Right after new results from his research on alcohol addiction and psychedelics emerged, Michael Bogenschutz confirmed his attendance at ICPR. A professor of Psychiatry at NYU Grossman School of Medicine and Director of the NYU Langone Center for Psychedelic Medicine, Dr. Bogenschutz is well known for launching the first contemporary study of psilocybin-assisted psychotherapy for alcohol use disorder in 2015. He has published extensively on the topic of addiction and the therapeutic potential of psychedelics.
Just one week ago, he reached another milestone in psychedelic research through his publication of the first double-blind randomized clinical trial of psilocybin for alcohol use disorder. This trial took a long time to complete, as the recruitment process took place from 2014 until 2020. But the wait seems worth it, as the final sample reached a total of 95 participants.
For Dr. Bogenschutz, this means a giant leap from his initial pilot study from 2015, which consisted of a sample of only 10 individuals – an issue that often looms over contemporary psychedelic research.
All the individuals who participated in the study struggled with excessive drinking. More specifically, those randomized to the psilocybin or placebo (diphenhydramine) group, respectively drank an average of 7.5 and 6.6 drinks per day. Both groups received 12 weeks of manualized psychotherapy and were administered either psilocybin or diphenhydramine at week 4 and week 8.
The study wanted to assess, most of all, whether the percentage of heavy drinking days was reduced following psilocybin. They found that the psilocybin group was associated with “robust decreases in percentage of heavy drinking days over and above those produced by active placebo and psychotherapy.”
The researchers assessed this 32 weeks after their first dosing session. The percentage of heavy drinking days was still 23,6% for the placebo group, meaning they drank heavily about once every four days, but for the psilocybin group, it was only 9.7% – once every ten days.
On top of that, there were also higher reports of individuals in the psilocybin group who had stopped drinking entirely. 24,4% of the placebo group did so, compared to 47.9% of the psilocybin group.
Through these results, Dr. Bogenschutz is genuinely changing the field of psychiatry, as there have been no new drug approvals in nearly twenty years for alcohol addiction. The only three approved conventional drugs for the treatment of alcohol use disorder are currently disulfiram, naltrexone, and acamprosate. Psilocybin, as such, might become a lifesaver for many people suffering from alcohol addiction.
But Dr. Bogenschutz is not done yet, as he recently announced that there will be a subsequent trial that aims to include more than 200 participants. This time the study will consist of only one single dose of psilocybin and will be compared to the vitamin niacin as another active placebo. The Food and Drug Administration has recently approved this trial. It will be the largest to date to examine the efficacy of psilocybin-assisted therapy for the treatment of alcohol use disorder.
In recent years, there has been an uptick in attention surrounding the substance known as 5-Meo-DMT. It is popularly known as a toad’s psychedelic gift – but is now also being scientifically studied in clinical research. The compound seems ideal as a fast-acting tool for ego-dissolution, with potential therapeutic use. The substance produces stunning effects that no other psychedelic seems to match, and does so within a manageable time frame.
And oh yes: it also happens to be legally available in many locales.
This is why 5-MeO-DMT might be one of the most fascinating – and potentially useful – psychedelics there is. Just like its first cousin DMT, 5-MeO-DMT is a naturally occurring compound. It can be found in both fauna and flora, like seeds, bark, and leaves from a number of plants in the Amazonian rainforest. The Sonoran Desert Toad, official name Incilius alvarius, is its most well-known carrier and has parotid glands that provide the toad’s primary defense system: a poison potent enough to kill a grown dog. This milky secretion also happens to contain 5-MeO-DMT, or 5-Methoxy-N,N-DiMethylTryptamine. If it is collected, dried, and smoked, the toxin produces a powerful, 15-20 minute psychedelic experience that completely differs in its effects from all the other classic psychedelic compounds – including DMT, its closest molecular cousin.
The fact that it hasn’t been scheduled in many countries facilitates research into the substance. Scientists and therapists wanting to work with substances like LSD and psilocybin, which have been put on international drug control lists, need to jump through many hoops in order to get research started.
‘Fast-acting therapeutic relief’
Maybe that’s part of the reason why scientific research into the useability of this substance has now taken off. In 2019, Maastricht University investigated the effects of 5-MeO-DMT. They found that in a naturalistic setting, a single inhalation resulted in enhanced satisfaction with life and decreased psychopathological symptoms, including depression, anxiety, and stress – all of which were sustained for up to 4 weeks after the experience. ¹
This year (2022), the group, led by Johannes Reckweg, published a review of the current knowledge of 5-MeO-DMT and hypothesized mechanisms underlying its effects. It mapped the workings of the drug, and weighed its potential utility for mental health. It concluded that ongoing research was justified: “The current therapeutic potential of 5-MeO-DMT is mainly hypothetical and based on preliminary evidence. […] Although limited, the studies offer converging evidence of the potential ability of 5-MeO-DMT to provide fast-acting, and potentially immediate, therapeutic relief for depression, anxiety, and stress-related disorders (such as PTSD) in particular.” ²
When a psychedelic molecule finds its way into the 5HT2A receptor binding site, depending on its shape and charge distribution (and thus the interactions formed within the binding site), it will distort the receptor and shift it into a distinct active conformation (ON state). pic.twitter.com/d4t2KQg9yD
Dr. Chris Timmermann has also been investigating the effects of 5-MeO-DMT at the Center for Psychedelic Research, at Imperial College London. He described the gripping psychedelic for us: “What makes 5-MeO-DMT truly unique,” Timmermann says, “is its apparent ability to induce states of ego dissolution in such a reliable fashion. The structure of the experience is fundamentally altered compared to other psychedelics – which usually provide a very rich visual experience. With ‘5-MeO’, users apparently experience a ‘white light’ that is closely associated with the ego-death experience. It is that ego-death experience that appears to have a radical impact on the user, especially in the case of addiction.”
According to Dr. Timmerman, the reliability with which 5-MeO-DMT appears to induce ego dissolution and non-dual consciousness is as interesting for consciousness research as it is for experimental psychiatry. Indeed, 5-MeO-DMT appears to induce a state of “non-dual consciousness,” which refers to a state of being in which subject and object are undifferentiated, similar to that reported by experienced meditators.
Unlike Ayahuasca, which has a clear indigenous lineage found in the shamanic traditions of amazonian tribes, the cultural heritage of 5-MeO-DMT remains unclear. Although numerous ceramic frog motifs found in the Santarem Territory of the Amazon suggest an indigenous connection to the animal, and some local names could allude to an elevated status of the toad, the evidence is often too ambiguous to make any direct connection to the psychedelic properties of Incilius Alvarius. Maybe future anthropological findings will shine more light into cultures that might have used it in the past. For now, its culture is a more modern tale.
5-MeO-DMT was first synthesized in 1936 by chemists Toshio Hoshino and Kenya Shimodaira but lay dormant as far as use went. Until 1983, when the book Bufo Alvarius: the psychedelic toad of the Sonoran Desert was published by a writer calling himself Albert Most. This latin name was used for the toad until its new classification as Incilius in 2006.
“Bufo Alvarius” is a seminal work describing the toad, its milky defense system and possible 5-MeO-DMT harvesting methods. The book opened the door to the modern culture of smoking the ‘toad venom’, as some tabloids called it and which -by the way- is an inaccurate term. In biology, ‘venom’ would mean the substance is injected by the toad, but it is not: it is sprayed.
That’s not the only confusion around the psychedelic toad. The taxonomy of the toad itself has changed. In 2006, it was classified as a member of the Incilius genus, so the book’s name is now dated. Also, the person laying the foundation for this new culture of toad toxin smoking, ‘Albert Most’, remained an enigma for many years.
The person behind the pseudonym was unknown for three decades, until he was revealed by psychonaut-journalist Hamilton Morris to be a man called Alfred Savinelli – who then was revealed to be an impostor by that same Hamilton Morris! In the third season premiere of his VICE Series Hamilton’s Pharmacopeia, Morris uncovers the lie of Savinelli, and exposes the real author of ‘Bufo Alvarius’ : Ken Nelson.
Nelson turns out to be a reclusive psychedelic researcher, environmentalist and veteran from Texas. To right past wrongs, Nelson and Morris released a new version of Nelson’s pamphlet, featuring Morris’ synthesis of 5-MeO-DMT.
There is still plenty of runway for the substance to create a culture of its own. It was readily available online as a ‘research chemical’ in the United States, and enjoyed limited attention. But its scheduling in the USA in 2011 provided a bolt of attention that increased its popularity. In 2019, the substance was potent enough to knock out former heavyweight boxing champion Mike Tyson, who openly talked about the spiritual awakening that resulted from his use of 5-MeO-DMT.
Soon after, others followed. Media outlets such as Forbes and the New-York Times featured stories about the transformative effects of the substance and included testimonials from ex-Navy SEAL Marcus Capone and his ongoing battle to help other Special Operations veterans access 5-MeO-DMT. All this media attention contributed to the mainstreaming of this compound in the last few years, despite its illegality.
These restrictions have hampered research into 5-MeO-DMT in the countries where it has been forbidden. But in countries like the Netherlands, multiple studies into 5-MeO-DMT are now underway.
As said, there is no indigenous ritual surrounding the use of 5-MeO-DMT, yet treatment centers using the toad’s poison have started to spring up incorporating rituals from other psychedelic cultures. These psychedelic sessions can set you back from $250 up to $8500.
This new popularity has not been good for the Sonoran Desert Toad itself, a risk voiced by Robert Anthony Villa, president of the Tucson herpetological society. Although the toad seems comfortable in human-made constructions like irrigation ditches, suburban yards and near water tanks on ranches – it is now often poached for psychedelic purposes, after which it is stressed out to produce its venom.
A solution for this animal cruelty could be a synthetic variant of the drug which would be preferable over one involving stressing out animals. That’s one of the reasons why Hamilton Morris included the synthesis process for 5-MeO-DMT in one of his episodes. The new edition of Bufo Alvarius: the psychedelic toad of the Sonoran Desert, also features Hamilton Morris’ synthesis of 5-MeO-DMT in a Mexican lab.
THE USER EXPERIENCE
When vaporized, a single deep inhalation of 5-MeO-DMT produces strong psychoactive effects within 15 seconds. After inhalation, the user usually experiences a warm sensation, euphoria, and strong visual and auditory hallucinations, due to 5-MeO-DMT’s high affinity for the 5-HT2A serotonin receptor subtype. The duration of these effects are comparable to those of DMT, lasting between 15 and 20 minutes. According to trip reports, at commonly-used doses, 5-MeO-DMT may possess the most complex and overwhelming effects of the classic psychedelic family.
Physical effects can include changes in perceived gravity, pupil dilation, muscle spasms, temperature regulation suppression, and feelings of loss of breath, but also an overwhelming intensity of physical and tactile sensations that can lead to the sensation of repeated, full-body orgasms.
Cognitive effects include distortion of space and time, amnesia, ego dissolution and auditory verbal hallucinations. Visual effects can include visual acuity enhancement, with drifting, color-shifting and morphing of complex geometrical patterns, but more often, reports mention visual suppression, where a blinding white light replaces all the visual complexity usually associated with hallucinogens. Much of this is often preceded by nausea, according to Drug Science UK.
An anonymous OPEN member described his 5-MeO-DMT experience for us as follows: “If LSD is a rollercoaster, 5-MeO-DMT is an intergalactic faster-than-light rocket that takes you to a wholly unrecognizable state of being. Landing back from a high-dose experience you are left with more questions than you came in with, but what an amazing ride it is.”
The combination of all these effects often results in transpersonal effects, during which the sense of identity of the individuals experiencing them extends beyond the personal level to humankind, nature and even the cosmos, which makes for the mystical quality of the experience. As mentioned earlier, 5-MeO-DMT also reliably induces ego dissolution, a phenomenon characterized by a complete change in normal, everyday, self-referential awareness.
So far, very little clinical research has been done on 5-MeO-DMT. The limited number of published studies suggest the compound might be safe and useful in a clinical context. If it turns out that 5-MeO-DMT does indeed have beneficial therapeutic effects, as anecdotal and early scientific evidence suggests, the promising aspects in terms of its practical use in a clinical context would be the duration of its effects.
The Beckley foundation has recently mentioned that MDMA or psilocybin-assisted therapy usually take up an entire working day for the therapist, which “poses a potential bottleneck to patient access in the future,” so a short-acting psychedelic like 5-MeO-DMT would help with both the clinical trial process and subsequent access to psychedelic therapy. As Michael Pollan mentioned in 2018: “a psychedelic therapist wants to be home for dinner too.”
Indeed, 15-20 minutes of medical and psychological supervision is a lot more manageable for clinical trials and therapists compared to the 3-6 hours that are necessary for psilocybin, or the 6-12 hours necessary for LSD. And this could eventually help in making the mystical experience more accessible.
LESS IS MORE?
The properties of 5-MeO-DMT lead to fascinating questions about its future potential utility in psychedelic-assisted therapy. But is the psychedelic indeed capable of the same types of transformations that have resulted from LSD, psilocybin and MDMA-assisted therapy? In other words: does the short-acting nature of 5-MeO-DMT come at the cost of its therapeutic benefit?
The answer to those questions is unclear as of yet. The potency of its effects suggests that the short-acting nature of the experience does not impede on its quality, but ongoing clinical trials could shed more light on them.
In many ways, ongoing research on 5-MeO-DMT will give us a window into the feasibility of short-acting psychedelic-assisted therapy, and might very well determine the fate of the emerging short-acting psychedelic field. ㅤ
There are many documentaries about psychedelics nowadays, but only so little time to watch them all, let alone figure out which one’s are worth it! That’s why we came up with a list of documentaries on psychedelics that you can watch, or binge, comfortably from your own living room. They’re selected for their scientific soundness, cultural insight, or overall high quality.
All of them are worthy study material before you join us at ICPR 2022 near Amsterdam – where some of the speakers are actually some of the people featured in these series and films. Their work is at the basis of this renaissance in psychedelic research and the new generation of documentaries that it has spawned. Enjoy our dose of inspiration.
If there is one documentary that hits all the marks when it comes to information about psychedelics, as well as other psychoactive drugs, while simultaneously delivering a high entertainment value, it is – without a doubt – Hamilton’s Pharmacopeia, of which there are now three seasons.
This documentary series is written, directed, and produced by Hamilton Morris, a journalist and scientific researcher who explores the history, chemistry, and social impact of various psychoactive substances across the globe.
Hamilton illustrates how ubiquitous psychedelic drugs are and goes out on a limb to try several of them himself – showcasing his dedication and genuine curiosity when it comes to studying the effects of these extraordinary substances. It is beyond the scope of this article to discuss the merits of every episode on its own, but we compiled a hit list of our favorite episodes shown at the end of this commentary. That’s right – more stuff to binge this coming summer! Just watching these will suffice for at least 8 hours of entertainment, where Hamilton Morris meets with underground chemists that illegally synthesized MDMA; travels to Huautla de Jimenez in Mexico to visit the family of the legendary curandera María Sabina’s to talk about psilocybin-containing mushrooms; smokes 5-MeO DMT in the Sonoran desert under supervision of a shaman; and talks with Amanda Feilding about how she helped to fund the very first neuro-imaging study of LSD. Be sure to absolutely check this series out!
Quote of the series
“It is so strange that these compounds exist. What is the purpose of any of this? 5-MeO-DMT? This? In a toad’s venom? And people may have only started using it 30 years ago? And it produces this peak experience of love? I can’t believe it! It is so amazing!” – Hamilton Morris
Our hitlist for best episodes:
Episode 4 – Magic Mushrooms in Mexico
Episode 6 – The Lazy Lizard School of Hedonism
Episode 1 – The Psychedelic Toad
Episode 2 – Peyote: The Divine Messenger
Episode 4 – Wizards of DMT
Episode 5 – Ketamine: Realms and Realities
Episode 6 – A Clandestine Chemist’s Tale
Episode 1 – Synthetic Toad Venom Machine
Episode 4 – Synthetic Ibogaine: Natural Tramadol
Episode 6 – UItra LSD
Descending the mountain (2021)
Filled with aesthetically pleasing images, jaw dropping cinematography, a great psychedelic soundtrack, and a pinch of neuroscience, Descending the Mountain excels at every front. The documentary includes renowned psychedelic researcher Prof. Dr. Franz Vollenweider and Zen master Vanja Palmers. Their mission? To set out to a monastery on top of mountain Rigi in Switzerland to conduct a novel experiment in which experienced meditators received psilocybin-containing mushrooms in a group setting for the first time in their life. This experiment was double-blind, where neither the researchers or the participants knew what dose they received. Some of the meditators received an active dose of psilocybin, whereas others were ‘unfortunate’ (in their words) and received a placebo. It is amazing, to say the least, how these experienced meditators were able to deepen their meditation due to psilocybin, even after thousands of hours of meditation practice. One individual was completely ecstatic from the beginning till the end and amazed by what he was experiencing. Others felt it to be a collective experience, rather than an individual one, as they were able to feel the energy in the room. Ultimately, placebo or no placebo, the group setting was conducive to the experience at the mountain.
Quote of the movie
“What can the mushrooms tell us today?” – Descending the Mountain
Halfway through the documentary, Prof. Dr. Vollenweider explains briefly how psychedelics work and that neuroscientific research of today has consistently demonstrated that they deactivate the Default Mode Network (DMN) – a key brain region involved in self-referential processing. With their experiment on Mount Rigi, they too found that the participants who received psilocybin were able to enter a deep(er) meditative state and showed less activity in the DMN when compared to the placebo group. Vollenweider explains how it: “makes you less focused on yourself because, in a way, you lose your ‘self’, and that this tends to make you focus more on others around you.” This dovetails neatly with the hypothesis that psychedelics are able to alter personality and political beliefs, something that the documentary explores briefly as well through asking significant questions as: “What can psychedelics do for society today? What will happen if great leaders take these substances and make us think about our place in the world?”
Michael Pollan’s How To Change Your Mind (2022)
Four years after the release of his book under the same name, Michael Pollan hit the big screen on Netflix with a documentary series: How to Change Your Mind. To say that his book had somewhat of an influence on the psychedelic renaissance is an understatement. Individuals even talk about a Pre-Pollan era and Post-Pollan era within psychedelic research. And now, with this new and cinematic tour du force, Pollan might continue to increase his reach by showcasing these tools to people all over the world sitting in their living room.
The documentary consists of a total of four episodes, each focusing on a specific psychedelic. The first episode focuses on the synthesis of LSD by Dr. Albert Hofmann in 1938, the research of its therapeutic use when treating alcoholism, and how it ultimately became a Schedule I substance – as it ended up on the streets through evangelist Timothy Leary and the CIA project MKUltra, that serendipitously turned on Ken Kesey. In the second episode, the viewer is brought to the world of psilocybin-containing mushrooms and features ICPR speakers William Richards, Paul Stamets, and Roland Griffiths. Here, Pollan discusses their historic use in religious settings, the introduction of the mushroom to the West, and how it is currently being researched for various debilitating psychiatric disorders, such as depression, end-of-life anxiety, obsessive compulsive disorder, and cluster headaches. The third episode features ICPR speaker Rick Doblin and is all about the therapeutic use of MDMA for the treatment of post-traumatic stress disorder. Pollan interviews Ann Shulgin, the wife of renowned chemist Alexander Shulgin, – who recently passed away – about her personal experiences with MDMA and how it ended up becoming illegal through the so-called “Second Summer of Love”’ during the 1980s. Finally, Pollan takes a deep dive into the ceremonial use of the peyote cactus by indigineous Americans that are part of the Native American Church.
The documentary provides a solid starting point for anyone who is new to the world of psychedelics and likes to be prepared for what we have to offer at ICPR. It presents some of the most recently conducted preliminary research studies and their implications. Contrary to contemporary media headlines, it is refreshing to see that Pollan remains centered throughout the entire documentary with regards to the therapeutic potential of psychedelics and messages to the audience to do the same. This is a welcoming message that is to be embraced if we do not wish to repeat past mistakes.
The Psychedelic Drug Trial (2021)
Major depressive disorder (MDD) is the leading cause of disability in the West, says ICPR speaker and Professor of Neuropsychopharmacology David Nutt. Across the globe, MDD is estimated to affect 350 million individuals and is responsible for more ‘years lost’ than any other psychiatric condition. Psychiatry has been desperate for novel treatments.
One of the current mainstays of treatment in psychiatry is escitalopram, a selective serotonin reuptake inhibitor (SSRI), better known under its brand name Lexapro. This psychotropic drug increases the amount of the neurotransmitter serotonin in the brain and has been proven by earlier clinical research to be effective and well tolerated in the treatment of MDD. But this begs the question: “How does escitalopram, or Lexapro, compare to psilocybin when used for treating depression?” This is what the research team in the Psychedelic Drug Trial set out to do.
Quote of the movie
“If psychedelics can change the world, let’s put it to the test.” – Dr. Robin Carhart-Harris
The documentary presents an extensive in-depth look into how the study was conducted by displaying easy-to-comprehend visuals and various infographics. The documentary really shines here and you immediately get a clear understanding of what the study design looked like. It also exemplifies how current psychedelic therapy operates and provides the three important stages involved, which includes: preparation before the dosing session, the psychedelic dosing session itself, and the integration that follows.
What is more, you get to know some of the recruited participants who were told that they are randomized to one of two conditions. They will either receive 1) psilocybin or 2) escitalopram, not both. Almost all of the participants have been on antidepressants for decades and suffer from various side effects, including weight gain, sleep paralysis, and a flat affect. The psilocybin trial represents a “lifeline” according to some of the participants – a viable alternative to their current situation of “concentrating on staying alive” and trying “to live with this joylessness.” One participant is at the end of her ropes and tells the camera: “I would probably end my life if I didn’t go [through the trial].”
Soon after this introduction, we are taken into a living room like environment where the psychedelic therapy session took place. Participants at this point are talking about their extraordinary experiences and the various symbols they encountered during their psychedelic dosing session. The documentary really excels here due to its slow presentation of recorded monologues and by displaying aesthetic visuals that are aimed at encapsulating the participants’ experience while on psilocybin. One participant talks about one of her peak experiences where she found herself at the roots of a tree and: “was connecting with everything up there. The thing I really felt most … was a joy. Joy like I’d never experienced. It is really, really powerful stuff.”
The documentary would not have been complete without a brief presentation by ICPR speaker David Nutt on how psychedelics such as psilocybin work in the brain and how they differ from escitalopram. Nutt first explains that antidepressants as escitalopram take about an average of six weeks to work and do so primarily in the limbic system, the emotional center of the brain that is overactive in depression: “It dampens the system and you become incubated against stress, which is good, but you also become incubated by everything else.” Psilocybin, on the other hand, works differently by targeting the serotonin 2A receptor, which are widely prevalent in the neocortex. Psilocybin also works through the disruption of the Default Mode Network that Franz Vollenweider similarly talked about in Descending the Mountain. Both professor Nutt and lead researcher of the study Dr. Robin Carhart-Harris believe that psilocybin works better and faster than escitalopram.
The results of this landmark study have been published in the highly esteemed The New England Journal of Medicine. Their conclusion? Both psilocybin and escitalopram work in the treatment of depression. But when taking into account secondary outcome measurements such as suicidality, psilocybin looks better than escitalopram. More recent neuroscientific findings of the current study have been published as well, which looked at how psilocybin affects the brain and how it differs from antidepressants. All in all, more research is needed as we venture forth in our pursuit to help people alleviate their depressive symptoms.
Journeys to the Edge of Consciousness (2019)
Journeys to the Edge of Consciousness is a unique animated film that chronicles the very first psychedelic experiences of Timothy Leary, Aldous Huxley, and Alan Watts. The film is interspersed with commentaries on these historical and influential events by ICPR speakers Rick Doblin and Amanda Feilding, and various other researchers within the psychedelic field.
The Dropout Drug
We first witness how Timothy Leary got involved with LSD through meeting Michael Hollingshead, a British researcher who studied psychedelics at Harvard University in the mid twentieth century. Leary’s first LSD trip was: “the most extraordinary experience of his life.” Yet to my surprise, he also felt a terrible sense of loss after this trip, as he did not know what to do with these new insights: “Once you see how it is all composed, it is hard to get back to the game.” This experience demonstrates that even psychedelic evangelists as Leary, a very intelligent man who was probably one of the most well-known proponents of psychedelics, would have benefitted from the importance of integration. The world would have been a very different place indeed if Leary underwent this integral part following psychedelic use. Instead, he decided to leave the highly esteemed university of Harvard and famously told students to: “tune in, turn off, and drop out.” This resulted in the then U.S. president Richard Nixon to call him the most dangerous man of America.
Commentaries from other experts on Leary’s psychedelic experience are very informative. They exemplify how psychedelics are able to lift the veil of ordinary reality, which can either facilitate, or in the case of Leary, diminish our well-being, because we see through the illusion, i.e., the play of life. You’re catapulted out of your ego and you can spend years of life making sense of it all, which might have happened to Timothy Leary according to Dr. Tim Read. Yet, Dr .Gabor Maté states that bad trips can also be interpreted differently: “Yes, a trip can be challenging, but what you need is proper integration. This is the work of healing. The psychedelic experience and its healing properties were lost during the 60s because there was a lack of intention.
The Doors of Perception
Next we get a close look at Aldous Huxley’s famous psychedelic experience with mescaline that led him to write his famous work The Doors of Perception: and Heaven and Hell. During his experience, he realizes that “this is how one ought to see” and that the ordinary mode of consciousness is but one form of consciousness. Huxley talks about the suchness of things while on mescaline and develops his metaphor of the reducing valve of the mind, which limits our view of reality and who we really are.
According to ICPR speaker Rick Doblin, Huxley’s insights demonstrate where we should put our meaning: “not on consuming, but on something deeper.” Other psychedelic researchers talk about how people ‘wake up’ after their psychedelic experience, including alterations of the perception of the self and various changes in their value system.
The Joyous Cosmology
Finally, we witness Alan Watts taking modest amounts of LSD while in California and who decided to casually go for a stroll. His first undertaking was to listen to a priest in a church during a mass. He witnesses how people are putting on an “act of a person”, which is one of the key phrases of Alan Watts. His feeling of self became no longer confined to the insides of his skin as he felt connected to everything: “my individual of being seems to grow out to the rest of the universe.” The animated re-enactment of Alan Watts’ psychedelic experience gives us a glimpse into how psychedelics helped shape his philosophy.
Quote of the movie
“Come off it shiva, you rascal, who do you think you’re kidding!? It’s a great act, but you’re not fooling me!” – Alan Watts
Neurons to Nirvana (2013)
Neurons to Nirvana is filled with numerous psychedelic researchers who will be attending ICPR, including Rick Doblin, William Richards, David Nutt, Roland Griffiths, and Amanda Feilding. The film gives a brief overview of classic psychedelics, including psilocybin, ayahuasca, and LSD. In addition, the entactogen MDMA is briefly discussed plus the medicinal benefits of other (non-)psychoactive substances as marijuana and cannabidiol.
The film starts with the serendipitous event of how psychedelics helped shape modern psychiatry and neuroscience. LSD, as it turns out, has a very similar structure to serotonin that led to the discovery of the serotonin neurotransmitter system. As a result, psychiatry started including brain chemistry into the disease process, whereas before all the accountability went to either the individual or the environment.
It was a revolutionary period for which the famous psychedelic researcher Ralph Metzner said that discovering psychedelics: “was like discovering another continent, like Marco Polo.” Both ICPR speakers Rick Doblin and David Nichols mention how psychedelics are able to occasion a mystical experience and how this helps experience the world as one as it breaks down certain barriers. Roland Griffiths adds: “there is this quantum change during a psychedelic experience – it belongs among the most spiritual and personal meaningful experiences of peoples’ lives.”
Quote of the movie
“What is being purged actually, is psychological contents that you’ve been holding onto. You’re purging anger, you’re purging pain, you’re purging some false story about the self.” –Gabor Maté M.D.
A great feature of the film that is worth mentioning here is that it shows the capability of human individuals being able to change their beliefs when it comes to esoteric substances such as psychedelic drugs. This is illustrated when Dr. Sanjay Gupta appears on the big screen, an Emmy award-winning doctor for his show on CNN who used to vehemently oppose the use of marijuana. This was until the year 2009, as the scientific evidence started accumulating and Dr. Gupta discovered that it was used for thousands of years. He also found out that before there was a strong focus on the negative. Most importantly, Dr. Sanjay Gupta was illuminated by the benefits of marijuana: “the science is there!”. This clearly demonstrates how scientific evidence can pave the way for reconstructing our beliefs about psychedelics. Hopefully, other physicians, researchers, and politicians will follow suit.
The Last Shaman (2016)
The Last Shaman follows young adult James who is battling with crippling bouts of depression ever since he went to university. He is desperate for a way out as he tried doing everything according to the book on both a medical and personal level. In general, this involved seeing several psychiatrists, taking antidepressants, and picking up a regular meditation practice. Despite his arduous efforts, he remains depressed. At the end of his ropes, he travels to Peru to meet several shamans that might be able to help him.
The documentary is not for the faint of heart and can be very shocking in demonstrating how debilitating depression can be. James suffers from extreme anhedonia, which refers to the inability to feel pleasure: “I see a beautiful woman or a sunset and I feel nothing.” He explains how his depression affects him in front of the camera and this raw footage makes the documentary feel very personal, but also heart-wrenching to watch at times, as his eyes are filled with tears and his voice is featured by a tremendous amount of frustration and despair. He ends up meeting various shamans in different regions and engages in multiple ceremonies to finally reach salvation.
James’ journey ends deep within the forest at the Shipibo community – a place that resembles just the right amount of authenticity he is looking for. Shamans here do the practice because it is a calling, whereas the business side of things are left aside. James ventures deeper into his emotions, revealing one layer from another layer, and becomes a passionate ascetic. He maintains a very strict diet and stays in isolation for a total of four months, eating nothing but fish and rice and smoking the Mapacho tobacco. This experience ripped him of all attachments of his previous life. He believes he: “no longer has an inferiority complex anymore” and feels no more anger towards his father.
Quote of the movie
“I’m here to be a very small part of something much larger than myself, and that is extremely liberating” – James
Iboga Nights (2014)
David Graham, the director and producer of the renowned and brutal documentary Detox or Die, returns to the big screen with Iboga Nights. His first documentary consists of his mission to cure himself of his opiate addiction through ibogaine – a psychedelic substance with dissociative properties that is extracted from the root bark of the iboga tree (Tabernanthe iboga). His film became a resounding success that resulted in an explosion of media, press and news articles. This inspired other addicts to follow in his footsteps by taking up ibogaine and get rid of their opiate addiction once and for all. Iboga Nights follows several of David’s ‘apprentices’.
Iboga Nights is basically split up in three sections. The first is where we are introduced to a shaman from the Netherlands who has treated an approximate of 1,000 patients with ibogaine for their opiate addiction. To my surprise, there was almost no guidance involved; the shaman plainly administers the drug and then lets ibogaine take its course while the participants stay in their assigned bedroom. It was quite astounding to see how most turned out fine and even managed to go through the treatment without experiencing any withdrawal symptoms. However, the documentary quickly takes a dark turn that illustrates the significance of taking into account proper screening and guidance. For instance, one participant stopped breathing due to an underlying heart condition and was taken away to the hospital. Ibogaine is known for slowing down the heart rate that might be fatal. Fortunately, he survived. But another participant left the house and was hit by a truck. David wanted to end the film right there: “how can I be a spokesperson for something so dangerous?”
After these horrific events, David meets up with Dr. Ben Sessa and Dr. Jeffrey Kamlet to talk about psychedelic research and ibogaine. Both share a pessimistic view with regards to pharmaceutical companies and how they supposedly “treat” patients, as they make billions of dollars on pain pills that generally require daily use. Naturally, they scoff at this predicament: “Why do they want ibogaine that requires one dose to cure people. That does not make money?”
Quote of the movie
“Does it not feel weird to have had that life, among such affluence, and now be living in a hotel shooting up crack and heroin and taking up methadone?” – David Graham
Fortunately, the documentary also contains the amazing journey of Sid who was severely addicted to morphine and completely transformed through his ibogaine treatment. He was sexually abused by an older man when he was only 11 years old. During his session, both David and Sid are serious by taking screening and guidance into account. For example, they check if Sid is allergic to ibogaine and during the ibogaine treatment will frequently measure his heart rate and blood pressure. It is astounding to see that even after fivedays of taking ibogaine and no morphine at all, any symptoms of withdrawal are virtually non-existent. But Sid knows that the real treatment starts after ibogaine, which requires integration and (simply) staying off the drug. Several months later David returns to visit Sid and witnesses another person in front of him. He has become a completely transformed person and has much more energy and life in his eyes. Sid talks briefly about his ibogaine experience: “I did not have many visions or anything, but it took my physical dependence away.” The urge, or craving to use drugs, is totally gone. Sid simply does not: “want to do that anymore.”
From Shock to Awe (2018)
The documentary From Shock to Awe chronicles the transformative journey of two military veterans that suffer from severe post-traumatic stress disorder (PTSD). Because of this, everything they encounter on a day-to-day basis within their natural environment signals danger. With their bodies still in war and drugged by an arsenal of pharmaceuticals, they turn to the Amazonian brew ayahuasca as a last resort.
Quote of the movie
“I left the warrior behind and let the sunlight take the steering wheel now.”
Both veterans are filmed during their ayahuasca retreat that consisted of four ceremonies, two during the day and two at night. During all dosing sessions, we see grueling raw footage of both veterans struggling with their deep-rooted trauma. The entire retreat resembles the archetypal hero’s journey of diving into the unconscious and coming back into the real world reborn. Through ayahuasca, they realized that all life is sacred, which is: “the exact opposite of what is learned during military training.” Their perception of everyday ‘signals as danger’ changed after only one weekend, as they heard a gunshot in the woods, locked eyes, and started laughing immediately. The PTSD response was no more.
If you’re interested in psychedelics, then you might have heard of the work of Robin Carhart-Harris, who conducted much of the most relevant research in the world of psychedelics together with his team at Imperial College in London.
In this look back at ICPR 2016 we will highlight the talk he held about his team’s trials with psychedelics-assisted psychotherapy, where he also showed some beautiful visuals of his team’s brain research, which happened to become some of the most famous psychedelic brain imagery known on the internet.
Like our upcoming ICPR 2022 near Amsterdam, the edition in 2016 strove to bring together as many relevant studies from psychedelics as possible, and Carhart-Harris’ talk was most certainly a highlight. His research has been cited often and his talk was one of the best-watched from that year’s ICPR on our Youtube channel.
In his talk, Carhart-Harris talks about the results of his research – that psychedelics can cause a rise in cognitive flexibility, neuroplasticity, creative thinking, imaginative suggestibility, emotional lability, positive moods, and optimism.
He also touches on the idea of depressive realism, a trend he has seen in patients suffering from depression. He describes their depression as a “sort of delusion”, where his patients “don’t see the world as it really is. There is this really quite evident pessimism bias, that is normalised post-treatment with psilocybin.”
A testimony of one of the participants is featured in the talk:
26:35 — ‘Although it’s early days yet, the results are amazing. I feel more confident and calm than I have in such a long time. My outlook has changed significantly too, I’m more aware that it’s pointless to get wrapped up in endless negativity. I also feel as if I’ve seen a much clearer picture. [Now] I can enjoy things the way I used to, without the cynicism, without the oppression. At its most basic. I feel like I used to before the depression.”
One way to go about investigating psychedelics is by making fMRI brain scans. These scans are made of healthy and depressed individuals before, during and after a psychedelic experience. This way, the brain can be observed for changes.
Through these scans, the team got insights into the inner workings of the brain during psychedelic trips, and how they correlate with described experiences of volunteers, like ego-death. This is a type of experience in which people who are under the influence of psychedelics describe a certain loss of self, and a deeper connection with the wider universe or nature.
Carhart’s studies have highlighted that the Default Brain Network may be connected with our sense of self – our ego – and that the lower activity of this network during a psychedelic session may be associated with the occurrence of ego-death.
12:40 — “We see quite reliably a relationship between the magnitude of the disintegration and the default brain network. [..] The greater the disintegration of the default mode network, the greater our volunteers’ ratings of ego-dissolution. ”
During the psychedelic experience induced with psilocybin, the parts of the brain associated with the Default Brain Network show a drastic reduction in activity, often creating the experience of ego-death. The compulsive activity of the Default Brain Network also has been associated with patients that scored higher in depression ratings.
The Default Brain Network and the Self
Robin Carhart-Harris’s argument is that the Default Brain Network may be the source of what most adult people call the ‘ego’. This network is known as the Default Mode Network because, during our daily lives, this brain network becomes more active when we are idle.
The Default Mode is actually a really important part of our mental stability. This network is responsible for keeping our routines in check, making sure that our pending matters stay afloat, and that we’re not overlooking anything.
The mental activity generated by the Default Mode Network is usually stable and consistent day after day. This daily consistency in addition to the fact the DMN is the ‘standard’ mental voice, may contribute to the illusion that the Default Mode Network is the self.
12:58 — [The Default Brain Network is]: “Arguably the best candidate we have for the neural substrates of the self, or the ego, or our identity and personality.” – Robert Carhart-Harris
By analyzing the brains of participants who consumed psilocybin, Carhart’s team noticed that there was a process of renewal happening within the structure of the brain, almost like a general mind reset. This process of rebirth has been reported many times by psychedelic subjects.
17:50 — “We can think of the mind or the brain is reset in the same way that you can think of a computer is malfunctioning and throwing up an error message and you are wondering what you can do. And then you press the reset button and it comes back working nice and smooth as it should.”
In more recent years, Carhart-Harris has worked on building a more unified model of the workings of psychedelics in the brain. He founded the Psychedelic Research Group at Imperial College in London and focuses on the action of psychedelic drugs in the brain, and their clinical utility as aides to psychotherapy, with a particular focus on depression. He still studies the brain effects of LSD, psilocybin (magic mushrooms), and MDMA.
Robin Carhart-Harris will not be speaking at ICPR 2022, but his colleague and the new head of the Psychedelic Research Group at Imperial College will: David Nutt.
Notes about the author: Alexandre Perrella is a writer for Cabbanis!
A Really Good Day : How Microdosing Made a Mega Difference in My Mood, My Marriage and My Life. Ayelet Waldman. Little, Brown Book Group. ISBN: 978-1472152893
A first-hand account of microdosing and its positive effects. Waldman charts her experience over the course of a month and looks into the newest research and policies governing LSD. This book will be interesting for anyone curious about how microdosing LSD can affect daily living.
How to Change Your Mind: The New Science of Psychedelics. Michael Pollan. The Penguin Press. ISBN: 9781594204227
A highly accessible and enjoyable read through the history of psychedelic research and use starting in the 1960s up to the present day. Pollan applies his quintessential experiential journalism approach to various psychedelic substances – starting off hesitantly, as he weaves through the research and has several personal experiences, Pollan becomes a measured advocate for the power psychedelics have to change our minds and more.
Background: Ketamine’s potent and rapid antidepressant properties have shown great promise to treat severe forms of major depressive disorder (MDD). A recently hypothesized antidepressant mechanism of action of ketamine is the inhibition of N-methyl-D-aspartate receptor-dependent bursting activity of the habenula (Hb), a small brain structure that modulates reward and affective states.
Methods: Resting-state functional magnetic resonance imaging was conducted in 35 patients with MDD at baseline and 24 hours following treatment with i.v. ketamine. A seed-to-voxel functional connectivity (FC) analysis was performed with the Hb as a seed-of-interest. Pre-post changes in FC and the associations between changes in FC of the Hb and depressive symptom severity were examined.
Results: A reduction in Montgomery-Åsberg Depression Rating Scale scores from baseline to 24 hours after ketamine infusion was associated with increased FC between the right Hb and a cluster in the right frontal pole (t = 4.65, P = .03, false discovery rate [FDR]-corrected). A reduction in Quick Inventory of Depressive Symptomatology-Self Report score following ketamine was associated with increased FC between the right Hb and clusters in the right occipital pole (t = 5.18, P < .0001, FDR-corrected), right temporal pole (t = 4.97, P < .0001, FDR-corrected), right parahippocampal gyrus (t = 5.80, P = .001, FDR-corrected), and left lateral occipital cortex (t = 4.73, P = .03, FDR-corrected). Given the small size of the Hb, it is possible that peri-habenular regions contributed to the results.
Conclusions: These preliminary results suggest that the Hb might be involved in ketamine’s antidepressant action in patients with MDD, although these findings are limited by the lack of a control group.
Rivas-Grajales, A. M., Salas, R., Robinson, M. E., Qi, K., Murrough, J. W., & Mathew, S. J. (2021). Habenula Connectivity and Intravenous Ketamine in Treatment-Resistant Depression. The international journal of neuropsychopharmacology, 24(5), 383–391. https://doi.org/10.1093/ijnp/pyaa089
Importance: Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression.
Objective: To investigate the effect of psilocybin therapy in patients with MDD.
Design, setting, and participants: This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population).
Interventions: Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay.
Main outcomes and measures: The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR).
Results: Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score).
Conclusions and relevance: Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression.
Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA psychiatry, 78(5), 481–489. https://doi.org/10.1001/jamapsychiatry.2020.3285
Depression is a widespread and devastating mental illness and the search for rapid-acting antidepressants remains critical. There is now exciting evidence that the psychedelic compound psilocybin produces not only powerful alterations of consciousness, but also rapid and persistent antidepressant effects. How psilocybin exerts its therapeutic actions is not known, but it is widely presumed that these actions require altered consciousness, which is known to be dependent on serotonin 2A receptor (5-HT2AR) activation. This hypothesis has never been tested, however. We therefore asked whether psilocybin would exert antidepressant-like responses in mice and, if so, whether these responses required 5-HT2AR activation. Using chronically stressed male mice, we observed that a single injection of psilocybin reversed anhedonic responses assessed with the sucrose preference and female urine preference tests. The antianhedonic response to psilocybin was accompanied by a strengthening of excitatory synapses in the hippocampus-a characteristic of traditional and fast-acting antidepressants. Neither behavioral nor electrophysiological responses to psilocybin were prevented by pretreatment with the 5-HT2A/2C antagonist ketanserin, despite positive evidence of ketanserin’s efficacy. We conclude that psilocybin’s mechanism of antidepressant action can be studied in animal models and suggest that altered perception may not be required for its antidepressant effects. We further suggest that a 5-HT2AR-independent restoration of synaptic strength in cortico-mesolimbic reward circuits may contribute to its antidepressant action. The possibility of combining psychedelic compounds and a 5-HT2AR antagonist offers a potential means to increase their acceptance and clinical utility and should be studied in human depression.
Hesselgrave, N., Troppoli, T. A., Wulff, A. B., Cole, A. B., & Thompson, S. M. (2021). Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. Proceedings of the National Academy of Sciences of the United States of America, 118(17), e2022489118. https://doi.org/10.1073/pnas.2022489118
Background: Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking.
Methods: In a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a selective serotonin-reuptake inhibitor, over a 6-week period. Patients were assigned in a 1:1 ratio to receive two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo (psilocybin group) or two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram (escitalopram group); all the patients received psychological support. The primary outcome was the change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16; scores range from 0 to 27, with higher scores indicating greater depression) at week 6. There were 16 secondary outcomes, including QIDS-SR-16 response (defined as a reduction in score of >50%) and QIDS-SR-16 remission (defined as a score of ≤5) at week 6.
Results: A total of 59 patients were enrolled; 30 were assigned to the psilocybin group and 29 to the escitalopram group. The mean scores on the QIDS-SR-16 at baseline were 14.5 in the psilocybin group and 16.4 in the escitalopram group. The mean (±SE) changes in the scores from baseline to week 6 were -8.0±1.0 points in the psilocybin group and -6.0±1.0 in the escitalopram group, for a between-group difference of 2.0 points (95% confidence interval [CI], -5.0 to 0.9) (P = 0.17). A QIDS-SR-16 response occurred in 70% of the patients in the psilocybin group and in 48% of those in the escitalopram group, for a between-group difference of 22 percentage points (95% CI, -3 to 48); QIDS-SR-16 remission occurred in 57% and 28%, respectively, for a between-group difference of 28 percentage points (95% CI, 2 to 54). Other secondary outcomes generally favored psilocybin over escitalopram, but the analyses were not corrected for multiple comparisons. The incidence of adverse events was similar in the trial groups.
Conclusions: On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons. Larger and longer trials are required to compare psilocybin with established antidepressants.
Carhart-Harris, R., Giribaldi, B., Watts, R., Baker-Jones, M., Murphy-Beiner, A., Murphy, R., Martell, J., Blemings, A., Erritzoe, D., & Nutt, D. J. (2021). Trial of Psilocybin versus Escitalopram for Depression. The New England journal of medicine, 384(15), 1402–1411. https://doi.org/10.1056/NEJMoa2032994