CCH attack frequency reduction after psilocybin correlates with hypothalamic functional connectivity
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CCH attack frequency reduction after psilocybin correlates with hypothalamic functional connectivity. / Madsen, Martin K.; Petersen, Anja Sofie; Stenbæk, Dea S.; Sørensen, Inger Marie; Schiønning, Harald; Fjeld, Tobias; Nykjær, Charlotte H.; Larsen, Sara Marie Ulv; Grzywacz, Maria; Mathiesen, Tobias; Klausen, Ida L.; Overgaard-Hansen, Oliver; Brendstrup-Brix, Kristoffer; Linnet, Kristian; Johansen, Sys S.; Fisher, Patrick M.; Jensen, Rigmor H.; Knudsen, Gitte M.
In: Headache, Vol. 64, No. 1, 2024, p. 55-67.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 381501213