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

Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges

Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by β-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as “ayahuasca tourism” in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca’s ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

The legal tango: The Native American Church v. The United States of America (ch 4) and Happy ending: Public Law 103-334 The American Indian Religious Freedom Act Amendments of 1994 (ch 5)

This book celebrates the endurance of the Native American Church, which now has some 80 chapters throughout the country. Prayer meetings, the sacramental use of peyote, and the significance of various practices and objects are described. Eloquent testimony of Church members from different tribes demonstrates that peyote is not used to obtain “visions” but to heal the body and spirit and to teach righteousness. The authors describe the legal battle to overturn the Supreme Court’s Smith decision of 1990, which cited peyote use to deny the Native American Church the First Amendment right to “the free exercise of religion”. The American Indian Religious Freedom ActAmendments, passed by Congress in 1994, providing an exemption allowing the use of peyote by the Native American Church, was overturned by the Supreme Court in 1997.

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.

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.”

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 Immortality Key: The Secret History of the Religion with No Name

Renegade scholars in the 1970s claimed the Greek potion was psychedelic, just like the original Christian Eucharist that replaced it. In recent years, vindication for the disgraced theory has been quietly mounting in the laboratory. The rapidly growing field of archaeological chemistry has proven the ancient use of visionary drugs. And with a single dose of psilocybin, the psycho-pharmacologists at Johns Hopkins and NYU are now turning self-proclaimed atheists into instant believers. No one has ever found hard, scientific evidence of drugs connected to Eleusis, let alone early Christianity. Until now.

The Falling Sky: Words of a Yanomami Shaman

The Falling Sky is a remarkable first-person account of the life story and cosmo-ecological thought of Davi Kopenawa, shaman and spokesman for the Yanomami of the Brazilian Amazon. In a close collaboration with anthropologist Bruce Albert, a friend since the 1970s, Davi Kopenawa paints an unforgettable picture of Yanomami culture, past and present, in the heart of the rainforest

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