Clinical studies of Magic Mushrooms — Part 2
By: Leafy Tunnel
Tags: Psychedelics, Venture Capital, Investment

Since Albert Hoffman invented LSD in 1938 and went on to isolate psilocybin from the Psilocybe Mexicana mushroom at Sandoz (former Novartis) laboratory in 1958, the golden age for psychedelic research started with more than a thousand scientific papers being published between 1950–65. The counterculture of the hippies did not create psychedelics, the science community did. Once pharmaceutical drugs escaped laboratories onto the street, in 1966 FDA banned further psychedelics research, followed by US and UN scheduling psychedelics in the most restrictive category of drugs with the highest harm and abuse potential and no medicinal value.

After the inclusion of psychedelic drugs in Schedule I, the main agency providing grants for research on psychedelics, the National Institute of Mental Health (NIMH), stopped funding studies into their therapeutic potential. At the same time, getting approval from the Drug Enforcement Agency (DEA) to have these drugs for preclinical studies, became a nearly impossible task. Hence, research into the therapeutic uses of psychedelics including psilocybin stopped abruptly[1]. The end of research into their medical applications has contributed to the public stigma that psychedelics drugs are dangerous. This dissonance between perceived and actual risks is especially striking considering that serious side effects from LSD or psilocybin are extremely rare, while legal substances such as alcohol and tobacco directly contribute to 10 million combined deaths per year across the globe.

The modern renaissance of psychedelics research started in 2006 with Rolland Griffiths‘s landmark paper “Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance”[2]. This was the first double-blind, placebo-controlled clinical study that was done in more than four decades. Thirty volunteers consumed a pill containing either synthetic psilocybin or placebo. Two-thirds of the participants rated the session as among the top five “most spiritually significant experiences” of their lives. In fourteen months follow-up, the volunteers reported significant improvements in “personal well-being, life satisfaction, and positive behavior change”. This clinical study sparked renewed interest in psychedelics research leading to numerous trials at John Hopkins and other universities using psilocybin to treat indications from depression in cancer patients and the general population, alcohol, and tobacco addiction to obsessive-compulsive and eating disorders.

Psychedelics research during the early period of this renaissance has focused largely on using psilocybin to ease the depression and anxiety of terminal cancer patients at the approach of death. Clinical studies for patients with terminal illnesses were taking place at UCLA, John Hopkins, and New York University from 2011 to 2016. During these studies, 80% of cancer patients showed clinically significant reductions in standard measures of anxiety and depression which lasted for at least six months. Many of the volunteers reported that the psilocybin experience allowed them to re-evaluate the prospect of dying and better cope with their fear of death. One of the researchers offered a reason for this improvement in the well-being of cancer patients that “individuals transcend their primary identification with their bodies and experience ego-free states before the time of their actual physical demise, and return with a new perspective and profound acceptance of the life constant: change.”[3] Clinical trials were still considered small involving 99 patients combined at UCLA, John Hopkins, and New York University[4].

When John Hopkins University brought results of their clinical trials for cancer patients to the FDA in order to obtain approval for larger clinical trials, to their surprise the FDA asked them to expand their focus and test whether psilocybin could be used to treat depression of the general population. European Medicine Agency, the FDA equivalent in Europe, was of the same view and both regulators saw that clinical data contained enough strong signal that psilocybin could relieve depression which is a much larger and acute problem for global society than existential distress[5].

There are two companies that are currently conducting the FDA phase II clinical trials of psilocybin to treat depression of the general population — Usona Institute (a not-for-profit organization) and Compass Pathways. Both companies received the FDA breakthrough therapy designations reflecting the enormity of the global need and limitations of available therapies. The Usona Institute will conduct a randomized, double-blind, placebo-controlled trial to evaluate the potential antidepressant effects of a single dose of psilocybin in 80 patients with Major Depressive Disorders[6]. Another company, Compass Pathways is conducting a randomized controlled phase IIb study of psilocybin therapy in 216 patients with treatment-resistant depression in 20 sites across Europe and North America. The study looks at the safety and efficacy of psilocybin therapy in treatment-resistant depression and aims to determine the optimal dose of psilocybin with three doses investigated[7].

Two weeks ago, John Hopkins University has recently published the results of their clinical trials using psilocybin with 24 people suffering from long-term depression. Results were impressive showing four times higher effectiveness of psilocybin compared to traditional antidepressants. Two-thirds of all participants showed a more than 50% reduction in depression symptoms at the one-week follow-up and 71% at the four-week follow-up. Overall, four weeks post-treatment, more than half of the participants were considered in remission — meaning they no longer qualified as being depressed[8]. This clinical study is an important proof of concept for the medical approval of psilocybin for the treatment of depression.

Another important proof of concept will result from clinical trials at Imperial College with 60 participants which will compare the treatment mechanisms of six weeks of daily Escitalopram (SSRI antidepressant) with two doses of psilocybin[9]. This study will be the first of its kind where psilocybin will be put into a test against the current standard of care. Results from this study are expected in early next year.

The next two years will be marked with important milestones towards worldwide recognition of psilocybin as medicine which will include results from clinical trials by Usona Institute, Compass Pathways, and Imperial College. Results from these studies will shed further light on the potential of psychedelics. So, let’s stay tuned!

[1] “Why were psychedelic drugs made Schedule 1?” article by Lauren Mackenzie Reynolds, Neuroscience, McGill University

[2] “How To Change Your Mind” book by Michael Pollan

[3] Hallucinogens Have Doctors Tuning In Again, By John Tierney, April 11, 2010, New York Times

[4] Psilocybin Investigator’s Brochure of Usona Institute dated 31 August 2020, page 20

[5] “How To Change Your Mind” book by Michael Pollan

[6] Usona Institute announcement: Clinical Trial of Psilocybin for Major Depressive Disorder Launching This Fall

[7] Compass Pathways website: https://compasspathways.com/

[8] https://www.hopkinsmedicine.org/news/newsroom/news-releases/psychedelic-treatment-with-psilocybin-relieves-major-depression-study-shows

[9] https://www.imperial.ac.uk/psychedelic-research-centre/trials/