Advocates of the therapeutic use of psychedelic drugs have argued that a promising approach to treatment was prematurely abandoned in the 1960s primarily because of Richard Nixon's 'War on ...Drugs'.This paper (1) briefly describes research in the 1950s and 1960s in North America on the use of LSD to treat alcohol dependence, anxiety in terminal illness, and anxiety and depression; and (2) discusses the factors that led to its abandonment.
An analysis of historical scholarship on psychedelic research in the 1950s, 1960s and 1970s in North America.
Research on psychedelic drugs in psychiatry was abandoned for a number of reasons that acted in concert. A major factor was that clinical research on psychedelic drugs was caught up in the tighter regulation of pharmaceutical research after the Thalidomide disaster in 1963. Psychedelic drugs also presented special challenges for randomised, placebo-controlled clinical trials in the 1970s that were not as positive as the claims made by their advocates in the 1950s and 1960s. Clinical research became more difficult after 1965 when Sandoz ceased providing psychedelic drugs for research and their nonmedical use was prohibited in 1970.
The demise of psychedelic drug research was not solely due to the 'War on Drugs'. It was hastened by tighter regulation of pharmaceutical research, the failure of controlled clinical trials to live up to the claims of psychedelic advocates, and the pharmaceutical industry's lack of interest in funding clinical trials.
Introduction
Emerging evidence suggests that psychedelic compounds, including the Amazonian botanical decoction ayahuasca, may provide clinical benefit in the treatment of alcohol or other drug use ...disorders. This study investigates associations between ayahuasca consumption in naturalistic settings and current alcohol and other drug use.
Methods
Online cross‐sectional study of people who have consumed ayahuasca in religious, traditional and non‐traditional settings in over 40 countries. A total of 8629 participants (53% male, average age 40 years) were included in the analysis. Logistic regressions were used to explore associations between ayahuasca drinking variables and the current use of alcohol and other drugs, as well as the influence of confounding factors, such as church or community membership.
Results
The number of times ayahuasca had been consumed was strongly associated with increased odds of never or rarely drinking alcohol, never or rarely engaging in ‘risky drinking’ and having not consumed a range of drugs in the past month, with these effects greater for those with a prior substance use disorder compared to those without. The strength of ayahuasca drinkers subjective spiritual experience, number of personal self‐insights obtained and drinking ayahuasca with an ayahuasca church were also associated with lower substance use in some models.
Discussion and Conclusions
Consumption of ayahuasca in naturalistic settings is associated with lower self‐reported current consumption of alcohol and other drugs for those with and without prior substance use disorders, with such effects present after adjusting for religious or social group effects.
•Illicit drugs seized by police were mainly methamphetamine, MDMA and cocaine.•Cocaine, 2C-B and GHB were more frequently adulterated with other substances.•Methamphetamine, MDMA, THC and heroin ...samples showed high purity.•Methamphetamine and MDMA contained also the largest variety of impurities.•Emerging NPS as adulterants are similar to that reported in Europe.
Impurities in commonly used illicit drugs raise concerns for unwitting consumers when pharmacologically active adulterants, especially new psychoactive substances (NPS), are used. This study examines impurities detected in illicit drugs seized in one Australian jurisdiction.
Queensland Health Forensic and Scientific Services provided analytical data. Data described the chemical composition of 9346 samples of 11 illicit drugs seized by police during 2015-2016. Impurities present in primary drugs were summarized and tabulated. A systematic search for published evidence reporting similar analyses was conducted.
Methamphetamine was the primary drug in 6608 samples, followed by MDMA (1232 samples) and cocaine (516 samples). Purity of primary drugs ranged from ∼30% for cocaine, 2-CB and GHB to >90% for THC, methamphetamine, heroin and MDMA. Methamphetamine and MDMA contained the largest variety of impurities: 22 and 18 variants, respectively. Drug adulteration patterns were broadly similar to those found elsewhere, including NPS, but in some primary drugs impurities were found which had not been reported elsewhere. Psychostimulants were adulterated with each other. Levamisole was a common impurity in cocaine. Psychedelics were adulterated with methamphetamine and NPS. Opioids were quite pure, but some samples contained methamphetamine and synthetic opioids.
Impurities detected were mostly pharmacologically active adulterants probably added to enhance desired effects or for active bulking. Given the designer nature of these drug cocktails, the effects of the adulterated drugs on users from possible complex multi-drug interactions is unpredictable. Awareness-raising among users, research into complex multi-drug effects and ongoing monitoring is required.
Abstract
Psilocybin and other serotonergic psychedelics have re-emerged as therapeutics for neuropsychiatric disorders, including addiction. Psilocybin induces long-lasting effects on behavior, ...likely due to its profound ability to alter consciousness and augment neural connectivity and plasticity. Impaired synaptic plasticity in obesity contributes to ‘addictive-like’ behaviors, including heightened motivation for palatable food, and excessive food seeking and consumption. Here, we evaluate the effects of psilocybin on feeding behavior, energy metabolism, and as a weight-lowering agent in mice. We demonstrate that a single dose of psilocybin substantially alters the prefrontal cortex transcriptome but has no acute or long-lasting effects on food intake or body weight in diet-induced obese mice or in genetic mouse models of obesity. Similarly, sub-chronic microdosing of psilocybin has no metabolic effects in obese mice and psilocybin does not augment glucagon-like peptide-1 (GLP-1) induced weight loss or enhance diet-induced weight loss. A single high dose of psilocybin reduces sucrose preference but fails to counter binge-like eating behavior. Although these preclinical data discourage clinical investigation, there may be nuances in the mode of action of psychedelic drugs that are difficult to capture in rodent models, and thus require human evaluation to uncover.
Background:
The classical psychedelics, psilocybin, peyote, ayahuasca/N,N-dimethyltryptamine, and lysergic acid diethylamide are considered promising new treatments for psychiatric illnesses, such as ...depression, anxiety, addiction, and obsessive-compulsive disorders. However, their profound and characteristic subjective effects raise concern for distinctive biases in randomized clinical trials.
Methods:
We performed a systematic literature search to identify all clinical trials on classical psychedelics with patient populations to examine descriptive data and determine the risk of bias. Two independent reviewers searched three databases (PubMed, Embase, and APA PsycNet) and extracted information on study design, study population, use of active or inactive placebo, dropouts, evaluation of blinding of intervention, and reporting of expectancy and therapeutic alliance.
Results:
We included 10 papers reporting on 10 unique trials. The trials generally included populations that were predominantly white and highly educated. The trials had small samples and considerable dropout. Blinding was either unsuccessful or not reported regardless of type of placebo. Few trials published protocols, statistical analysis plans (SAPs), and outcomes relating to psychotherapy fidelity. All trials but one were rated as high risk of bias.
Conclusion:
Successful blinding of intervention is a significant challenge in this field. To better accommodate this, we suggest that future trials use a parallel-group design and utilize an active placebo on a psychedelic-naïve population. Future trials should publish trial protocol and SAPs, use clinician-rated outcomes accessed by a blinded rater, evaluate blinding of intervention, and consider measuring expectancy and therapeutic fidelity.
Background:
Psilocybin is the psychoactive component in Psilocybe mushrooms (‘magic mushrooms’). Whether and how the quality of the psilocybin-induced experience might mediate beneficial health ...outcomes is currently under investigation, for example, in therapeutic applications. However, to date, no meta-analysis has investigated the dose-dependency of subjective experiences across available studies.
Aim:
Establishing dose–response relationships of the subjective experiences induced by psilocybin in healthy study participants and a comparison of patient groups.
Method:
We applied a linear meta-regression approach, based on the robust variance estimation framework, to obtain linear dose–response relationship estimates on questionnaire ratings after oral psilocybin administration. Data were obtained from the Altered States Database, which contains data extracted from MEDLINE-listed journal articles that used standardized and validated questionnaires: the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire and the Hallucinogen Rating Scale.
Results:
Psilocybin dose positively correlated with ratings on most factors and scales, mainly those referring to perceptual alterations and positively experienced ego dissolution. Measures referring to challenging experiences exhibited small effects and were barely modulated by dose.
Conclusion:
Psilocybin intensified almost all characteristics of altered states of consciousness assessed with the given questionnaires. Because subjective experiences are not only determined by dose, but also by individual and environmental factors, the results may only apply to controlled laboratory experiments and not to recreational use. This paper may serve as a general literature citation for the use of psilocybin in experimental and clinical research, to compare expected and observed subjective experiences.
Charles Raison1 INTRODUCTION As jurisdictions continue to reform psychedelics laws, lawmakers should consider how these new laws will impact the popular practice of microdosing- regularly taking very ...small amounts of a psychedelic, such as psilocybin, to improve one's quality of life.2 That is the thesis of Mason Marks, I. Glenn Cohen, Jonathan Perez-Reyzin, and David Angelatos's engaging and timely article, Microdosing Psychedelics Under Local, State, and Federal Law. "16 And it has been speculated that the psychedelic-assisted therapy "bubble" may burst, given the tremendous hype but modest results as of yet in treating mental health conditions.17 If a workable below-perceptual threshold version of psychedelics could exist, then health care would logically prefer the (safer, cheaper, and more predictable) taking of sub-perceptual threshold doses over above-perceptual doses. "26 Microdosing may result in improved mood, focus, concentration, creativity, energy, social benefits, lowered anxiety, and other cognitive advantages.27 Despite microdosing's growing popularity jurisdictions that have legalized, or proposed legislation to legalize, psychedelics for therapy have largely overlooked the practice.28 These jurisdictions have instead focused on regulating "big trip" psychedelic-assisted therapy.29 One can go to a facility and arrange to take a standard or large dose of psilocybin under the supervision of a guide.30 But the possession or use of minuscule amounts of psilocybin needed for microdosing could remain a felony under these legal frameworks.31 As the authors explain, this paradoxical result-an explicit or implicit minimum dose requirement-raises numerous equity and public health-related concerns.32 To remedy this, Marks and his coauthors recommend several microdosing implementation models for legislators, including decriminalization, supported adult use, retail sales, and medical frameworks.33 Despite its growing popularity, microdosing may have drawbacks. The claimed benefits (or challenges) of microdosing could be illusory-due to the placebo effect rather than any actual physiological effect.34 Some microdosers experience challenges, rather than benefits, such as physical discomfort, a level of disconnection from self, and impaired, rather than improved, mood, focus, and energy.35 And there is speculation that taking microdoses for prolonged periods could be linked to heart damage, given similar activation of serotonin receptors compared to the (now withdrawn) diet medication Phen/Fen.36 Much about microdosing is still unclear and begs further research; it may not be the mental health panacea some claim it to be.37 Citizen science indicates, though, that microdosing is helping many who engage in the practice.38 Marks and his coauthors are thus correct that psychedelics laws and regulations should allow people to microdose without the threat of arrest or prosecution.
Recent research highlighted the therapeutic potential of ayahuasca, a psychoactive plant brew used ritually in traditional Amazonian medicine (TAM). The present study evaluates the impact of ...integrating ayahuasca and TAM with psychotherapy on depression and anxiety in an inpatient addiction treatment program. Male patients (N = 31) were evaluated pre and post treatment using the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI). Clinical and sociodemographic characteristics, motivation, quality of life, spirituality, and treatment satisfaction were also measured and analyzed by means of two tailed t-test, one way ANOVA and Spearman test. From pre- to post-treatment, patients showed significant reductions in scores of anxiety (from 20.8 to 11.6, p < .002) and depression (from 18.7 to 7.5, p <.001). Similarly, patients showed higher scores of quality of life (p < .001) and spirituality (p < .001) upon discharge, which correlated with their reduction in scores of anxiety and depression. While future results will evaluate the efficacy of this treatment on measures of addiction at follow-up, the present results build upon previous research to bring further support to the use of Ayahuasca and Amazonian medicine in mental health treatments with a transpersonal focus.
Objective
Research into psychedelic therapy models has shown promise for the treatment of specific psychiatric conditions. Mystical‐type experiences occasioned by psilocybin have been correlated with ...therapeutic benefits and long‐term improvements in positive mental outlook and attitudes. This article aims to provide an overview of the topic, highlight strengths and weaknesses in current research, generate novel perspectives and discussion, and consider future avenues for research.
Design
This narrative review was designed to summarise and assess the state of research on psilocybin occasioned mystical‐type experiences and applications for the treatment of specific psychiatric conditions.
Results
Contemporary methods on the quantification of mystical‐type experiences and their acute subjective effects are discussed. Recent studies provide some understanding of the pharmacological actions of psychedelics although the neurological similarities and differences between spontaneous and psychedelic mystical‐type experiences are not well described. Applicability to modern clinical settings is assessed. Potential novel therapeutic applications include use in positive psychology interventions in healthy individuals.
Conclusions
Since 2006 significant advancements in understanding the therapeutic potential of psilocybin‐assisted psychotherapy have been made; however, more work is required to understand the neuromechanistic processes and applicability in modern clinical settings. Despite promising results in recent studies, funding issues for clinical trials, legal concerns and socio‐cultural resistance provide a counterpoint to experimental evidence.
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