Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function

The purpose of this paper is to provide an integrative review and offer novel insights regarding human research with classic psychedelics (classic hallucinogens), which are serotonin 2A receptor (5-HT2AR) agonists such as lysergic acid diethylamide (LSD), mescaline, and psilocybin. Classic psychedelics have been administered as sacraments since ancient times. They were of prominent interest within psychiatry and neuroscience in the 1950s to 1960s, and during this time contributed to the emergence of the field of molecular neuroscience. Promising results were reported for treatment of both end-of-life psychological distress and addiction, and classic psychedelics served as tools for studying the neurobiological bases of psychological disorders. Moreover, classic psychedelics were shown to occasion mystical experiences, which are subjective experiences reported throughout different cultures and religions involving a strong sense of unity, among other characteristics. However, the recreational use of classic psychedelics and their association with the counterculture prompted an end to human research with classic psychedelics in the early 1970s. We provide the most comprehensive review of epidemiological studies of classic psychedelics to date. Notable among these are a number of studies that have suggested the possibility that nonmedical naturalistic (non-laboratory) use of classic psychedelics is associated with positive mental health and prosocial outcomes, although it is clear that some individuals are harmed by classic psychedelics in non-supervised settings. We then review recent therapeutic studies suggesting efficacy in treating psychological distress associated with life-threatening diseases, treating depression, and treating nicotine and alcohol addictions. We also describe the construct of mystical experience, and provide a comprehensive review of modern studies investigating classic psychedelic-occasioned mystical experiences and their consequences. These studies have shown classic psychedelics to fairly reliably occasion mystical experiences. Moreover, classic-psychedelic-occasioned mystical experiences are associated with improved psychological outcomes in both healthy volunteer and patient populations. Finally, we review neuroimaging studies that suggest neurobiological mechanisms of classic psychedelics. These studies have also broadened our understanding of the brain, the serotonin system, and the neurobiological basis of consciousness. Overall, these various lines of research suggest that classic psychedelics might hold strong potential as therapeutics, and as tools for experimentally investigating mystical experiences and behavioral-brain function more generally

Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes

Mescaline is a naturally occurring psychoactive alkaloid that has been used as a sacrament by Indigenous populations in spiritual ritual and healing ceremonies for millennia. Despite promising early preliminary research and favorable anecdotal reports, there is limited research investigating mescaline’s psychotherapeutic potential. We administered an anonymous online questionnaire to adults (N = 452) reporting use of mescaline in naturalistic settings about mental health benefits attributed to mescaline. We assessed respondents’ self-reported improvements in depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol and drug use disorders (AUD and DUD). Of the respondents reporting histories of these clinical conditions, most (68–86%) reported subjective improvement following their most memorable mescaline experience. Respondents who reported an improvement in their psychiatric conditions reported significantly higher ratings of acute psychological factors including mystical-type, psychological insight, and ego dissolution effects compared to those who did not report improvements (Cohen’s d range 0.7 – 1.5). Many respondents (35–50%) rated the mescaline experience as the single or top five most spiritually significant or meaningful experience(s) of their lives. Acute experiences of psychological insight during their mescaline experience were associated with increased odds of reporting improvement in depression, anxiety, AUD and DUD. Additional research is needed to corroborate these preliminary findings and to rigorously examine the efficacy of mescaline for psychiatric treatment in controlled, longitudinal clinical trials.

The epidemiology of mescaline use: Pattern of use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects

Background: Mescaline is a naturally occurring psychoactive phenethylamine found in several cacti and historically used ceremonially by Indigenous and Latin American populations. Broader recognition of its possible therapeutic value in Western science began in the 1950s; however, knowledge of the safety profile of mescaline and the extent of its use remains limited. The primary aim of this study is to examine the epidemiology of mescaline use among English-speaking adults. Methods: About 452 respondents completed a web-based survey designed to assess their previous experience with mescaline (subjective effects, outcome measures, and mescaline type used). Results: Most respondents reported that they had consumed mescaline infrequently (⩽once/year), for spiritual exploration or to connect with nature (74%). A small number of respondents reported drug craving/desire (9%), whereas very few reported legal (1%), or psychological problems (1%) related to its use, and none reported seeking any medical attention. Overall, respondents rated the acute mystical-type effects as “moderate,” ego-dissolution and psychological insight effects as “slight,” and challenging effects as “very slight.” Most respondents reported that they used Peyote and San Pedro in their most memorable mescaline experience. Overall, the intensity of acute mescaline effects did not differ between mescaline types. About 50% of the sample reported having a psychiatric condition (i.e. depression, anxiety, etc.), and most (>67%) reported improvements in these conditions following their most memorable experience with mescaline. Conclusion: Findings indicate that the mescaline in any form may produce a psychedelic experience that is associated with the spiritual significance and improvements in the mental health with low potential for abuse. Keywords: 3,4,5-trimethoxyphenethylamine; Mescaline; epidemiology; survey.

New mescaline concentrations from 14 taxa/cultivars of Echinopsis spp. (Cactaceae) (“San Pedro”) and their relevance to shamanic practice

Abstract Aim of the study The aim of the present study is to determine in a procedurally uniform manner the mescaline concentrations in stem tissue of 14 taxa/cultivars of the subgenus Trichocereus of the genus Echinopsis (Cactaceae) and to evaluate the relationship (if any) between mescaline concentration and actual shamanic use of these plants. Materials and methods Columnar cacti of the genus Echinopsis, some of which are used for diagnostic and therapeutic purposes by South American shamans in traditional medicine, were selected for analysis because they were vegetative clones of plants of documented geographic origin and/or because they were known to be used by practitioners of shamanism. Mescaline content of the cortical stem chlorenchyma of each cactus was determined by Soxhlet extraction with methanol, followed by acid–base extraction with water and dichloromethane, and high-pressure liquid chromatography (HPLC). Results By virtue of the consistent analytical procedures used, comparable alkaloid concentrations were obtained that facilitated the ranking of the various selected species and cultivars of Echinopsis, all of which exhibited positive mescaline contents. The range of mescaline concentrations across the 14 taxa/cultivars spanned two orders of magnitude, from 0.053% to 4.7% by dry weight. Conclusions The mescaline concentrations reported here largely support the hypothesis that plants with the highest mescaline concentrations – particularly E. pachanoi from Peru – are most associated with documented shamanic use.

The psychedelic explorer’s guide: Safe, therapeutic, and sacred journeys

Called “America’s wisest and most respected authority on psychedelics and their use,” James Fadiman has been involved with psychedelic research since the 1960s. In this guide to the immediate and long-term effects of psychedelic use for spiritual (high dose), therapeutic (moderate dose), and problem-solving (low dose and microdose) purposes, Fadiman outlines best practices for safe, sacred entheogenic voyages learned through his more than 40 years of experience—from the benefits of having a sensitive guide during a session (and how to be one) to the importance of the setting and pre-session intention. Fadiman reviews the newest as well as the neglected research into the psychotherapeutic value of visionary drug use for increased personal awareness and a host of serious medical conditions, including his recent study of the reasons for and results of psychedelic use among hundreds of students and professionals. He reveals new uses for LSD and other psychedelics, including microdosing, extremely low doses for improved cognitive functioning and emotional balance. Cautioning that psychedelics are not for everyone, he dispels the myths and misperceptions about psychedelics circulating in textbooks and clinics as well as on the internet. Exploring the life-changing experiences of Ram Dass, Timothy Leary, Aldous Huxley, and Huston Smith as well as Francis Crick and Steve Jobs, Fadiman shows how psychedelics, used wisely, can lead not only to healing but also to scientific breakthroughs and spiritual epiphanies.

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