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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>
That's not frankincense you smell at the "holy of the holies."
- Cannabis and frankincense were discovered at the "holy of holies" shrine in Tel Arad, Israel.
- Both substances were mixed with animal dung to promote heating.
- This marks the first time cannabis has been found in the Kingdom of Judah.
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>
Researchers at the University of Copenhagen might have discovered a cure.
How Meditation Can Manage Chronic Pain and Stress | Daniel Goleman<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="003f88caa581ddd99ae8bdae9fd40e8e"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/yAd-JGbaRp8?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>A <a href="https://www.embopress.org/doi/full/10.15252/emmm.201911248" target="_blank">new study</a> at the University of Copenhagen might have uncovered a breakthrough in chronic pain relief. Published in the journal EMBO Molecular Medicine, researchers achieved complete pain relief in a group of mice by using a compound, Tat-P4-(C5)2, that was produced after a decade of development. </p><p>According to the team, this peptide only targets dysfunctional nerves causing the pain. In previous studies the team discovered it also helps reduce addiction. These two uses are not separate: chronic pain often leads to opioid addiction. By reducing pain, dependency on pain relievers may also be reduced. </p><p>So far, co-author Kenneth L. Madsen, Associate Professor at the Department of Neuroscience in Copenhagen, says there have been no side effects. Pain medicine often results in lethargic states, a condition not observed in the mice. Madsen hopes to turn this discovery into a business model. </p><p style="margin-left: 20px;">"Now, our next step is to work towards testing the treatment on people. The goal, for us, is to develop a drug, therefore the plan is to establish a biotech company as soon as possible so we can focus on this."</p>
Oxycodone pain pills prescribed for a patient with chronic pain lie on display on March 23, 2016 in Norwich, CT. On March 15, the U.S. Centers for Disease Control (CDC), announced guidelines for doctors to reduce the amount of opioid painkillers prescribed, in an effort to curb the epidemic.
Photo by John Moore/Getty Images<p>Chronic pain is most often prevalent in the back, muscles, bones, neck, joints, and face. Associated problems include headache, sleeping problems, fatigue, and anxiety. It has been known to last anywhere from weeks to years. Other factors that lead to chronic pain include diabetes and psychological factors, such as anxiety or depression.</p><p>Self-care treatments include regular physical exercise, stress management techniques, and relaxation. A combination of cardiovascular exercise, strength training, yoga, and meditation can help mitigate chronic pain. Of course, depending on pain location and severity, some of these interventions might not be tenable. </p><p>Besides the above treatments, there are pharmaceutical interventions, such as analgesics and narcotics. The problem, as the researchers note, is the addiction that follows. These drugs do not cure the problem. They only mask symptoms. Long-term side effects sometimes turn out worse than the pain itself. </p><p>Human trials will be next in the development of this peptide. There is always the possibility that it reacts differently in humans. Still, this is a positive step forward that could help millions of people find relief from one of the most frustrating and debilitating conditions known.</p><p> --</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a> and <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank">Facebook</a>. His next book is</em> "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</p>
A new study on rats suggests that using marijuana as an adolescent "reprograms the initial behavioral, molecular, and epigenetic response to cocaine."
- In the study, adolescent and adult rats were first given a synthetic cannabinoid and then cocaine.
- The results showed that the young rats' brains were more sensitive to the effects of cocaine, but these effects weren't observed in the adult rats.
- The researchers suggest that research like this can help to develop better treatments for substance abuse disorders.
Fig 1. Cross-sensitization between WIN and cocaine in adolescent rats is associated with histone hyperacetylation in the PFC.
Scherma et al.<p>The results showed that young rats who had been exposed to WIN were more sensitive to the effects of cocaine. This early exposure "reprograms the initial behavioral, molecular, and epigenetic response to cocaine" in young rats. These changes were not observed in adult rats.</p><p>Past research has shown that young rats that have been exposed to cannabinoids become "cross-sensitized" to cocaine, and that cross-sensitization can alter the extent to which rats crave cocaine and experience withdrawal symptoms. </p><p>The new study took a close look at how cannabinoids prime bodily systems for cocaine. </p>