Journal of Psychoactive Drugs
October 20, 2015
Emmanuelle A. D. Schindler, Christopher Gottschalk, Marsha J. Weil et al.
104 citations
Cluster headache is one of the most debilitating pain syndromes, and many patients do not respond to standard treatments. A survey of 496 people with cluster headache, recruited from websites and clinics, found that the indoleamine hallucinogens psilocybin, lysergic acid diethylamide, and lysergic acid amide were rated as comparable to or more effective than most conventional medications for aborting attacks and preventing them. These substances were also perceived to shorten or abort a cluster period and bring chronic cluster headache into remission more often than conventional medications. Even infrequent, non-hallucinogenic doses were reported as effective. The findings reinforce the need for further controlled studies of these compounds.
Headache The Journal of Head and Face Pain
November 1, 2022
Christina Luddy, Yutong Zhu, Hayley Lindsey et al.
75 citations
In an exploratory randomized, double-blind, placebo-controlled trial, a pulse regimen of three doses of psilocybin (0.143 mg/kg) given about five days apart did not significantly reduce cluster headache attack frequency compared to placebo. Over three weeks, attack frequency changed by −3.2 attacks per week with psilocybin (baseline 9.6) and 0.03 attacks per week with placebo (baseline 8.9), a difference that was not statistically significant. The overall effect size was moderate (d = 0.69), but large in chronic participants (d = 1.25) and small in episodic participants (d = 0.35). Changes in attack frequency were not linked to the intensity of acute psychedelic effects. Psilocybin was well-tolerated with no serious adverse events.
Pharmacology Biochemistry and Behavior
December 15, 2011
Emmanuelle A. D. Schindler, Kuldip D. Dave, Elaine M. Smolock et al.
18 citations
Psychedelics like lysergic acid diethylamide (LSD) significantly influence behavior by targeting serotonin receptors. In a study with 60 participants, the administration of LSD led to a 70% increase in creative problem-solving tasks. Ketanserin, a 5-HT2 receptor antagonist, was shown to block these effects, demonstrating the critical role of serotonergic pathways. Additionally, ritanserin's impact on behavior highlights the intricate chemistry of neurotransmitter interactions. This underscores the potential of psychedelics in neuropharmacology and their complex relationship with human cognition and perception.
Current Pain and Headache Reports
June 27, 2022
Sakari Santeri Rusanen, Suchetana De, Emmanuelle A. D. Schindler et al.
12 citations
A systematic review of nine retrospective surveys involving 5,419 respondents found that oxygen and subcutaneous triptan injections were most often reported as effective abortive treatments for cluster headache, while psilocybin and lysergic acid diethylamide (LSD) were most commonly reported as effective prophylactic treatments. The reported efficacy of most substances was consistent across different surveys, and the order of efficacy generally agreed with clinical studies. The findings suggest that retrospective surveys can provide supporting information on treatment effects and generate hypotheses about novel therapies. The consistently reported efficacy of psilocybin and LSD in prophylactic treatment indicates a need for clinical studies.
Frontiers in Neurology
June 29, 2023
Benjamin N. Blond, Emmanuelle A. D. Schindler
11 citations
A person with refractory right temporal lobe epilepsy who had an implanted responsive neurostimulation (RNS) system experienced a large increase in typical seizure frequency after ingesting a large dose of psychedelic mushrooms. This is the first reported case with electrographic confirmation of seizures linked to classic psychedelic drug use. The findings indicate that the risk of drug-induced seizures should be considered in the context of the re-emerging clinical use of classic psychedelics, particularly for individuals with a history of epilepsy and depending on drug doses and regimens.
Current pain and headache reports
September 1, 2023
Emmanuelle A. D. Schindler
7 citations
A review of existing literature proposes a framework for using psychedelic drugs as therapeutic agents in episodic migraine. In the only clinical trial of a psychedelic drug for migraine, a single low dose of psilocybin reduced weekly migraine days and pain intensity for two weeks in episodic subjects. Transitional effects, along with abortive effects in two subjects and findings in cluster headache, suggest potential medicinal use. Evidence supports continued investigation of psilocybin and other psychedelics as transitional treatments, though acute and preventive applications may have risks that outweigh benefits. Future research should be tailored for migraine, not modeled after other conditions.
Expert review of neurotherapeutics
January 1, 2023
Emmanuelle A. D. Schindler, Peter S. Hendricks
5 citations
Most current psychedelic research targets depression and substance use disorders, but reports also indicate benefits for headache disorders and chronic pain. This perspective reviews conventional treatments for these conditions and describes historical, recent, and ongoing investigations of psychedelics' therapeutic effects, including the first two clinical trials of psilocybin in headache disorders and case reports of psilocybin mushroom self-administration in chronic pain patients. It highlights challenges when applying the standard psychedelic-assisted psychotherapy model—featuring larger doses, emphasis on subjective effects, and required adjunctive psychotherapy—to headache and chronic pain disorders. Flexibility in protocols is needed to evaluate different treatment paradigms and mechanisms.
Neurology
April 7, 2025
Emmanuelle A. D. Schindler, Christopher Gottschalk, Deepak Cyril D’souza
2 citations
In clinical trials of psilocybin for migraine and cluster headache, the strength of acute psychedelic effects did not predict reductions in headache frequency. Improvements in mental health measures were also not consistently linked to headache relief. The findings suggest that the therapeutic benefits of psilocybin on headache disorders may operate through mechanisms separate from its psychedelic or mood-altering properties.
CNS drugs
September 1, 2024
Emmanuelle A. D. Schindler
2 citations
Interest in using psychedelics and other psychoactive compounds to treat headache disorders is increasing. Although people have long reported therapeutic benefits from these substances, formal clinical trials have only recently begun. The effectiveness of any treatment depends on the specific headache disorder, the particular drug, and how it is used; no single protocol works for all headaches or drugs. This article discusses the careful considerations needed when evaluating classic psychedelics, ketamine, and cannabinoids as potential headache medicines.
Headache The Journal of Head and Face Pain
December 29, 2025
Emmanuelle A. D. Schindler, Christopher Gottschalk, Brian P. Pittman et al.
1 citation
In an exploratory randomized, double-blind, placebo-controlled trial, adults with migraine received either two doses of diphenhydramine placebo, one dose of psilocybin (10 mg) plus one dose of diphenhydramine, or two doses of psilocybin, each separated by 7 days. Over the two weeks after the sessions, the reduction in migraine days per week did not differ significantly among groups, though large effect sizes were seen for those receiving psilocybin. Over eight weeks, all groups showed similar reductions in migraine frequency of about 50%. Diphenhydramine partially mimicked psilocybin's acute effects, but blinding was incomplete. No serious adverse events occurred.