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
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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.
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.
A systematic study of microdosing psychedelics
The phenomenon of ‘microdosing’, that is, regular ingestion of very small quantities of psychedelic substances, has seen a rapid explosion of popularity in recent years. Individuals who microdose report minimal acute effects from these substances yet claim a range of long-term general health and wellbeing benefits. There have been no published empirical studies of microdosing and the current legal and bureaucratic climate makes direct empirical investigation of the effects of psychedelics difficult. In Study One we conducted a systematic, observational investigation of individuals who microdose. We tracked the experiences of 98 microdosing participants, who provided daily ratings of psychological functioning over a six week period. 63 of these additionally completed a battery of psychometric measures tapping mood, attention, wellbeing, mystical experiences, personality, creativity, and sense of agency, at baseline and at completion of the study. Analyses of daily ratings revealed a general increase in reported psychological functioning across all measures on dosing days but limited evidence of residual effects on following days. Analyses of pre and post study measures revealed reductions in reported levels of depression and stress; lower levels of distractibility; increased absorption; and increased neuroticism. To better understand these findings, in Study Two we investigated pre-existing beliefs and expectations about the effects of microdosing in a sample of 263 naïve and experienced microdosers, so as to gauge expectancy bias. All participants believed that microdosing would have large and wide-ranging benefits in contrast to the limited outcomes reported by actual microdosers. Notably, the effects believed most likely to change were unrelated to the observed pattern of reported outcomes. The current results suggest that dose controlled empirical research on the impacts of microdosing on mental health and attentional capabilities are needed.
Set, setting, and clinical trials: colonial technologies and psychedelics
This chapter brings together ethnographic work on technologies of healing, pharmaceutical and psychedelic clinical trials, and ceremonial uses of the Amazonian herbal brew ayahuasca. Building on a review of anthropological work on clinical trials, we argue that randomised controlled trials (RCTs), even psychedelic ones, have been captured by the pharmaceutical industry in its quest to grow profits rather than reduce illness. We track the role that the category of technology plays in continued industrialised, colonial, genocidal, and dispossessive violence. This includes institutions of intellectual property, evidence-based medicine, RCTs, pharmaceuticals, drugs, active ingredients, industrial medicine, diagnostic standards, investment capital, and treatment sovereignty. Using the idea of container technologies, we discuss how psychedelic clinical trials attempt to expand the magic bullet experimentally, to reveal set and setting. We contrast this with arguments by Indigenous scholars that ayahuasca is not a psychedelic, and that ceremonial work cannot be separated from ongoing colonial violence. Holding space for ceremonial work means refusing to know what the problem is ahead of the encounter with the plant spirit. Such settings are explicitly anti-causal, unpredictable, and deeply paradoxical, allowing something to happen that is not reducible to action, intention, or the act of containing.
Background and aims Set and setting function both as a concept that guides research and practice with psychedelic drugs and as a meme aimed at reducing harm among psychedelic users. Referring to non-pharmacological factors that shape drug experiences, the concept of set and setting was popularized in the West during the mid-20th century. However, little theoretical development has occurred regarding what falls under the umbrella of set and setting since its conception. Methods By bridging set and setting theory with research from the fields of social psychology and sociology of medicine, this review calls attention to how race can contribute the set and setting for a psychedelic experience. Results I argue that psychosocial factors influencing racial differences in mental health also constitute meaningful differences in set. Furthermore, I suggest that the character of race relations in the United States provides a distinct cultural setting for racialized psychedelic users, both in therapeutic and naturalistic contexts. In turn, racial identification may contribute to the variation in framing and interpretation of psychedelic experiences. Conclusion These considerations have important implications beyond understanding non-pharmacological influences on psychedelic experiences, including developing protocols for clinical applications of psychedelics, educating future practitioners, and meeting the needs of diverse patient populations.
Use patterns and self-reported effects of Salvia divinorum: An internet-based survey
Background There is growing use of Salvia divinorum (SD), a psychoactive plant that produces hallucinogen-like effects through a kappa opioid receptor (KOR) mechanism. Little is known about KOR agonist effects in humans and about users of SD. Objectives To characterize the reasons, methods, and reported consequences of SD use. Methods Individuals reading SD-related pages of a drug-information website were invited to anonymously complete an online questionnaire if they had used SD. Results Participants (N = 500) were 92.6% male and 23.4 ± 8.7 (mean ± s.d.) years old. They had used a median of six times (range 1–250). 80.6% probably or definitely would use SD again. Most participants (92.6%) typically smoked or vaporized SD product. When smoked, the drug’s main effects were estimated to last 14.1 ± 12.8 (range 0.5–120) minutes. When asked to compare SD effects to other methods of altering consciousness, the most common answer was that SD was unique (38.4%). 25.8% reported persisting (≥24 h) positive effects (often described as increased sense of well-being) on at least one occasion. 4.4% reported persisting negative effects (most often anxiety). Conclusions SD is typically smoked, acute effects are brief, and persistent adverse effects are uncommon. In addition to acute hallucinogenic effects, SD may produce subacute increases in subjective well-being. Such a subacute effect would be unusual for a drug that is used non-medically, as withdrawal from other drugs typically either does not affect mood or causes dysphoria. Findings from this convenience sample should be confirmed and extended using surveys of random samples and controlled clinical studies.
Salvia (Sage): A Review of its Potential Cognitive-Enhancing and Protective Effects
Genus Salvia, commonly known as sage, is the largest genus in the Lamiaceae family. It comprises many species traditionally used as brain-enhancing tonics. In vitro and animal studies have confirmed that several Salvia species contain a large array of active compounds that may enhance cognitive activity and protect against neurodegenerative disease. In this review, the active constituents in plants belonging to the genus Salvia are summarised, and their influence on pharmacodynamics pertinent to cognitive activity are detailed. In particular, the effects of plants belonging to the genus Salvia and their constituents on cognitive skills including memory, attention and learning are detailed. Their potential effects in dementia, including Alzheimer’s disease, are also examined. Completed human trials are summarised, and factors influencing the potency of Salvia plants are covered. Finally, directions for future research are proposed to enhance our understanding of the potential health benefits of Salvia plants. Key Points Salvia plants and their constituents can influence several biological mechanisms associated with cognition including their effects on amyloid-β, cholinergic activity, neurotrophins, oxidative stress, inflammation and anxiolytic/antidepressant behaviours. Several studies have confirmed the many Salvia species have promising, cognitive-enhancing effects in human adults. Further research is required to examine the longer-term cognitive-enhancing effects of Salvia species on cognition, memory and the treatment of neurodegenerative diseases such as Alzheimer’s disease.
Hallucinogens and dissociative agents naturally growing in the United States
It is usually believed that drugs of abuse are smuggled into the United States or are clandestinely produced for illicit distribution. Less well known is that many hallucinogens and dissociative agents can be obtained from plants and fungi growing wild or in gardens. Some of these botanical sources can be located throughout the United States; others have a more narrow distribution. This article reviews plants containing N,N-dimethyltryptamine, reversible type A monoamine oxidase inhibitors (MAOI), lysergic acid amide, the anticholinergic drugs atropine and scopolamine, or the diterpene salvinorin-A (Salvia divinorum). Also reviewed are mescaline-containing cacti, psilocybin/psilocin-containing mushrooms, and the Amanita muscaria and Amanita pantherina mushrooms that contain muscimol and ibotenic acid. Dangerous misidentification is most common with the mushrooms, but even a novice forager can quickly learn how to properly identify and prepare for ingestion many of these plants. Moreover, through the ever-expanding dissemination of information via the Internet, this knowledge is being obtained and acted upon by more and more individuals. This general overview includes information on the geographical range, drug content, preparation, intoxication, and the special health risks associated with some of these plants. Information is also offered on the unique issue of when bona fide religions use such plants as sacraments in the United States. In addition to the Native American Church’s (NAC) longstanding right to peyote, two religions of Brazilian origin, the Santo Daime and the Uniao do Vegetal (UDV), are seeking legal protection in the United States for their use of sacramental dimethyltryptamine-containing “ayahuasca.”
In recent years, the study of psychedelic science has resurfaced as scientists and therapists are again exploring its potential to treat an array of psychiatric conditions, such as depression, post-traumatic stress disorder, and addiction. The scientific progress and clinical promise of this movement owes much of its success to the history of indigenous healing practices; yet the work of indigenous people, ethnic and racial minorities, women, and other disenfranchised groups is often not supported or highlighted in the mainstream narrative of psychedelic medicine. This review addresses this issue directly: first, by highlighting the traditional role of psychedelic plants and briefly summarizing the history of psychedelic medicine; second, through exploring the historical and sociocultural factors that have contributed to unequal research participation and treatment, thereby limiting the opportunities for minorities who ought to be acknowledged for their contributions. Finally, this review provides recommendations for broadening the Western medical framework of healing to include a cultural focus and additional considerations for an inclusive approach to treatment development and dissemination for future studies.