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.
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Do drugs have religious import? A 40-Year Retrospective
Four decades ago, Huston Smith published one of the mostinfluential articles ever written on psychedelics, titled “Do Drugs Have Religious Import?” As part of “The Oral History of PsychedelicResearch Project,” he was interviewed and invited to revisit this topic. The interview covers his personal experiences, as well as the influences of psychedelic experiences on religious traditions and contemplative practices. Examples of such influences that are discussed include the ancient Vedic tradition and Eleusinian mysteries, and the contemporary Native American Church. At the social level, he reflects on factors that limited the effectiveness of the psychedelic movement of the 1960s in producing significant socialchange, the state of contemporary culture, society, and drug policy, and the role of elders in society.
The ketamine story–past, present and future
The history of ketamine begins in the 1950s at Parke-Davis and Company’s laboratories in Detroit, Michigan, USA. At that time, Parke-Davis were searching among cyclohexylamines for an ‘ideal’anaesthetic agent with analgesic properties.
A narrative synthesis of research with 5-MeO-DMT
Background: 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring, short-acting psychedelic tryptamine, produced by a variety of plant and animal species. Plants containing 5-MeO-DMT have been used throughout history for ritual and spiritual purposes. The aim of this article is to review the available literature about 5-MeO-DMT and inform subsequent clinical development. Methods: We searched PubMed database for articles about 5-MeO-DMT. Search results were cross-checked against earlier reviews and reference lists were hand searched. Findings were synthesised using a narrative synthesis approach. This review covers the pharmacology, chemistry and metabolism of 5-MeO-DMT, as well epidemiological studies, and reported adverse and beneficial effects. Results: 5-MeO-DMT is serotonergic agonist, with highest affinity for 5-HT1A receptors. It was studied in a variety of animal models, but clinical studies with humans are lacking. Epidemiological studies indicate that, like other psychedelics, 5-MeO-DMT induces profound alterations in consciousness (including mystical experiences), with potential beneficial long-term effects on mental health and well-being. Conclusion: 5-MeO-DMT is a potentially useful addition to the psychedelic pharmacopoeia because of its short duration of action, relative lack of visual effects and putatively higher rates of ego-dissolution and mystical experiences. We conclude that further clinical exploration is warranted, using similar precautions as with other classic psychedelics.
LSD: a new treatment emerging from the past
Psychedelics fell from medical grace nearly half a century ago, but recent activity suggests that some researchers have “high hopes” for their return.1,2 Over 60 years ago, Albert Hofmann at Sandoz Pharmaceutical Laboratories in Switzerland first synthesized lysergic acid diethylamide (LSD) and personally experienced its effects (later described as a voyage into madness or a chemically induced psychosis) in 1943. Hofmann’s drug opened up a new era of hallucinogenic research. Over the next 15 years, more than a thousand articles on the use of LSD appeared in medical and scientific publications. In 1957, that work gave rise to the term “psychedelic” to describe a mind-manifesting response, described by some as an experience that brought to light matters that had previously been part of the unconscious.
Psychedelic crossings: American mental health and LSD in the 1970s
This article places a spotlight on lysergic acid diethylamide (LSD) and American mental health in the 1970s, an era in which psychedelic science was far from settled and researchers continued to push the limits of regulation, resist change and attempt to revolutionise the mental health market-place. The following pages reveal some of the connections between mental health, LSD and the wider setting, avoiding both ascension and declension narratives. We offer a renewed approach to a substance, LSD, which bridged the gap between biomedical understandings of ‘health’ and ‘cure’ and the subjective needs of the individual. Garnering much attention, much like today, LSD created a cross-over point that brought together the humanities and arts, social sciences, health policy, medical education, patient experience and the public at large. It also divided opinion. This study draws on archival materials, medical literature and popular culture to understand the dynamics of psychedelic crossings as a means of engendering a fresh approach to cultural and countercultural-based healthcare during the 1970s.
Opening to Awe: Psychedelic‐Assisted Self‐Transcendence and Positive Adult Development
Recent studies implicate the use of psychedelic substances in the treatment of psychiatric conditions. However, this literature also suggests that the psychedelics may have utility in the promotion of positive adult development. Accordingly, this paper outlines a study exploring this premise. An online sample (n=684) of psychedelic users and non-users (age range: 18–24 to 75–84; median=25–34) was recruited. Conditional process analysis was used to assess whether the relationship between psychedelic use and two facets of adult development, adjustment and growth, would be mediated by openness to experience, awe-proneness, and mystical experiences, and whether these relationships would be moderated by drug-use reflection/integration. Results show that the direct relationship between psychedelic use and growth was moderated by drug-use reflection/integration. In addition, the indirect relationship between psychedelic use and adjustment was mediated through awe-proneness, while the indirect relationships between psychedelic use and growth were mediated via awe- proneness and openness to experience; drug-use reflection/integration moderated these mediated relationships. In addition, drug-use reflection/integration directly predicted openness, awe-proneness, and growth. These findings suggest that, when used with self-expansive intentions and actively refected upon and integrated post use, psychedelics may augment positive adult development.
The success of modern medicine creates a growing population of those suffering from life-threatening illnesses (LTI) who often experience anxiety, depression, and existential distress. We present a novel approach; investigating MDMA-assisted psychotherapy for the treatment of anxiety in people with an LTI. Participants with anxiety from an LTI were randomized in a double-blind study to receive MDMA (125 mg, n = 13) or placebo (n = 5) in combination with two 8-h psychotherapy sessions. The primary outcome was change in State-Trait Anxiety Inventory (STAI) Trait scores from baseline to one month post the second experimental session. After unblinding, participants in the MDMA group had one open-label MDMA session and placebo participants crossed over to receive three open-label MDMA sessions. Additional follow-up assessments occurred six and twelve months after a participant’s last experimental session. At the primary endpoint, the MDMA group had a greater mean (SD) reduction in STAI-Trait scores, − 23.5 (13.2), indicating less anxiety, compared to placebo group, − 8.8 (14.7); results did not reach a significant group difference (p = .056). Hedges’ g between-group effect size was 1.03 (95% CI: − 5.25, 7.31). Overall, MDMA was well-tolerated in this sample. These preliminary findings can inform development of larger clinical trials to further examine MDMA-assisted psychotherapy as a novel approach to treat individuals with LTI-related anxiety.
A systematic literature review of clinical trials and therapeutic applications of ibogaine
Background: Iboga and its primary alkaloids, ibogaine and noribogaine, have been of interest to researchers and practitioners, mainly due to their putative efficacy in treating substance use disorders (SUDs). For many SUDs, still no effective pharmacotherapies exist. Distinct psychoactive and somatic effects of the iboga alkaloids set them apart from classic hallucinogens like LSD, mescaline, and psilocybin. Aims: The study team performed this systematic review focusing on clinical data and therapeutic interventions involving ibogaine and noribogaine. Methods: The team conducted a search for all publications up to December 7, 2020, using PubMed and Embase following PRISMA guidelines. Results: In total, we identified 743 records. In this review, we consider 24 studies, which included 705 individuals receiving ibogaine or noribogaine. This review includes two randomized, double-blind, controlled clinical trials, one double-blind controlled clinical trial, 17 open-label studies or case series (including observational or retrospective studies), three case reports, and one retrospective survey. The published data suggest that ibogaine is an effective therapeutic intervention within the context of SUDs, reducing withdrawal symptoms and craving. Data also point toward a beneficial impact on depressive and trauma-related psychological symptoms. However, studies have reported severe medical complications and deaths, which seem to be associated with neuro- and cardiotoxic effects of ibogaine. Two of these fatalities were described in the 24 studies included in this review. Conclusion: Treatment of SUDs and persisting comorbidities requires innovative treatment approaches. Rapid-onset therapies such as the application of ibogaine may offer novel treatment opportunities for specific individuals. Rigorous study designs within medical settings are necessary to warrant safe application, monitoring, and, possibly, medical intervention.
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.