Repeated psilocybin doses eased OCD symptoms in a 15-person trial

Most published psilocybin trials have tested a single dose or two. A trial published this month in the Journal of Psychopharmacology took a different approach for obsessive-compulsive disorder (OCD), testing up to eight weekly psilocybin sessions in a small, randomized, double-blind comparison against an active placebo [s1].

The design

Fifteen participants with OCD were randomized into a two-phase trial [s1]. In the double-blind Phase 1 (five participants per group), they received four weekly sessions of either high-dose psilocybin (300 μg/kg), low-dose psilocybin (100 μg/kg), or an active placebo — lorazepam, a benzodiazepine chosen because it produces some subjective effects, unlike an inert placebo [s1]. All participants then proceeded to a single-blind Phase 2, receiving four additional high-dose psilocybin sessions regardless of their original group assignment [s1]. OCD severity was measured with the Yale-Brown Obsessive Compulsive Scale (YBOCS) after each session and followed prospectively for six months [s1]. Safety was tracked through systematic adverse event assessment, a suicide severity rating scale, and psychosis screening [s1].

What it found

Psilocybin was generally well tolerated: no serious adverse events, no psychotic symptoms, and no significant changes in suicide severity scores were reported [s1]. Psilocybin — but not the lorazepam placebo — produced a significant reduction in YBOCS scores [s1]. By the end of the eight-week treatment period, after participants had received at least four high-dose psilocybin sessions, 73.3% were classified as responders, defined as at least a 35% reduction in YBOCS score, and 40% were in remission [s1]. Those effects diminished somewhat but remained substantial at the six-month follow-up [s1]. A post-hoc analysis found that higher cumulative psilocybin dosing correlated with larger YBOCS score reductions by the end of treatment [s1].

Reading the trial size

Fifteen people is a very small trial, even by the standards of early-phase psychedelic research, and the double-blind comparison phase split those 15 across three groups of five each — meaning the placebo-controlled portion of the trial, the part best equipped to isolate a genuine drug effect from expectation or the passage of time, rests on just five people per arm. The strongest response numbers reported — 73.3% response, 40% remission — come after Phase 2, when all participants, including those originally assigned to low-dose psilocybin or lorazepam, had received multiple high-dose psilocybin sessions and the trial was no longer blinded to a placebo comparison. That's a meaningful design detail: the headline response rate describes an open-label, repeated-dosing phase, not the placebo-controlled comparison alone.

What this does and doesn't establish

Current OCD treatments — serotonin reuptake inhibitors and cognitive behavioral therapy — leave many patients without adequate relief, which is the clinical gap this trial's authors cite as motivation [s1]. The repeated-dosing design (up to eight sessions) is itself a departure from the single-or-double-dose protocols used in most psilocybin depression trials, and the post-hoc dose-response correlation is a hypothesis-generating finding rather than a confirmed one, given the trial wasn't designed or powered to test dosing frequency as its primary question. The authors themselves describe the results as showing psilocybin "appears to be safe and potentially effective" and explicitly call for larger trials [s1] — language that reflects the exploratory, safety-focused nature of a 15-person study.

What to watch

Whether a larger, adequately powered, placebo-controlled trial replicates the OCD symptom reduction seen here, and whether the dose-response relationship holds up as a genuine finding rather than a product of the small sample. Psilocybin is not approved for OCD or any indication; this article describes investigational drug trial results and is not medical advice.

Sources

1. A randomized clinical trial of repeated doses of psilocybin for the treatment of obsessive-compulsive disorder — Journal of Psychopharmacology, 13 March 2026