TY - JOUR

T1 - CCH attack frequency reduction after psilocybin correlates with hypothalamic functional connectivity

AU - Madsen, Martin K.

AU - Petersen, Anja Sofie

AU - Stenbæk, Dea S.

AU - Sørensen, Inger Marie

AU - Schiønning, Harald

AU - Fjeld, Tobias

AU - Nykjær, Charlotte H.

AU - Larsen, Sara Marie Ulv

AU - Grzywacz, Maria

AU - Mathiesen, Tobias

AU - Klausen, Ida L.

AU - Overgaard-Hansen, Oliver

AU - Brendstrup-Brix, Kristoffer

AU - Linnet, Kristian

AU - Johansen, Sys S.

AU - Fisher, Patrick M.

AU - Jensen, Rigmor H.

AU - Knudsen, Gitte M.

N1 - Publisher Copyright: © 2023 American Headache Society.

PY - 2024

Y1 - 2024

N2 - 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 (pFWER = 0.008). One patient experienced 21 weeks of complete remission. Changes in hypothalamic–diencephalic FC correlated negatively with a percent change in attack frequency (pFWER = 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.

AB - 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 (pFWER = 0.008). One patient experienced 21 weeks of complete remission. Changes in hypothalamic–diencephalic FC correlated negatively with a percent change in attack frequency (pFWER = 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.

KW - cluster headache

KW - functional connectivity

KW - functional magnetic resonance imaging

KW - hypothalamus

KW - psilocin

KW - psilocybin

U2 - 10.1111/head.14656

DO - 10.1111/head.14656

M3 - Journal article

C2 - 38238974

AN - SCOPUS:85182653955

VL - 64

SP - 55

EP - 67

JO - Headache

JF - Headache

SN - 0017-8748

IS - 1

ER -