Psilocybin-Assisted Therapy Well-Tolerated in Patients with Fibromyalgia

Psilocybin-assisted therapy (PAT) is well-tolerated among individuals with fibromyalgia, according to preliminary findings from a small open-label trial, establishing a basis for larger randomized controlled trials.1

Jacob S. Aday, PhD, from the department of anesthesiology at the University of Michigan Medical School, led a team of investigators in this open-label trial. The team highlighted that while PAT is an emerging combined drug-therapy intervention option being explored for different conditions such as chronic pain, there had been a general lack of studies to-date that explored PAT’s use in fibromyalgia.2

“In summary, converging lines of research support the mechanistic potential of PAT in the treatment of [fibromyalgia],” Aday et al. wrote.1 “However, clinical studies assessing the safety and tolerability of psilocybin and associated therapy in people with [fibromyalgia] are limited. Thus, in the current pilot study, we evaluated the preliminary safety and effectiveness of PAT in the treatment of [fibromyalgia] using an open-label design among five individuals.”

The investigative team carried out their open-label clinical trial at the University of Michigan Chronic Pain and Fatigue Center located in Ann Arbor. Those deemed to be eligible as trial participants were adults between the ages of 25 - 64 who did not smoke cigarettes and either had a formal fibromyalgia diagnosis or had reported symptoms of this condition for the previous year at minimum.

During the time of their screening, all subjects also met the 2016 FM survey criteria for fibromyalgia. PAT sessions occurred both in-person at the Sleep and Circadian Research Laboratory and remotely through the use of Zoom for select meetings. The therapeutic framework for this study was adapted from The Yale Manual for Psilocybin-Assisted Therapy of Depression (using Acceptance and Commitment Therapy).

Tailoring of the manual to fibromyalgia was done using various modifications by the investigators, with guidance from Fluence—a professional education organization that specializes in PAT. It was also done through the use of consultation with experienced PAT clinicians. Each person taking part in the analysis was supported throughout the study by a consistent pair of therapists: a lead therapist alongside a co-therapist.

The psilocybin implemented during the analysis was manufactured by the analytical chemistry laboratory located at the Usona Institute. It was provided in 15 mg and 25 mg gel capsule formulations and subjects were provided with 2 doses, beginning with 15 mg and followed by 25 mg approximately 2 weeks later. This sequential dosing strategy was implemented thanks to protocols from prior research.

The investigative team's primary outcome was safety, and they assessed such results through monitoring of dosing sessions through heart rate and blood pressure measurements. These findings were tracked more broadly by documenting adverse events from baseline through the 64-day mark at the conclusion of the study.

In terms of safety findings, transient increases in blood pressure and heart rate were observed during dosing sessions, but these normalized by the conclusion of PAT. No serious adverse events were shown to have taken place. The investigators found that 4 out of 5 subjects reported temporary headaches following dosing sessions.

In terms of secondary outcomes, clinically meaningful improvements were observed by the investigative team 1 month following the second psilocybin dose. Compared to baseline, those involved in the study demonstrated large effect sizes (reported as Cohen’s d) in the following areas: pain-related interference [d = −1.8, 95% CI (−3.27 to −0.24)], pain severity level [d = −2.1, 95% CI (−3.7 to −0.49)], and disturbances in sleep [d = −2.5, 95% CI (−4.21 to −0.75)].

In the Patient Global Impression of Change assessment findings, 1 participant described their symptoms as “very much improved,” 2 reported “much improved,” and 2 reported “minimally improved.” The team's analysis ended recruitment early as a result of concerns related to generalizability and in response to updated FDA guidance on psychedelic clinical research.

“Some participants reported clinically meaningful improvements in pain severity, pain interference, anxiety, and sleep disturbance, with small improvements in chronic pain acceptance,” they wrote.1 “Nonetheless, given the study limitations, larger, controlled studies with a more clinically translational design are necessary to understand whether this therapy is safe and effective in the treatment of [fibromyalgia].”

References

1. Aday JS, McAfee J, Conroy DA, et al. Preliminary safety and effectiveness of psilocybin-assisted therapy in adults with fibromyalgia: an open-label pilot clinical trial. Front Pain Res (Lausanne). 2025 Mar 18;6:1527783. doi: 10.3389/fpain.2025.1527783. PMID: 40171515; PMCID: PMC11958999.

2. Bonnelle V, Smith W, Mason N, et al. Analgesic potential of macrodoses and microdoses of classical psychedelics in chronic pain sufferers: a population survey. Br J Pain. (2022) 16:1–13. 10.1177/2049463722111496.