Preliminary safety and effectiveness of psilocybin-assisted therapy in adults with fibromyalgia: An open-label pilot clinical trial

Jacob Aday ¹ Jenna Mcafee ¹ Deirdre Conroy ¹ Avinash Hosanagar ¹ Vijay Tarnal ¹ Cody Weston ¹ Katharine Scott ¹ Dana Horowitz ¹ Steven Harte ¹ Niloufar Pouyan ¹ Nicolas Glynos ¹ Anne Baker ¹ Jeffrey Richard Guss ² Alan K Davis ³ Helen J. Burgess ¹ George A. Mashour ¹ Daniel J Clauw ¹ Kevin Boehnke ^1*

• ¹ University of Michigan, Ann Arbor, United States
• ² New York University, New York City, New York, United States
• ³ The Ohio State University, Columbus, Ohio, United States

is the prototypical nociplastic pain condition, characterized by widespread pain and issues with cognition, mood, and sleep. Currently, there are limited treatment options available that effectively treat FM symptoms. Psilocybin-assisted therapy (PAT) is an emerging combined drug-therapy intervention, but no studies to-date have investigated PAT for FM. Here, we report findings from an open-label, pilot clinical trial of PAT for FM (N=5). In conjunction with psychotherapy (two preparatory, four integration sessions), participants received two doses of oral psilocybin (15mg and 25mg) delivered two weeks apart. Regarding safety (primary outcome), there were transient elevations of blood pressure or heart rate during dosing which normalized by the end of treatment, with no serious adverse events. Four of five participants reported transient headaches following dosing. Compared to baseline, participants reported clinically meaningful improvements in the following secondary outcomes one month following their second psilocybin dose (reported as Cohen's d): pain severity (d=-2.1, 95% CI[-3.7 to -0.49]), pain interference (d=-1.8, 95% CI [-3.27 to -0.24]), and sleep disturbance (d=-2.5, 95% CI [-4.21 to -0.75]). Using the Patient Global Impression of Change, one participant reported their symptoms "very much improved," two reported "much improved," and two reported "minimally improved." We stopped recruitment early because of concerns about generalizability and changes in FDA guidance for psychedelic clinical trials that occurred data collection.Nonetheless, this small open-label trial preliminarily supports that PAT is well-tolerated by people with FM, establishing a basis for larger randomized controlled trials.