Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial.
Emmanuelle A. D. Schindler, R Andrew Sewell, Christopher Gottschalk, L Taylor Flynn, Yutong Zhu, Brian Pittman, Nicholas V. Cozzi, Deepak C D'Souza
Journal of the Neurological Sciences May 15, 2024 DOI: 10.1016/j.jns.2024.122993 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled study (extension phase) Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | People with cluster headache who completed the first round of the trial |
| Intervention | Psilocybin |
| Dose | 10 mg/70 kg, 3 doses, 5 days apart |
| Duration | 8 weeks after first drug session, with diaries kept from 2 weeks before to 8 weeks after |
| Topics | Psilocybin |
| Keywords | Cluster headache Headache disorders Preventive treatment Transitional treatment Drug trials Psychedelics hallucinogens Entheogens Migraine treatment Pain management Controlled studies |
| Citations | 37 |
| Registration | NCT02981173 |
| Key points | Repeating a pulse of psilocybin (10 mg/70 kg, three doses) significantly reduced cluster headache attack frequency by about 50% from baseline, regardless of prior response to the drug. |
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.