This article was originally published on Psychedelic Spotlight and appears here with permission.
While psychedelic studies now number in the thousands since Western research began in the 1950s, we unpack five of the most important in recent years as psychedelics are on the cusp of becoming mainstream medicines.
When it comes to drugs such as psilocybin and MDMA, culturally, our society is undergoing a major transformation as more psychedelic studies come to light. Whereas in the relatively recent past, these compounds were thought to be the domain of druggies and degenerates, they are increasingly coming to be seen as medicines.
This perceptual pivot has picked up steam over the last few years, as evidence of the healing effects of psychedelics have expanded from whispered anecdotes of becoming whole again at an illegal ayahuasca retreat, to carefully collected clinical data measuring their effectiveness in treating a range of mental health conditions. And while there are too many to cover in one article, several recent trials have been so influential that they have accelerated our timeline for the legalization of psychedelics as medicines.
In this article, I cover the 5 most influential psychedelic medicine clinical trials of recent years.
As a brief and simplified reminder, in order for a new drug to be approved in the United States, it must pass through several “phases” of clinical trials. First, in Phase 1, a drug must be shown to be safe for a small group of healthy humans to take. If this is successful, we move to Phase 2, where the effectiveness of the drug in treating a specific condition is measured in a larger, though still small, population of dozens of people. Often Phase 2 is split between Phase 2a and 2b, with the first testing a range of dose levels against each other, and the second testing a specific dose. Finally, Phase 3 tests the treatment in a larger group, often with 100+ patients. If it is found to be more effective than current treatments in two separate Phase 3 trials, the drug can be approved.
MAPS Phase 3 Trial: Treating PTSD with MDMA Therapy
In 2021, the Multidisciplinary Association of Psychedelic Studies (MAPS) released data on their first Phase 3 trial, treating severe PTSD with MDMA therapy. The 90 patient study included war veterans and sexual assult survivors who, on average, had suffered from PTSD for 14.8 years. As this was the first ever Phase 3 trial for any psychedelic medicine, the stakes were high.
They did not disappoint. In fact, their results were so positive they made the front page of the New York Times, ushering in a new paradigm for psychedelic medicines.
Two months after treatment ended, of those who had received the MDMA therapy, 88% continued to see a reduction of their symptoms by at least 50%. Even more impressive, 67% of those who received the treatment improved so much they “no longer met the diagnostic criteria for PTSD”. Rick Doblin, Founder and Executive Director of MAPS, believes this data to be so positive that MDMA therapy to treat PTSD will be legalized as soon as 2023, after they complete their second Phase 3 trial.
To learn more about MAPS’ Phase 3 trial, treating PTSD with MDMA therapy, read this article.
Awakn Life Sciences Phase 2 Trial: Treating Alcohol Use Disorder with Ketamine Therapy
Of all the psychedelics in this article, only ketamine is currently a legal medicine in the USA. Used primarily as an anesthetic since the 1970s, in recent years clinics have been opening across North America to use the psychedelic in therapy sessions, treating everything from depression to addiction. But despite its apparent popularity, there has been limited clinical trial evidence of its effectiveness.
Until now.
In January 2022, Awakn published the results of their Phase 2 trial attempting to treat Alcohol Use Disorder in 96 patients. The company found that 6 months post-treatment, 86% of those treated with Ketamine Therapy remained abstinent from alcohol, compared to just 2% who were abstinent before the trial began. Furthermore, the rate of relapse was 2.7 times lower than for those in the placebo group, and the mortality rate in the year following treatment decreased by 90%.
These numbers are so positive that they represent a paradigm change for what we consider possible in treating addiction. For example, under current treatments, 75% of heavy drinkers return to their destructive habits within a year. Awakn’s trial is sure to spur not only more research into ketamine assisted therapy, but also accelerate the popularity of legal ketamine clinics world wide.
To learn more about Awakn’s phase 2 trial treating Alcohol Use Disorder with Ketamine therapy, read this article.
Compass Pathways Phase 2b Trial: Treating Treatment-Resistant Depression with Psilocybin Therapy
In late 2021, Compass Pathways released data on the largest ever psychedelic clinical trial, a Phase 2b trial with 233 patients, attempting to treat Treatment-Resistant Depression (TRD). TRD is a severe form of depression, where a patient has previously attempted at least two other forms of treatment, without avail.
The results of this trial, while not as revolutionary as the two above examples, were nevertheless positive. It found that three weeks after the end of treatment, of those who received 25mg of psilocybin combined with therapy, 36.7% saw a decrease in their symptoms by 50% or more, and 29.1% of these patients improved enough to enter remission.
It is important to remember that every patient had a severe form of depression, and other standard treatments had already failed on them. With this context, having almost a third of participants enter remission is a significant achievement. Nevertheless, in the future, Compass hopes to achieve better results in their Phase 3 trials after improving their treatment regimen.
Hopefully, after improving their regimen, we can see Phase 3 results more akin to other psilocybin for depression studies we have seen, such as the Open Label Compass sponsored study that saw 80% of patients with Major Depression Disorder have a decrease in their symptoms of 50% or more, and 50% of patients enter remission.
To learn more about Compass’ Phase 2b trial treating TRD with psilocybin therapy, read this article.
Imperial College of London’s Phase 2 Trial: Psilocybin vs SSRIs for Depression
While it is obviously important that psychedelic medicines perform well against a placebo in clinical trials, it’s arguably more pertinent to study how they perform against current treatments. This is what Dr. Robin Carhart Harris’s team at the Imperial College of London did when they compared the effectiveness of psilocybin therapy in treating Major Depressive Disorder against the most prevalent treatment option, SSRIs.
In the Phase 2 study’s primary outcome of reduction in depressive symptoms using the Qids-SR-16 scale, the researchers found that psilocybin was equally as effective in treating depression as escitalopram, the SSRI used. In fact, the results for the psilocybin group were slightly better, though the population was not large enough to be able to say that there was a “significant difference” between the two compounds. The psilocybin group saw their depressive symptoms fall 8 points on the 27 point scale, while the SSRI group’s fell 6 points
It is when looking at the secondary outcomes of this trial that the advantage of psilocybin over escitalopram became more obvious. For example, it was found that 6 weeks after treatment, 70% of those in the psilocybin group saw their symptoms decrease by 50% or more, as compared to 48% in the SSRI group. Furthermore, 58% of those in the psilocybin group were considered in remission 6 weeks after treatment ended, as compared to 28% of patients in the SSRI group.
Those in the psilocybin group also “reported greater perceived improvements in the ability to cry and feel compassion, intense emotion, and pleasure and reported feeling less drowsy than those in the escitalopram group.” This is important, as a criticism of SSRIs is that while it can be effective in treating severe depressive symptoms, it seems to do so by muting your emotions in general. In contrast, psilocybin appears to make you confront your emotions, and tackle the underlying causes of your depression.
While this study was exciting, its small population size of 59 patients limits how much we can extrapolate from its data. Hopefully in the future we will see larger head to head studies of psilocybin therapy vs. SSRIs, so that we can have a better understanding of their comparative effects.
Small Pharma’s Phase 1 DMT Safety Trial
I may be slightly biased in putting this trial in a list of the most influential psychedelic medicine clinical trials. While the four above were all Phase 2 trials, this one was only Phase 1. Nevertheless, as I find DMT to be the most mysterious of the classic psychedelics, with side effects including blasting your consciousness off into a completely different world where you can interact with autonomous beings, any step we take towards understanding this “spirit molecule” is exciting.
In 2021, Small Pharma released data from their Phase 1 safety trial, the world’s first Phase 1 DMT clinical trial. The headline number was that of the 24 patients who received an intravenous dose of DMT, ZERO people had a drug-related serious adverse event. Furthermore, during the three months after dosing, there were no statistically significant negative effects on anxiety and well-being. In other words, DMT was safe to take.
While we did not get any data on the effectiveness of DMT in treating a specific condition, having the first clinical trial showing the substance to be safe is an exciting step. Small Pharma has now progressed the drug to phase 2a trials, testing it in treating Major Depressive Disorder. I can’t wait to see that data.
