In brief
- A Johns Hopkins team tested two psilocybin doses (20 mg and 30 mg) over two weeks in people with obsessive-compulsive disorder (OCD).
- The group treated immediately showed a greater reduction in Y-BOCS scale scores compared to the waitlist group, with improvements sustained one month after the second dose.
- This is an open-label, non-blinded trial with 37 participants, published as a preprint—meaning it has not yet undergone peer review.
Researchers at the Johns Hopkins University School of Medicine have published results on medRxiv from a psilocybin trial involving individuals with OCD who had previously failed to respond to evidence-based medication or psychotherapy. The study’s novelty lies in its protocol: two sessions over the course of two weeks rather than a single administration. According to the authors, the treatment was well tolerated and associated with a reduction in symptoms.
How the trial was conducted
The study included 37 participants with a mean age of 38.4 years, 56.75% of whom were women. All had previously attempted pharmacological treatment or therapy, such as exposure and response prevention. Participants were divided into two groups: one received psilocybin in the first month after enrollment, while the other waited eight weeks—with the same level of support—before receiving the identical regimen.
The protocol consisted of two doses over two weeks: 20 mg for the first session and 30 mg for the second, provided the first was well tolerated, all within a supportive environment. OCD severity was measured using the Y-BOCS scale, administered by clinicians one week after each session and one month after the second. Thirty participants (81.08%) completed the one-month follow-up.
What they found
Of the 30 who completed the follow-up, 16 were in the immediate treatment group and 14 in the waitlist group. The former showed a greater reduction in Y-BOCS scores than the latter (F(2,56)=16.17; p<0.001). After the crossover, the improvement was maintained one month after the second dose in both groups (F(3,84)=29.91; p<0.001).
The authors also measured subjective experiences during the sessions. Reductions in Y-BOCS scores correlated with several of these measures, including total scores on the mystical experience questionnaire and specific factors from questionnaires regarding challenging experiences and altered states of consciousness. The abstract does not detail response or remission figures, nor specific adverse events; it merely describes the regimen as tolerable. Our analysis is therefore limited to what was published in that summary.
The study is registered under number NCT05546658 and received philanthropic support from Charlie Scheeler and Mary Ellen Pease, according to the preprint.
What it implies
The trial is open-label, meaning there is no masking; participants knew what they were receiving, and with a substance that produces such recognizable effects, this can potentially inflate perceived improvement. The sample size is small, the comparison with the waitlist lasts only eight weeks, and the subsequent follow-up is one month. Furthermore, as a preprint, the results may change following peer review.
Even so, the design provides a concrete piece of data: comparing a multi-dose regimen against a randomized waitlist. The authors themselves call for further research into repeated-dose protocols. We have previously covered another study on treatment-resistant OCD and psilocybin from Yale, which examined the role of mystical experiences. For an overview of the substance, you can consult our Psychedelics Guide on psilocybin and magic mushrooms.
Source
- Tiwari P, Nayak SM, Sepeda ND, et al. An Open-Label Multidose Psilocybin Intervention for Obsessive-Compulsive Disorder. medRxiv (preprint), October 5, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
