CCH attack frequency reduction after psilocybin correlates with hypothalamic functional connectivity

Abstract

ObjectiveTo 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).BackgroundCCH 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.MethodsIn 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.ResultsThe 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.ConclusionOur results indicate that psilocybin may have prophylactic potential and implicates the hypothalamus in possible treatment response. Further clinical studies are warranted.

Review of Psilocybin Use for Depression among Cancer Patients after Approval in Oregon

“…Research indicates that psilocybin administration can lead to effects such as silliness, laughter, and playfulness, which may be perceived as unconventional but can be modulated to align with the desired clinical outcomes [94]. It is important to note that psilocybin has potent psychedelic properties and is illegal in most countries, with reports of serious negative health-related outcomes in non-clinical settings due to poorly regulated behavior [95][96][97]. Studies have found that younger individuals are more likely to require emergency medical treatment after using psilocybin than older individuals.…”

Use of Prescribed and Non-Prescribed Treatments for Cluster Headache in a Swedish Cohort

“…A Danish study reports a 30% reduced attack frequency in patients suffering from chronic CH. Also, a negative correlation of changes in hypothalamic-diencephalic functional connectivity with relative reduction in attack frequency was found [20]. The second study by Schindler et al recruited both episodic (ECH) and chronic (CCH) CH patients.…”

“…According to a report by the Swedish Health Agency from 2020, cannabis use is generally lower in Sweden than many other European countries. Cannabis use is most prevalent in the age group [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] with an estimated 8% of men and 5% of women that age using it (https://www.folkhalsomyndigheten.se/livsvillkor-levnadsvanor/andts/andts-anvandningoch-ohalsa/anvandning/narkotikaanvandningen-och-utvecklingen/cannabis-och-folkhalsa/ (accessed on 12 March 2024)). Though the Swedish Health Agency reports a more positive attitude toward cannabis use as compared to other narcotics in the general Swedish population, the majority still believe it should not be legal.…”