Repeated psilocybin doses for OCD: a small randomized phase 1 trial in 15 people

The question

Is it safe to give people with obsessive-compulsive disorder (OCD) several doses of psilocybin, and do their symptoms improve?

What they did

Fifteen adults with OCD took part. In the first phase, neither participants nor researchers knew who got what: five received four weekly high doses of psilocybin (300 µg/kg), five received four weekly low doses (100 µg/kg), and five received an active placebo (the sedative lorazepam). In a second phase, everyone received four more high-dose sessions, with only the participants kept unaware of the design details. OCD severity was measured with a standard rating scale (the Yale-Brown Obsessive Compulsive Scale, or YBOCS) after each session and followed for six months. Safety checks included systematic tracking of side effects, a suicide severity rating and screening for psychotic symptoms.

What they found

Psilocybin was generally well tolerated. There were no serious adverse events, no psychotic symptoms, and no significant change in suicide severity scores. Psilocybin, but not the placebo, significantly lowered YBOCS scores. After eight weeks of treatment, by which point participants had received at least four high doses, 73.3% were classed as responders (a drop of 35% or more in YBOCS scores) and 40% were in remission. The effects were smaller at six months but the authors describe them as still substantial. A post-hoc (after-the-fact) analysis found that the total amount of psilocybin received was correlated with the size of the symptom reduction at the end of treatment.

The fine print

Only 15 people took part, with five per group in the blinded phase, so the results are fragile and could easily change in a larger trial. The second phase was single-blind and gave everyone psilocybin, so there was no comparison group for the later sessions. Lorazepam as an active placebo may not fully mask who received psilocybin. The response rate at six months is described only in words, not numbers, and this summary is based on the abstract alone.

What it means

In a small, carefully monitored research setting, repeated psilocybin dosing appeared safe and was linked to meaningful drops in OCD symptoms, but the study is far too small to establish that it works.

Evidence grade: Very low. A randomized trial, but a very small phase 1 study with only five people per group and a single-blind second phase, so the results are preliminary.

This summary is based on the study’s published abstract.