chrome on Windows PCs and Mac computers. As Google continues to dominate our access to the web, information through its search engine, and services like Gmail or YouTube, Chrome is a powerful entry point in the company's vast toolbox. While Google championed web standards that worked across many different browsers back in the early days of Chrome, more recently its own services often ignore standards and force people to use Chrome.
Chrome, in other words, is being used in the same way that Internet Explorer 6 was back in the day '-- with web developers primarily optimizing for Chrome and tweaking for rivals later. To understand how we even got to this stage, here's a little (a lot) of browser history. If you want to know why saying "Chrome is the new Internet Explorer 6" is so damning, you have to know why IE6 was a damnable problem in the early '00s.
A brief history of browsersMicrosoft's PC dominance with Windows peaked 16 years ago. Alongside Intel, Microsoft spent at least $1 billion promoting the release of Windows XP, with a TV commercial featuring Madonna's Ray of Light. It was an era before the iPod, Gmail, or YouTube, and Microsoft didn't even have competition from Google at the time. Microsoft acted like a company that could do what it wanted, and it pretty much did. After crushing its Netscape competition, the era of Internet Explorer 6 was born.
Internet Explorer 6 on Windows XP Internet Explorer 6 debuted with Windows XP, and was tied closely to many of its features. As XP grew in popularity, so did the web. IE6 arrived just as the ''dot com'' bubble was collapsing, and internet usage in the US was growing rapidly. For many, Internet Explorer was the primary way of accessing the internet, and the logo became synonymous with the internet. At its peak, Internet Explorer 6 dominated 90 percent of the entire browser market.
Microsoft controlled the way that millions of people accessed the web, and with Internet Explorer 6, it started to flex its muscles. As the web was becoming far more popular, standards were emerging that would help developers build sites and applications that would work across multiple devices and browsers. Internet Explorer 6 largely ignored web standards at the time, and set Microsoft and web developers on a path of painful decisions for years to come.
Ignoring web standards meant that developers started to code their sites around Internet Explorer specifically, and would recommend that their customers only accessed their site through Internet Explorer. Internet Explorer 6 existed for a full five years ignoring web standards and with a number of security flaws, but rivals started to emerge. In 2004, the Mozilla Foundation, founded by former browser maker Netscape, released Firefox 1.0. It introduced tabbed browsing and a pop-up blocker, and fans raised cash to pay for a full-page ad in the New York Times. It was heralded as the Internet Explorer killer, and it was the first serious alternative since Netscape.
Microsoft hit back with Internet Explorer 7 in 2006, adding tabbed browsing and other features that mostly kept people loyal to the Windows default. IE7 didn't improve Microsoft's web standards support enough, and criticism over Microsoft ignoring web standards started to grow stronger. Even the creator of the World Wide Web, Tim Berners-Lee, criticized Microsoft's efforts.
At the time of Firefox's release, Google was rapidly growing its search and advertising business. Instead of building its own Chrome browser, it was busy creating the Google Toolbar. (Notably, it was one of the very first major projects led by now-CEO Sundar Pichai.) The toolbar was an add-on for Internet Explorer or Firefox that added a pop-up blocker and easy access to Google search. It acted as a Trojan horse to add extra features into browsers, and direct people to Google services. Google promoted it heavily on its search engine pages, and the pop-up blocker was particularly popular with Internet Explorer 6 users.
As Firefox popularity grew and frustrations over Internet Explorer intensified, Google entered the market in 2008 with its own Chrome browser. Google focused on web standards and respected HTML5, passing both the Acid1 and Acid2 tests with the first release of Chrome '-- something Microsoft had been failing badly at. Developers flocked to Chrome because it enabled them to build better websites based on web standards, and it started a consumer war of market share between Internet Explorer, Firefox, and Chrome.
While Chrome has never managed to capture 90 percent of all desktop browsing market share, it's now the dominant way people access the internet across devices. Netmarketshare, W3Counter, and StatCounter all place Chrome at around 60 percent of desktop browsing, with Safari, Firefox, IE, and Edge all far behind with up to 14 percent market share each (depending on who you trust). Either way, Chrome now has the type of dominance that Internet Explorer once did, and we're starting to see Google's own apps diverge from supporting web standards much in the same way Microsoft did a decade and a half ago.
Works best (or only) with ChromeWhether you blame Google or the often slow moving World Wide Web Consortium (W3C), the results have been particularly evident throughout 2017. Google has been at the center of a lot of ''works best with Chrome'' messages we're starting to see appear on the web. Google Meet, Allo, YouTube TV, Google Earth, and YouTube Studio Beta all block Windows 10's default browser, Microsoft Edge, from accessing them and they all point users to download Chrome instead. Google Meet, Google Earth, and YouTube TV are also not supported on Firefox with messages to download Chrome. Google has publicly promised to support Earth on Edge and Firefox, and the company is ''working to bring YouTube TV to more browsers in the future.''
Hangouts, Inbox, and AdWords 3 were all in the same boat when they first debuted. It's led to one developer at Microsoft to describe Google's behavior as a strategic pattern. ''When the largest web company in the world blocks out competitors, it smells less like an accident and more like strategy,'' said a Microsoft developer in a now-deleted tweet.
Google isn't alone in its ''works best with Chrome'' approach either, as other web companies have started to reveal that their websites work best in Chrome. Groupon, Airbnb, and Seamless are all guilty of it, even prompting one Chrome team member to state ''please don't build sites for just Chrome.'' It's a useful piece of advice that Google isn't putting into practice itself, though.
So why is this happening? ''Of the dozens of web projects being worked on at any given time at Google, only a small fraction of those require Chrome at some point in their development cycle, primarily due to resource or technology constraints,'' explains Ben Galbraith, director of the Chrome Web Platform in a statement to The Verge. ''In every case, we work to try to overcome these constraints whenever possible because we believe that an open web is critical to building a better web.''
A lot of this probably comes down to pure engineering resources at Google and other web companies, rather than a conspiracy to crush Firefox or Edge. Google employees use Gmail, Google, and Chrome, and so do most of their customers, so it's understandable they'd optimize for Chrome. Google's Chrome team is still a big proponent of the open web, but if the rest of Google is optimizing services for Chrome then it creates this bad look.
''One issue is that Google developers often create many of the new standards, they are extremely active in new feature development for the web,'' explains Jason Ormand, a performance engineer at Vox Media. ''They write up proposals and get them through the working standards group, W3C, so that they become standards.'' That often means Google is the first to ship with these standards, because the company has been advocating for them. Mix that together with a lot of developers using Chrome for web development and the issues are obvious.
It's hard to imagine this Chrome-only situation getting any better, though. Google moved away from WebKit and towards its Blink rendering engine years ago, and there have been lots of optimizations to open source libraries, frameworks, and other parts of the engine that cause bugs in other browsers. You'll notice this if you try and use Safari, Firefox, or Edge in certain sites where developers have initially targeted Chrome, and its easier for website support staff to simply recommend downloading Chrome than rewrite parts of their code. Developers have also spent years optimizing for Chrome, and working around some of its quirks with Chrome-only fixes or changes.
Google.com Chrome download prompts Google also controls the most popular site in the world, and it regularly uses it to push Chrome. If you visit Google.com in a non-Chrome browser you're prompted up to three times if you'd like to download Chrome. Google has also even extended that prompt to take over the entire page at times to really push Chrome in certain regions. Microsoft has been using similar tactics to convince Windows 10 users to stick with Edge.
The troubling part for anyone who's invested in an open web is that Google is starting to ignore a principle it championed by making its own services Chrome-only '-- even if it's only initially. Given the amount of times this has occurred already, the most recent Chrome-only Google app, YouTube TV, isn't likely to be the last one.
''This is really not acceptable,'' says Jen Simmons, a member of the CSS working group and developer advocate at Mozilla, referencing Groupon optimizing its site for Chrome. ''Web devs, you can do better. Develop for the web, not one browser. Otherwise you are screwing over your users.''
John Gruber, author of the Daring Fireball blog and inventor of the Markdown publishing format, warns there could be more of this to come. ''There is so much Chrome-only stuff right now,'' says Gruber. ''If you think Google isn't building a proprietary Chrome platform, your head is in the sand.''
There's some hope, though. ''Helping to establish developer habits that support the growth of the open web remains a focus for the Chrome team and Google overall in 2018,'' says Google's Ben Galbraith. It's a focus that both the Chrome and Google's web teams will need to closely align on to avoid Chrome-only sites.
Microsoft might have celebrated the death of Internet Explorer 6, but if Google isn't careful then it might just resurrect an ugly era of the internet where ''works best with Chrome'' is a modern nightmare.
Update, 2:20PM ET: Clarified additional detail on Google's services support for Firefox and Edge browsers.
Poppie$
A nonaddictive opioid painkiller with no side effects? USC researchers think it's possible | USC News
Sun, 07 Jan 2018 14:59
What if scientists could develop an opioid-based painkiller that is not addictive and has limited side effects?
That is possible based on new findings by an international team of scientists that included contributions from top researchers at the Bridge Institute at the USC Michelson Center for Convergent Bioscience.
The international team captured the crystal structure of the kappa opioid receptor '-- critical for providing pain relief '-- in action on the surface of human brain cells. The researchers also made another important discovery: a new opioid-based compound that, unlike current opioids, activates only the kappa opioid receptor, raising hopes that they may develop a painkiller that has no risk of addiction and, therefore, none of the devastating consequences and side effects that accompany it.
The findings were published Jan. 4 in the journal Cell. They are an example of how USC Michelson Center scientists collaborate with a range of experts in multiple disciplines to conduct groundbreaking research, including the opioid addiction.
First, do no harmThe current challenge facing scientists in drug research and development is twofold: develop new alternatives to ease pain while minimizing side effects. Amid an opioid addiction crisis, this is a tall order, and it is urgent. More than 1 in 10 Americans suffer chronic pain, according to the National Institutes of Health. At the same time, millions of Americans are addicted to opioids.
Captained by researchers at the University of North Carolina at Chapel Hill, the team of 24 scientists on this latest study included three USC Michelson Center scientists who are among the most-recognized names in research on the special receptors found on the surface of the neuron: Raymond C. Stevens, Vadim Cherezov and Vsevolod ''Seva'' Katritch. All three are affiliated with the USC Dornsife College of Letters, Arts and Sciences.
The G protein-coupled receptors, found on the surface of the membrane, are the gatekeepers of communication with cells and are therefore the intended target of most therapeutics. The solution to pain, disease and other conditions begins with understanding '-- and seeing very clearly '-- the structure of the receptors when they are inactive and when they are active, interacting with a drug compound.
Typically, scientists determine the structure of receptors by forcing the proteins into a crystal lattice that they then expose to X-rays. Essentially, they want to create an accurate model of the receptor when it does and does not interact with a drug compound.
However, these G protein-coupled receptors are challenging to capture in a stabilized state with traditional X-ray crystallography. Like ill-behaving toddlers, they are highly dynamic, move frequently and very fragile. That is why Stevens, Cherezov and Katritch developed some breakthrough techniques for this special class of proteins that have led to more accurate crystallography.
At a cellular level, their work has led to a greater understanding of the receptors and their behaviors. From a holistic perspective, their research is explaining how humans respond to drugs. Furthermore, they have set the foundation for a new wave of therapeutics that are much more precisely targeted than their predecessors to address illnesses and conditions with fewer unintended side effects.
The power of threeStevens is a molecular biologist and chemist hailed as a pioneer in solving the structures of G protein-coupled receptors. He developed a method of experimenting known as ''high-throughput crystallography'' in structural biology, which uses robotics, data processing and management software, as well as liquid handling devices and detectors to conduct millions of tests.
Cherezov is a structural biologist who developed new ways to herd capricious membrane proteins like the G protein-coupled receptors into well-behaved crystals. He uses lipids similar to those found in cell membranes to form a special ''cubic phase.'' This technique ensures that the receptors behave as if they had never left their home on the membrane, even as they form crystals.
The Lipidic Cubic Phase technology has been successfully applied to a majority of the GPCRs that have been solved, including the previous kappa opioid receptor structure in its inactive state, according to Cherezov. By adding a stabilizing nanobody, the researchers are able to capture the structure in a fully active state, he said.
Katritch, a biophysicist and computational biologist, has developed computer models of receptor interactions with ligands that activate or inactivate receptors. This allows scientists to quickly test the receptor interactions with millions of ligands in a virtual lab '-- his computer '-- so that they may select the molecules that have the most beneficial therapeutic properties for more testing.
In the case of the kappa opioid receptor, his computer analyses enabled the scientists to modify the chemistry of the ligands so that eventually they developed ligands that affected only the kappa opioid receptor.
Currently, most opioids bind to several opioid receptors on the membrane of brain cells, which has its share of drawbacks. They alleviate pain but cause a range of side effects, from nausea to numbness, constipation, anxiety, severe dependency, hallucinations and even death by respiratory depression.
In this study, the computer models revealed the formulations that would create the strongest bond between the ligand and the kappa opioid receptor without affecting other receptors.
Katritch said the latest research may pave the way for a major drug breakthrough.
''We have already found the structure of the inactive kappa opioid receptor highly useful for discovering potential candidates for a new painkiller,'' Katritch said. ''Now with the structure of the active receptor, we have a template for designing new types of pain medications that have no disruptive side effects for patients and would reduce the burden that opioid addiction has placed on society.''
Other collaborators from USC were Saheem Zaidi, Gye Won Han and Ming-Yue Lee of the USC Michelson Center and USC Dornsife College.
The National Institutes of Health, The Mayday Foundation and the Peter F. McManus Trust funded the research.
Collaborators included scientists from UNC-Chapel Hill, RTI International, Virginia Commonwealth University, Arizona State University, the Institute of Natural Resources and Environmental Audits in China and Vrije Universiteit Brussels in Belgium.
More stories about:Addiction, Michelson Center for Convergent Bioscience, Research
Mac & Cheese
Producer Dustin on Kraft cheese
Commodity Prices:
Yes! I just heard on Thursday's episode (997) your comment about packaged food
analysts interested in only 2 things: Less ingredients, more addictive.
In 2001, when I moved to Madison, WI, I worked with
programmers that had used to work for Kraft's IT department in the area. They
said that Kraft's goal at the time was to lower the amount of real cheese. The
reason: It was a commodity that went up & down in price. More sawdust (and
now plastics) was a fixed cost they could count on.
-------
Mars Chocolate story:
Give me a break, main stream chocolate companies
are using 11% cacao in their chocolate at best. The rest is GMO corn syrup and
choco flavoring. A serious chocolate bar will brag it's percentages anywhere
from 65% to 86%.
Hillary & Huma
Trump Demands Prison for Huma Abedin | Frontpage Mag
Thu, 04 Jan 2018 22:16
'‹President Trump is demanding former top Hillary Clinton aide Huma Abedin be imprisoned for violating national security protocols and that an investigation be opened into former FBI Director James Comey.
At 7:48 a.m. Tuesday President Trump tweeted:
Crooked Hillary Clinton's top aid[e], Huma Abedin, has been accused of disregarding basic security protocols. She put Classified Passwords into the hands of foreign agents. Remember sailor[']s pictures on submarine? Jail! Deep State Justice Dep[ar]t[ment] must finally act? Also on Comey & others[.]
With the connivance of the Obama administration, Abedin and Clinton also purloined call logs, scheduling documents, and files described as ''Muslim Engagement'' from the Department of State when they left their jobs there. They labeled the government-owned documents ''private.'' Clinton also took with her a physical file of what has been described as ''the log of the Secretary's gifts with pictures of gifts,'' which may contain proof of bribes provided to Clinton.
Although it is unusual for a president to seek prosecution of his defeated enemies, the Clinton crime family is so corrupt and so sinister that failing to act against these reprobates is to commit a grave injustice. The brazen criminality of Hillary Clinton and those around her in the previous election cycle is utterly unprecedented in modern American politics, far surpassing the relatively minor-league shenanigans of President Richard Nixon in seriousness. To ignore Clinton's unlawful activities would be to discard the rule of law and affirm that powerful elites are not held to the same standards as ordinary Americans.
Clinton's campaign aggressively sought out new frontiers in unethical conduct, funding the Russian dossier compiled by Fusion GPS, a tainted political opposition research paper that Comey's FBI apparently relied on during its investigation. In the discredited dossier based in part on Kremlin-provided information, it was claimed Trump hired Russian prostitutes to urinate on a hotel bed.
The dossier was just one of many outrageous dirty tricks by Clinton's campaign. Clinton used the Democratic National Committee to snuff out Bernie Sanders' bid for her party's nomination, and personally authorized the illicit efforts of socialist felon Bob Creamer and organizer Scott Foval who fomented violence at Trump campaign rallies, as James O'Keefe's Project Veritas group revealed in undercover videos.
Trump's comments came after the Department of State released classified emails located on the laptop computer of Abedin's now-imprisoned sex offender husband, former Rep. Anthony Weiner (D-N.Y.). The document dump came last week in response to a Freedom of Information Act lawsuit filed by good government group Judicial Watch.
The FBI's announcement that it was probing the emails gave Trump an extra line of attack against Clinton in the final days of the 2016 election campaign. For her part, Clinton herself can't stop whining about what the FBI did and blaming the agency that exposed her wrongdoings for her humiliating electoral defeat.
Abedin used an un-secure Yahoo email address to conduct official State Department business, often forwarding sensitive government documents to the Yahoo address, apparently in violation of federal law.
''She would use these accounts if her (State) account was down or if she needed to print an email or document,'' according to a previously released FBI report. ''Abedin further explained that it was difficult to print from the DoS system so she routinely forwarded emails to her non-DoS accounts so she could more easily print.''
Emails previously revealed Abedin gave foreign leaders and activists special access to Clinton when she was secretary of state after they donated to the congenitally corrupt Bill, Hillary and Chelsea Clinton Foundation.
The emails, also obtained by Judicial Watch, appear to show Abedin serving as a gatekeeper auctioning access to the presidential candidate in exchange for donations to the Clinton Foundation. When individuals wanted to meet with Hillary, Abedin would say no, and introduce them to the foundation. After the ''donation'' was received, access to Clinton would be approved.
During the 2016 election cycle, then-FBI Director Comey was essentially an unofficial Clinton campaign staffer. He gave preferential treatment to Mrs. Clinton by refusing to recommend charges against her for her private email scheme after saying there was no proof of criminal intent on Clinton's part, a legal element not actually required by the nation's espionage laws. Trump fired the bungling Comey last year for his corruption and incompetence.
Last summer, Comey admitted he orchestrated the leaking of his notes '' which were his work product and therefore government property '' regarding conversations with Trump to the New York Times. Comey said he did it to cause a special counsel investigation to be created to examine possible collusion between the Trump campaign and Russia.
In Trump's tweet this week, he referred to the case of Petty Officer First Class Kristian Saucier, who pled guilty to mishandling classified information after using a cellphone to take photos of the classified engine room aboard the nuclear submarine on which he served.
Meanwhile, Abedin's cousin, Omar Amanat, another fan of Yahoo email, has been jailed as a flight risk after being convicted of fraud last week. The judge involved said Amanat showed a ''disdain for the courts and legal process.''
According to a report,
Court documents also depict him trying to destroy potential evidence, saying he emailed his brother to ''delete all of my emails from the yahoo site,'' expressing ''concern about them [subpoenaing] yahoo at some point,'' while concocting other fake documents to show the jury.
Amanat was accused of bilking investors by lying to them about the precarious financial condition of a tech concern called Kit Digital. ''The evidence of their criminal schemes was so overwhelming that Amanat actually tried to fool the jury by introducing fake emails into the record as exculpatory 'evidence' in this trial,'' said acting Manhattan U.S. Attorney Joon H. Kim.
Amanat entered into a partnership with Russian-born Vladislav Doronin in 2013 to buy a luxury resort for $358 million. Doronin previously worked for Marc Rich, the fugitive financier pardoned by President Bill Clinton on his final day in office.
The Clintons' political careers may be over, but their ties to the criminal underworld live on in Amanat and Abedin.
And Huma Abedin's intergenerational ties to the Muslim Brotherhood and Islamofascist terrorism have barely begun to be explored.
Six Week Cycle
FBI: Man wanted to attack San Francisco's Pier 39 on holiday - Washington Times
Sun, 07 Jan 2018 14:27
SACRAMENTO, Calif. (AP) - The FBI said Friday that it found a martyrdom letter and several guns in the home of a former Marine who said he wanted to carry out a Christmas Day attack on San Francisco's Pier 39, a popular tourist destination.
Everitt Aaron Jameson, 26, a Modesto tow-truck driver, was charged Friday with attempting to provide material support to a foreign terrorist organization.
Jameson told an undercover agent he believed to be associated with senior leadership of the Islamic State group that he wanted to conduct a violent attack on Pier 39, which is packed with restaurants, bars and souvenir shops, because it is heavily crowded, according to an FBI affidavit.
He told the undercover agent that Christmas Day would be ''the perfect day to commit the attack'' and that he ''did not need an escape plan because he was ready to die,'' the affidavit said.
He asked for help obtaining a fully automatic military assault rifle, either an M-16 or an AK-47, along with ammunition and materials to make explosives, including nails, timers and remote detonators, the affidavit said.
However, Jameson told the undercover agent Monday that he had reconsidered and felt he could not carry out the attack after all, the affidavit says. He denied the allegations during a hearing in federal court Friday.
His father, Gordon Jameson, said he believes the FBI has the facts wrong.
''He wouldn't do that to innocent people,'' the elder Jameson told the Merced Sun-Star . ''He's a loving, kind person that would never hurt nobody.''
Everitt Jameson was under surveillance and ''the public was never in imminent danger,'' FBI spokeswoman Katherine Zackel said in a statement.
She and San Francisco Acting Mayor London Breed both said there are no other known threats, though police increased their presence throughout the city after being notified of the FBI investigation several days ago.
''San Francisco is a city that proudly champions democracy, freedom and liberty. Sadly, that makes our home a target,'' Breed said in a statement. ''We will not allow the thwarted attempts of one dangerous individual to disrupt our way of life. We will remain vigilant and continue to protect our city from any threat.''
Jameson had posted radical jihadist messages online, including expressing support for the Halloween terror attack in New York City in which a driver used his truck to kill eight people, the FBI said.
''I'm glad to know we Muslims are finally hitting back,'' Jameson told an agency informant. He offered to use his tow truck to support the cause, the affidavit says.
The FBI began investigating in mid-September when it learned that Jameson was expressing support for posts that favored terrorism or the Islamic State group. He ''loved'' an online post that showed Santa Claus threatening an attack in New York with a box of dynamite.
Agents raided his home Wednesday, finding a martyr's letter signed with an Islamic variation of his name, along with his last will and testament updated in November. They also found fireworks, two rifles and a 9mm handgun.
During the search, Jameson ''stated his support of ISIS and terrorism and discussed aspects of the plan to carry out an attack, noting that he would be happy if an attack was carried out,'' the affidavit says.
He was arrested Friday and faces up to 20 years in prison if convicted. At a court hearing, he was ordered held for a Dec. 28 detention hearing.
The federal defender representing Jameson, Eric Kersten, did not return telephone and email messages seeking comment.
Jameson had attended Marine basic recruit training in 2009 and earned a sharpshooter rifle qualification. He was discharged for failing to disclose a history of asthma, the affidavit said.
He referred to his military service in comments to undercover agents.
''I have been trained in combat and things of war,'' Jameson told one agent.
Jameson made a pledge to the Muslim faith two years ago at an Islamic center in Merced, according to the affidavit. A message left at the Islamic Center of Merced was not immediately returned.
''The threat from radical Islamic terrorism is real - and it is serious,'' Attorney General Jeff Sessions said in a statement, but federal agents are protecting the nation from what he called ''an alleged plot to kill Americans.''
CLIPS & DOCS
VIDEO - Trump Wants Mandatory Drug Testing To Collect Unemployment Benefits! - YouTube
Sun, 07 Jan 2018 15:47
VIDEO - FCC Chairman Cancels Electronics Show Speech After Death Threats Related To Net Neutrality - YouTube
Sun, 07 Jan 2018 15:45
VIDEO - CDC TRAINING FOR NUCLEAR BOMB DETONATION INSIDE THE UNITED STATES! - YouTube
Sun, 07 Jan 2018 15:43
VIDEO - Message To Jeff Sessions! "I'm Getting High Today! Tomorrow! And EVERYDAY TILL I DIE!" - YouTube
Sun, 07 Jan 2018 15:42
VIDEO - State Dept. Announces Suspension of Security Assistance Money to Pakistan - YouTube
Sun, 07 Jan 2018 15:37
VIDEO - Scarborough's 'Can you read' story about Trump in 2018 different from 2015 - YouTube
Sun, 07 Jan 2018 15:37
VIDEO - Jake Tapper cuts off interview with White House adviser Stephen Miller - YouTube
Sun, 07 Jan 2018 15:35
VIDEO - Alcohol Boosts Cancer Risk by Damaging Stem Cell DNA : study shows - YouTube
Sun, 07 Jan 2018 15:25
VIDEO - Ontario premier calls Tim Hortons founder's children of bullying employees | CTV News
Sun, 07 Jan 2018 15:02
TORONTO -- The premier of Ontario lashed out at the children of Tim Hortons' billionaire co-founders on Thursday for reducing the benefits of their employees in response to the latest minimum wage increase, calling it a "clear act of bullying."
Kathleen Wynne said if Ron Joyce Jr., whose father co-founded the coffee shop chain, was opposed to the Liberal government's decision to raise the minimum wage, he should have picked a fight with her, not the workers.
"I'd be happy if this man were making a statement about the government or about the policy," she said. "What I think is really unfair, and where I think the bullying comes in, is that he's taking this out on his employees. He's behaving in a way that I think is so unfair to his employees, people who are trying to make ends meet."
In a letter sent late last month, Joyce Jr. and his wife, Jeri Horton-Joyce -- daughter of the company's other co-founder, Tim Horton, told employees at two Tim Hortons restaurants they own in Cobourg, Ont., that as of Jan. 1, they would no longer be entitled to paid breaks, and would have to pay at least half of the cost of their dental and health benefits.
The couple said the measures were aimed at helping their company -- Ron Joyce Jr. Enterprises Ltd. -- offset the $2.40 hourly rate jump.
Wynne, who faces a tough bid for re-election this spring, has staked her political future on policies like the minimum wage plan.
"When I read the reports about Ron Joyce, Jr., who is a man whose family founded Tim Hortons, the chain was sold for billions of dollars, and when I read how he was treating his employees, it just felt to me like this was a pretty clear act of bullying," she said.
Wynne has talked for months about themes of fairness and opportunity in Ontario's growing economy with the caveat that some workers are being left behind. The premier has said her minimum wage plan, which saw the rate jump from $11.60 an hour to $14 an hour this week, is about helping low income earners. It will increase another dollar to $15 on Jan. 1, 2019.
The plan has angered many in the business community, who say they don't object to the increase itself but the speed with which it is being implemented.
While the changes announced by Joyce Jr. are not a violation of Ontario's Employment Standards Act, Wynne said she wants him to reverse the decision.
"I hope that he understands this is really not a decent thing to be doing in a place as wealthy as Ontario," she said. "I hope he recognizes that his employees need to be treated decently."
In their letter to employees, Joyce Jr. and his wife complained about "lack of assistance and financial help" from Tim Hortons' head office and the government.
"We apologize for these changes," the letter, widely circulated on social media, read. "Once the costs of the future are better known we may bring back some or all of the benefits we have had to remove."
The Great White North Franchisee Association, a group created last year to give voice to the concerns of some Tim Hortons franchisees, said in a statement Thursday evening that the Joyce family are "hard-working small business owners who are striving to keep their business viable and keep all of their employees employed."
The association said Wynne and her government have shown no understanding of small business in Ontario.
The $2.40 an hour increase in the minimum wage is only part of the increase in costs felt by small business owners, the group said.
Increases in other employment-related costs -- such as pension, employment insurance, and vacation pay contributions -- make the total increase to the employer $3.35 an hour, it claimed.
"For one full-time employee at a Tim Hortons location, this would amount to approximately $6,968.26 per annum in increased costs to the owner," it said.
"What the Joyce family have implemented in their two Cobourg stores has been legally done to help them cope with the added business pressures the impact of Bill 148 has placed upon their establishments."
FULL STATEMENT:
Premier Kathleen Wynne released the following statement today on the minimum wage increase:
''Like many others I was upset to read reports about how Ron Joyce Jr '' a man whose family founded the Tim Horton's chain which was sold for $11.4 billion '' is treating his employees and responding to the recent rise in the minimum wage.
The many people who get up and put in a full day's work in this province deserve to be paid decently and, just as importantly, they deserve to be treated decently. Asking minimum wage workers to sign a pledge acknowledging that their breaks will now go unpaid or agreeing to only receive eight hours pay for a nine hour day is not decent and it's not fair. It is the act of a bully.
If Mr. Joyce wants to pick a fight, I urge him to pick it with me and not those working the pick-up window and service counter of his stores. Tim Horton's is an important part of the daily life of many Canadian families. Paying our workers a decent living wage is also important. I hope Mr. Joyce will choose to reverse his approach.''
VIDEO - The Company that Bought Your Journalist - YouTube
Sun, 07 Jan 2018 14:49
VIDEO - Israeli Arrested In Cyprus For Organ Trafficking! - YouTube
Sun, 07 Jan 2018 14:18
VIDEO - Heather Mac Donald: How Much More Delusional Can University Students Get? - YouTube
Sun, 07 Jan 2018 14:05
VIDEO - Watching Microsoft's Windows Mixed Reality demo will actually get you excited about Windows again '' BGR
Sun, 07 Jan 2018 03:59
Once upon a time, Windows was a software platform so exciting that it had its very own flock of fanboys. Yes, it's difficult to envision now for most people, but Microsoft's operating system was so beloved that it drew the kind of devotion we now see with Google's Android platform and Apple's iOS software. Windows also spurred the kind of arguments now common among hardcore iOS and Android fans.
Today, Windows is just a boring old desktop OS to most people who use it, while the excitement lies on their smartphones. But that may soon change when you get a load of a new demo video of Windows Mixed Reality that Microsoft just posted.
You probably didn't even realize it, but Microsoft held an event on Tuesday in San Francisco. It was tiny and it didn't get much coverage, but the company unveiled a new range of virtual reality headsets from a number of partner companies. Samsung, Acer, Lenovo, HP, Dell, and Asus will all be releasing new VR headsets beginning on October 17th, and prices will start at a very reasonable $399.
Far more interesting than the headsets themselves, however, was the awesome Windows Mixed Reality demo that was presented along with them. The entire 35-minute presentation is embedded below, and we highly recommend watching as much of it as you can. What you see just scratches the surface of what Windows Mixed Reality brings to the table. And best of all, this is all with just standard VR headsets; augmented reality headsets like Microsoft's HoloLens will push things even further.
We're excited about Windows for the first time in as long as we can remember, and you will be too after you watch the demo below.
VIDEO - Heather Mac Donald: How Much More Delusional Can University Students Get? - YouTube
Sun, 07 Jan 2018 01:19
VIDEO - JonBenet Ramsey's brother sues CBS for $750 million over TV special | Fox News
Sat, 06 Jan 2018 18:15
The brother of JonBenet Ramsey, the 6-year-old beauty queen found dead in the basement of her family's Colorado home in 1997, is suing CBS and orthers for $750 million, arguing the network's special "The Case of JonBenet Ramsey" ignored evidence to falsely point the finger at him.
In the lawsuit filed Wednesday, Burke Ramsey claims that the network, its production company and the experts interviewed in the series on the unsolved murder conspired to defame him for publicity and profit. The series, called "The Case of JonBenet Ramsey," aired in September ahead of the 20th anniversary of JonBenet's death.
The lawsuit says CBS and its featured experts set out to conduct a "sham reinvestigation" of the murder with "the preconceived the story line" that Ramsey killed his sister and conspired with his parents to cover it up.
"The accusation that Burke Ramsey killed his sister was based on a compilation of lies, half-truths, manufactured information, and the intentional omission and avoidance of truthful information about the murder of JonBen(C)t Ramsey," the lawsuit says.
CBS spokesman Dustin Smith declined to comment on the lawsuit, which is the second Burke Ramsey has filed over the television series.
Burke Ramsey's lawsuit also pointed out that in 2008 Mary Lacy, then the Boulder County District Attorney, cleared the Ramsey family as suspects after DNA analysis.
Current District Attorney Stan Garnett said two weeks ago that Lacy's public letter was not binding and that his office was still investigating the case.
The CBS special looked into theories that Burke Ramsey possibly could have killed his sister -- accusations he claimed were entirely false. He was 9 at the time of JonBenet's death.
Investigators have said they were looking at new DNA testing technology that they hoped would further the investigation. The move cames after an investigation by the Daily Camera newspaper in Boulder and KUSA-TV in Denver that apparently uncovered flaws in the interpretation of previous DNA testing.
JonBenet Ramsey's body was found beaten and strangled at her family's home in Boulder on Dec. 26, 1997.
Garnett said much of the new testing would target previously screened items to see if new information could emerge.
The Associated Press contributed to this report.
VIDEO - Eric Weinstein and Dave Rubin on Fake News, Trump, and the Mathematical Mind (Full Interview) - YouTube
Sat, 06 Jan 2018 17:46
VIDEO - SEC warns bitcoin investors at risk
Fri, 05 Jan 2018 12:24

SEC warns bitcoin investors at risk | Reuters.comHTTP/1.1 301 Moved Permanently Server: CloudFront Date: Fri, 05 Jan 2018 12:24:49 GMT Content-Type: text/html Content-Length: 183 Connection: keep-alive Location: https://www.reuters.com/video/2018/01/04/sec-warns-bitcoin-investors-at-risk?videoId=378225883&feedType=VideoRSS&feedName=LatestVideosUS&videoChannel=5&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+reuters%2FUSVideoLatest+%28Video+%2F+US+%2F+Latest+Video%29 X-Cache: Redirect from cloudfront Via: 1.1 b06057d522f80c65400aebb1c06a2d72.cloudfront.net (CloudFront) X-Amz-Cf-Id: FYiUzrk6wkmelJFJsuPSNa5Lmu3PIimk-8bh7ZaKwxULpwJ8hvciaA== HTTP/1.1 200 OK Content-Type: text/html;charset=UTF-8 Content-Length: 22976 Connection: keep-alive Access-Control-Allow-Headers: Access-Control-Allow-Origin,charset Access-Control-Allow-Origin: http://admin.reuters.com Content-Encoding: gzip Date: Fri, 05 Jan 2018 12:24:21 GMT Expires: Fri, 5 Jan 2018 12:19:19 GMT Server: nginx Vary: Accept-Encoding X-Cache: Miss from cloudfront Via: 1.1 0f3bddd6b971cf08b18fedb5c0a9f2f6.cloudfront.net (CloudFront) X-Amz-Cf-Id: pqd-G39TCDQW4qV-lgxirXLCBD-Ai8JsOYROGO719Y-amdMroDk1gw==
Eikon
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VIDEO - Seth Meyers on hosting Globes amid sexual allegations | Reuters.com
Fri, 05 Jan 2018 12:24

Eikon
Information, analytics and exclusive news on financial markets - delivered in an intuitive desktop and mobile interface
Elektron
Everything you need to empower your workflow and enhance your enterprise data management
World-Check
Screen for heightened risk individuals and entities globally to help uncover hidden risks in business relationships and human networks
Westlaw
Build the strongest argument relying on authoritative content, attorney-editor expertise, and industry defining technology
ONESOURCE
The most comprehensive solution to manage all your complex and ever-expanding tax and compliance needs
CHECKPOINT
The industry leader for online information for tax, accounting and finance professionals
VIDEO - Harrington: The Media 'Latch Onto the Most Petty Gossip' to Ignore Important Stories
Fri, 05 Jan 2018 11:42

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