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 2024 DOI: 10.1111/head.14656 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 Hallucinogen Communication |
| Citations | 29 |
| Key findings | 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.