Pilot study of single-dose psilocybin for serotonin reuptake inhibitor-resistant body dysmorphic disorder

Recruitment yielded 198 inquiries, 37 psychiatric assessments and 12 eligible participants (8 women, 4 men). Comorbid diagnoses included major depressive disorder (n=4), ADHD (n=2), PTSD (n=1) and generalised anxiety disorder (n=1). Two participants were taking stimulant medications. Participants' primary appearance concerns most commonly involved face/nose/ears (n=6) or hair/head (n=3). During follow‑up, two participants discontinued their non‑study psychotherapy, and one began an SRI at week 4 because of increased social stressors; for categorical analyses that participant was counted as a non‑responder after week 4, and a sensitivity analysis carrying forward week 3 scores did not change primary significance. All 12 participants completed dosing and all scheduled follow‑up visits, providing complete outcome data. The BDD‑YBOCS total score showed a significant change over 12 weeks (repeated‑measures ANOVA: F(1.92,21.13) = 13.08, p < 0.001) with a large effect size (partial eta squared = 0.54). Pairwise testing indicated BDD‑YBOCS scores were significantly lower than baseline at each timepoint except week 9, which was at trend level (p = 0.059). There were no significant differences between timepoints from week 1 to week 12, indicating maintenance of the early improvement. At week 12 the mean change from baseline was reported as −13.33 (95% CI −3.43 to −23.23). Using a response threshold of >30% reduction in BDD‑YBOCS (and equivalently CGI‑Improvement of 1 or 2), seven of 12 participants (58.33%) were responders at week 12. Seven participants demonstrated >30% decrease sustained at every follow‑up, and four of those met sustained remission criteria (BDD‑YBOCS <16 at every follow‑up). Secondary clinician‑rated and self‑report measures of BDD symptom components, conviction of belief, negative affect, depression, psychological insight and disability showed significant improvement over 12 weeks; positive affect did not show a significant change. No serious adverse events or suicidal ideation were reported, and there were no clinically significant changes in laboratory values or vital signs. Mild adverse effects beginning and resolving within two days occurred in 11 participants: fatigue (n=5), headache (n=3), nausea (n=2), somnolence (n=1), lightheadedness (n=1), insomnia (n=1) and a sensation of spaciness (n=1). Other intercurrent illnesses included one case each of mild COVID‑19 and pneumonia. One participant experienced possibly drug‑related events persisting or arising beyond the first week: transient low libido for two weeks, brief mood disturbances in weeks 2–3, and four brief visual hallucination episodes (5–45 minutes) occurring in weeks 3 and 7; the participant retained insight and reported only mild disturbance. The investigators note that resting‑state fMRI findings will be reported separately.

Schneier and colleagues interpret these results as preliminary support that a single 25 mg dose of psilocybin given with psychological support is feasible, tolerable, safe and may produce clinically meaningful reductions in BDD symptoms in adults whose disorder had been unresponsive to at least one prior SRI trial. Feasibility was indicated by successful recruitment and completion of all study procedures despite restrictive eligibility criteria; tolerability and safety were evidenced by completion of all visits and absence of persistent or serious adverse events in this small sample. The authors highlight robust improvement on the primary outcome (BDD‑YBOCS) that emerged early and was largely maintained through 12 weeks, with concordant improvements on several secondary measures including conviction of belief, depression, negative affect, psychological insight and disability. They note that some participants reported reduced distress despite little change in the content of appearance beliefs, and that reductions in BABS scores suggest increased insight may have contributed to clinical improvement. The observed week 12 response rate of 58.3% is lower than uncontrolled SRI trials in BDD (reported at 70–80%), but those studies did not focus on an SRI‑resistant sample; direct comparisons are therefore limited. Key limitations acknowledged by the investigators include the uncontrolled, open‑label design, which leaves room for nonspecific effects such as expectancy; a small sample with limited socioeconomic diversity; and the concomitant, naturalistic psychotherapy that may have contributed to outcomes. Additionally, most participants had not necessarily received guideline‑recommended full courses (>12 weeks at maximum dose) of SRIs or a full course of BDD‑specific CBT before enrolment, limiting interpretation about treatment‑refractory status. Safety monitoring did not systematically capture non‑serious experiences during the dosing session unless they persisted to the session end. The occurrence of transient visual hallucinations up to week 7 in one participant raises the possibility of rare perceptual sequelae and underlines the importance of careful screening and provision of psychological support. The authors conclude that these preliminary findings justify controlled trials to more rigorously evaluate efficacy, durability and safety of psilocybin in BDD.