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.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cited by 31
- Addressing blinding in classic psychedelic studies with innovative active placebos. The International Journal of Neuropsychopharmacology April 1, 2025
- Psilocybin for the treatment of Alzheimer’s disease Frontiers in Neuroscience July 10, 2024
- Psilocybin as a novel treatment for chronic pain British Journal of Pharmacology November 29, 2024
- Classic Psychedelics in Pain Modulation: Mechanisms, Clinical Evidence, and Future Perspectives ACS Chemical Neuroscience June 6, 2025
- Current Evidence for the Role of Rapid-Acting Antidepressants in Bipolar Depression: A Perspective and Plan for Action Biological Psychiatry March 8, 2025
and 26 more in the library
Cites 20
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
and 15 more in the library