Topic starter
There is a new scientific article which investigates whether psilocybin can reduce the number of attacks in chronic cluster headaches, and whether that is related to changes in brain connectivity.
In it, we discuss:
The researchers conducted a small open-label clinical trial in 10 patients with chronic cluster headache. The participants kept a headache diary for 10 weeks. In weeks 5, 6 and 7, they received an oral dose of psilocybin of 0.14 mg/kg on the first day each. The first 4 weeks counted as baseline and the last 4 weeks as follow-up. In addition, functional connectivity of the hypothalamus was examined with fMRI one day before the first dose and one week after the last dose.
The real focus of this article is not only on symptom change, but also on the mechanism behind it. Cluster headaches have long been strongly associated with the hypothalamus. Therefore, the authors investigated whether changes in hypothalamic connectivity correlated with clinical response to psilocybin.
The outcomes were positive but preliminary. The treatment was well tolerated and seizure frequency fell by an average of 31 per cent from baseline to follow-up. In one patient, a complete remission of 21 weeks even occurred. This is striking, but due to the small number of participants, this still needs to be interpreted with caution.
The researchers also found that changes in hypothalamic-diencephalic functional connectivity correlated strongly negatively with the percentage change in seizure frequency. In other words, the stronger this connectivity change, the greater usually the decrease in seizure frequency. According to the authors, this points to the hypothalamus as a potentially relevant target of treatment.
Importantly, however, this is a small open-label study without a placebo group. As a result, expectancy effects, natural fluctuations in disease progression and other confounding factors cannot be properly excluded. So this article mainly shows a promising first signal, not definitive proof of efficacy.
In one sentence, this paper shows that three doses of psilocybin in chronic cluster headache were associated with fewer attacks, and that this improvement was strongly linked to changes in connectivity around the hypothalamus.
Spoiler
New article description
Abstract
Objective: To evaluate the feasibility and prophylactic effect of psilocybin as well as its effects on hypothalamic functional connectivity (FC) in chronic cluster headache (CCH).
Background: Clinical trials have shown a prophylactic effect of psilocybin in migraine and anecdotal reports suggest similar effects in cluster headache and support the involvement of the hypothalamus.
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.
Keywords: Cluster headache; functional connectivity; functional magnetic resonance imaging; hypothalamus; psilocin; psilocybin.
Posted : 18 March 2026 15:02