Griffiths · Psychopharmacology 2006 · randomized active-controlled crossover trial · n=36

Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance.

Cited 1705 times in the scientific literature.

Level 2 - randomized trial

Double-blind randomized controlled crossover trial

PubMed 16826400 · doi:10.1007/s00213-006-0457-5 · record verified 2026-08-30

What was done

A double-blind crossover trial evaluated the acute and 2-month psychological effects of oral psilocybin (30 mg/70 kg) compared with an active control, methylphenidate hydrochloride (40 mg/70 kg). Participants were 36 hallucinogen-naive adults reporting regular participation in religious or spiritual activities. Thirty volunteers received psilocybin and methylphenidate in counterbalanced order across individual 8-hour sessions separated by 2-month intervals in supportive conditions. Six additional volunteers received methylphenidate in their first two sessions and unblinded psilocybin in a third session to obscure the design. Measures included in-session monitor behavioral ratings, immediate and 2-month participant-rated drug effect and mystical experience questionnaires, and community observer assessments of participant attitudes and behavior.

What was found

The abstract reports no numerical values, test statistics, or p-values. Psilocybin acutely produced perceptual changes, subjective experiences, labile moods including anxiety, and increased mystical experience scores relative to methylphenidate. At 2 months, participants rated the psilocybin experience as possessing substantial personal meaning and spiritual significance, attributing to it sustained positive changes in attitudes and behavior that were corroborated by community observer ratings.

Why it matters

This study provided early rigorous experimental evidence that psilocybin can reliably occasion profound mystical-type experiences with enduring personal significance, catalyzing modern psychedelic science and clinical research.

Limits

The abstract provides no quantitative data or effect sizes. The sample was small (n = 36) and limited to hallucinogen-naive individuals already engaged in religious or spiritual practices, restricting generalizability. Functional unblinding remains a significant concern despite an active control due to the distinctive psychoactive effects of high-dose psilocybin, and follow-up was limited to 2 months.

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