Can Psychedelics Provide Relief for Autistic Individuals?

By Jasmine Virdi

There is a growing community of neurodivergent and autistic folks using psychedelics, but how does it help them? We took a deep look at the growing body of research and anecdotes to find out.

Current estimates have it that between 1-2% of the world’s population is autistic. In addition to higher levels of social anxiety, depression, and ADHD, autistic individuals meet unique challenges as they seek effective therapeutic treatment methods available to them; psychedelic-assisted therapy is now seen as an attractive alternative for this often sidelined and marginalized population.

There are promising signs that indicate psychedelics could help autistic individuals manage social anxiety, recover from trauma, reduce depression and anxiety, as well as work through the unique hurdles on their path. However it may be the case that for people with lower-functioning capabilities, psychedelics might not have nearly the same effect. Despite innumerable anecdotal reports from individuals who have benefited from psychedelics in a multitude of ways, there is still a significant lack of research regarding how psychedelics could be useful for those with Autism Spectrum Disorder (ASD) diagnoses.

What Is Autism?

Before delving into how psychedelics can be helpful for autistic individuals, it is first important to understand what autism actually is. Defining it can be tricky because there is still no agreed upon mechanistic, neurological basis for the condition. Despite this, there is research to suggest that neurodivergent brains exhibit higher levels of functional connectivity, believed to contribute to the intense sensitivity to sensory input and sense of overwhelm that autistic individuals experience in certain environments.

Moving away from stereotyped definitions of ASD as a social impairment, many believe sensory processing issues to be at the core of autism. Typically, autistic individuals have hypersensitivity or hyposensitivity to sounds, touch, and lights, among other stimuli. As such, autism is characterized by unique, atypical ways of interacting with and processing information. Even so, everyone inherits their own unique neurocognitive version of autism, and although autistic individuals share basic neurological features as well as a common diagnosis, behaviors and traits can vary dramatically from person-to-person.

The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), defines autism in terms of deficits in social communication and interaction, and repetitive patterns of behavior and/or interests that are present (but not always noticed) in the early developmental period. However, such definitions of autism have led to false stereotypes. Looking at autism through this lens of pathology, scientists have long sought out a “cure.” However, pathologizing autism in this way is both harmful and damaging.

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In his book, NeuroTribes: The Legacy of Autism and the Future of Neurodiversity, Steve Silberman reflects historically how the controversial roots in early psychology have led to widespread misunderstanding of what autism is, and how our societal failure to embrace neurodiversity has been inherently damaging. Further, Silberman speaks to the fact that embracing neurodiversity can benefit our existence in that neurodivergent individuals are often endowed with unique, specialized ways of seeing the world.

Within psychiatry, autism is classified as a “disorder,” however, in recent years this conception is being actively challenged by advocates of neurodiversity. When defining autism, Nick Walker, queer autistic scholar and Associate Professor of Somatic Psychology at California Institute of Integral Studies, makes a distinction between what he refers to as the “neurodiversity paradigm” and the “pathology paradigm.” Walker describes the neurodiversity paradigm as a perspective that “recognizes neurodiversity as a naturally-occurring form of human diversity.”

Comparatively, autistics are marginalized through the pathology paradigm, which rests on the assumption that there is only one “right” way to be and that if you stray from the dominant conception of normal there is something wrong with you. He adds, “In the context of a society designed around the sensory, cognitive, developmental, and social needs of non-autistic individuals, autistic individuals are almost always disabled to some degree.”

Although certain features of autism can be disabling, many of the challenges that autistics face aren’t necessarily related to their diagnosis, but rather, arise from the way in which society treats those who don’t fit the mold of  “normal.” Many autistic individuals grow up feeling that their way of inhabiting the world is flawed because they do not conform to certain, socially-conditioned ways of being.

Difficulty meeting certain social expectations often ends in social rejection, stifling autistic individuals’ ability to interact with others. Accordingly, autism is often misrepresented as a social deficit by those who are ignorant of the fact that social difficulties in autistic populations are simply by-products of the heightened intensity of their sensory experience. Through the lens of neurodivergence, autism is a neurotype, and labelling it as a “disorder” reflects a value judgement more than anything else.

Looking Into the Research on Psychedelics and Autism

In the early 1960s, when LSD was beginning to be used experimentally in research and psychotherapy, a series of controversial studies were published around treating young children who were believed to have severe forms of autism and childhood-onset schizophrenia (COS) with LSD. Due to misconceptions surrounding autism, it was previously thought to be closely related to juvenile schizophrenia.

The driving justification for experimenting with a powerful psychoactive substance on children was that all other treatment methods had previously failed. Scientists gave a total of 91 children, aged between six and ten, LSD at differing dosage levels and fluctuating frequencies of administration with different treatment schedules, finding that the most effective results were produced at doses of 100 micrograms given daily or weekly for extended periods of time. Undoubtedly, such a study would be unacceptable to an ethics committee today.

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Positive outcomes were reported with the use of LSD, with researchers summarizing the most consistent effects as improved speech, increased emotional responsiveness, frequent laughter, positive mood, and a decrease of compulsive behavior. In one such example, researchers observed that the children “appeared flushed, bright eyed, and unusually interested in the environment.” Despite these promising results, positive outcomes were largely dismissed due to the fact that the study designs were greatly flawed, and were not as scientifically rigorous as those of today’s standards because they lacked experimental controls.

Since this early research, there have been very few studies that have looked into the clinical uses of psychedelics for autistic populations. One of the first to do so was clinical psychologist and MDMA researcher Alicia Danforth’s 2013 doctoral dissertation, which explored how autistic adults experience the subjective effects of MDMA. Danforth looked at qualitative data collected via online surveys from 100 autistic individuals who had taken MDMA alongside a comparison group of 50 autistic individuals who were MDMA naïve.

MDMA is sometimes referred to as an “empathogen” or “entactogen” because it is a substance that has the ability to facilitate experiences of increased empathy, oneness, emotional connectivity, and emotional openness. In part, MDMA is able to do this because it encourages the release of oxytocin, sometimes referred to as “the love hormone,” which is associated with social connection and enhancing responses to positive emotions while decreasing the ability to perceive negative facial cues.

The group who had taken MDMA reported sustained benefits such as improvement in social anxiety and healing from trauma. Most notably after MDMA use, 91% of participants reported increased feelings of empathy and social connectedness, while 86% felt that communication came more easily with the effects lasting two years or longer for 15% of individuals.

Building on the positive trends identified in her dissertation, in 2016 Danforth published a paper detailing the rationale behind and protocol for a pilot study using MDMA-assisted therapy to treat social anxiety in autistic adults. In 2018, Danforth and her team conducted the first randomized, double-blind, placebo-controlled experiment with psychedelics and autistic adults.

Broadly speaking, social anxiety is characterized by a heightened fear of what others think about you, feeling an intensified fear of scrutiny alongside the avoidance of social interactions. Research has shown that social anxiety commonly co-occurs with ASD, and part of Danforth’s rationale behind the study was to explore MDMA as a treatment modality for individuals with an increased need.

One of the principal aims of the study was to explore the safety of MDMA-assisted psychotherapy for reduction of social fear and avoidance for individuals with ASD, finding no evidence of harm to participants. Although the study was small in size, recruiting only 12 participants, results were promising. Participants took part in two full-day sessions in which they were either given MDMA or a placebo. The study used the Liebowitz Social Anxiety Scale to measure changes in social anxiety. Subjects who received MDMA showed a significantly greater reduction in social anxiety than the placebo group. Reductions in social anxiety symptoms were long-lasting, still holding true at a 6-month follow-up.

In her work, Danforth is careful to emphasize the fact that MDMA and other psychedelics do not “cure” autism, rather when used in a psychotherapeutic setting, they can help to alleviate social anxiety and manage other concomitant issues prevalent in autistic populations.

Reflecting on the study, Danforth shared that there were substantial recruitment delays. As anxiety and depression are both common in autistic adults, many participants were ruled out because they were using conventional psychiatric medications such as SSRIs. In addition, many of these adults were often unemployed and living in social isolation, less likely to have access to information about the study.

Beyond this small study, Danforth also created guidelines to psychedelic practitioners working with neurodivergent individuals on how to be mindful of surroundings so as to create an “autism-friendly” treatment space, such as paying careful attention to lighting and taking extra measures to minimize noise. 

Beyond the scope of autism, there is a growing body of research that has sought to examine how psychedelics affect social behaviour more generally. A 2020 study done by a team of researchers from McGill University examined the effect of LSD on social behavior in mice, whilst measuring their brain activity.

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Under the influence of low doses of LSD, the mice became notably more social and friendly towards unfamiliar mice. While it was already known that LSD activates serotonin 5-HT2A receptors, this study illuminated that LSD’s activation of the 2A receptors also triggered a cascade activation of the AMPA receptor and the protein complex mTORC1, working together to encourage social interaction. This is important because dysregulation of mTORC1 has been linked to autism and social anxiety disorders more generally.

Obviously, behavior and brain function in mice cannot directly be translated to that in humans, however, understanding the foundational mechanism of LSD’s prosocial behavioral effects opens up the door for future research. It also advances the understanding of how the substance could be useful to autistic populations, as well as those that suffer from general social anxiety.

An earlier study conducted in 2013 also showed that both psilocybin and ketamine altered the way that the brain responds to fearful faces. People under the influence of these two psychedelics were less able to identify negative expressions when presented with images of people with angry or upset expressions.

In the same vein, a 2010 study done with MDMA demonstrated that the substance reduced people’s accuracy in distinguishing negative facial cues. Not only does MDMA enhance emotional openness and connectivity, it also impairs the capacity to notice negative emotions in others’ facial expressions. Similarly, LSD has been shown to have an effect on emotional processing, enhancing feelings of trust, closeness to others, and emotional empathy, while weakening the ability to detect sad and fearful facial expressions.

In addition, psilocybin, LSD, and MDMA, all work to reduce the activity of the amygdala, a brain region that is associated with emotional processing and stress response. Brain imaging studies with autistic individuals have shown that the amygdala is differentially activated when presented with anxiety-inducing stimuli compared to the general population.

Psychedelics’ ability to enhance states of social connection and empathy joined with their simultaneous capacity to diminish the detection of negative facial expressions make them a promising therapeutic modality for those that suffer with social anxiety disorders, including autistic individuals.

Even though research into psychedelics and autism is still very limited, we can still draw much insight from psychedelic research into non-autistic individuals and the body of anecdotal evidence that is growing quickly as more and more neurodivergent people share their healing stories.

Beyond Social Anxiety: Navigating Neurodivergence with Psychedelics

For Aaron Orsini, author of Autism on Acid: How LSD Helped Me Understand, Navigate, Alter & Appreciate My Autistic Perceptions, editor of the new anthology Autistic Psychedelic: The Self-Reported Benefits & Challenges of Experiencing LSD, MDMA, Psilocybin & Other Psychedelics As Told By Neurodivergent Adults navigating ADHD, Alexithymia, Anxiety, Asperger’s, Autism, Depression, PTSD, OCD & Other Conditions, and co-founder of the online community for neurodivergent individuals, Autistic Psychedelic, experimenting with LSD led him to understand and appreciate his autism, allowing him to “bridge the neurotypical divide.” 

Aaron Orsini’s new book, Autistic Psychedelic, is an anthology of self reported benefits and challenges of neurodivergent folk exploring psychedelics

The altered state produced by psychedelics helped Orsini better understand how he was prioritizing sensory input, realizing that he had been stuck in a particular mode of seeing and experiencing the world, awakening a deep sense of interoceptiveness.

Interoception is the awareness of what is going on inside one’s own body at any given moment and the ability to take action based on one’s inner experience. For example, noticing dryness in the mouth might serve as an indication that we are thirsty, encouraging us to take action by drinking water. In general, autistic folk tend to have lower interoceptive awareness when compared with average populations.

“If my body was a car, psychedelics allowed me to realize that my fuel light was low, that I needed food, rest, or felt a certain way,” Orsini says. “By being able to notice and interpret the cues coming in, I became able to navigate any situation.”

Speaking about his initial experience with psychedelics, Orsini shares, “ I felt connected to myself, nature, and other people—it was a relief from repetitive thinking, and from there it became the foundation upon which I could rebuild my relationship with myself, my physical and mental wellness, and lead a functional life.”

Orsini draws on the concepts of “monotropism” and what he calls “polytropism” to explain how psychedelics were able to modulate his consciousness. Monotropism, believed to be a key feature of autism, refers to a cognitive strategy in which one has a narrow set of interests and is only able to focus one’s attention on a limited number of inputs at a given time. On the one hand, monotropic thinking can lend itself to deep thinking and flow states, however, it is also limiting in that information which exists outside of the attention tunnel often gets filtered out, and it can be hard to disengage with a given task or activity when one is so fully absorbed in it.

Comparatively, polytropism designates the proclivity to process multiple inputs at once. Naturally, both types of cognitive processing have their pros and cons, however, when it comes to autistic individuals, polytropic processing is generally harder to access. In Orsini’s experience, LSD was able to occasion a state of polytropic awareness, which he committed himself to working with after his psychedelic experience. 

By facilitating novel perceptions, psychedelics could also help autistic individuals learn to embrace their neurocognitive disposition and unique way of inhabiting the world. Many autistic people engage in a behavior referred to as “masking” in which they camouflage certain challenges by observing and mimicking neurotypical ways of acting in social situations. In some sense, masking is a survival strategy used to conceal behaviors that are felt to be socially unacceptable. Often, masking is the result of trauma, as individuals feel they need to hide their true selves in order to fit in.

“Autistic behaviors could be patterned off of early life traumas that are likely because of the sensitivity inherent to an autistic individual,” says Orsini. “I might not have been through war, but I was prone to a more intense sensory experience.”

Independent of neurotype, psychedelics allow for a reappraisal of our default modes of seeing, and a breaking free from the rigid patterns of perception that become habitual. In mental health conditions like anxiety, depression, and OCD, an interconnected group of brain regions referred to as the default mode network (DMN) linked to introspective functions such as self-reflection and self-criticism, tend to be overactive.

Psychedelics have been shown to dampen the function of the DMN, allowing for a kind of “reset” in the brain in which it becomes easier to separate ourselves from ways of thinking and seeing the world that have become ingrained. If psychedelics are beneficial to the general population in this way, why can’t they also be valuable to autistic folk for the same reason?

To date, there is no evidence to suggest that having an ASD diagnosis is a contraindication for psychedelic use. “In general, whether it is in a research or retreat setting, there is less certainty on how to navigate autism and so it is often sidelined,” says Orsini. “However, there is nothing obvious about autism that makes it a contraindication or makes it less safe to explore these toolsets.”

Unfortunately, more often than not, larger subsets of the population get attention first, and according to the World Health Organization, a whopping 264 million people worldwide suffer from depression. Comparatively, autistics make up a minority population that often gets overshadowed.

Expressing his hopes for future psychedelic research, Orsini shares, “What I’d like to see is keeping autistics in the conversation when it comes to their ongoing access, and keep them in the domain of people that are considered for early clinical trials.” Additionally, when psychedelic-assisted therapy becomes legalized throughout the US, just as it has in Oregon, Orsini hopes that medical or retreat centers don’t exclude autistic people.

A Future Therapeutic Modality for Autistics: Psychedelic-Assisted Immersion Therapy

Based on his extensive self-experimentation with LSD, Orsini proposed a model therapeutic approach for navigating neurodivergence with psychedelics called: “LSD-assisted immersion therapy.” Immersion therapy is different from conventional psychedelic-assisted psychotherapy in that it is formulated with the idea of facilitating social and interpersonal learning as opposed to a purely inwardly-directed experience. In this context, Orsini suggests that a moderate dose of the substance is preferable so as not to elicit a full blown mystical experience.

Moving beyond a therapist dyad, LSD-assisted immersion therapy, or more generally psychedelic-assisted immersion therapy, involves ingesting the substance in a group setting. “If I was to have this LSD, and simply reflect on my social challenges in isolation, I may come to an intellectual conclusion, but it is not the same as actually being involved with other people,” says Orsini.

“I envision a future setting in which individuals who are seeking to work on interpersonal issues and skills would be able to do so in the comfort of other individuals who are equally familiar with them,” says Orsini. “These issues have to do with one’s personal self inventory, but there is a natural therapeutic component to engaging with others in an enhanced state.”

Experiencing challenge around social interaction isn’t specific to autistic individuals, and psychedelic-assisted immersion therapy, or simply psychedelic group therapy, has the potential to help a wide range of people. Current clinical studies into the therapeutic potentials of psychedelics often overlook an important dimension of real-life psychedelic use, namely, the social dimension.

To some extent, psychedelic insights can be like training wheels on a bike. Once a person is able to access a specific way of thinking in the psychedelic state, it becomes much easier to cultivate the same state in day-to-day life. In the case of autism, people might feel more confident and empowered in daily life, finding comfort in the level of social connection that they were able to achieve in the psychedelic state.

Although pushing for the legalization and acceptance of psychedelics through the lens of medicalization is somewhat of a necessity, there is an inherent problem-solving dynamic that emerges in which psychedelics are viewed exclusively as tools that are effective in treating given issues. However, looking at psychedelics through the lens of neurodiversity, they need not be used to target a given concomitant issues associated with autism, rather they can simply help people understand and embrace their differences. Healing happens when we can move beyond a narrow view of how society should be and encourage people to flourish as they are, instead of attempting to make everyone conform.

*Even though this article speaks to the benefits of autistic adults using psychedelics, it is no way advocated that such individuals should seek to self-medicate. In sharing his story, Orsini makes it clear that he is not advocating for others to self-experiment as he did, rather, his aim is to spark interest in researchers to find more data on this in hopes of providing relief for others.


About the Author

Jasmine Virdi is a freelance writer and editor. Since 2018, she has been working for the fiercely independent publishing company Synergetic Press, where her passions for ecology, ethnobotany, and psychoactive substances converge. Jasmine is also a writer for Psychedelics Today, Chacruna.net, Lucid News, and Cosmic Sister. She is currently pursuing an MSc in Spirituality, Consciousness, and Transpersonal Psychology at the Alef Trust with the future aim of working in psychedelic integration therapy. Jasmine’s goal as an advocate for psychoactive substances is to raise awareness of the socio-historical context in which these substances emerged in order to help integrate them into our modern-day lives in a safe, grounded and meaningful way.

Should Society Legalize Psychedelics? A Breakdown of the Intelligence Squared Debate

By Mike Alexander

Rick Doblin and Bia Labate debated Jeffery Lieberman and Keven Sabet on whether or not psychedelics should be legalized, and the results may surprise you.

Last week, we received an invite to attend an early screening of the newest debate in Intelligence Squared US’s online debate series: “Should Society Legalize Psychedelics?” Being immersed in the world of Psychedelics Today, it seems like we’re constantly involved in various similar conversations around legalization, decriminalization, benefits and dangers, and the less-discussed idea of drug exceptionalism. So while I was curious to see how a question like this would be handled by a more mainstream outlet, I also wondered if they’d get it right. When I saw who would be involved, I knew this would be worth watching. 

Arguing for the motion to legalize psychedelics were Rick Doblin, Founder & Executive Director of MAPS, as you likely know if you’re on this site, and Bia Labate, anthropologist, drug policy expert, and executive director of Chacruna. Against the motion were Jeffrey Lieberman, former President of the American Psychiatric Association and Chair of Columbia University’s Department of Psychiatry, and Keven Sabet, three-time White House drug policy advisor, president and CEO of Smart Approaches to Marijuana, and author of Smokescreen: What the Marijuana Industry Doesn’t Want You to Know. What instantly caught my eye was psychedelic legend Rick Doblin going against a three-time White House drug policy advisor (i.e. “The Man”), and I wanted to see exactly how Doblin would choose to wipe the floor with him. But this was a debate, and debates don’t care solely about facts, which to me, is exactly what makes them so interesting.

After a brief and somewhat cringeworthy performance by “psychedelic comedian” Sarah Rose Siskind (which felt very odd to me—if we’re taking this seriously, why are we starting it out with bad jokes about drugs?), moderator John Donvan came on and asked us all to cast a vote before the debate started. We’d be casting another one after the debate, and the winner would be declared by calculating which side’s numbers increased more, or really, which side won over more of the undecided voters.

I personally feel that this is a very nuanced topic that probably can’t be answered with a simple yes or no, but decided to vote “yes” anyway. 

The debate started and right away, I noticed a classic juxtaposition between Doblin and the Against Legalization team: Lieberman and Sabet wore black sportcoats and white collared shirts with crisp, stylized hair, while Doblin looked to be wearing a Hawaiian shirt, hair as out-of-control as always. Lieberman looked to be sitting in a professional office with hundreds of journals and important books proudly staged behind him, while Doblin looked like someone dug a chair out of the piles of papers in his office and placed him on it shortly after waking him up. The For Legalization team argued passionately, with a more freestyle tone drawing from personal stories, while the Against Legalization team spoke more slowly and seemed to have more prepared statements (Lieberman seemed to be reading off a script several times).

Screen shot of Rick Doblin of the “For Legalization” team at the Intelligence Squared debate.

The opening round consisted of each participant getting a few minutes to make as many points as they wanted. Doblin started out by listing what he believed his opponents would agree with him on, and introduced the idea of “licensed legalization,” where the ability to use drugs legally would be handled the way a driver’s license allows you to drive a car (and would therefore be taken away with abuse or misuse). Labate focused on the prevalence of drug use throughout all of history, the racism and failure of the drug war, and how “the sky didn’t fall” when other countries have legalized drugs. 

From the Against Legalization team, Lieberman made it clear that while he has plenty of experience with psychedelics and absolutely sees a benefit, they should be decriminalized only and studied for therapeutic use. He also called out MAPS’s mission statement, saying that their effort to develop cannabis into prescription medicines is a “ruse” to get around prohibition, and posited the idea that the gateways to creativity and spirituality people experience were maybe just the drugs fooling them. Sabet performed pretty strongly here, saying that the historical use Labate talked about couldn’t be further from what would happen if the US legalized psychedelics, which he imagines as stereotypically US as possible, with Super Bowl-level mass commercialization, major lobbyists promoting their agendas, and the rich getting richer off of an addiction-for-profit model. He also said that opioids and alcohol kill more people than all illegal drugs combined, partly because they’re legal and therefore used more.

Round two was more of an open discussion with Donvan moderating. Some good points were made by the For Legalization team: decriminalization means impure drugs; classic psychedelics are not addictive; there actually is a lot of ceremonial use already in the US; commercialization doesn’t mean a psychedelic boogeyman is going to create addictive psychedelics; and decriminalization is not freedom and still comes with fines. 

Meanwhile, the Against Legalization team didn’t seem to grasp why decriminalization wasn’t enough, but made some great points about how legalization doesn’t always mean purer and better (look at tobacco and cigarettes), and if we haven’t gotten this stuff right in all this time, why would we suddenly get it right when it comes to the legalization of psychedelics? Much time was spent on the need for scientific proof over tons of anecdotal stories. The open discussion showed some heat, and also exposed some debater flaws, like Lieberman rambling to the point of me entirely missing his point and Labate not realizing when her time was up and talking over everyone several times.

Screen shot of all the debaters and moderator from the Intelligence Square debate, “Should Society Legalize Psychedelics?”

Round three went back to each participant making closing statements for two minutes. Doblin spoke passionately about how much he and his wife have benefited from regular MDMA use, and said opponents shouldn’t let the fear of overcommercialization from “Big Psychedelic” spoil something so many could benefit from. Labate talked about how the US is the “land of freedoms” (which I laughed out loud at), and we’re going to look back on this time in shame, saying that a lot of what had been said against psychedelics was based on fear, a false narrative, and science’s attempt to control everything. Lieberman said that this would be a very dangerous social experiment, and then spent an odd amount of time talking about Prometheus and Frankenstein. 

Sabet, on the other hand, really killed it here, spending a good chunk of his allotted time reading a quote from Robert Corry (one of the writers of Amendment 64 on Colorado’s 2012 statewide ballot that permitted recreational sales of cannabis), who fully regrets what he has done after seeing the massive commercialization of the industry. He ended by echoing his main point again: “It’s one thing to advocate for decriminalization, ending the war on drugs. It’s another thing to advocate for the commercialization and normalization,” saying that this would create an industry that cared only about profits, to the detriment of everyone’s health and safety.

The pre-recorded debate ended, and those of us who were able to attend the sneak preview were then sent to a live check-in with all the participants. Here, huge points that were missed in the debate were finally made. Doblin asked Sabet if he’s so against big corporations getting rich off drugs, does that mean he’s OK with cartels getting rich instead? 

Labate pointed out that the time people were the most reckless with alcohol was during prohibition. Lieberman hurt himself by making it clear that he felt medical use and recreational use have to be completely separate, and the same drug couldn’t be used for both. Sabet made his same points again, but hurt my view of him a bit by making sure to have the cover of his book prominently displayed twice in his background (I’ve never been a fan of shameless plugs).

My favorite parts of the debate were in this live session. The first was when Founder and Chairman of Intelligence Squared US, Robert Rosenkranz, joined in and made Doblin’s point about money even stronger: If something is bought, that means someone is selling it, so why does the amount of profit and who it’s going to matter so much to Sabet? It can go to corporations and be regulated, or go to criminals and stay unregulated. Which is better?

Labate also shut down Lieberman in extraordinary fashion. Lieberman had already established himself as being extremely focused on science, studies, and needing proof for everything, but also had a really odd moment where he was certain he had more psychedelic experiences under his belt than Doblin. I cringed at this, thinking, “Really? You’re arguing for keeping psychedelics illegal and talking about their dangers while bragging about breaking the law to enjoy them?” So I was filled with joy when he said that he had had wonderful experiences on psychedelics, and Labate immediately hit him with: “But there’s no proof that your experience was wonderful. There’s no peer-reviewed study. How do you know it was wonderful?” Yeah, take that, pal.

There was a place to submit questions, but the live session was kept to a half hour, leaving most questions unanswered. I wanted to know if the Against Legalization team would be for legalization if it was presented in a “licensed legalization” manner—the way Doblin had explained in his first segment (which wasn’t discussed again because it was outside of the main argument). Wesley Thoricatha of Psychedelic Times asked another great question in the chat window: “If our society believes that the benefits of alcohol legalization outweigh the observable risks, how can there be any valid case against legalizing these non-addictive substances that clearly have more potential benefits and less overall risks?” Since the pros didn’t address these thoughts, I guess it’s now the job for all of us to keep asking these questions and having these conversations on our own time. 

All said and done, I really enjoyed this debate and found the arguments really interesting. Sabet’s “why would we get it right this time?” overcommercialization argument really hit home with me, as I’m quickly becoming disgusted with the money-grabs, ridiculous patent-filing, and dangerous “magic pill” narrative that keeps proliferating this movement, while constantly being reminded of the ineffectiveness and rampant corruption in the government. But I wondered if he really meant that, or if he was just trying to win the debate by cashing in on the “rich people are evil” attitude he guessed many viewers would have. And while his vision of the future is ugly, was his point (or any others made by the Against Legalization team) any stronger than Doblin’s argument for taking money out of the hands of criminals in favor of safer drugs?

I loved Labate’s passion and realness and she made some great points, but her talking over people hurt her. Lieberman was very organized and prepared, but his rigidity and inability to make strong, understandable arguments hurt him. So this felt more like a debate between Doblin and Sabet, and after breaking it down more, it really felt like hope, compassion, and common sense were going up against pessimism and fear.

At the end of the debate, the results were tallied. My view was a little more nuanced and I was more open to discussion, but I still generally sided with the For Legalization team. This was not the case for others. Before the debate, 65% of viewers voted to legalize psychedelics, while 15% disagreed with the motion and 20% were undecided. After the debate, however, even though the For Legalization vote increased to 67%, the Against Legalization vote grew to 24%, giving them a 9% total increase over the For Legalization’s 2%. Therefore, in the preliminary vote, Against Legalization ended up winning the debate.

Intelligence Squared US then posted the video and encouraged people to watch, leaving voting open for a week for a separate “online audience” tally. I assumed that a larger audience would trend more towards legalization and I’d get my win here, but I couldn’t have been more wrong. Not only did the Against Legalization vote jump from 11% pre-debate to 30% post-debate, but the For Legalization vote dropped from 74% to 62% too, leaving me to wonder what arguments swayed people so much.

In the end, as I assumed it would, this debate just highlighted the importance of nuance and looking at huge, important topics like this from all angles. I’m not sure that “should society legalize psychedelics?” is a question we should even be asking (can it really be answered with a simple yes or no?), but the beauty of it is that these questions are even being asked and debated, especially by such big names on such a mainstream platform. And as a culture, we’re now making available both sides of the argument, to be heard by anyone who wants to listen. These conversations need to be had, bad arguments need to be called out, and strong points by the other side need to be looked at fairly. While the complete adult-use legalization of all psychedelics may never happen, this is the only way we’re ever going to get close. 



About the Author

Mike Alexander works for Psychedelics Today. He writes the show notes for each podcast, handles most of the email, edits video and audio, helps with the blog, and annoys the rest of the team on Slack. He eats a lot of pizza, spends a lot of time in the woods, and spends most of his money on Phish tour. 

Op-Ed: Re-evaluating the Results of the Recent Trial of Psilocybin vs Escitalopram for Depression

By Court Wing

Taking a deep look at the trial’s Supplementary Appendix, the response from the psychedelic science community, and the choice to measure the results using the QIDS depression rating scale.

On April 15, 2021 the New England Journal of Medicine published a study comparing the efficacy of psilocybin-assisted therapy to a popular SSRI antidepressant, escitalopram (sold under the brand names Lexapro, Cipralex, and others): titled: Trial of Psilocybin versus Escitalopram for Depression. The landmark paper written by the team at Imperial College London’s Centre for Psychedelic Research, concluded that the “trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients”, which caused a bit of an uproar in the psychedelic science community.

Reactions and questions came quickly on social media: Was the paper edited too heavily by the New England Journal of Medicine? Were appropriate rating scales used to judge the effectiveness of psilocybin? Are the “real” results hidden in the study’s appendix? As a participant in NYU’s study on psilocybin-assisted therapy for major depressive disorder in 2020 who received incredible benefits (my depression of five years went completely into remission and has remained there), I felt it was necessary to try and explain the latest results in more depth.

The study in question, under lead authors Robin Carhart-Harris, Ph.D, David Nutt, MD,  Rosalind Watts, D.Clin.Psy and others, was a double-blind randomized trial with 59 participants for six weeks to compare the efficacy of psilocybin versus a leading antidepressant in treating depression. Each trial started with a psilocybin dose day; one group received a high dose of 25 mg, the other a negligible dose of 1 mg. Then, the high dose group proceeded to receive a daily placebo while the low dose group received 10 mg of escitalopram each day for the first three weeks. At three weeks, the psilocybin group received a second 25 mg dose of the magic mushroom compound and continued with the daily placebo. The SSRI group received a second placebo, 1 mg dose of psilocybin and also had their daily dose of escitalopram increased to 20 mg. Both groups received an equal amount of extensive psychotherapeutic support and counseling, totaling around 35 to 40 hours during the six week-trial using Watts’s ACE therapeutic model: Accept, Connect, Embody.

Prior to the start of the trial, both groups received multiple and extensive depression assessments, using four different depression rating scales; QIDS- SR-16, HAM-D-1A, BDI-17, and MADRS. Of the four depression inventories, QIDS-SR-16 is the newest, designed for convenience of use so patients can “self-rate” (that’s what the SR stands for), and crucially for this trial, it was the primary scale used to compare psilocybin and escitalopram’s efficacy in fighting depression. However, lead author Robin Carhart-Harris has now stated that should have been better considered because QIDS-SR-16 is the least established of the four scales used. There are several issues as to why it was not the best rating scale to use and its results should be viewed as less accurate, and we will explain those issues below, but first let’s review the trial results as published.

In the abstract, the NEJM concluded:

“On the basis of the change in depression scores on the QIDS-SR-16 at week 6, [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]  this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients.”

This is an extremely conservative and staid summary for all the rating scales and secondary outcomes. Even so, in my opinion, this alone is phenomenal because they are stating that psilocybin, a psychedelic compound, is at least as effective as a leading SSRI for treating patients with major depressive disorder. But the real results are in the data contained within the appendices and tables, many published in the Supplementary Appendix rather than in the abstract or main study itself, so let’s examine them.

Analyzing the Supplementary Appendix

In clinical research, the two main items to track in depression scores are the “response” rates and the “remission (remitter)” rates. A response rate means there is an improvement in depression symptoms in at least 50% of patients. A remission rate means that a patient no longer has enough symptoms to qualify for a medical diagnosis of depression; for all intents and purposes, it’s effectively gone. So even when we look at the solely at QIDS scores for those two rates, the difference is striking:

“A QIDS-SR-16 response occurred in 70% of the patients in the psilocybin group and in 48% of those in the escitalopram group… QIDS-SR-16 remission occurred in 57% [psilocybin] and 28% [escitalopram]… 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.”

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In both ratings for the QIDS scale we see psilocybin outperform escitalopram by nearly double with only two doses as opposed to six weeks of daily doses. But also notice the statement at the end about secondary outcomes favoring psilocybin and that adverse events were similar.

Honestly, these are significant understatements when you look at the secondary outcomes directly in the appendices and tables. Certainly, as a leading scientific journal it’s a far better position to conservatively report the outcome rather than promote the results, but consider the following: In the three other well-established depression inventories, HAM-D, BDI, and MADRS, the response rate for psilocybin at the 6-week mark was between 67.9 and 76.7% while for the SSRI it was only 20.7 to 41.4%. Even more striking are the remission rates, lying between 28.6 and 56.7% for psilocybin while the SSRI produced remission at 6 weeks in 6.9 to 20.7% of participants. (Check out the Supplementary Appendix, pg. 13 to see for yourself.)

As this is a two-dose study, there was a similar outperformance after the first psilocybin dose; in two scales (QIDS and BDI) 33.3 to 51.7% of participants no longer qualified as being depressed by the end of the first week. In my opinion, it can’t be overstated how miraculous these remission rates are; these are patients that have often been non-responsive to other treatments for depression, and have likely been through a gamut of approaches, including psychotherapy, exercise, other antidepressants, alternative therapies, and had yet to find relief, let alone remission after a single week.

When we look at secondary outcomes, there are even more revelations. In a score known as “wellbeing”, participants in the psilocybin group increased 15.8 points after six weeks while those in the SSRI group only improved 6.8 points. This not only shows a reduction in depression symptoms, but a marked improvement in patients’ happiness with their sense of self. This is similarly reflected in the “Flourishing Scale” which found the psilocybin group to improve 14.4 points while the SSRI group only improved by 8.9 points after six weeks.

Other similar secondary outcomes also demonstrated remarkable efficacy for psilocybin including reductions in suicidal ideation, trait anxiety, experiential avoidance, anhedonia (which has implications for chronic pain), emotional breakthrough inventory, psychotropic related sexual dysfunction, and others. A key line to take from the caption for Supplementary Table S1 that compares depression inventory rates across all six weeks is: “All contrasts favored psilocybin. None favored escitalopram.” These are well established depression inventories that are used as the standard of comparison in nearly every modern study testing efficacy against nearly any method or medication for relieving depression, but because they were not chosen as the primary scales, they were classified as secondary outcomes. But if all these scores had been corrected against each other, including the QIDS, psilocybin would have shown to be clearly superior.

So why was QIDS chosen as the primary evaluation instead of the much more frequently employed MADRS inventory? As someone who had to take the MADRS inventory repeatedly in order to qualify for NYU’s investigational study of psilocybin for major depressive disorder, I will tell you it is surprisingly precise and accurate, making it nearly impossible to hide the depths of your disease from yourself. As much as we may mask the symptoms of our disorder to others in order to function in our day to day lives, we may in fact find we mask the severity of our symptoms to an even greater degree to ourselves. According to Carhart-Harris, the choice to use QIDS was almost arbitrary and now considered ill-advised in hindsight. And other professionals on Twitter and elsewhere online are largely in agreement, arguing that QIDS was a scale not designed to measure depression so much as one designed for patient convenience and to measure response to classic SSRIs. For example, QIDS has no measure for wellbeing, emotional breakthrough, experiential avoidance or, dare we say, mystical experiences.

SSRIs modulate and downregulate distressing feelings, but do not generally resolve them, much like a daily salve that keeps negative emotions just under conscious awareness. Psilocybin not only goes to the heart of engaging the origin of troubling feelings, but due to its ability to induce neuroplasticity, it’s theorized that the psychedelic compound directly aids in a cortical reorganization of prior maladaptive circuits and strongly held associations that create the framework of a patient’s life experience and the events in it.

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Evaluating the Choice to Use the QIDS Scale

Worth noting about the QIDS scale relative to the other inventories in the study is a concept in statistics known as a confidence interval or CI. When a study is performed, it’s obviously not done on the entire population but on a sample of the population. A confidence interval is a measure of how likely the mean average of the results in the study population would match the mean average of results in the general population. It’s also a measure of how likely those same results would occur if scientists were to repeat the test multiple times.

In a study like this one where two medications are being compared against each other for efficacy, their confidence intervals can be laid out on a table or graph known as a forest plot. When the CIs are displayed on a forest plot, they are shown as a range of most likely results (i.e. -2 to -15). This is key because that allows researchers to demonstrate their confidence that a given range of results would occur for 95% of the general population or in repeated studies. 95% is the agreed upon standard for proof of any statistical significance in patient response to medication for this type of study. However, if on a forest plot, your CI crosses zero (which is the midline between the two groups), there is a far greater likelihood that there is no difference in effect between the groups.

So recall now that Carhart-Harris said that choice of QIDS was arbitrary as the main depression scale for the study and that their team of researchers predicted no difference in effect size between the psilocybin and escitalopram when they submitted the pre-req application to run the study. For more than a week before the study was released, Carhart-Harris did a daily thread on Twitter describing effect size, how different measurements may in fact be measuring the same issue and could be condensed, that NEJM analysis of the results are extremely conservative, but most of all he “implored” readers to view the supplementary tables and appendices, and to particularly look at the confidence intervals for the main inventory and then the confidence intervals for the secondary outcomes.

Carhart-Harris made a very careful note that confidence intervals that do not cross zero are considered statistically significant and those that do cross zero are considered insignificant. He directed us to look at Figure S1 and Table S4 where you will see at the top that the only inventory that crosses zero is the QIDS scale, which strongly implies its result is a false negative in showing no difference in outcome between the SSRI and psilocybin, and we can be confident of that because of the redundancy of the other evaluations they also used. Every other inventory and measure shows psilocybin far out pacing escitalopram by nearly a two to one margin. You can take a look yourself by accessing the study’s Supplementary Appendix, and turning to Section S6. Supplemental Figure S4: Mean change for primary and secondary outcomes with confidence intervals (pg. 16).

Conclusion

Between the extraordinary results in the secondary outcomes, the fact that the QIDS scale was the only inventory to cross zero in the forest plot, and the strong likelihood that modern depression scales aren’t designed to capture the full range of positive personality change that underpin psilocybin’s cortical mechanisms, it’s hard to see how this is not an overwhelming win for psilocybin.

It would certainly be remiss for me to not once again state I was a participant in a very similar study myself who experienced full remission and know others who experienced the same. I would be equally remiss to not mention that for many who took the two doses, their depression returned after a few months—but not all of them. However, this is already the case with standard daily antidepressants. And with psilocybin, there are no sexual side effects, you can actually feel a full range of emotions, and the frequency of dosing is far less. But for people that have either found themselves unresponsive to standard SSRIs, or experience untenable daily side effects from antidepressant medication, psilocybin appears to offer an equal, if not superior, opportunity to recover their happiness and effectiveness in their daily lives.


About the Author

Court Wing has been a professional in the performance and rehab space for the last 30 years. Coming from a performing and martial arts background, Court served as a live-in apprentice to the US Chief Instructor for Ki-Aikido for five years, going on to win the gold medal for the International Competitors Division in Japan in 2000 and achieving the rank of 3rd degree black belt. In 2004, Court became the co-founder of New York’s largest and oldest crossfit gym, and has been featured in the New York Times, Sunday Routine, Men’s Fitness, and USA Today. He is also a certified Z-Health Master Trainer, using the latest interventions in applied neuro-physiology for remarkable improvements in pain, performance, and rehabilitation. You can find out more on his website: https://courtwing.com