Repeated Weekly Psilocybin Doses Show Promise for Treatment-Resistant Obsessive-Compulsive Disorder

A randomized, double-blind, placebo-controlled study of 15 adults (18-65) with moderate-to-severe, treatment-resistant OCD was conducted at the University of Arizona. Participants received weekly oral psilocybin or an active placebo (lorazepam) over eight weeks: a four-week double-blind phase followed by a four-week single-blind phase. Sessions lasted ten hours with eyeshades, music, and facilitators. Symptom severity was measured with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before treatment, after each session, and at follow-up. Findings appeared in the *Journal of Psychopharmacology*.

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OCD care—cognitive-behavioral therapy and SSRIs—fails for many patients. Early case reports, a 1997 observation by psychiatrist Francisco A. Moreno, suggested psychedelics might alleviate refractory symptoms. The trial was led by Moreno, professor of psychiatry at the University of Arizona, with co-authors Katja E. Allen, Christopher B. Wiegand, Rajan Dunne, James I. Prickett, Brian Bayze, and John J. B. Allen.

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• Response: 73 % of participants receiving >=4 doses achieved >=35 % Y-BOCS reduction.

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• Remission: 40 % reached remission by week 8.

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• Durability: Benefits persisted, though modestly reduced, at six-month follow-up.

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• Safety: No serious adverse events, psychosis, or increased suicidality; mild nausea occurred mainly in low-dose sessions.

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The data indicate that controlled, repeated psilocybin dosing can deliver rapid, lasting relief for individuals unresponsive to conventional therapies, addressing a critical unmet need in psychiatric care.

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Investigators reported a favorable safety profile in a screened cohort and a clear dose-response trend, while noting that high-dose psilocybin’s intense effects challenge blinding despite low-dose and active-placebo controls. They called for larger studies to confirm efficacy and refine dosing.

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Key limitations are the small sample size, limiting statistical power and generalizability, and possible selection bias toward motivated participants with strong support. The study lacked a direct comparison with standard pharmacotherapies, and the effect of recent serotonergic medication discontinuation remains unclear.

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• “In the mid-1990s I met a patient with treatment-resistant OCD who reported having had lasting benefit from OCD while using psychedelics,” — Francisco A. Moreno, Professor of Psychiatry

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• “We pursued a pilot study of various doses of psilocybin to explore safety and signal of efficacy acutely for OCD and published this in 2006,” — Francisco A. Moreno

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• “The fact that most people who benefited from psilocybin initially remained well at 6 months was nice to see,” — Francisco A. Moreno

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• “Further research is needed in larger-scale studies to demonstrate clinical utility,” — Francisco A. Moreno

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The team plans expanded trials to determine optimal dose ranges, session frequency, and mechanisms of action using functional imaging. Ongoing work will also explore subjective experience correlates.

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