Clinical trials by Janssen Pharmaceuticals showed troubling results.
- A new analysis in The British Journal of Psychiatry claims the FDA approval process for ketamine was rushed.
- Only one of three clinical trials showed efficacy, while the discontinuation trial produced troubling outcomes.
- Ketamine's side effects include anxiety, poor appetite, delusions, hallucinations, paranoia, rage, and craving.
The Experimental Ketamine Cure for Depression<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="43bebca1d3e1193062837ab7fc595469"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/PAfLnXFIENk?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>While treatment-resistant depression sounds extreme, Horowitz notes the definition: patients unsuccessful with two different antidepressants, a low bar for the term "resistant." The problem with trying esketamine, he writes, falls back on the FDA fast-tracking of the drug.</p><p style="margin-left: 20px;">"Out of the three short-term trials conducted by Janssen only one showed a statistically significant difference between esketamine and placebo. These were even shorter than the 6–8 week trials the FDA usually requires for drug licensing."</p><p>Each trial lasted only four weeks. The FDA normally requires that two such trials show better results than the placebo; in this case, only one achieved this goal. The successful trial showed a four-point margin on a scale that goes to 60. </p><p>Failing to provide two effective trials, the FDA allowed Janssen to submit a discontinuation trial as evidence. This 16-week trial let patients either continue or stop treatment. The problem: side effects were treated as evidence of relapse, not withdrawal symptoms. </p><p>Ketamine users have a long history of withdrawal issues, including anxiety, poor appetite, delusions, hallucinations, paranoia, addiction, rage, and craving. The discontinuation trial considers such effects as proof of ketamine's efficacy, not as symptoms of withdrawal. </p><p>Science writer Peter Simons <a href="https://www.madinamerica.com/2020/06/esketamine-depression-repeating-mistakes-past/" target="_blank">explains</a> why this is worrisome: </p><p style="margin-left: 20px;">"Perhaps even more concerning is the fact that, within the discontinuation trial, a single site in Poland drove the apparent finding of efficacy. Data from this site suggested that 100% of the placebo group supposedly relapsed (compared with about 33% of the placebo group in all the other sites)—an unlikely result. When data from this suspicious outlier was removed, the study analysis showed no evidence that esketamine was better than the placebo."</p><p>Add to this that six people in the esketamine group died during the trials, including three by suicide—two of whom had previously shown no signs of suicidal ideations—and a troubling picture emerges. The FDA accepted Janssen's explanation: the problem wasn't esketamine, but their underlying condition. This is possible, but the company did not provide conclusive evidence. </p>
Jennifer Taubert, executive vice president and worldwide chairman of Janssen Pharmaceuticals, Johnson & Johnson, testifies before the Senate Finance Committee on "Drug Pricing in America: A Prescription for Change, Part II" February 26, 2019 in Washington, DC. The committee heard testimony from a panel of pharmaceutical company CEOs on the reasons for rising costs of prescription drugs.
Photo by Win McNamee/Getty Images<p>According to Horowitz, this is a chronic problem with clinical trials and governing agencies. </p><p style="margin-left: 20px;">"It would seem that themes from history are repeating: a known drug of misuse, associated with significant harm, is increasingly promoted despite scant evidence of efficacy and without adequate longterm safety studies."</p><p>He also notes that half of the patients experienced disassociation and one-third experienced dizziness. On this point, allow me to break the fourth wall. I've been experimenting with psychedelics since 1994 and am <a href="http://herosdose.com/" target="_blank">writing a book</a> on psychedelics in ritual and therapy. I ingested a range of substances during my college years. By far, the most troublesome was ketamine. While I'm now aware of Parecelsus's dictum—what is beneficial in small doses is toxic in large doses—I wasn't measuring it out in the 1990s. </p><p>Administered doses in Janssen's trials were considered similar to recreational usage. I recall that a bump provided an energetic lift, yet when I'd occasionally snort a line, all bets were off. After a hearty dose one evening, I laid down, sat up, and stood in succession. I couldn't tell the difference between those three physical positions. Ketamine is the most dissociative substance I've ever taken, and I stopped shortly after that last instance. </p><p>Psychedelics are the next wave of mental health treatments—call it a continuation, given their role in traditional rituals. We came to rely on pharmacology too much in the twentieth century; hopefully we're learning from those mistakes. As Horowitz points out, however, it appears we're not. </p><p>The important word in psychedelic therapy is <em>ritual</em>. There are environmental and social factors entwined with our health. In the right context, psychedelics have tremendous healing power. And to be fair, some <a href="https://www.fieldtriphealth.com/blog/introduction-to-ketamine-therapy" target="_blank">ketamine clinics</a> are taking proper right safety precautions as well as designing treatment rooms to be more conducive to healing than sterile white rooms. Patients are anecdotally reporting success in depression treatment with ketamine. This isn't an either-or situation. </p><p>But we cannot make the <a href="https://www.vox.com/the-goods/2018/11/1/18024806/cbd-oil-vape-hemp" target="_blank">same mistake</a> we've made with CBD and believe these substances are cure-alls. We also can't afford to designate ketamine under the umbrella term "psychedelics." As Alan Watts <a href="https://bookshop.org/books/the-joyous-cosmology-adventures-in-the-chemistry-of-consciousness/9781608682041" target="_blank">wrote</a>, <em>hallucinogen</em> is not a proper definition of the psychedelic experience, though it's fitting when describing ketamine. Conflating substances will only further confusion during a time when we need clarity. If the addictive properties and dangerous side effects of ketamine play out widely, it endangers the entire psychedelic therapy model. </p><p>We can hope for a clinically-effective dosage and delivery mechanism of ketamine. We can't, as Horowitz's analysis shows, make the same mistakes over. Pharmacological intervention has a place in psychiatry, but it's come to dominate the industry, <a href="https://bookshop.org/books/anatomy-of-an-epidemic-magic-bullets-psychiatric-drugs-and-the-astonishing-rise-of-mental-illness-in-america/9780307452429" target="_blank">often no better</a> than placebo and psychotherapy. We need healing, not <a href="https://www.madinamerica.com/2020/06/review-documents-short-long-term-withdrawal-effects-psychiatric-drugs/" target="_blank">more side effects</a>.</p><p>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
Why do so many people encounter beings after smoking large doses of DMT?
- DMT is arguably the most powerful psychedelic drug on the planet, capable of producing intense hallucinations.
- Researchers recently surveyed more than 2,000 DMT users about their encounters with 'entities' while tripping, finding that respondents often considered these strange encounters to be positive and meaningful.
- The majority of respondents believed the beings they encountered were not hallucinations.
What are DMT beings?<p>Do DMT entities actually exist in some other dimension, or are they hallucinations that the brain generates when its visual processing system is overwhelmed by a powerful tryptamine?<br></p><p>The late American ethnobotanist Terence McKenna believed that DMT beings — which he called "machine elves" — were real. Here's how he once <a href="https://www.ranker.com/list/dmt-machine-elves-facts/inigo-gonzalez" target="_blank">described</a> one of his DMT experiences:</p><p style="margin-left: 20px;">"I sank to the floor. I [experienced] this hallucination of tumbling forward into these fractal geometric spaces made of light and then I found myself in the equivalent of the Pope's private chapel and there were insect elf machines proffering strange little tablets with strange writing on them, and I was aghast, completely appalled, because [in] a matter of seconds... my entire expectation of the nature of the world was just being shredded in front of me. I've never actually gotten over it.</p><p style="margin-left: 20px;">These self-transforming machine elf creatures were speaking in a colored language which condensed into rotating machines that were like Fabergé eggs but crafted out of luminescent superconducting ceramics and liquid crystal gels. All this stuff was just so weird and so alien and so un-English-able that it was a complete shock — I mean, the literal turning inside out of [my] intellectual universe!"</p><p>McKenna believed machine elves exist in alternate realities, which form a "<a href="https://www.irishtimes.com/culture/books/old-favourites-the-archaic-revival-1991-by-terence-mckenna-1.3924887" target="_blank">raging universe of active intelligence that is transhuman, hyperdimensional, and extremely alien.</a>" But he was far from the first to believe that DMT is a doorway to other realms.</p><p>Indigenous peoples of the Amazon basin have used ayahuasca in religious ceremonies for centuries, though no one is quite sure when they first started experimenting with the psychedelic brew. The Jibaro people of the Ecuadorian rainforest believed ayahuasca allowed regular people, not just shamans, to <a href="https://atrium.lib.uoguelph.ca/xmlui/bitstream/handle/10214/17902/RichardsonG_202004_HonThesis.pdf?sequence=3" target="_blank">speak directly to the gods</a>. The 19th-century Ecuadorian geographer Villavicencio wrote of other Amazonian shamans who used ahaysuca (known as the "vine of the dead") to contact spirits and foresee enemy battle plans.</p><p>In the West, research on DMT experiences has been sparse yet interesting. The psychiatrist Rick Strassman conducted some of the first human DMT trials at the University of New Mexico in the early 1990s. He found that <a href="https://www.erowid.org/chemicals/dmt/dmt_article3.shtml" target="_blank">"at least half"</a> of his research subjects had encountered some form of entity after taking DMT.</p><p style="margin-left: 20px;">"I was neither intellectually nor emotionally prepared for the frequency with which contact with beings occurred in our studies, nor the often utterly bizarre nature of these experiences," Strassman wrote in his book "DMT The Spirit Molecule".</p>
Manuel Medir / Getty<p style="margin-left: 20px;">"Whenever I tried to pull any information out of the entities regarding themselves, the data that was given up was always relevant only to me. The elves could not give me any piece of data I did not already know, nor could their existence be sustained under any kind of prolonged scrutiny."</p><p>It's also worth noting that not all people who smoke DMT see beings, and that some see beings that look <a href="https://www.erowid.org/chemicals/dmt/dmt_article3.shtml" target="_blank">nothing like elves or aliens</a>. The diversity of these reports seems to count against the argument that DMT beings exist in some objective alternate reality.</p><p>In other words, if DMT beings exist in some other dimension, shouldn't they appear the same to anyone who visits that dimension? Or do the beings assume a different appearance based on who's looking? Or are there many types of beings in the DMT universe, but most look like elves? </p><p>You might start seeing elves just trying to sort this stuff out.</p><p>Ultimately, nobody knows exactly why DMT beings take the forms they do, or whether they're just figments of overstimulated imaginations. And the answers might be beside the point. </p><p>In the recent survey, 60 percent of participants said their encounter with DMT beings "produced a desirable alteration in their conception of reality whereas only 1% indicated an undesirable alteration in their conception of reality."</p><p>DMT beings may be nothing more than projections of the subconscious mind. But these bizarre encounters do help some people find real meaning, whether it's through personal revelation or the raw power of ontological shock.</p>
Just for giggles, would it be a good idea to have our leaders take shrooms?
- The idea of mass ingestion of psychedelics to drive people to environmental activism has been put forward lately, inspiring much debate.
- Suppose we gave it to people with power instead. It seems like it would be more effective.
- While psychedelics can offer some benefits, they won't necessarily be the right ones to get the job done.
One pill makes you larger, and one pill makes you small….<div class="rm-shortcode" data-media_id="ByKYCJ3i" data-player_id="FvQKszTI" data-rm-shortcode-id="009f695fee0c95369dd34c00a41accb5"> <div id="botr_ByKYCJ3i_FvQKszTI_div" class="jwplayer-media" data-jwplayer-video-src="https://content.jwplatform.com/players/ByKYCJ3i-FvQKszTI.js"> <img src="https://cdn.jwplayer.com/thumbs/ByKYCJ3i-1920.jpg" class="jwplayer-media-preview" /> </div> <script src="https://content.jwplatform.com/players/ByKYCJ3i-FvQKszTI.js"></script> </div> <p>Psychedelics have a variety of increasingly well-documented effects. Their use is associated with an increase in openness to new experiences and ideas, shifts in worldview, reduction in anxiety and <a href="https://bigthink.com/surprising-science/microdosing-lsd" target="_blank">depression</a>, increases in creativity and <a href="https://www.tandfonline.com/doi/full/10.1080/02791072.2019.1580804" target="_blank">empathy</a>, and a newfound love of progressive rock.</p><p>Furthermore, they are known to decrease authoritarian <a href="https://journals.sagepub.com/doi/full/10.1177/0269881117748902%0A" target="_blank">tendencies</a> in people which are, in turn, shown to be tied to a disregard for the <a href="https://www.reuters.com/article/us-brazil-politics/igniting-global-outrage-brazils-bolsonaro-baselessly-blames-ngos-for-amazon-fires-idUSKCN1VB1BY" target="_blank">environment</a>. </p><p>It is easy to see why the suggestion of giving our political leaders the stuff would be made. Several of these traits seem like they could be good for anybody. If people with power gained these traits, perhaps they would make the world a better place.</p>
Plus, imagine how entertaining the State of the Union address would be if everybody there were tripping.
Photo by Toni L. Sandys/The Washington Post via Getty Images<p>The idea that we ought to give all of our politicians drugs isn't a new one. Somewhat disturbingly, it is also one that has been suggested several dozen times throughout the past fifty or so years.<br></p><p>More of the more amusing suggestions came from the Beatles after they discovered marijuana and psychedelic drugs. In the <em>Beatles Anthology</em>, they discuss how they once felt that giving all of our leaders the stuff would put an end to wars.</p><p>Grace Slick, the lead singer of Jefferson Airplane, once even planned to spike the tea of Richard Nixon with 600 micrograms of LSD- roughly as much as your conspiracy theorist uncle took the day he realized the lizard people had taken over the world – to give him a new perspective on the world. Luckily for everybody <a href="https://ultimateclassicrock.com/grace-slick-president-nixon-acid-1970/" target="_blank">involved</a>, they didn't let her onto white house grounds when they saw her bodyguard was Abbie Hoffman. </p>
Time to kill the vibe for you hippies.<p>However, there are more than a few reasons why we might not want to drug our politicians and why it might not even be all that effective for getting society to the point that proponents of psychedelics wish to.</p><p>While it is easy to rage at politicians who don't do exactly what you want them to, you must remember that they didn't spontaneously generate — they were elected. Every climate change denying scoundrel in office was put there by an electorate of their peers. </p><p>Fixing one person — or even a few hundred elected ones — doesn't change that, and then you've only won until the next election anyway.</p><p>Secondly, the traits that are fostered by psychedelics don't always make for capable politicians. While an acid trip might make a Machiavellian politician care more for the environment, it would likely also make them less likely to use the dirty tricks they currently employ to make actual change happen. President Lyndon Johnson might have been an <a href="https://www.forbes.com/sites/johncoleman/2018/07/30/the-johnson-treatment-pushing-and-persuading-like-lbj/#46b753b84201" target="_blank">awful person</a>; he was also effective. Increasing his empathy levels might have been a good thing, but it might also have diminished his effectiveness at promoting The Great Society. </p><p> You need people in power with both concern and skill to change things. If you think that a bunch of people coming down from psychedelics are going to be effective at running a democratic government faced with a crisis, go watch the board meeting of any housing co-op deal with a major issue. </p><p>This point, sans psychedelics, was made five hundred years ago by Machiavelli in his masterpiece, <em>The Prince. </em>In it, he argues that the traits that make for a good person are not the same as those that make a great statesman. While that might seem obvious to some of you, it is a controversial point that landed the book on the Catholic Church's list of prohibited texts. </p><p>He considers the case of <a href="https://en.wikipedia.org/wiki/Girolamo_Savonarola" target="_blank">Girolamo Savonarola</a>, a Catholic Clergyman who came to power in Renaissance Florence. Even if you accept his vision of the New Jerusalem in Florence as a society worthy of creating, which you probably don't, you have to admit that he wasn't very good at statecraft once he and his supporters came to power. </p><p>This lack of skill undermined any attempt at good he could have made. If he had been a little less godly, perhaps he could have built more of the New Jerusalem. </p><p>The lesson rings true to this day. We need not only politicians who care about the right things or are made to care about them by public pressure, but who have the skills necessary to affect change. While an acid test with all of our current leaders would be extremely entertaining, it probably wouldn't amount to much. </p><p>Should we have all of our politicians take shrooms to get them to take action on certain topics? Probably not. But just because this wouldn't work doesn't mean there aren't other ways to make a difference. While this idea is amusing, there are other ones.</p>
How did psychedelics and computers converge?
- Steve Jobs was influenced by an important counterculture and computing periodical.
- San Francisco went from hippie haven to technological hub in the years that followed the 1960s.
- The Homebrew Computer Club was founded by a draft resister and spawned dozens of tech companies.
Psychedelics are crude drugs. Could neuroscience and super-intelligent AI help us design something better?
- The illegal status of psychedelic substances is a terrible thing, says Ben Goertzel. With everything happening behind closed doors, our societies are not developing the right set of cultural institutions to guide people in the productive use of psychedelics.
- Once scientists have mastered artificial general intelligence (AGI), the psychedelic experience could be engineered for the modern world – it would be safer, less haphazard, and more meaningful. We would "trip" by jacking our brains into the superhuman AGI mind cloud.
- "We're going to be exploring states of consciousness that go way beyond anything we can imagine now and way beyond anything that the very crude psychedelic drugs that exist allow us access to," Goertzel says.