Investigating the potential of psychedelics for mental health

By Sean O’Malley, Senior Writer

Despite promising results as far back as the 1960’s, the clinical study of all psychedelic drugs as a potential therapeutic for treatment-resistant depression and other major mental illnesses was banned for decades for largely political reasons. That freeze on research has lifted in recent years, with several small studies showing promising results.

Recently, one of the world’s most prestigious medical journals, the New England Journal of Medicine (NEJM), published the largest clinical trial of its kind on the potential benefits of psilocybin, the active ingredient in “magic mushrooms”, for treatment-resistant depression.

The purpose of the clinical trial was to investigate the safety and efficacy of psilocybin at different doses. One group of participants was given a large dose, while others received a moderate dose, or a placebo-like dose. All participants received psychological support prior to, during, and after the psilocybin dosing sessions. The trial took place at 22 sites in 10 countries, and CAMH was the only Canadian site to participate.

In an accompanying editorial, the NEJM called the results of its clinical trial “intriguing and sobering.” Intriguing because the results showed that one in three study participants with depression that had previously been treatment-resistant reported a complete absence of symptoms. The results were also sobering because psilocybin’s safety has not yet been established and there were serious adverse effects among participants in all three treatment arms, among these, self-harm and suicidal ideation. It remains unknown whether those adverse effects were because of the drug itself or a result of distress from participants who did not benefit from participation in the trial.

More clinical trials will be necessary to determine if psilocybin can be used safely in a clinical setting.

We asked him how he got involved in this area of mental health research and how he sees the future of clinical research into psychedelic drugs:

Tell us about your background and how you came to CAMH?
“I have been at CAMH for five years. I am Canadian but was born in Pakistan and completed my medical and research training in the U.K., so I consider myself a citizen of the world. My research involves assessing new ways of treating mood disorders, from novel trials including those involving psychedelic drugs, to assessment of low-cost scalable treatments in low-resource settings like Nigeria and Pakistan. My research program aims to improve outcomes for mood disorders across populations and settings.”

How much stigma is there regarding the study of psychedelics?
“There continues to be some stigma within the scientific community as well in the public with regards to therapeutic use of psychedelic drugs. I think that stigma has reduced substantially in the past 15 years because of growing preliminary data showing that these substances may be potentially safe and effective. Research methodologies have improved so much over the last few decades that now is the time to continue to build on these findings to truly assess whether psychedelic drugs can truly help those with mental illness and addictions.”

How would you describe the results of the study?
“Even though some might consider the results of the present study to be modest, a response rate of almost 40 per cent, and a remission rate of almost 35 per cent of participants showing a total absence of depressive symptoms so rapidly with a single-dose treatment is actually very rare. If you look at the results of this study and compare it to other medications currently used for treatment-resistant depression, I would say that they are very encouraging.”

What would you say to people who express an interest in using psilocybin for depression as a result of this study?
“I would warn the general public that although the findings from the studies being published are promising, they are being done in very controlled settings with very selected groups of individuals. For example, anybody who has a family or personal history of any type of psychotic illness was excluded from this study. Further studies are still needed to determine whether psilocybin is safe and effective for clinical use. CAMH is involved in these studies and we are building a program of research in psychedelic science that we hope will address some unanswered questions about the value of psilocybin in treating patients with mental health conditions like depression, but for now it remains very much an experimental treatment.”