OPEN Foundation

R. Sewell

Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin

Abstract

While anecdotal evidence suggests that select 5-hydroxytryptamine 2A (5-HT2A) receptor ligands, including psilocybin, may have long-lasting therapeutic effects after limited dosing in headache disorders, controlled investigations are lacking. In an exploratory double-blind, placebo-controlled, cross-over study, adults with migraine received oral placebo and psilocybin (0.143 mg/kg) in 2 test sessions spaced 2 weeks apart. Subjects maintained headache diaries starting 2 weeks before the first session until 2 weeks after the second session. Physiological and psychological drug effects were monitored during sessions and several follow-up contacts with subjects were carried out to assure safety of study procedures. Ten subjects were included in the final analysis. Over the 2-week period measured after single administration, the reduction in weekly migraine days from baseline was significantly greater after psilocybin (mean, – 1.65 (95% CI: – 2.53 to – 0.77) days/week) than after placebo (- 0.15 (- 1.13 to 0.83) days/week; p = 0.003, t(9) = 4.11). Changes in migraine frequency in the 2 weeks after psilocybin were not correlated with the intensity of acute psychotropic effects during drug administration. Psilocybin was well-tolerated; there were no unexpected or serious adverse events or withdrawals due to adverse events. This exploratory study suggests there is an enduring therapeutic effect in migraine headache after a single administration of psilocybin. The separation of acute psychotropic effects and lasting therapeutic effects is an important finding, urging further investigation into the mechanism underlying the clinical effects of select 5-HT2A receptor compounds in migraine, as well as other neuropsychiatric conditions. Clinicaltrials.gov : NCT03341689.

Schindler, E., Sewell, R. A., Gottschalk, C. H., Luddy, C., Flynn, L. T., Lindsey, H., Pittman, B. P., Cozzi, N. V., & D’Souza, D. C. (2021). Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 18(1), 534–543. https://doi.org/10.1007/s13311-020-00962-y

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Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey

Abstract

Cluster headache is one of the most debilitating pain syndromes. A significant number of patients are refractory to conventional therapies. The Clusterbusters.org medication use survey sought to characterize the effects of both conventional and alternative medications used in cluster headache. Participants were recruited from cluster headache websites and headache clinics. The final analysis included responses from 496 participants. The survey was modeled after previously published surveys and was available online. Most responses were chosen from a list, though others were free-texted. Conventional abortive and preventative medications were identified and their efficacies agreed with those previously published. The indoleamine hallucinogens, psilocybin, lysergic acid diethylamide, and lysergic acid amide, were comparable to or more efficacious than most conventional medications. These agents were also perceived to shorten/abort a cluster period and bring chronic cluster headache into remission more so than conventional medications. Furthermore, infrequent and non-hallucinogenic doses were reported to be efficacious. Findings provide additional evidence that several indoleamine hallucinogens are rated as effective in treating cluster headache. These data reinforce the need for further investigation of the effects of these and related compounds in cluster headache under experimentally controlled settings.

Schindler, E. A., Gottschalk, C. H., Weil, M. J., Shapiro, R. E., Wright, D. A., & Sewell, R. A. (2015). Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey. Journal of psychoactive drugs, 1-10. http://dx.doi.org/10.1080/02791072.2015.1107664

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Unauthorized Research on Cluster Headache

Perhaps the greatest triumph of unauthorized research on visionary plants and drugs to date is the discovery that small doses of LSD, psilocybin, and LSA (lysergic acid amide) are more effective than any conventional medication in treating the dismal disorder, cluster headache. Five years ago, no one other than cluster headache patients or neurologists had ever heard of cluster headache. Now, treatment of cluster headache is routinely listed among potential therapeutic uses for psychedelics, and has even penetrated popular culture to the point that the character Gregory House, M.D. has used a psychedelic drug to treat headache on the TV show House not once, but twice (Kaplow 2006; Dick 2007)!

The first mention of therapeutic effect from a psychedelic on headache comes from Drs. D. Webster Prentiss and Francis P. Morgan, professors of medicine and pharmacology at Columbian University (now George Washington University), who began to conduct animal and human experiments with peyote in 1894 in order to determine whether or not it had any valuable medicinal properties. Two years later, their report concluded: “The conditions in which it seems probable that the use of mescal buttons will produce beneficial results are the following: In general ‘nervousness,’ nervous headache, nervous irritative cough… [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][etc.].” In their account are a number of cases, including #5: “The same gentleman reports that his wife formerly used to take the tincture [anhalonium 1] for nervous headaches and that it always relieved her. She has them so seldom now that she does not use it” (Prentiss & Morgan 1896).

Sewell, R. A. (2008). Unauthorized Research on Cluster Headache. The Entheogen Review, 16(4), 117-125.
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Response of cluster headache to psilocybin and LSD

Abstract

The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. Research on the effects of psilocybin and LSD on cluster headache may be warranted.

Sewell, R. A., Halpern, J. H., & Pope, Jr., H. G. (2006). Response of cluster headache to psilocybin and LSD. Neurology, 66(12), 1920–1922. http://dx.doi.org/10.1212/01.wnl.0000219761.05466.43
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Hallucinogenic botanicals of America: A growing need for focused drug education and research

Abstract

Botanical sources for medicines in America have been known since long before the arrival of Columbus. Nevertheless, both scientists and the general public are often unaware that some of these botanical drugs are also potent intoxicants. We provide a quick overview of hallucinogenic and dissociative drugs harvested from nature or that are openly and legally cultivated in the United States. Examples of harmful outcomes reported in the media are contrasted with existing responsible ingestion by others, some of whom have the protected right to do so for traditional or sacramental religious purposes. Despite an ongoing and expensive effort to warn people of the potential harms of recreational drug use, little is known about the extent of use of these psychoactive botanicals, and the recent explosion of information available via the Internet could herald a storm of morbidity to come. Mounting more targeted research and educational efforts today may reduce later use and abuse, inform society about the special circumstances of religious use, and better prepare clinicians and other health care providers about the issues involved when people choose to indigenously source psychoactive drugs for human consumption.

Halpern, J. H., & Sewell, R. A. (2005). Hallucinogenic botanicals of America: A growing need for focused drug education and research. Life sciences, 78(5), 519-526. https://dx.doi.org/10.1016/j.lfs.2005.09.005
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27 June - Spiritual & Existential Dimensions in Psychedelic Care: Challenges & Insights

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