Mary and the Mushroom: Psilocybin, Chronic Depression and Me (4)

A note to new readers: I have recently applied to be included in a Health-Canada-approved study into the use of psilocybin in the management of treatment-resistant depression (TRD). I have survived the first few stages of the screening process and I hope to join the study in a couple of months. I will share the experience with interested readers here. In the meantime, how I got to this point is the subject of this series of blog posts.

I apologize in advance for the clinical terminology and references I have included in this post, but I wanted to get the wording right for those who like to follow the science. You can skip over any terms, definitions or references that aren’t of interest to you – I hope I’ve written the post in such a way that the citations, links, etc. don’t interfere with your understanding of what I am trying to say.

What I Know About Psychedelics So Far

There has been an explosion of news and media attention relating to psychedelics since I started this blog series. As of January 5, 2022, Health Canada has expanded its Special Access Program to include the psychotherapeutic use of psychedelics and MDMA in the treatment of severe or life-threatening conditions. At the end of January, the Canadian Psychedelic Association announced that the University of Ottawa will soon start offering a master’s degree program in psychedelic research. Numerous clinical trials are now underway or are being planned in various locations across the country and in the USA.

Outside of clinical studies like the one to which I have applied, the Special Access Program in Canada allows psilocybin treatments only for those “with a serious or life-threatening condition on a case-by-case basis when other therapies have failed and where there is sufficient evidence of safety and efficacy for the treatment of the patient’s condition.” Despite the restrictions, psychedelics are poised to become big business – as was the case with cannabis when it was approved for medical use in Canada several years ago. So it is no surprise that since this announcement, dozens of business groups, clinics, psilocybin manufacturers and organizations are fighting for attention in their efforts to attract investors and future customers. (Try Googling “psychedelics mental health” for a sample of what I mean.)

Although most articles relating to recent advances in the therapeutic use of psychedelics do talk about the almost immediate relief they’ve offered many patients with chronic depression, PTSD and end-of-life distress, they don’t talk too much about how and why the treatments work. In the past year or so, I have read and heard quite a bit about these drugs in general, and psilocybin in particular, but as is the case with any complex subject, I still feel as though I don’t know very much. Perhaps I won’t know much more until I’ve actually had a psychedelic experience, but I’m sharing what I know so far and hoping that others who have additional information or perspectives will share them with the rest of us in the comments.

What Is Psilocybin?

You can get a crash course in the chemical composition, sources, nature, history and uses of psilocybin on Wikipedia. Basically, it is a “tryptamine alkaloid” that affects certain serotonin receptor sites in the brain. It occurs in a variety of genera of fungi located in various parts of the world

These mushrooms have been used by Indigenous cultures since the beginning of time, primarily for spiritual or religious purposes.[1] It wasn’t until the middle of the last century, however, that a Swiss chemist named Albert Hofmann became the first person on record to synthesize and ingest lysergic acid diethylamide (LSD), a substance that is extracted from a fungus found in grain – to startling and somewhat terrifying (to him) effect. (After his brain started tripping, he took a bicycle home from work to lie down. The anniversary of the day he did that, April 19, 1943, continues to be celebrated as “Bicycle Day” by psychedelic enthusiasts.) Hofmann also later identified the compound, psilocybin, that produces psychedelic effects in “magic” mushrooms.

The use of LSD and psilocybin in both controlled studies and non-therapeutic (“recreational”) settings “mushroomed” (sorry) in the 1960s, primarily due to the efforts of Timothy Leary and Richard Alpert. These two psychologists were at Harvard until their experiments with psychedelics, and their subsequent enthusiastic promotion of LSD for use by young people, started attracting a lot of negative attention. It was largely due to the misguided efforts of these two and others that the drugs became banned or controlled substances in many countries.

Despite their illegal status, mushrooms (often called “shrooms” in recreational settings, although scientists avoid this term) ­­­are not hard to come by and are pretty widely available on the street. (I do not know which street, so don’t ask.)

What Happens When You Ingest Psilocybin?

The effects of psilocybin, which turns into psilocin when ingested, typically set in approximately 30 to 60 minutes after the drug is ingested, and they peak at between 90 and 180 minutes. The onset of symptoms can be measured externally by monitoring heart rate and blood pressure (which increase), and by watching participants’ behaviour. Over the next five or six hours, the effects gradually recede.

What happens on the inside (i.e., from the perspective of the ingester)? According to Health Canada, “Taking magic mushrooms may cause you to see, hear or feel things that are not there, or to experience anxiety, fear, nausea and muscle twitches accompanied by increased heart rate and blood pressure. In some cases, the consumption of magic mushrooms can lead to ‘bad trips’ or ‘flashbacks’.”

The possible physical manifestations of taking psilocybin as set out by Health Canada may make the experience sound highly unappealing, but keep in mind that the agency is also obliged to remind its readers that “The production, sale and possession of magic mushrooms are illegal in Canada.” However, the site is of value for its scientific summaries and for its link to Health Canada approved studies that are currently underway.

It is the hallucinogen part of psychedelics (“see[ing], hear[ing] or feel[ing] things that are not there”) that is of interest to psychologists, psychiatrists and their patients. The hallucinogens are undoubtedly why these substances gained traction in the religious rites of early Indigenous cultures. (Michael Pollan points out in his book, How to Change your Mind (p. 13), that the Inuit were the only early Indigenous culture not to have used plant-based hallucinogens of one kind or another – most likely, he points out, because magic mushrooms and other mind-altering plants didn’t grow in the regions where they lived .)

Psilocybin is generally said to cause a feeling that the individual ego has disappeared, allowing those who take it to feel more connected with others and with the world as a whole. The psychedelic experience has been said to lead users to observe phenomena as children do, in a fresh way, unimpeded by the intervening repetitive experiences that, to adults, may make them seem routine, ordinary and uninteresting.

In an article in Quartz entitled “Scientists Studying Psychoactive Drugs Accidentally Prove that the Self is an Illusion” (I love this title), Ephrat Livni reports that in a study published in 2017, “Participants showed significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping.”

In addition to the feeling that consciousness has fallen away, hallucinogenic experiences induced by psychedelics seem to contribute to a sense that the mind is creating new connections to the mystical/spiritual. I am beginning to understand the “falling away of consciousness” part of that statement thanks to my investigation of meditation and my ongoing efforts to attain a meditative state for minutes rather than seconds at a time (sigh. See my next post for more on this), but the second part is beyond my ability to conceive at the moment. However, others have gone where I have not, yet, and they warn that the experience can be great or terrible. Or both.

Sam Harris writes, “If [ …] a person ingests 100 micrograms of LSD, what happens next will depend on a variety of factors, but there is no question that something will happen. And boredom is definitely not in the cards. Within the hour the significance of his existence will bear down upon him like an avalanche” (p. 193, Waking Up). In his own experience, he says, a psychedelic trip can be ”More sublime than I could have imagined or can now faithfully recall,” but it can also be “so painful and confusing as to be indistinguishable from psychosis” (p. 194).

“Ingesting a powerful dose of a psychedelic drug is like strapping oneself to a rocket without a guidance system.”

Sam Harris, Waking Up

Using a similar metaphor to Harris’s “rocket,” Michael Pollan compares his first experience with psilocybin to other psychedelics he has tried as “more like being strapped into the front car of a cosmic roller coaster, its heedless headlong trajectory determining moment by moment what would appear in my field of consciousness” (How to Change Your Mind, p. 261). He goes on to point out, however, that when he took off the eye mask he’d been given to wear during the “trip,” he had a better feeling of connection to the real world, and also experienced the commonly reported amazement at the beauty of the physical world around him.

John Hopkins Study

In a ground-breaking article that appeared in Psychopharmacology in 2006 (“ground-breaking” primarily because it was one of the first reports on a study of spiritual experience to appear in a peer-reviewed, scientific journal), R.R. Griffiths, W.A. Richards et al. reported that two months after receiving doses of psilocybin in a controlled situation, participants in their study reported “mystical-type experiences having substantial and sustained personal meaning and spiritual significance.” These individuals attributed “sustained positive changes in attitudes and behavior” to the psilocybin, and the behavioural changes were confirmed by family and friends.

The article is fascinating and well worth reading. To summarize, 36 well educated, healthy individuals who reported “regular participation in religious or spiritual activities” and who had never before used hallucinogens were recruited for the study. Most said they’d agreed to participate out of “curiosity about the effects of psilocybin and the opportunity for extensive self-reflection…” (p. 2). Each participant had either two or three 8-hour monitored drug sessions, during one of which they were administered a dose of psilocybin. For comparison, during the other session they received another drug, methylphenidate hydrochloride, which has effects similar to psilocybin but without the hallucinogenic component.

In advantage of the drug-treatment session, each participants spent eight hours with their monitor(s) to build trust, which is “believed to minimize the risk of adverse reactions to psilocybin (Metzner et al. 1965)”(Griffiths et al., p. 3) and to manage expectations (“It is widely believed that expectancy plays a large role in the qualitative effects of hallucinogens [Metzner]”). Participants also completed questionnaires intended to measure “psychiatric symptoms, personality measures, quality of life, and lifetime mystical experiences” (p. 3). Some of these and other questionnaires were also administered immediately after the drug sessions and/or two months later, and volunteers met with monitors for four sessions of one hour each following the treatments. The drug-session monitors as well as pre-selected family and friends of the participants were also surveyed on various topics before, during and/or after the drug sessions. (For precise details on the various questionnaires and how the double-blind study was conducted, please refer to the actual paper.)

For many, the road to “substantial and sustained” positive outcomes was not smooth: “Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety” (Griffiths et al., p. 1). “Eleven of the 36 volunteers after psilocybin and none after methylphenidate rated …. Their experience of fear sometime during the study to be ‘strong’ or ‘extreme’,” and four said that “the entire session was dominated by anxiety or unpleasant psychological struggle” (p. 11). However, “These effects were readily managed with reassurance,” and “no volunteer rated the experience as having decreased their sense of well-being or life satisfaction” (p. 12).

The Discussion section of the Griffiths paper includes an interesting exploration of the issue of “empirical analysis of mystical experience,” but the relevant finding can be found in the first paragraph of that section. “The […] study shows that psilocybin, when administered under comfortable, structured, interpersonally supported conditions […] occasioned experiences which had marked similarities to classical mystical experiences and which were rated by volunteers as having substantial personal meaning and spiritual significance. Furthermore, the volunteers attributed to the experience sustained positive changes in attitudes and behavior that were consistent with changes rated by friends and family” (p. 12).

How Do Psychedelics Work on Depression?

Some reports (see this PubMed paper, for example) indicate that psilocybin may have an antidepressant effect through its action on the serotonin system, serotonin being a neurotransmitter whose “biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vasoconstriction” (Wikipedia). But this can’t be all of it: the antidepressants I’ve been taking for many years also work with the serotonin system, and they don’t produce out-of-body experiences or induce “sustained positive changes in attitude and behavior.”

Writing in Psychology Today, Scott Aaronson M.D. opines that “The use of psychedelics — in particular psilocybin, which is among the therapies [Aaronson is] investigating — seems to make patients more amenable to changing the thought patterns that underlie depression; these treatments work as, and with, therapy, not instead of it.”

The “suggestibility” occasioned by psychedelics is repeated often in the literature, primarily in relation to the importance of individuals considering their expectations and goals before the drug is taken. However, the fact that one becomes suggestible under the influence of these drugs leads to other issues. Like Pollan at the beginning of his investigation of psychedelics, one of my many questions is whether the “mystical experiences” reported by so many people who have consumed psychedelics are themselves hallucinations. (Then again, maybe life itself is a hallucination, but I’m not going there. At least not yet.)

Set and Setting

It is believed that “set” (being a shortened form of the word “mindset”) and “setting” have an important influence on the outcome of a psychedelic experience.

“Set” is the mental state that a person brings to the experience, such as thoughts, mood and expectations (Wikipedia). This relates to the “suggestibility” component of hallucinogenic drugs and seems to be why there is so much interest in studying the therapeutic uses of these substances in combination with “talk therapy,” rather than just offering patients psilocybin or LSD to trip with, context-free. As mentioned above, volunteers in the study by Griffiths et al. met with a monitor for eight hours before their drug treatment session, and for four hours afterwards.

 “Setting” is the physical and social environment in which the psychedelic experience occurs (Wikipedia). The psilocybin treatments in the Griffiths study were conducted in a peaceful setting, with the patient reclining and using a facemask and headphones to reduce outside distractions.

Negative Outcomes (Bad Trips and Other Stuff)

The paper by W..W. Griffiths et al. contrasted their generally extremely positive results from administering psilocybin to a study known as “The Good Friday Experiment” (Pahnke, 1963), in which ten theological students were given a dose of psilocybin and another ten were given nicotinic acid in a group setting during a religious service. While the participants who received psilocybin did show “significant elevations on the Pahnke Mystical Experiences Questionnaire [link added by me], and reported positive changes in attitudes and behavior at 6 months and at a 25-year follow up,” (Griffiths et al., p. 13) things got a bit weird (and the study’s double-blind component was broken) when some of the participants who’d received the psilocybin began to act “bizarrely,” affecting the experience of the others in the group.

Most of us have all heard reports of people tripping on psychedelics who have been found running around in traffic or throwing themselves off high buildings. We have also heard of people who had trips that were almost entirely horrifying, and led to all kinds of mental distress even when the drugs had left their systems. And then there are the “flashbacks” (officially known as hallucinogen persisting perception disorder, or HPPD) which causes a small percentage of people who have used psychedelics to have occasional or even (rarely) persistent psychedelic symptoms. According to an article published on BigThink, there is no known cure for HPPD.

All of these outcomes and side-effects sound terrible.

Concerns about effects like these on the masses of young people who were using psychedelics at the urging of Timothy Leary and Richard Alpert in the 1960s (“Turn on, tune in, drop out”) was what got the two men fired from Harvard, and eventually contributed to the banning or at least restricted use of psychedelics in many countries, including Canada and the U.S.

However, the risks of using psychedelics seem to be greatly diminished by close attention to “set and setting” in comparison to their being used in uncontrolled situations. Michael Pollan reports that “Many of the most notorious perils are either exaggerated or mythical” (How to Change your Mind, p. 14). In addition, overdosing on LSD or psilocybin is almost impossible, and these substances do not lead to addiction: most people decide early on that one or two doses is enough, and the effects of these substances are reduced with repeated use. (In fact, they show promise in the treatment of other addictions, including to tobacco and alcohol.)

Since the revival of sanctioned psychedelic research beginning in the 1990s, more than a thousand volunteers have been dosed, and not a single serious adverse event has been reported.

Michael Pollan

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So there you have it: all I know, and then some.

In the next post, I’m going to try to put into words what I have been thinking about meditation as it relates to therapeutic treatment with psychedelics, but if that kind of meandering thought doesn’t stir your interest, you can skip that one and wait for the one after that. If you want to subscribe to this blog, which is free of course, you can put your email address into the little “Sign me up!” box on the upper right of this webpage. Then you will get a notice whenever I get around to posting something here.

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[1] “These mushrooms] may be depicted in Stone Age rock art in Africa and Europe, but are most famously represented in the Pre-Columbian sculptures and glyphs seen throughout North, Central and South America.” (https://en.wikipedia.org/wiki/Psilocybin_mushroom#History )