Psychedelic compound reduces cluster headache frequency by 50% in new study – PsyPost

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A recent study published in the Journal of the Neurological Sciences has found that psilocybin, the psychoactive compound in psychedelic “magic mushrooms,” can reduce the frequency of cluster headaches. This research builds on anecdotal reports and preliminary studies, offering the first controlled evidence of psilocybin’s potential as a treatment for this debilitating condition.
Cluster headaches are one of the most excruciating types of headaches, often characterized by severe, burning, or piercing pain that typically occurs around one eye or one side of the head. These headaches, which can last from 15 minutes to three hours, often strike suddenly and recur multiple times a day, frequently at the same time each day.
The pain is so intense that it has been nicknamed “suicide headache” due to the desperation it can cause in sufferers. Unlike migraines, cluster headaches are generally not accompanied by nausea or sensitivity to light and sound, but they can be accompanied by other symptoms such as redness in the eye, nasal congestion, and restlessness.
Anecdotal reports and preliminary research suggested that psilocybin might offer relief, but there was a lack of rigorous scientific evidence to support these claims. This drove Emmanuelle A. D. Schindler, an assistant professor of neurology at Yale School of Medicine, and her colleagues to investigate whether psilocybin could provide a safe and effective treatment for cluster headache sufferers.
The study was designed as an extension of a pilot study that had previously examined the effects of psilocybin on cluster headaches. The researchers recruited 16 adults aged 21 to 65 years who experienced cluster headaches but had no other serious medical or psychiatric conditions. These participants had previously been involved in the initial study and were eligible to return for a second round of participation after at least six months from their last test day.
Participants were randomly assigned to receive either three doses of psilocybin or a placebo, with sessions spaced approximately five days apart. The psilocybin was administered in a carefully controlled setting, with both participants and research staff blinded to the dose given. Participants maintained headache diaries starting two weeks before and continuing until eight weeks after the first session, documenting the frequency, duration, and intensity of their headaches.
The study was approved by the necessary regulatory bodies, including the Veterans Affairs Connecticut Healthcare System and Yale University, and was conducted under an Investigational New Drug application with the U.S. Food and Drug Administration. Funding for the extension phase came from Ceruvia Lifesciences.
Schindler and her team found that psilocybin significantly reduced the frequency of cluster headaches. Participants who received psilocybin experienced nearly a 50 percent reduction in the number of headache attacks per week. On average, the weekly attacks decreased from 18.4 to 9.8, marking a substantial improvement. This reduction was observed in both episodic and chronic cluster headache sufferers, although the effects approached but did not always reach statistical significance in some subgroups.
Additionally, the study noted that the therapeutic benefits of psilocybin appeared to be independent of its hallucinogenic effects. This suggests that the relief provided by psilocybin might not be linked to its ability to induce altered states of consciousness, which is a key finding for considering psilocybin’s broader therapeutic applications.
The researchers also reported significant reductions in pain severity and the need for abortive medications. Pain severity dropped by about 10 percent on a numerical rating scale, and the use of medications to stop attacks fell by 37 percent, indicating an overall improvement in the quality of life for participants.
Importantly, the study reported no serious adverse events, reinforcing the safety of psilocybin when administered in a controlled setting. Common side effects included nausea, fatigue, and cluster attacks during the dosing sessions, but these were self-limiting and manageable.
While the results of this study are encouraging, there are several caveats to consider. First, the sample size was small, with only 10 participants completing the extension phase. This limits the generalizability of the findings and underscores the need for larger studies to confirm these results. The study was also did not include a comparison with other preventive treatments, making it difficult to assess how psilocybin stacks up against existing options.
Despite these limitations, the study represents a significant step forward in understanding the potential of psilocybin as a treatment for cluster headaches. The findings suggest that psilocybin can reduce the frequency and severity of attacks, offering hope to those who have found little relief from traditional treatments. However, further research with larger, more diverse samples and longer follow-up periods is necessary to fully gauge the safety and efficacy of psilocybin for this condition.
The study, “Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial,” was authored by Emmanuelle A.D. Schindler, R. Andrew Sewell, Christopher H. Gottschalk, L. Taylor Flynn, Yutong Zhu, Brian P. Pittman, Nicholas V. Cozzi, and Deepak C. D’Souza.
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