OPEN Foundation

Cluster headache

Psilocybin – Summary of knowledge and new perspectives

Abstract

Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is nowadays given a lot of attention in the scientific community as a research tool for modeling psychosis as well as due to its potential therapeutic effects. However, it is also a very popular and frequently abused natural hallucinogen. This review summarizes all the past and recent knowledge on psilocybin. It briefly deals with its history, discusses the pharmacokinetics and pharmacodynamics, and compares its action in humans and animals. It attempts to describe the mechanism of psychedelic effects and objectify its action using modern imaging and psychometric methods. Finally, it describes its therapeutic and abuse potential.

Tylš, F., Páleníček, T., & Horáček, J. (2014). Psilocybin – Summary of knowledge and new perspectives. European Neuropsychopharmacology, 24, 342-365. http://dx.doi.org/10.1016/j.euroneuro.2013.12.006

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The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series

Introduction

Cluster headache (CH) is a stereotyped primary headache characterized by strictly unilateral severe orbital or periorbital pain and categorized as either episodic or chronic (1,2). Its prevalence is 0.1% (3). Oxygen and sumatriptan are the treatments of choice for individual attacks, whereas verapamil, lithium, corticosteroids and other neuromodulators can suppress attacks during cluster periods (1). All standard medication treatments may be ineffective. Surgical treatment may be an option for medication non-responders, including deep brain (4) or occipital nerve stimulation (5). However, serious complications from brain surgery, including death, can occur (6).

An Internet survey of 53 CH patients reported on claims that psilocybin is better at aborting acute attacks than either oxygen or sumatriptan and that LSD and psilocybin are both better at triggering and extending remission than standard drugs (7). However, due to hallucinogenicity and the absence of established medical indication, these drugs are criminalized and placed within the most restrictive Schedule I of the Controlled Substances Act, which sanctions only limited research use. Although the hallucinogenic properties of LSD and psilocybin are undesirable from both regulatory and patient safety perspectives, it was unclear to us at the outset whether a non-hallucinogenic analog could also provide meaningful relief to CH patients. To address the question of whether the CH relief associated with these two structurally diverse compounds is related to the mechanisms triggering intoxication, we decided to investigate the efficacy of a non-hallucinogenic analog of LSD. LSD’s hallucinogenic effects are completely lost when the double bond in the D ring is saturated and with substitution at R2 (e.g. by bromination in 2-bromo-LSD) (BOL-148) (8). BOL-148 has been studied in volunteers (up to 20 mg per os) (9) and in patients suffering from vascular headaches but not, apparently, in patients with CH (9,10). These past studies [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”][…]

Karst, M., Halpern, J. H., Bernateck, M., & Passie, T. (2010). The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series. Cephalalgia, 30(9), 1140-1144. https://dx.doi.org/10.1177/0333102410363490
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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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30 April - Q&A with Rick Strassman

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