In the first week of November, Oregon legalized psilocybin (you can read more about this here and here) and a new study about psilocybin therapy was published in JAMA Psychiatry. Exciting times!

24 patients with moderate and severe depression (many who suffered from it for years) were treated with what the researchers call “psilocybin enhanced psychotherapy.” The study took place at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland.

What did the treatment look like?

Patients were randomized to two groups. One that proceeded to treatment right away, while the other waited for 8 weeks¹. All patients, besides receiving two doses of psilocybin separated by about a week, received intense psychotherapy. The goal of the therapy was to prepare the patients for the experience, guide them through it, and then help them integrate what they discovered into their lives. On average, each patient received 11 hours of therapy. This is not a trivial amount. (If one sees their therapist for an hour once a week, this would equal to almost 3 months of therapy.)

How does psilocybin work?

Psilocybin, an active ingredient in the so-called “magic mushrooms,” is what we consider a classic psychedelic. There are two major groups of psychedelics, one with similarity to tryptamine (e.g. LSD, psilocybin, and dimethyltryptamine (DMT). The second category includes variations on the structure of phenethylamine (e.g. mescaline, the main psychoactive agent in the peyote).

Mazatec Indians called the mushrooms “the flesh of gods” and used them for centuries for spiritual and ritualistic purposes. However, Psilocybin, the main psychoactive substance of the Psilocybe cubensis, wasn’t isolated until 1950s. And yet, despite early successes in its use and great interest among the psychiatric community in the 1950s and 1960s, the research efforts came to a halt in the 1970s, when the US government put it on the list of schedule I substances (“having no medicinal value.”)

How does psilocybin work for depression?

Psilocybin works through the serotonin system by stimulating serotonin 2A receptors. The most commonly used antidepressants today belong to the group of Selective Serotonin Re-uptake Inhibitors (SSRIs). The SSRIs appear to work through the serotonin system as well. By blocking the pre-synaptic re-uptake of serotonin, they increase the time serotonin is available and able to bind to the receptor.

But here the similarities end. Those who took psilocybin almost invariably describe their experience as unique, changing how they experienced time and space. Psychedelics change our perception, thoughts, and mood akin to what we experience in dreams or may experience “during contemplative and religious exaltation.” Some experience what we would call a “mystical experience.”

The uniqueness of psilocybin is that despite its power to change the subjective experience so profoundly, it does not produce physical addiction, craving, confusion, or loss of memory. Contrary to the mainstream opinion, it typically does not cause frank hallucinations either.

And now, it seems, it may change the paradigm of pharmacological treatment of depression.

What did the study show?

The results are powerful. Overall, 71% of patients had significant response (defined as 50% drop in depression score) and more than half were considered being in remission at 4 weeks following the administration of psilocybin. For complete results, see the manuscript here.

The effect of psilocybin therapy was 4 times greater that antidepressant medications or psychotherapy alone.

Of course, the study was small and relatively short (the researchers, however, followed the patients for a year after, and these results will be published separately).

It is incredibly difficult to do research with psychedelics today. This study’s overwhelmingly positive results open doors to a new paradigm of treatment that may change not only the way depression is treated but also many other psychiatric disorders, including addiction or PTSD.

1. This allowed the researchers to compare the immediate results of treatment within the first group with the “delayed” cohort. Such design also attempts to control for the “uplifting” effect of an enrollment in a study. And, in the end, allows the researchers to treat both groups identically. ↩