CCH attack frequency reduction after psilocybin correlates with hypothalamic functional connectivity
Anja Sofie Petersen, Inger Marie Sørensen, Harald Schiønning, Tobias Fjeld, Sara Marie Ulv Larsen, Tobias Mathiesen, M. Madsen, Dea Siggaard Stenbæk, Charlotte H. Nykjær, Maria Zofia Grzywacz, Ida L. Klausen, Oliver Overgaard‐hansen, Kristoffer Brendstrup‐brix, Kristían Línnet, Sys Stybe Johansen, Patrick M. Fisher, Rigmor Jensen, Gitte M. Knudsen
Headache The Journal of Head and Face Pain January 1, 2024 DOI: 10.1111/head.14656 via OpenAlex
Summary
AI-generated from the abstractIn a small open-label trial, ten people with chronic cluster headache received three doses of psilocybin (0.14 mg/kg) over three weeks. Attack frequency dropped by an average of 31% from the four-week baseline to the four-week follow-up, and one patient had 21 weeks of complete remission. Changes in hypothalamic–diencephalic functional connectivity correlated negatively with the reduction in attack frequency, suggesting this neural pathway may be involved in the treatment response. The treatment was well tolerated. The results indicate psilocybin may have prophylactic potential for chronic cluster headache, though larger controlled studies are needed.
Study at a glance
| Characteristics | Open-label clinical trial Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Patients with chronic cluster headache |
| Intervention | Psilocybin |
| Dose | 0.14 mg/kg |
| Duration | 10 weeks (4-week baseline, 3 weekly doses in weeks 5-7, 4-week follow-up) |
| Topics | Psilocybin |
| Keywords | Functional connectivity Reduction mathematics Neuroscience Psychology |
| Citations | 29 |
| Key finding | Psilocybin reduced attack frequency by 31% in patients with chronic cluster headache, and changes in hypothalamic–diencephalic functional connectivity correlated with the reduction. |
Abstract
Abstract Objective To evaluate the feasibility and prophylactic effect of psilocybin as well as its effects on hypothalamic functional connectivity (FC) in patients with chronic cluster headache (CCH). Background CCH is an excruciating and difficult‐to‐treat disorder with incompletely understood pathophysiology, although hypothalamic dysfunction has been implicated. Psilocybin may have beneficial prophylactic effects, but clinical evidence is limited. Methods In this small open‐label clinical trial, 10 patients with CCH were included and maintained headache diaries for 10 weeks. Patients received three doses of peroral psilocybin (0.14 mg/kg) on the first day of weeks five, six, and seven. The first 4 weeks served as baseline and the last 4 weeks as follow‐up. Hypothalamic FC was determined using functional magnetic resonance imaging the day before the first psilocybin dose and 1 week after the last dose. Results The treatment was well tolerated. Attack frequency was reduced by mean (standard deviation) 31% (31) from baseline to follow‐up ( p FWER = 0.008). One patient experienced 21 weeks of complete remission. Changes in hypothalamic–diencephalic FC correlated negatively with a percent change in attack frequency ( p FWER = 0.03, R = −0.81), implicating this neural pathway in treatment response. Conclusion Our results indicate that psilocybin may have prophylactic potential and implicates the hypothalamus in possible treatment response. Further clinical studies are warranted.