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Mushrooms / Psilocybin

The persistence of the subjective in neuropsychopharmacology: observations of contemporary hallucinogen research

February 26, 2010 / Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Salvia / Salvinorin A / By /

Abstract

The elimination of subjectivity through brain research and the replacement of so-called ‘folk psychology’ by a neuroscientifically enlightened worldview and self-conception has been both hoped for and feared. But this cultural revolution is still pending. Based on nine months of fieldwork on the revival of hallucinogen research since the ‘Decade of the Brain,’ this paper examines how subjective experience appears as epistemic object and practical problem in a psychopharmacological laboratory. In the quest for neural correlates of (drug-induced altered states of) consciousness, introspective accounts of test subjects play a crucial role in neuroimaging studies. Firsthand knowledge of the drugs’ flamboyant effects provides researchers with a personal knowledge not communicated in scientific publications, but key to the conduct of their experiments. In many cases, the ‘psychedelic experience’ draws scientists into the field and continues to inspire their self-image and way of life. By exploring these domains the paper points to a persistence of the subjective in contemporary neuropsychopharmacology.

Langlitz, N. (2010). The persistence of the subjective in neuropsychopharmacology: observations of contemporary hallucinogen research. History of Human Sciences, 23(1), 37-57. http://dx.doi.org/10.1177/0952695109352413
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Psychedelics and the Human Receptorome

February 2, 2010 / DMT, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Publications / By /

Abstract

We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT2A (and possibly 5-HT2C) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective for these two receptors. This manuscript is a reference work on the receptor affinity pharmacology of psychedelic drugs. New data is presented on the affinity of twenty-five psychedelic drugs at fifty-one receptors, transporters, and ion channels, assayed by the National Institute of Mental Health – Psychoactive Drug Screening Program (NIMH-PDSP). In addition, comparable data gathered from the literature on ten additional drugs is also presented (mostly assayed by the NIMH-PDSP). A new method is introduced for normalizing affinity (Ki) data that factors out potency so that the multi-receptor affinity profiles of different drugs can be directly compared and contrasted. The method is then used to compare the thirty-five drugs in graphical and tabular form. It is shown that psychedelic drugs, especially phenylalkylamines, are not as selective as generally believed, interacting with forty-two of forty-nine broadly assayed sites. The thirty-five drugs of the study have very diverse patterns of interaction with different classes of receptors, emphasizing eighteen different receptors. This diversity of receptor interaction may underlie the qualitative diversity of these drugs. It should be possible to use this diverse set of drugs as probes into the roles played by the various receptor systems in the human mind.

Ray, T. S. (2010). Psychedelics and the Human Receptorome. PLoS ONE, 5(2). http://dx.doi.org/10.1371/journal.pone.0009019
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Unauthorized Research on Cluster Headache

December 3, 2008 / Headache Pain and Neurological Disorders, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychiatry & Medicine, Publications / By /

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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Serotonin-Related Psychedelic Drugs

November 5, 2008 / LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , ,

Abstract

Serotonergic hallucinogens include the prototypical compounds such as mescaline, psilocybin, and LSD, representing the chemical classes of phenethylamines, tryptamines, and ergolines. Known as psychedelics, these compounds induce dramatic alterations of perception, affect, consciousness, and the experience of self. As first discovered in animal studies and recently confirmed in humans, the psychological effects of psychedelics are primarily attributable to the activation of the 5-HT2A subtype of serotonin receptors in brain. Research on psychedelic compounds has provided important insights into the neurobiology of consciousness and naturally occurring psychotic states and may lead to further advances in the development of psychiatric pharmacotherapeutics.

Geyer, M. A., Nichols, D. E., & Vollenweider, F. X. (2009). Serotonin-related psychedelic drugs. 10.1016/B978-008045046-9.01160-8
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Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines

November 1, 2008 / DMT, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Publications / By /

Abstract

Background: Although man’s first encounters with hallucinogens predate written history, it was not until the rise of the sister disciplines of organic chemistry and pharmacology in the nineteenth century that scientific studies became possible. Mescaline was the first to be isolated and its chemical structure determined. Since then, additional drugs have been recovered from their natural sources and synthetic chemists have contributed many more. Given their profound effects upon human behavior and the need for verbal communication to access many of these effects, some see humans as ideal subjects for study of hallucinogens. However, if we are to determine the mechanisms of action of these agents, establish hypotheses testable in human subjects, and explore the mechanistic links between hallucinogens and such apparently disparate topics as idiopathic psychosis, transcendental states, drug abuse, stress disorders, and cognitive dysfunction, studies in animals are essential. Stimulus control by hallucinogens has provided an intuitively attractive approach to the study of these agents in nonverbal species.

Objective: The intent of this review is to provide a brief account of events from the time of the first demonstration of hallucinogen-induced stimulus control to the present. In general, the review is limited to lysergic acid diethylamide (LSD) and the hallucinogenic derivatives of phenethylamine and tryptamine.

Results: The pharmacological basis for stimulus control by LSD and hallucinogenic phenethylamines and tryptamines is serotonergic in nature. The 5-HT2A receptor appears to be the primary site of action with significant modulation by other serotonergic sites including 5-HT2C and 5-HT1A receptors. Interactions with other neurotransmitters, especially glutamate and dopamine, are under active investigation. Most studies to date have been conducted in the rat but transgenic mice offer interesting possibilities.

Conclusions: Hallucinogen-induced stimulus control provides a unique behavioral tool for the prediction of subjective effects in man and for the elucidation of the pharmacological mechanisms of the action of these agents.

Winter, J. C. (2009). Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines. Psychopharmacology, 203(2), 251–263. http://dx.doi.org/10.1007/s00213-008-1356-8
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The Phenomenology and Potential Religious Import of States of Consciousness Facilitated by Psilocybin

October 30, 2008 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By /

Abstract

Accompanying the resumption of human research with the entheogen (psychedelic drug), psilocybin, the range of states of consciousness reported during its action, including both nonmystical and mystical forms of experience, is surveyed and defined. The science and art of facilitating mystical experiences is discussed on the basis of research experience. The potential religious import of these states of consciousness is noted in terms of recognizing the reality of the spiritual, in better understanding the biochemistry of revelation, and in exploring the potentially positive contributions that mystical consciousness may effect in psychological treatment.

Richards, W. A. (2008). The Phenomenology and Potential Religious Import of States of Consciousness Facilitated by Psilocybin. Archive for the Psychology of Religion, 30, 189-199. http://dx.doi.org/10.1163/157361208X317196
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Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later

July 1, 2008 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

Psilocybin has been used for centuries for religious purposes; however, little is known scientifically about its long-term effects. We previously reported the effects of a double-blind study evaluating the psychological effects of a high psilocybin dose. This report presents the 14-month follow-up and examines the relationship of the follow-up results to data obtained at screening and on drug session days. Participants were 36 hallucinogen-naïve adults reporting regular participation in religious/spiritual activities. Oral psilocybin (30 mg/70 kg) was administered on one of two or three sessions, with methylphenidate (40 mg/70 kg) administered on the other session(s). During sessions, volunteers were encouraged to close their eyes and direct their attention inward. At the 14-month follow-up, 58% and 67%, respectively, of volunteers rated the psilocybin-occasioned experience as being among the five most personally meaningful and among the five most spiritually significant experiences of their lives; 64% indicated that the experience increased well-being or life satisfaction; 58% met criteria for having had a ‘complete’ mystical experience. Correlation and regression analyses indicated a central role ofthe mystical experience assessed on the session day in the high ratings of personal meaning and spiritual significance at follow-up. Of the measures of personality, affect, quality of life and spirituality assessed across the study, only a scale measuring mystical experience showed a difference from screening. When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences that, at 14-month follow-up, were considered by volunteers to be among the most personally meaningful and spiritually significant of their lives.

Griffiths, R. R., Richards, W. A., Johnson, M. W., McCann U. D., & Jesse, R. (2008). Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. Journal of Psychopharmacology, 22(6), 621-632.22: 621-632; http://dx.doi.org/10.1177/0269881108094300
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Human hallucinogen research: guidelines for safety

July 1, 2008 / Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications, Salvia / Salvinorin A / By / , ,

Abstract

There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action (‘bad trip’), which could lead to potentially dangerous behaviour such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow-up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science.

Johnson, M. W., Richards, W. A., & Griffiths, R. R. (2008). Human hallucinogen research: guidelines for safety.  Journal of Psychopharmacology, 22(6), 603–620. http://dx.doi.org/10.1177/0269881108093587
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[Hallucinogen-induced psychological disorders]

June 1, 2008 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , ,

Abstract

OBJECTIVE:

The purpose of this article is to provide an overview of the current research on hallucinogen induced psychiatric disorders. In addition to LSD and psilocybin hallucinogens of biologic origin are increasingly used by adolescents and young adults.

METHODS:

Relevant literature and related articles were identified by means of a computerized MEDLINE search including the years 1997 – 2007. As keywords “hallucinogen induced psychosis”, “hallucinogen induced flashback”, “hallucinogen persisting perception disorder (HPPD)” were used. Finally, 64 journal articles and books out of 103 were included in the review.

RESULTS:

Acute psychotic syndromes in adolescents are rarely due to intoxications with hallucinogenic drugs. However, clinical relevance of flashback phenomena as post-hallucinogenic psychiatric disorder has to be disputed. Because of the high popularity of biogenic hallucinogens and LSD knowledge of intoxications and resulting psychiatric disorders as well as medical complications and therapeutical approaches are clinically important. Especially intoxications with drugs of herbal origin like tropanalcaloids play an important role in emergency situations.

Hermle, L., Kovar, K. A., Hewer, W., & Ruchsow, M. (2008). [Hallucinogen-induced psychological disorders]. Fortschritte der Neurologie-Psychiatrie, 76(6), 334-342. http://dx.doi.org/10.1055/s-2008-1038191
Link to full text [Article in German]

Selective 5-HT2A agonist hallucinogens: A review of pharmacological interaction and corollary perceptual effects

May 23, 2008 / DMT, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By /

Abstract

The most potent tryptamine hallucinogens – such as DMT, psilocybin, and LSD – are all active at the 5-HT2A receptor subtype and all produce similar visual perceptual results that are immediately recognizable as uniquely psychedelic. Although it is widely accepted that selective serotonin receptor subtype 2A agonism is directly responsible for producing the distinct hallucinations seen on a psychedelic trip, no single theory has yet explained why this is so. Utilizing what we know about psychedelic tryptamine receptor interaction, sensory processing circuits in the neocortex, and EEG scans of psychedelics in action, this review will propose a novel multi-state theory of psychedelic action which invokes a variety of neural processing mechanisms, including phase-coupled neural oscillators; network excitation, disinhibition, and destabilization; recurrent feedback excitation; and neural circuit spike synchrony and brainwave cohesion to close the knowledge gap between the pharmaceutical interactions of selective 5-HT2A hallucinogens, their direct effects on perception and consciousness at varying dose ranges, and their potential long-term adverse effects.

Kent, J. (2008). Selective 5-HT2A agonist hallucinogens: A review of pharmacological interaction and corollary perceptual effects. Beta Review.

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