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Studying the Effects of Classic Hallucinogens in the Treatment of Alcoholism: Rationale, Methodology, and Current Research with Psilocybin

March 1, 2013 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Substance Use Disorder / By /

Abstract

Recent developments in the study of classic hallucinogens, combined with a re-appraisal of the older literature, have led to a renewal of interest in possible therapeutic applications for these drugs, notably their application in the treatment of addictions. This article will first provide a brief review of the research literature providing direct and indirect support for the possible therapeutic effects of classic hallucinogens such as psilocybin and lysergic acid diethylamide (LSD) in the treatment of addictions. Having provided a rationale for clinical investigation in this area, we discuss design issues in clinical trials using classic hallucinogens, some of which are unique to this class of drug. We then discuss the current status of this field of research and design considerations in future randomized trials.

Bogenschutz, M. P. (2013). Studying the Effects of Classic Hallucinogens in the Treatment of Alcoholism: Rationale, Methodology, and Current Research with Psilocybin. Current Drug Abuse Reviews, 6(1), 17-29.
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Research on psychedelic substances

July 6, 2012 / Humanities & Art, LSD, Papers, Psychology, Publications / By / ,

Introduction

The term ‘psychedelic ’ (i.e. mind-manifesting) was coined by Humphrey Osmond to characterize a grou p of substances that are capable of liberating human perception from cultural conditioning, providing an op ening to the transcendent qualities of being human. Osmond claimed that LSD and similar drugs may give people insightful experiences that enable them to better understand themselves and their relationships with the world. Psychedelic substances have the potential to show mindmanifesting properties under appropriate internally and externally supported conditions. They can offer lucid insights into one’s psychological make-up and functioning. They are also capable of inducing a spectrum of inner experiences, sometimes
referred to as ‘religious’ or ‘mystical’. Another commonly used term for these substances is ‘hallucinogens’, although this synonym is viewed as controversial because of the implication that they somehow cause hallucinations, which they do very rarely. Most psychedelic substances produce visual alterations of perceived objects and pseudohallucinations which are understood by the subject to be ‘illusionary’ in character […]
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Brandt, S. D., & Passie, T. (2012). Research on psychedelic substances. Drug testing and analysis, 4(7-8), 539-542. https://dx.doi.org/10.1002/dta.1389
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Quantitative Analysis of Narrative Reports of Psychedelic Drugs

June 1, 2012 / Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Publications, Salvia / Salvinorin A / By / , ,

Abstract

Background

Psychedelic drugs facilitate profound changes in consciousness and have potential to provide insights into the nature of human mental processes and their relation to brain physiology. Yet published scientific literature reflects a very limited understanding of the effects of these drugs, especially for newer synthetic compounds. The number of clinical trials and range of drugs formally studied is dwarfed by the number of written descriptions of the many drugs taken by people. Analysis of these descriptions using machine-learning techniques can provide a framework for learning about these drug use experiences.

Methods

We collected 1000 reports of 10 drugs from the drug information website Erowid.org and formed a term-document frequency matrix. Using variable selection and a random-forest classifier, we identified a subset of words that differentiated between drugs.

Results

A random forest using a subset of 110 predictor variables classified with accuracy comparable to a random forest using the full set of 3934 predictors. Our estimated accuracy was 51.1%, which compares favorably to the 10% expected from chance. Reports of MDMA had the highest accuracy at 86.9%; those describing DPT had the lowest at 20.1%. Hierarchical clustering suggested similarities between certain drugs, such as DMT and Salvia divinorum.

Conclusion

Machine-learning techniques can reveal consistencies in descriptions of drug use experiences that vary by drug class. This may be useful for developing hypotheses about the pharmacology and toxicity of new and poorly characterized drugs.

Coyle, J. R., Presti, D. E., Baggott, M. J. (2012). Quantitative Analysis of Narrative Reports of Psychedelic Drugs.
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LSD effective in the treatment of alcohol addiction

December 6, 2021 / LSD, Publications, Substance Use Disorder / By

alcoholismLSD can be effective in the treatment of alcoholism, according to a new study of a Norwegian research team. This study, published in the Journal of Psychopharmacology, shows that administration of LSD in alcoholics can contribute to the success of the treatment.

In this meta-analysis, the results of six randomized clinical trials that were published between 1966 and 1970 were used. In these studies LSD was administered in a total of 325 cases, and a placebo in 211 cases. Of the patients that received LSD 59% percent improved during the treatment, compared to only 38% of the persons receiving a placebo. The researchers conclude that there is evidence for a positive effect of LSD in the treatment of alcoholism.

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials

March 8, 2012 / LSD, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36–2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.

Krebs, T. S., & Johansen, P. Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 26(2), 994-1002. http://dx.doi.org/10.1177/0269881112439253
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In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in MDMA and Hallucinogen Users

June 6, 2011 / Ayahuasca, DMT, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Salvia / Salvinorin A / By / , , , , , ,

Abstract

Context:
Both hallucinogens and 3,4-methylenedioxy-methamphetamine (MDMA or “ecstasy”) have direct agonistic effects on postsynaptic serotonin 2A receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.

Objective:
To assess the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin2Areceptor binding.

Design:
A positron emission tomography study of 24 young adult drug users and 21 nonusing control partici-pants performed with carbon 11 (11C)–labeled 3-amino-4-[2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzo-nitrile (DASB) and fluorine 18 (18F)–labeled altanserin, respectively. Scans were performed in the user group after a minimum drug abstinence period of 11 days, and the group was subdivided into hallucinogen-preferring users (n = 10) and MDMA-preferring users (n = 14).

Participants:
Twenty-four young adult users of MDMA and/or hallucinogenic drugs and 21 nonusing controls.

Main Outcome Measures:
In vivo cerebral SERT and serotonin 2A receptor binding.

Results:
Compared with nonusers, MDMA-preferring users showed significant decreases in SERT nondisplaceable binding potential (neocortex, −56%; pallidostriatum, −19%; and amygdala, −32%); no significant changes were seen in hallucinogen-preferring users. Both cortical and pallidostriatal SERT nondisplaceable binding potential was negatively correlated with the number of life-time MDMA exposures, and the time of abstinence from MDMA was positively correlated with subcortical, but not cortical, SERT binding. A small decrease in neocortical serotonin 2A receptor binding in the serotonin 2A receptor agonist users (both user groups) was also detected.

Conclusions
We found evidence that MDMA but not hallucinogen use is associated with changes in the cerebral presynaptic serotonergic transmitter system. Because hallucinogenic drugs primarily have serotonin 2A receptor agonistic actions, we conclude that the negative association between MDMA use and cerebral SERT binding is mediated through a direct presynaptic MDMA effect rather than by the serotonin 2A agonistic effects of MDMA. Our cross-sectional data suggest that subcortical, but not cortical, recovery of SERT binding might take place after several months of MDMA abstinence.

Erritzoe, D., Frokjaer, V. G., Holst, K. K., Christoffersen, M., Johansen, S. S., Svarer, C., … Knudsen, G. M. (2011). In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) and Hallucinogen Users. Archives of General Psychiatry, 68(6), 562-576. http://dx.doi.org/10.1001/archgenpsychiatry.2011.56
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Start Your Own Religion: New York State’s Acid Churches

February 23, 2011 / Humanities & Art, LSD, Papers, Publications / By /

Abstract

This paper describes a radical and short-lived spiritual movement that emerged in New York State in the 1960s. With Dr. Timothy Leary as the figurehead, two of these psychedelic religions rose to brief cultural prominence in period of 1963–1968 when Leary and his communal group made their home in the small village of Millbrook, New York. Due to negative media attention and a subsequent law enforcement crackdown brought upon at least partially by the increasingly provocative stance of the leaders of these psychedelic groups, they were forced to flee the state by early 1968. This paper establishes the historical significance of New York State’s Acid Churches within the culture of the 1960s and draws the link to today’s Neopagan and New Age movements and the rebirth of the use of psychedelic substances within the modern scientific, psychological, and therapeutic communities.

Lander, D. R. (2011).  Start Your Own Religion: New York State’s Acid Churches. Nova Religio: The Journal of Alternative and Emergent Religions, 14(3), 64–80. http://dx.doi.org/10.1525/nr.2011.14.3.64
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Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens

January 20, 2011 / Ayahuasca, DMT, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

Serotonergic hallucinogens produce profound changes in perception, mood, and cognition. These drugs include phenylalkylamines such as mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM), and indoleamines such as (+)-lysergic acid diethylamide (LSD) and psilocybin. Despite their differences in chemical structure, the two classes of hallucinogens produce remarkably similar subjective effects in humans, and induce cross-tolerance. The phenylalkylamine hallucinogens are selective 5-HT(2) receptor agonists, whereas the indoleamines are relatively non-selective for serotonin (5-HT) receptors. There is extensive evidence, from both animal and human studies, that the characteristic effects of hallucinogens are mediated by interactions with the 5-HT(2A) receptor. Nevertheless, there is also evidence that interactions with other receptor sites contribute to the psychopharmacological and behavioral effects of the indoleamine hallucinogens. This article reviews the evidence demonstrating that the effects of indoleamine hallucinogens in a variety of animal behavioral paradigms are mediated by both 5-HT(2) and non-5-HT(2) receptors.

Halberstadt, A. L., & Geyer, M.A. (2011). Multiple receptors contribute to the behavioral effects of indoleamine hallucinogens. Neuropharmacology, 61(3), 364-381. http://dx.doi.org/10.1016/j.neuropharm.2011.01.017
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Characterization of behavioral and endocrine effects of LSD on zebrafish

December 25, 2010 / LSD, Papers, Publications / By / , , , , , ,

Abstract

Lysergic acid diethylamide (LSD) is a potent hallucinogenic drug that strongly affects animal and human behavior. Although adult zebrafish (Danio rerio) are emerging as a promising neurobehavioral model, the effects of LSD on zebrafish have not been investigated previously. Several behavioral paradigms (the novel tank, observation cylinder, light–dark box, open field, T-maze, social preference and shoaling tests), as well as modern video-tracking tools and whole-body cortisol assay were used to characterize the effects of acute LSD in zebrafish. While lower doses (5–100 μg/L) did not affect zebrafish behavior, 250 μg/L LSD increased top dwelling and reduced freezing in the novel tank and observation cylinder tests, also affecting spatiotemporal patterns of activity (as assessed by 3D reconstruction of zebrafish traces and ethograms). LSD evoked mild thigmotaxis in the open field test, increased light behavior in the light–dark test, reduced the number of arm entries and freezing in the T-maze and social preference test, without affecting social preference. In contrast, LSD affected zebrafish shoaling (increasing the inter-fish distance in a group), and elevated whole-body cortisol levels. Overall, our findings show sensitivity of zebrafish to LSD action, and support the use of zebrafish models to study hallucinogenic drugs of abuse.

Grossman, L., Utterback, E., Stewarta, A., Gaikwada, S., Chunga, K. M., Suciua, C., … Kalueff, A. V. (2010). Characterization of behavioral and endocrine effects of LSD on zebrafish. Behavioural Brain Research, 214(2), 277-284. http://dx.doi.org/10.1016/j.bbr.2010.05.039
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Psychobiology of Drug-Induced Religious Experience: From the Brain 'Locus of Religion' to Cognitive Unbinding

November 13, 2010 / Ayahuasca, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

The recent interest in the psychopharmacological underpinnings of religious experiences has led to both the laboratory characterizations of drug-induced mystical events and psychobiological models of religious experiences rooted in evolution and fitness. Our examination of this literature suggests that these theories may be congruent only within more modern religious and cultural settings and are not generalizable to all historical beliefs, as would be expected from an evolutionarily conserved biological mechanism. The strong influence of culture on the subjective effects of drugs as well as religious thoughts argues against the concept of a common pathway in the brain uniquely responsible for these experiences. Rather, the role of personal beliefs, expectations and experiences may interject bias into the interpretation of psychoactive drug action as a reflection of biologically based religious thought. Thus, psychobiological research proposing specific brain mechanisms should consider anthropological and historical data to address alternative explanations to the “fitness” of religious thought. A psychobiological model of the religious experience based on the concept of cognitive unbinding seems to accommodate these data better than that of a specific brain locus of religion.

Nencini, P., & Grant, G. A. (2010). Psychobiology of Drug-Induced Religious Experience: From the Brain ‘Locus of Religion’ to Cognitive Unbinding. Substance Use & Misuse, 45(13), 2130–2151. http://dx.doi.org/10.3109/10826081003713803
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