Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial.

In a blinded extension of a prior randomized trial, ten people with cluster headache received a second round of three doses of psilocybin (10 mg/70 kg, five days apart) at least six months after their first round. Attack frequency dropped significantly from a baseline of 18.4 attacks per week to 9.8 attacks per week in the three weeks after the first dose, a reduction of about 50%. This benefit occurred regardless of whether the participant had responded to psilocybin in the first round. No serious or unexpected adverse events occurred. The findings suggest that repeating a pulse of psilocybin can substantially reduce cluster headache attacks and that prior response does not predict the effect of retreatment.

Study at a glance

Abstract

In a recent randomized, double-blind, placebo-controlled study, we observed a nonsignificant reduction of attack frequency in cluster headache after pulse administration of psilocybin (10 mg/70 kg, 3 doses, 5 days apart each). We carried out a blinded extension phase to consider the safety and efficacy of repeating the pulse regimen. Eligible participants returned to receive a psilocybin pulse at least 6 months after their first round of study participation. Participants kept headache diaries starting two weeks before and continuing through eight weeks after the first drug session. Ten participants completed the extension phase and all ten were included in the final analysis. In the three weeks after the start of the pulse, cluster attack frequency was significantly reduced from baseline (18.4 [95% confidence interval 8.4 to 28.4] to 9.8 [4.3 to 15.2] attacks/week; p = 0.013, d' = 0.97). A reduction of approximately 50% was seen regardless of individual response to psilocybin in the first round. Psilocybin was well-tolerated without any unexpected or serious adverse events. This study shows a significant reduction in cluster attack frequency in a repeat round of pulse psilocybin administration and suggests that prior response may not predict the effect of repeated treatment. To gauge the full potential of psilocybin as a viable medicine in cluster headache, future work should investigate the safety and therapeutic efficacy in larger, more representative samples over a longer time period, including repeating the treatment. NCT02981173.