Psilocybin-induced reduction in chronic cluster headache attack frequency correlates with changes in hypothalamic functional connectivity
M. Madsen, Anja Sofie Petersen, Dea Siggaard Stenbæk, Inger Marie Sørensen, Harald Schiønning, Tobias Fjeld, Charlotte H. Nykjær, Sara Marie Ulv Larsen, Maria Zofia Grzywacz, Tobias Mathiesen, Ida L. Klausen, Oliver Overgaard-Hansen, Kristoffer Brendstrup‐brix, Kristían Línnet, Sys Stybe Johansen, Patrick M. Fisher, Rigmor Jensen, Gitte M. Knudsen
medRxiv July 10, 2022 preprint DOI: 10.1101/2022.07.10.22277414 via OpenAlex
Summary
AI-generated from the abstractIn a small open-label clinical trial, three low-to-moderate doses of psilocybin reduced attack frequency by an average of 30% from baseline to follow-up in patients with chronic cluster headache. One patient experienced 21 weeks of complete remission. The treatment was well-tolerated with no serious adverse reactions. Changes in hypothalamic-diencephalic functional connectivity correlated negatively with the relative reduction in attack frequency, suggesting this neural pathway is involved in treatment response. Further studies are needed to confirm safety and prophylactic efficacy.
Study at a glance
| Characteristics | Open-label clinical trial |
|---|---|
| Population | Patients with chronic cluster headache |
| Intervention | Psilocybin |
| Dose | three low-to-moderate doses |
| Topics | Psilocybin |
| Keywords | Cluster headache Adverse effect Pathophysiology Functional connectivity |
| Citations | 5 |
| Registration | NCT04280055 |
| Key finding | Three low-to-moderate doses of psilocybin reduced attack frequency by an average of 30% and were well-tolerated, with changes in hypothalamic-diencephalic functional connectivity linked to treatment response. |
Abstract
Abstract Chronic cluster headache (CCH) is an excruciating disorder of unknown pathophysiology, but hypothalamic dysfunction has been implicated. CCH is difficult to treat but on a case-basis, the psychedelic compound psilocybin is said to have beneficial effects. In this first-ever clinical trial ( NCT04280055 ), we evaluate in a small open-label study of CCH patients the feasibility and prophylactic effect of three low-to-moderate doses of psilocybin as well as effects on hypothalamic functional connectivity (FC), using functional magnetic resonance imaging. The treatment was well-tolerated and without serious adverse reactions. Attack frequency was on average reduced by 30% 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 relative reduction in attack frequency, implicating this neural pathway in treatment response. Further clinical studies are warranted to confirm the safety and prophylactic efficacy of psilocybin for CCH and hypothalamic involvement in treatment response.