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. 2025 Mar 18:6:1527783.
doi: 10.3389/fpain.2025.1527783. eCollection 2025.

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

Jacob S Aday  1   2 , Jenna McAfee  1 , Deirdre A Conroy  3 , Avinash Hosanagar  3   4 , Vijay Tarnal  1   2 , Cody Weston  3 , Katherine Scott  1 , Dana Horowitz  4 , Jamarie Geller  2   3 , Steven E Harte  1   2   5 , Niloufar Pouyan  1   2   5 , Nicolas G Glynos  1   2 , Anne K Baker  1   2 , Jeffrey Guss  6 , Alan K Davis  7   8   9 , Helen J Burgess  3 , George A Mashour  1   2   5 , Daniel J Clauw  1 , Kevin F Boehnke  1   2
Affiliations

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

Jacob S Aday et al. Front Pain Res (Lausanne). .

Abstract

Introduction: Fibromyalgia (FM) 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.

Methods: 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 (15 mg and 25 mg) delivered two weeks apart.

Results: 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.

Discussion: This small open-label trial preliminarily supports that PAT is well-tolerated by people with FM, establishing a basis for larger randomized controlled trials.

Clinical trial registration: ClinicalTrials.gov, identifier, (NCT05128162).

Keywords: clinical trial; fibromyalgia; pilot; psilocybin; psilocybin-assisted therapy.

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Conflict of interest statement

JSA's effort on this publication was partially supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under T32AR007080-44S1. JSA has received speaking fees for lectures at The Women's Center of Southeastern Michigan, Massachusetts General Hospital, and Bicycle Day SF. KFB has received grant funding from the National Institute on Drug Abuse and the National Institutes of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health, as well as from the State of Michigan Veteran Marijuana Research Program. KFB has received speaking fees for lectures from the Medical Cannabis Research Advocacy Alliance, Provide Holy Cross Medical Center, the Southern Pain Society, and the Michigan Center of Clinical Systems Improvement. KFB received an honorarium for developing a podcast on fibromyalgia with Viatris Inc. JRG is a consultant and teacher with Fluence, International and receives no grant funding. AD is supported by the Johns Hopkins Center for Psychedelic and Consciousness Research, funded by private philanthropic funding from Tim Ferriss, Matt Mullenweg, Craig Nerenberg, Blake Mycoskie, and the Steven and Alexandra Cohen Foundation. AD is also supported by the Center for Psychedelic Drug Research and Education, funded by anonymous private donors, and the Comprehensive Cancer Center at Ohio State University. AD is also a board member at Source Research Foundation. AH is a sub investigator in a COMPASS pathways Psilocybin research study ongoing at the University of Michigan. VT serves as the site Principal Investigator at the University of Michigan for a project supported by funding from Takeda Development Center Americas, Inc. SEH is supported by grants from NIH and Arbor Medical Innovations, is a member of Arbor Medical Innovations, and consults for Memorial Sloan Kettering Cancer Center, Dana Farber Cancer Institute, Indiana University, and Wayne State University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. DC has received consulting fees from AbbVie Inc, Heron Therapeutics Inc, Aptinyx Inc, Neumentum Inc, Regeneron Pharmaceuticals Inc, Swing Therapeutics Inc, Virios Inc, Allergan Sales LLC, Eli Lily and Company, H. Lundbeck A/S, Pfizer Inc, Samumed LLC, and Tonix Pharmaceuticals Inc. DC has received payment for expert testimony from Fasken Martinueau DuMoulin LLP, Marks & Clerk Law LLP, Pfizer Inc, Nix Patterson LLP, Zuber Lawler & Del Duca LLP as well as Kellogg, Hansen, Todd, Figel & Frederick PLLC. HB serves on the scientific advisory board for Natrol, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overall study design.
Figure 2
Figure 2
CONSORT diagram.
Figure 3
Figure 3
Heart rate in beats per minute after dosing. D1: Dose 1 (15 mg). D2: Dose 2 (25 mg). 001 D2 was 15 mg rather than 25 mg per request of the participant.
Figure 4
Figure 4
Systolic and diastolic blood pressure after doses 1 and 2. D1: Dose 1 (15 mg). D2: Dose 2 (25 mg). If a participant had blood pressure >200 systolic or >110 diastolic for >15 min, they would be transferred to the emergency department.
Figure 5
Figure 5
CPAQ: chronic pain acceptance questionnaire. Pain Severity reported as change in aggregate pain score from the 7 days prior to the intervention to the end of the intervention. Sleep disturbance, pain interference, physical function, anxiety, depression, fatigue, participation in social activities, and cognitive abilities are all reported as T-scores per PROMIS scoring. Negative change scores indicate improvement for pain severity, pain interference, sleep disturbance, FM score, anxiety, depression, and fatigue. Positive change scores indicate improvement for CPAQ, physical function, participation in social activities, and cognitive abilities.
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