PSILORIS

Educational resource only. Not medical advice. Psilocybin remains illegal or restricted in many jurisdictions.

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Candidate / early signal

Obsessive-Compulsive Disorder: psilocybin research evidence

Early open-label work, published case reports, and a modern Yale RCT (preprint primary results plus peer-reviewed qualitative nested analysis) show clinically meaningful OCD symptom reductions after supervised psilocybin. Larger confirmatory trials are still needed, so PSILORIS keeps OCD as a candidate indication.

Last reviewed: 2026-07-26

Evidence narrative

Evidence section. Peer-reviewed findings and evidence-graded interpretation only.

What the early signal showed

In a very small modified double-blind dose-ranging pilot, Moreno et al. (2006) observed marked acute decreases in Yale-Brown Obsessive Compulsive Scale scores after psilocybin. Independent case reports of self-administration and a prospective trial-linked case report later described large, sometimes durable Y-BOCS improvements.

What is happening now

  • Yale RCT (NCT03356483): Protocol and nested qualitative work are peer-reviewed; a preprint of primary clinical results reports large 48-hour A-YBOCS reductions versus niacin and high one-week response rates after a single 0.25 mg/kg dose.
  • PsilOCD uses an active-controlled pharmacological challenge design with EEG and cognitive-flexibility endpoints.
  • An open-label psilocybin-assisted psychotherapy pilot protocol targets treatment-resistant OCD feasibility and preliminary clinical effects.

Why this remains a candidate

  • Confirmatory multi-site peer-reviewed pivotal RCTs are not yet the field standard for OCD the way depression RCTs are.
  • The classic Moreno sample was tiny; self-administration case reports cannot verify dose/purity.
  • Dose-response, durability, therapist-model intensity, and generalisability remain open questions.

Negative or mixed considerations

Not all obsessive or compulsive presentations will respond similarly. Acute intensification of intrusive content is theoretically possible during a session, so screening and monitoring standards matter as much as efficacy hopes.

Citations

[1] randomized controlled trial · 2025

Psilocybin for Treatment-Resistant OCD: A Randomized Controlled Trial

Kelmendi B, Ching THW, Pittenger C, et al. — OSF Preprints / Sciety (preprint; peer-review status evolving)

Preprint report of NCT03356483 (n=28): single 0.25 mg/kg psilocybin produced large acute Y-BOCS reductions versus niacin at 48 hours, with high one-week response rates and benefit persisting through 12 weeks in the psilocybin arm.

[2] observational · 2025

Acute and post-dosing effects of single-dose psilocybin for obsessive-compulsive disorder in a randomized, double-blind, placebo-controlled trial: an interpretative phenomenological analysis

Ching THW, et al. — Frontiers in Psychiatry

IPA of participant narratives from the Yale OCD RCT describes acute perceptual/metacognitive/emotional effects and post-dosing shifts in OCD symptoms and illness self-appraisal under unstructured psychological support.

DOI: 10.3389/fpsyt.2025.1726818

[8] review · 2018

Psychiatry & the psychedelic drugs. Past, present & future

Rucker JJH, Iliff J, Nutt DJ — Neuropharmacology

Reviews historical and contemporary psychiatric use of psychedelics, including safety considerations, study design challenges, and research priorities.

DOI: 10.1016/j.neuropharm.2017.12.040

[9] case report · 2014

Psilocybin and Obsessive Compulsive Disorder

Wilcox JA — Journal of Psychoactive Drugs

Case description of a treatment-refractory OCD patient reporting multi-year symptom relief with intermittent self-administered psilocybin mushrooms (~2 g dried every few weeks).

DOI: 10.1080/02791072.2014.963754

Anecdotal reports

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Anecdote section. Not clinical evidence. Included for context and research-question generation only.