Psychedelics: are they a super effective treatment for some mental health afflictions?

February 1st, 2022 <20 minute read. >6,500 words

Are some psychedelics very beneficial or dangerous, and for whom and how and why?

There has been a huge resurgence in interest in recent years in psychedelics for treating mental health issues, with many psychedelic compounds currently being progressed through clinical trials, with this note providing some background and a quick snapshot of some of the latest developments.

But firstly, in many countries the possession or use of psychedelics is highly illegal and can result in long prison sentences for its possession or use. It can be a “schedule one” drug ie viewed by the authorities as one of the most dangerous drugs; Schedule 1 is for drugs that have a high potential for abuse, no accepted safety under medical standards, and no currently accepted medical use. Heroin is schedule 1, (but cocaine is not) in the USA. (After 1970, LSD, psilocybin and mescaline were legally designated ‘Schedule 1’ substances, meaning that they could not be prescribed by medical doctors outside of authorised research. Funding for research dried up in the wake of hardening socio-political attitudes towards psychoactive drugs in general. MDMA became illegal in 1984.) But psychedelics are legal or in a grey area in some countries.

Secondly, many drugs work in different ways on different people, so there is a risk that something that may be very beneficial for one person may seriously harm another and cause permanent damage. So individual qualified medical advice should be sought for any affliction.

Thirdly, the author is not a medical doctor nor scientist so any comments must not be construed as medical advice or encouragement to use any drugs at all. Proper medical advice must be obtained for any ailments that someone may be seeking help for. And any information presented here is thought to be accurate at the date of writing but may change at a moments notice and this note will not be updated.

It is worth noting that there had been amore than one thousand scientific papers on psychedelic drug therapy before 1965, involving more than 40,000 subjects. Beginning in the 1950’s and continuing in to the 1970s, psychedelic compounds had been used to treat a variety of conditions, including alcoholism, depression, obsessive-compulsive disorder, and anxiety at end of life (eg when terminally ill with cancer) frequently with impressive positive results. (But few of the studies were well controlled by modern standards.) Many studies were conducted at Esalen, the legendary retreat in Big Sur, California. 83% of subjects in a 1960s study said they “had glimpsed a higher power, or ultimate reality”.

So I review the current state of play in psychedelics in the following sections:

1) What are psychedelics (and associated substances)?

2) What do they do and where are they used?

3) What is their history?

4) Who is undertaking scientific research and what have they found?

5) Should I invest in the space and if yes, how, where and who?

6) Summary

See also the websites in the references at the end of this blog for more detail than presented here eg tripsafe.org; michaelpollan.com; thethirdwave.co Note: The author has not independently verified data on the site.

What appears to come out of the review is that, should you decide to undertake some psychedelic experience(s):

1) You might be well advised to try to establish the root cause of your issue(s), if possible, possibly through work with a psychotherapist, and then match your chosen psychedelic and treatment approach with your personal situation; and

2) Combine your treatment with psychotherapy sessions... you could well be undergoing "psychedelic assisted psychotherapy."

1) What are psychedelics (and associated substances)?

Psychedelics can be described as physically non-addictive compounds which temporarily alter the state of one’s consciousness, and can change the connectivity in the brain.

Psychedelics work in part by stimulating the serotonin system in the brain in an unusual way. The serotonin system is partly responsible for regulating our mood and levels of anxiety.

This increased connectivity could explain some of the reports by individuals who have ingested psilocybin as experiencing a “new perspective on self and previous experiences”, thereby providing a permanent cure for some people that were “trapped in a negative thought cycle”. Or rather, it can cause permanent changes to the “Default Mode Network” ie a constant cycle of thinking a certain way.

Depending on the drug and dose, psychedelic therapy can last from about 2 to 12 hours.

The prevailing opinion in the USA and many other countries is that there are drugs that have legal status and are either relatively safe or at least have acceptable risks, and there are other drugs that are illegal and have no legitimate place at all in society. This opinion is widely held and vigorously promoted, but, for psychedelics, there appears to be a slow a change of opinion in some circles, if the psychedelics are correctly administered to certain people. Just to be clear, there are many illegal drugs that should never be taken under any circumstances, are hugely addictive and could fairly rapidly, or over the long term, kill the user and destroy many lives. We are only looking at psychedelics in this note and implore any reader to avoid other illegal drugs, and even some legal drugs eg opioids.

Patients (at Kings College, London) receiving psychedelics describe it as like a ‘waking dream’. The key difference to a dream is that people tend to remember the experiences they have with psychedelics. Like a dream, unusual experiences can occur; these can be both pleasant or unpleasant. These experiences are not likely physically harmful to you, but may give you pause for thought.

Some people report that their experiences with psychedelic therapy have been very helpful. Some people have reported negative and distressing experiences with psychedelic therapy that have nonetheless allowed them to understand why they are suffering, which has then been helpful. Some people have reported negative and distressing experiences with psychedelic therapy that have not been helpful, or made them feel worse. Some experts don’t know how psychedelic therapy does this and not everyone reports these experiences.

It is worth noting the following chart complied by David Nutt et al “Drug harms in the UK: a multi-criteria decision analysis” of The Harm of Drugs in the UK, where it is split in to harm to self and harm to others. Researchers led by Professor David Nutt, a former chief drugs adviser to the British government, asked drug-harm experts to rank 20 drugs (legal and illegal) on 16 measures of harm to the user and to wider society, such as damage to health, drug dependency, economic costs and crime.

Obviously, as one reviews the above list, some drugs take much longer to have the negative (or positive) effects than others. And the setting or rather environment in which the drugs are taken can have a large effect on the outcome of the experience(s). And it is worth noting that the active ingredient in mushrooms, psilocybin, ranks at the bottom of the list.

Or the harm caused by drugs chart with more detail:

The above chart implies that mushrooms can have amongst the lowest risks, but can have a risk of impairment of mental functioning… but it appears for only a small proportion of people, and beforehand it can be hard to work out who this might occur for.

The current standards of care for depression, anxiety and addiction and PSTD (Post Traumatic Stress Disorder), often prove to be very ineffective eg SSRIs (Selective Serotonin Reuptake inhibitors, or SNRIS- serotonin -norepinephrine reuptake- both second generation drugs).(A number of the leading anti depressants are FDA approved for use in indications beyond Major Depressive Disorder (“MDD”), including Obsessive Compulsive Disorder (“OCD”); General anxiety disorder (“GAD”); Panic Disorder, social anxiety disorder (“SAD”); Premenstrual Dysphoric Disorder (“PMDD”) and PSTD and bulimia.

So more and more scientific groups are studying the use of psychedelics to treat mental health issues, and some are finding, for some, that these can be very effective, and much more effective than existing drugs, spurring enthusiasm for further research.

There are a number of different psychedelics, each with a different mechanism of action ie the way it works, and different types can be used for different issues.

The FDA is currently expected to approve the controlled use of MDMA (aka ecstasy) by 2025/26 and approve the controlled use of psilocybin before 2026. But of course it may not happen depending on what the clinical trials show, or political or public opinion interference.

A short list of some different psychedelics and associated products is set out below:

Psilocybin (aka “magic mushrooms”)

Targetted for treatment resistant Depression (“TRD”).

Potential other uses: Major depressive disorder, Anorexia; autism; Bipolar disorder; Chronic cluster headache; Body Dismorphic Disorder.

Psilocybin is a naturally occurring plant alkaloid found in the psilocybe genus of mushrooms. There are >150 species of psychedelic or hallucogenic mushrooms worldwide, and of course many other mushrooms that can kill you!

>100million people worldwide suffer from TRD. (SSRIS, commonly used for depression, can have slow onset and do not work well for many and can cause emotional blunting, as well as many other potential negative side effects).

A full trip may last 5 to 8 hours, and results may be very much affected by “set” (ie the individuals phenotype) and setting (the environment, your specific guides etc), so it is important to get this right.

Some psilocybin types of mushrooms:

Or the chemical structure of the active ingredient:

In 2020 The State of Oregon and Washington DC decriminalised the substance found in magic mushrooms.

Pysilocybin may be easier to progress through to medical use as many fewer people have heard of it, and it does not carry the cultural baggage of LSD.

A short video that can give a useful overview on psilocybin includes Rhonda Patricks video: Can Psilocybin Treat Depression? (foundmyfitness.com).

Microdosing: It is said that there are many people microdosing (ie 1/10th the average dose where one gets some effects and can still function normally; and sub-hallucinogenic) psilocybin in Silicon Valley. Microdosing is frequently undertaken to improve mood, cognitive function and mental concentration, as well as to enhance creativity and problem-solving skills. Also, some individuals microdose to self-medicate for cluster headaches, depression and anxiety, among other conditions.

There are some 4 types of popular regimens: Perhaps the most popular schedule was proposed by James Fadiman, consisting of two consecutive days of dosing followed by two days without dosing (Fadiman, 2011).

The second approach involves dosing on weekdays, from Monday to Friday, without dosing on Saturdays and Sundays.

A third approach is based on two out of every three days.

Finally, some users dose every day.

Dosing periods are highly variable, ranging between one week and several years.

In the case of psilocybin mushrooms, microdoses are within the range of 0.1 g to 0.5g of dried mushroom material.

The efficacy of microdosing to enhance mood, creativity and cognition and to reduce anxiety and depression is supported by anecdotal accounts. However these reports are self reported and may suffer from confirmatory bias.

There has not been research to establish if microdosing is a safe practice leading to desirable effects. However some scientists interviewed by the author are not positive on microdosing at present, believing that it may have long term negative effects, primarily concerned that a continual “erasing” might have negative long term effects.

And if you ever do a full trip, the constant recommendation from experienced users is that you must not fight it, if you find something scary, go towards it… Be curious and interrogate those scary things eg death… surrender to the experience… however frightening or bizarre..

“Some 70 percent of people will say that they have had one of the most meaningful experiences of their lives…”(Roland Griffiths quote.. but may be biased or highly exaggerated..).

And mushrooms, a fungi, has a job in nature to break down complex organic molecules. Without them, the earth would long ago have become a vast, uninhabitable waste heap of dead and undecomposed plants and animals. (If you want to read more about mushrooms read books by Paul Stamets). Note that Pencillin is a product of a fungus.

Psilocybin has been found to exert its clinical evidence through activation of the 5HT2a serotonin receptor and downstream neuroplasticity in default mode network circuits of the brain. While the exact cause and features of the increased post-dosing neuroplasticity has not been well characterized, brain imaging has shown near term and lasting changes to neuronal signalling in patients after psilocybin treatment.

MDMA (aka “ecstasy”).

Targetted for PTSD.

Potential other uses: general anxiety disorder.

For much more and useful background, view show notes/ listen to Peter Attias , The Drive podcast: #65 – Rick Doblin, Ph.D.: MDMA — the creation, scheduling, toxicity, therapeutic use, and changing public opinion of what is possibly the single most important synthetic molecule ever created by our species”. (2019). #65 - Rick Doblin, Ph.D.: MDMA — the creation, scheduling, toxicity, therapeutic use, and changing public opinion of what is possibly the single most important synthetic molecule ever created by our species - Peter Attia (peterattiamd.com)

It is important to note that you will also realize from the Doblin discussion just how different MDMA is compared to the average psychedelic.

There is no dissociation; no hallucination; and you remember the experience as though you’re completely awake.

MDMA is an Empathogen; a class of psychoactive drugs that produce experiences of emotional communion, oneness, relatedness, emotional openness—that is, empathy or sympathy.

It’s also similar to mescaline, but it doesn’t have the ego dissolving, sort of visual classic psychedelic properties that mescaline has.

Some clinics/ retreats give ecstasy / MDMA the night before the psilocybin trip treatment, to make the psilocybin treatment more effective.

There were some press reports of people dying from taking ecstasy, however counter stories were that people on ecstasy would dance continuously at nightclubs and not drink the clubs alcohol for sale (where the clubs profits were) , just take water, so the nightclubs turned off all water in the toilets and would not serve water, so some people overheated and died…

But you can also get “Hyponatremia” where as people drink too much water they dilute their blood. In therapy some use fruit juices or things with electrolytes- it is better to drink stuff with electrolytes than water if you’re doing MDMA.

Doblin does not think MDMA is likely to be helpful for people with bipolar disorder, and needs to handled differently for people with schizophrenia.

Set and setting is also important. But with MDMA compared to other psychedelics, Doblins states you have much more control of the direction of the experience.

The FDA has approved MDMA for compassionate use.

Ketamine /Esketamine:

Targetted for addiction.

Potential other uses: TRD.

Many clinics are available, and some say that it is also good for depression. Eg Insight Ketamine in Santa Fe, NM. Insight Ketamine of Santa Fe | Begin the Path to a Happier and Healthier Life. OR Ketamine Therapy - Santa Fe, NM - Ten Thousand Waves OR Blue Sky Ketamine - Santa Fe, NM

Currently, ketamine is the only psychedelic substance available outside of research for use in clinical practice.

Ketamine comes in several forms. The only one that the FDA has approved as a medication for depression is a nasal spray called esketamine (Spravato). It’s for adults who either haven’t been helped by antidepressant pills, have major depressive disorder, or are suicidal. They continue on their antidepressant and receive esketamine at a doctor’s office or in a clinic, where a health care provider watches over them for 2 hours after the dose.

For treatment-resistant depression, patients usually get the nasal spray twice a week for 1 to 4 weeks; then once a week for weeks 5 to 9; and then once every week or 2 after that.

(Received FDA breakthrough Therapy designation for TRD in 2013 and for the treatment of MDD with imminent risk of suicide in 2016.)

Ketamine causes what doctors call a “dissociative experience” and what most anyone else would call a “trip.” That’s how it became a club drug, called K, Special K, Super K, and Vitamin K among others. Partiers inject it, put it in drinks, snort it, or add it to joints or cigarettes.

“Ketamine can produce feelings of unreality; visual and sensory distortions; a distorted feeling about one’s body; temporary unusual thoughts and beliefs; and a euphoria or a buzz,” says John Krystal, MD, chief of psychiatry at Yale-New Haven Hospital and Yale School of Medicine in Connecticut, where he is a leader in studying ketamine’s antidepressant effects.

From webMD:

The trip lasts about 2 hours. But there are risks of casual use. The most serious are unconsciousness, high blood pressure, and dangerously slowed breathing. The drug could also cause long-term problems, such as ulcers and pain in the bladder; kidney problems; stomach pain; depression; and poor memory. Ketamine could be fatal for people who abuse alcohol or if you take it while you’re drunk.

To be clear: Casual use is not a treatment for depression. But doctors have developed a protocol for medically supervised use that may help people who don’t get relief from other medications.

Ketamine comes in several forms. The only one that the FDA has approved as a medication for depression is a nasal spray called esketamine (Spravato). It’s for adults who either haven’t been helped by antidepressant pills, have major depressive disorder, or are suicidal. They continue on their antidepressant and receive esketamine at a doctor’s office or in a clinic, where a health care provider watches over them for 2 hours after the dose.

For treatment-resistant depression, patients usually get the nasal spray twice a week for 1 to 4 weeks; then once a week for weeks 5 to 9; and then once every week or 2 after that.

The spray has a “black box” warning about the risk of sedation and trouble with attention, judgment, and thinking, as well as risk for abuse or misuse of the drug and suicidal thoughts and behaviors.

Other forms of ketamine not approved by the FDA for mental health conditions include IV infusion, a shot in the arm, or lozenges. Most research looks at ketamine given by IV. You can only get it by IV or shot in a doctor’s office. Some doctors will prescribe lozenges for at-home use -- often to keep depression at bay between infusions.

The IV infusion lasts about 40 minutes. The dissociative experience starts quickly and takes about 15 to 20 minutes to wear off after the drip ends. A doctor is always on site during the whole process. The doctor isn’t necessarily in the room with the person being treated but is available if they need anything or become anxious or confused.

While the patient is on the drip, Stewart says, they look asleep. Most don’t move or talk. Though some, he says, may talk or make a comment about the music playing on their headphones or some part of their experience or perhaps ask where they are. Unless they need something, Stewart says, no one interferes.

Christa Coulter-Scott, a pediatric nurse from Athens, GA, got treatment in a similar setting in Gainesville, GA. She says she didn’t want to wake up. “It was like a spiritual journey. I felt warm, safe, and confident. As the treatment went on, all the weight of stress was taken off of me in layers. I felt like I had the power of the universe at my fingertips.”

At Stewart’s clinic, after the mind-altering part of the ketamine experience is over, a health provider sits and talks with the patient in a process called integration. Other clinics may recommend that patients continue their talk therapy elsewhere.

“It’s my sense that this is important,” Stewart says. “When people come out of this really profound experience, they have a lot to say, and these are people who have a lot of baggage and a lot of experiential pain. A lot of times, ketamine leads to an unpacking of that baggage.”

Weeks, months, or years after their first series of six to eight doses, patients may return for a booster. There is no standard recommendation for when or if people need a booster. They discuss it with their doctor if symptoms of depression start to reappear.

“For about 30% of people who complete the whole series, that’s it. They never come back,” Stewart says. “For those who come back for boosters, it seems the boosters get further and further apart until they eventually don’t need them again.”

“It may not matter, but it does concern me, personally, that ketamine works through an opioid mechanism,” he says. The worry, which other researchers have mentioned in studies of ketamine, is that people might require larger and larger doses of ketamine over time in order to feel its effects -- as is the case with opioid painkillers. The spreading and tapering of treatments over time should help reduce this risk.

Of course, any comparison to opioids raises the question of the risk of addiction.

“I think it’s probably less addictive than opioids, but it’s not without its risks,” says Shatzberg, who is the director of Stanford University’s Mood Disorders Center. Indeed, case studies have described people who showed signs of addiction or abused the drug.

Because it’s an off-label treatment, it may be too soon to tell whether the risk of addiction or tolerance outweighs the possible benefits. It’s important to note though that some recommendations suggest it may not be safe for people who have a history of substance abuse. Many clinical trials have barred people with substance use problems.

It also may not be safe for people who have schizophrenia. “At the antidepressant dose, ketamine transiently worsens their symptoms of psychosis,” Krystal says.

As for the drug’s action on glutamate receptors: Regrowing and reactivating synapses helps the brain’s ability to change, which may help it shift out of depression. That may also explain why antidepressants or psychotherapy that didn’t help before ketamine may help afterward.

Stewart says “That wasn’t a temporary change,” he says. “It was a shift in who I am, how I approach the world, and my feelings towards my own emotions.”

Ibogaine:

Targetted for Opioid use disorder

DMT:

Targetted for TRD and MDD- Major depressive disorder.

(aka “The Toad”) Is active for 5 to 30 minutes. The main active ingredient in the tribal ritual, called, Ayahausca.

For more information see two stock market listed pharma companies: DMT Therapies - Treatment Journey - Small Pharma or GH Research. Home | GH Research

LSD: (Lysergic acid diethylamide)

Targetted for depression, anxiety, addiction.

LSD alters communication among regions of the human brain. A study using functional magnetic resonance imaging (fMRI) showed that a very low dose of LSD sufficed to alter the functional connectivity between the amygdala and several cortical regions.

The trip can be 8 to 12 hours.

LSD is one of the most potent classical hallucinogens available, with active doses between 0.5 and 2 mcg/kg (100–150 mcg per dose). Its half-life is approximately 3 hours, varying between 2 and 5 hours, and its psychoactive effects are prolonged over time (up to 12 hours depending on the dose, tolerance, weight and age of the subject). Recently LSD has been used in microdoses as low as 10 mcg to enhance performance.

The usual mental effects of LSD are distortion of sense of time and identity, alteration in depth and time perception, visual hallucinations, sense of euphoria or certainty, distorted perception of the size and shape of objects, movements, colour, sounds, touch and body image and delusions.

Concerning safety, the administration of classical hallucinogens carries some risks. One of them is the so-called “bad trip” or “challenging experience”, described as an acute state of anxiety, dysphoria and confusion, which can lead to unpredictable behaviour in uncontrolled or unsupervised environments. Another possible risk is the exacerbation of psychotic disorders or the generation of prolonged psychotic reactions, which could be related to the subject's previous predisposition. Another possible adverse effect is a modest increase in blood pressure and heart rate; therefore, patients with severe cardiovascular disease should be excluded from the administration of this agent. Other usual absolute contraindications are pregnancy, epilepsy or paranoid personality traits. Classical hallucinogens in general, and LSD in particular, exhibit very low physiological toxicity, even at very high doses, without evidence of organic damage or neuropsychological deficits.

A researcher at Sussex University, studies how the brain helps us perceive the world within and without, and is intrigued by what psychedelics such as LSD can tell us about how the brain creates these perceptions. He described his experiences on LSD: “He revelled in a sense of well-being and marvelled at the “fluidity of time and space”. He found himself staring at clouds and seeing them change in to faces of people he was thinking of. If his attention drifted, the clouds morphed in to animals.”

It should be noted in the 1960s some two million people were said to have tried LSD, but there was also a surge of people on LSD showing up in emergency rooms with acute symptoms of paranoia, mania, catatonia, and anxiety, and also “acid flashbacks”- a spontaneous recurrence of symptoms days or weeks after ingesting LSD. And young people at risk for schizophrenia, an LSD trip can trigger their first psychotic episode. But it could be that the right set and setting notably reduces the likelihood of negative outcomes.

Ayahuasca:

Main active component is DMT. The researcher at Sussex University also tried Ayahuasca, a hallucinogenic brew made from a shrub and a vine native to South America and often used in shamanistic rituals there. This time, he had a more emotional trip that dredged up powerful memories. Some celebrities go off to Peru for their experience, and others do it closer to home. Many report getting very sick and vomiting during the ritual.

Again, it is worth listening to a podcast from the super smart medical Doctor and researcher Peter Attia (podcast: The Drive): [August 2019] “ #65 – Rick Doblin, Ph.D.: MDMA — the creation, scheduling, toxicity, therapeutic use, and changing public opinion of what is possibly the single most important synthetic molecule ever created by our species”.

2) What do they do and where are they used?

Much research is being undertaken to try to work out why and how psychedelics work, but much is not fully conclusive as yet. However many drugs under development have specific targets and mechanisms of action identified.

Here’s why scientists think it works: When someone takes a psychedelic, there is a decrease in blood flow and electrical activity in the brain’s “default mode network,” a group of brain structures found in the frontal and pre-frontal cortex. The default mode network is primarily responsible for our ego or sense of self; it “lights up” when we daydream or self-reflect.

When we trip, our default mode network slows down. With the ego out of commission, the boundaries between self and world, subject and object dissolve. These processes may be related to something called the “primary mystical experience,” a phenomena highly correlated with therapeutic outcomes. As Matthew Johnson, a principal investigator in Johns Hopkins’s psilocybin studies, explains, these experiences include a “transcendence of time and space,” a sense of unity and sacredness and a deeply felt positive mood.

Robin Carhart-Harris, a neuroscientist with Imperial College London, notes that the default mode network is responsible for a lot of our rigid, habitual thinking and obsessions. Psychedelics help relax the part of the brain that leads us to obsess, which makes us calmer. And they can help “loosen if not break” the entrenched physical circuits responsible for addictive behaviour. The right intervention from your guide may help shift the default mode network, perhaps resulting in a permanent change for some.

There’s also an increase in activity between different parts of the brain that don’t normally communicate — what scientists call “cross-talk.” That may be why we hallucinate while on psychedelics; the brain’s visual-processing centers are interacting in strange ways with the parts of the brain that control our beliefs and emotions.

There are many retreats globally, such as retreats in Jamaica, and whilst it is a “grey area” ie not totally clear, they are viewed by many as being legal in Jamaica. (The source for whether it is legal in Jamaica is the Atman Clinic, that administers psilocybin.) For Jamaica retreats see Atman Retreat - Safe, Legal Psilocybin Experiences in Jamaica; Silo Wellness, Jamaica; Soltara Healing Center, and Costa Rica (Ayahusca focus) Soltara Healing Center Ayahuasca Retreats In Costa Rica.

Or Synthesis in Amsterdam Synthesis: Legal Psychedelic Retreat in Amsterdam (synthesisretreat.com) A users experience there is available on the Guardian newspaper. A psychedelic retreat proves a healing trip | Amsterdam holidays | The Guardian Or another review: What happens when you stay 3 days in a psychedelic retreat — a psilocybin experiment | by Isra García | The Startup | Medium

The Goop founder and actress Gwyneth Paltrow made a Netflix movie, and also list ten centers for psychedelics treatments by different type of psychedelic. 10 Psychedelic Therapy Centers & Retreats For Healing | Goop

The Goop Lab movie on Netflix videos and talks about their persons experiences at a psilocybin retreat, see Netflix and Goop Lab, the “Healing Trip”.

But emphasized everywhere, is the high importance of the correct set and setting, and dosage, ie where and what environment you get your treatment done, and who you are with ie your guide or guides, and how much you take. The guides can hopefully make sure you have the best possible experience. Get this wrong and you may have “bad trip” and possibly negative consequences… The role of the guide appears to be crucial. People under the influence of psychedelics are extraordinarily suggestible. The work is typically referred to as “psychedelic therapy,” but it would be more accurate to call it “psychedelic-assisted psychotherapy.”

The experience, recounted from a newspaper review:

The standard protocol for aboveground psychedelic therapy, and the role of the guide at each of the three principal stages of “the journey.” First comes a series of preparation sessions, in which volunteers are told what to expect, asked to set an intention (to quit smoking, say, or confront their fear of death) and offered a set of “flight instructions” for the journey ahead. These generally advise surrendering to the experience, whatever it brings and however disturbing it might become. (“Trust, let go, be open” is one mantra he recommends, or, borrowing from John Lennon, “Turn off your mind, relax and float downstream.”) If you feel as if you are “dying, melting, dissolving, exploding, going crazy, etc. — go ahead.” Richards stressed how important it is for the guide to quickly establish a rapport with volunteers, so that during the session “they can let themselves ‘die’ or go crazy — that requires an awful lot of trust!” Because the patients’ ego defenses are likely to be disabled by the drug, it’s crucial that they feel safe.

The second stage is the journey itself. Richards showed a slide of the Hopkins treatment room, decorated to look like the office of a psychiatrist with an interest in Eastern religion and indigenous peoples, with shelves holding large-format art books and spiritual tchotchkes, including a Buddha and a large ceramic mushroom. The volunteer stretches out on a couch and puts on eyeshades and headphones to encourage an inward journey free of distraction. (Richards has put together a playlist consisting mainly of classical compositions arranged to support and structure the experience.) Two guides, typically one male, the other female, sit with the volunteer for the duration but say very little, allowing the journey to unfold according to its own logic. Mostly the guide is present to offer a comforting hand if the journeyer is struggling, jot down anything she has to say and generally keep an eye on the volunteer’s physical well-being while she is roaming her psychic landscape. Because it is the drug and the mind that drive the journey and not the therapist, the guide’s role calls for an unusual degree of humility, restraint and patience — the sessions can last for hours. (No snoozing or checking of email; meditating, however, is O.K.) Richards describes the session as the “pièce de résistance” of the work, “in which you’re focused intensely on one human being as if that’s all that exists in the world. It’s a great way to get exhausted!”

The last stage is integration, which typically takes place the following day. Here the guide helps the volunteer make sense of what can be a confusing and inchoate experience, underscoring important themes and offering ideas on how to apply whatever insights may have emerged to the conduct of the volunteer’s life. The challenge, as Richards put it, is to help the volunteer transform “flashes of illumination” (he’s quoting Huston Smith, the late scholar of religion) experienced during the trip “into abiding light” — into a new, more constructive way to regard your self and situation.

But the leading researchers at Kings College London state: By using psilocybin before it has been properly tested, retreat centers may be undermining their own credibility and the credibility of the wider field. And “retreat centers offering paid experiences with psilocybin truffles have opened in some countries, often using early phase clinical trial data as a basis for bold, public facing claims. This seems unwise.” These researchers report that around 2.5 million individuals in the UK population report a lifetime history of use of psilocybin mushrooms, but that seems way too high for me (around 3% of the population..?) .

3) What is their history?

Psychedelics were used extensively in the 60s eg LSD, and given the propensity for users to “drop out” and refuse to fight, the Government railed against them partly as it needed young men to go to fight communism in Vietnam. They then ran propaganda campaigns against all forms of drugs, entrenching many views that appear to have remained to this day. Having said this, some drugs, improperly taken, can have huge negative consequences for their users, some are hugely addictive and ultimately kill their users and destroy their lives and that of their friends and family.

Tim Leary was a clinical psychologist at Harvard University, Leary worked on the Harvard Psilocybin Project from 1960 to 1962. He tested the therapeutic effects of lysergic acid diethylamide (LSD) and psilocybin, which were still legal in the United States at the time.

Leary believed that LSD showed potential for therapeutic use in psychiatry. He used LSD himself and developed a philosophy of mind expansion and personal truth through LSD. After leaving Harvard, he continued to publicly promote the use of psychedelic drugs and became a well-known figure of the counterculture of the 1960s. He popularized catchphrases that promoted his philosophy, such as "turn on, tune in, drop out", "set and setting", and "think for yourself and question authority". He also wrote and spoke frequently about transhumanist concepts of space migration, intelligence increase, and life extension. Leary developed the eight-circuit model of consciousness in his book Exo-Psychology (1977) and gave lectures, occasionally billing himself as a "performing philosopher". Many considered that he hugely exaggerated the benefits of psychedelics.

During the 1960s and 1970s, Leary was arrested 36 times worldwide. USA President Richard Nixon once described Leary as "the most dangerous man in America".

Alexander (“Sasha”) and Ann Shulgin were also leaders in this space. They wrote “PiKHAL – a chemical love story.” (Pikhal was an abbreviation of “Phenethylamines / Psychedelics I have known and Loved” and then followed it up with “TiHKAL, The continuation” – “Tryptamine I have known and loved”. Both books were outlawed but now can be bought new on Amazon. Shulgin was a pharmacologist and chemist that designed, tried and ranked and recorded experiences on hundreds of psychedelics, and the two books mentioned here are chemical cookbooks- ie precise recipes and steps of how to make each psychedelic, and the effects felt by Shulgin. He resynthesized MDMA. Each book has some pages devoted to the authors experiences and life story. Shulgin spent most of his adult life investigating the actions of drugs.

If you are ever considering taking drugs you should read the introduction in PiKHAL, where Sasha makes the case for psychedelics ahead of other drugs, and reviews his experiences, methodology and philosophies.

The mission of the founders of Compass Pathways, the leading company researching psilocybin, George Goldsmith and Ekaterina Malievskaia, was to find a solution for their depressed son.

A highly recommended book to read is the writer Michael Pollans “How to change your mind, the new science of psychedelics”.

4) Who is undertaking scientific research and what have they found?

Many of the companies listed in the next section are leaders in scientific research and many have products in FDA reviewed clinical trials.

There are multiple leading Universities and medical establishments undertaking research on psychedelics, such as Imperial College London ; Centre for Psychedelic Research | Research groups | Imperial College London ; Kings College London Psilocybin Trials (kcl.ac.uk) ; John Hopkins Center for Psychedelic & Consciousness Research (hopkinspsychedelic.org) ; Yale Yale Psychedelic Science Group < Psychiatry ; Stanford: Research | Stanford Psychedelic Science Group | Stanford Medicine; NYU, Center for Psychedelic Medicine | NYU Langone Health and many more.

Some leading researchers include people such as Dr Robin Carhart-Harris, Faculty of Medicine, Department of Brain Sciences, Imperial College, London, Home - Dr Robin Carhart-Harris (imperial.ac.uk) and Head of the Center for Psychedelic research. Centre for Psychedelic Research | Research groups | Imperial College London.

Also James Rucker and Allan Young at Kings College London are leading figures in this space.

5) Should I invest in the space and if yes, where and who?

The leading companies in the space are Compass Pathways (listed, CMPS) and ATAI (Listed, ATAI), both backed by the polymath billionaire Christian Angermayer. Angermayer is an evangelist for finding new solutions to improve mental health, and publicly states that he has had a full psilocybin trip, in a jurisdiction where it is legal, rates it as one of the most profound experiences he has ever had, and led to him devoting much of his time to developing psychedelics as a therapy for many with mental health issues. He funded Compass Pathways (psilocybin only firm, in stage two clinical trials, the most advanced company here)- owning c. 25% of it, and then founded ATAI, Home - atai which is a diversified psychedelics platform researching and looking to commercialise a wide range of psychedelics (and non psychedelics also) from Psilocybin, and DMT to Ketamine and so on. Compass Pathways candidate COMP360 (a high purity polymorphic crystalline formulation of psilocybin) is targeted for use in TRD.

In full disclosure I am currently an investor in Compass Pathways and ATAI, and have co-invested in other healthcare focused companies alongside Christian Angermayer (private and Public). Some psychedelics appear to be so effective they can permanently cure the user after one session, and require staff and a clinic to correctly administer the product (expensive) , which can be a bad business model! However there are so many people with mental health issues then the market could grow strongly for many years, and also be very beneficial for many people. Due to the effectiveness, for some, of some psychedelics, then companies such as ATAI are also developing drugs for regular use at home.

There are many companies sprouting up with a range of business plans (not unlike the cannabis boom resulting in the formation of many new companies, many of questionable merit) and many are simply “opportunistic” and, IMHO, potentially dangerous companies and / or investments.

ATAIs positioning (Jan 2022) and their comparison to other TRD programs is as follows:

The Montgomery–Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes, which is used to evaluate the effectiveness of such drug therapies. Given that this brief note is focussed on psychedelics I will not address this further.

With each depressive episode, the risk of re occurance increases 16%. Reported depression is twice as prevalent in women compared to men. Close to 800,000 people die by suicide each year, and it is the second leading cause of death in people 15 to 29 years old. It is also worth noting that depression causes loss of brain cells, and therefore loss of cognitive ability over time.

There are dozens of stock market listed psychedelics companies and more and more conferences being arranged by investment banks on psychedelics, and many of the listed companies have very volatile stock prices. There are many different approaches, from simply rolling out clinics in which to treat people with psychedelics, to firms focused on only one substance eg DMT, or psilocybin, or ketamine, or MDMA etc.

But whatever happens, especially after Covid 19, there will be a large market for effective mental health drugs.

Source: Financial Times, 2021

6) Summary

Should anyone have a mental health issue they need to address, they may end up exploring their options using psychedelics, and match the right psychedelic to their specific issue(s), especially if current medical standards of care are ineffective, and take expert medical advice.

I do not encourage anyone to try any drugs, it is “buyer beware”, but hopefully the above note, very brief and not at all comprehensive, provides an initial list of pros and cons and warnings of trying such substances, and perhaps point some in the right direction for further research.

And be warned, there are some stories of people that have taken such drugs and have had negative experiences, with permanent damage inflicted. But those stories appear to be in a small minority of cases and the full circumstances are not known.

But it appears that some psychedelics, correctly administered, can cause permanent and beneficial changes to some peoples brains and outlook on life. Only the individual and their medical advisor can establish if this is a good route to explore.

So if you decide to become a psychonaut, then I hope that it goes really well for you and it turns out to be a hugely positive experience and the right solution for what you are seeking!

References (Not exhaustive):

1. Michael Pollan, “How to change your mind”. The new science of Psychedelics. 2018. Penguin Books. [The Author of this note highly recommends this as a first read]

2. “PiKHAL: a chemical love story”. Alexander Shulgin & Ann Shulgin. 2020. Transform Press.

3. “TiHKAL: the continuation.” Alexander Shulgin & Ann Shulgin. 2020.

4. Peter Attia, The Drive podcast and show notes. #65 – Rick Doblin, Ph.D.: MDMA — the creation, scheduling, toxicity, therapeutic use, and changing public opinion of what is possibly the single most important synthetic molecule ever created by our species” (2019)

5. Lancet, Nov., 1, 2010. Harm of drugs chart

6. “Microevidence for microdosing with psilocybin mushrooms: a double-blind placebo-controlled study of subjective effects, behavior, creativity, perception, cognition, and brain activity.” Cavanna, 2021.

7. Read: My Adventures With the Trip Doctors - The New York Times (nytimes.com)

8. Research-backed education for psychedelics | TripSafe.org 👽

9. Third Wave | Psychedelic Education, Resources & Community (thethirdwave.co)

10. www.michaelpollan.com

11. What is Ketamine? How it Works and Helps Severe Depression (webmd.com)

12. Numerous websites and personal interviews

Some “fun facts”

- 23 primates (including humans) consume mushrooms and know how to distinguish good from bad

- Paul Stamets, a leading mushroom expert, stated “mushrooms have taught me the interconnectedness

of all life forms and the molecular matrix that we share..” “ I am part of the stream of molecules that are

flowing through nature..”

- The brains of experienced mediators look much like the brains of people on psilocybin