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.

Ayahuasca: Pharmacology, neuroscience and therapeutic potential

Ayahuasca is the Quechua name for a tea obtained from the vine Banisteriopsis caapi, and used for ritual purposes by the indigenous populations of the Amazon. The use of a variation of the tea that combines B. caapi with the leaves of the shrub Psychotria viridis has experienced unprecedented expansion worldwide for its psychotropic properties. This preparation contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT) from P. viridis, plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties from B. caapi. Acute administration induces a transient modified state of consciousness characterized by introspection, visions, enhanced emotions and recollection of personal memories. A growing body of evidence suggests that ayahuasca may be useful to treat substance use disorders, anxiety and depression. Here we review the pharmacology and neuroscience of ayahuasca, and the potential psychological mechanisms underlying its therapeutic potential. We discuss recent findings indicating that ayahuasca intake increases certain mindfulness facets related to acceptance and to the ability to take a detached view of one’s own thoughts and emotions. Based on the available evidence, we conclude that ayahuasca shows promise as a therapeutic tool by enhancing self-acceptance and allowing safe exposure to emotional events. We postulate that ayahuasca could be of use in the treatment of impulse-related, personality and substance use disorders and also in the handling of trauma. More research is needed to assess the full potential of ayahuasca in the treatment of these disorders.

Soma and haoma: Ayahuasca analogues from the Late Bronze Age

In this article, the origins of the cult of the ritual drink known as soma/haoma are explored. Various shortcomings of the main botanical candidates that have so far been proposed for this so-called “nectar of immortality” are assessed. Attention is brought to a variety of plants identified as soma/haoma in ancient Asian literature. Some of these plants are included in complex formulas and are sources of dimethyl tryptamine, monoamine oxidase inhibitors, and other psychedelic substances. It is suggested that through trial and error the same kinds of formulas that are used to make ayahuasca in South America were developed in antiquity in Central Asia and that the knowledge of the psychoactive properties of certain plants spreads through migrants from Central Asia to Persia and India. This article summarizes the main arguments for the botanical identity of soma/haoma, which is presented in my book, The Tawny One: Soma, Haoma and Ayahuasca (Muswell Hill Press, London/New York). However, in this article, all the topics dealt with in that publication, such as the possible ingredients of the potion used in Greek mystery rites, an extensive discussion of cannabis, or criteria that we might use to demarcate non-ordinary states of consciousness, have not been elaborated.

Ayahuasca Shamanic Visions: Integrating Neuroscience, Psychotherapy, and Spiritual Perspectives

Spontaneous imagery narratives—or, more precisely, spontaneous waking visual and kinesthetic transformative imagery narratives—have been widely reported in many cultures throughout recorded history. Our research findings concerning the experiences reported after ingestion of the Amazonian psychoactive brew ayahuasca, which has its origins in shamanism, agree with prior research literature that ayahuasca often elicits spontaneous imagery narratives that are reported to be very intense and meaningful, and often related to psychological and physical healing, problem solving, knowledge acquisition, creativity, spiritual development, divination, community cohesion, and encounters with disincarnate entities or beings. Although ayahuasca recipes differ, the most widespread and well-studiedbrew combines the leaves of Psychotria virdis, containing the psychoactiveagent N,N-dimethyltryptamine (DMT), with the pulverized Banisteriopsiscaapi vine, which contains beta-carboline alkaloids (MAO inhibitors). DMT is not orally active, but when it is combined with the caapi vine, the resulting brew stimulates an altered state of consciousness that usually lasts from threeto five hours. Reviews of the history of the ethnobotanical study and neuro-pharmacology of ayahuasca are available, and later in this chapter some of the brew’s bodily correlates will be described.Because ayahuasca has been reported to reliably facilitate profound healing and creative and spiritual experiences, and because it can be studied in neuroscience laboratory settings, it offers extraordinary opportunities for the kind of research bridging neuroscience and the humanities that is advocated in this book. This chapter offers an example of ayahuasca research as apart of this new metafield. The central question of the inquiry is: How canthe spontaneous imagery narratives that are so prominent during the use of ayahuasca produce the widely reported benefits? To answer this question I will draw from neuroscience, psychology, anthropology, religion, and my own research. Recent neuroscience evidence and theory offer exciting new insights into the specific brain processes that possibly occur, and this may lead to enhanced applications in psychotherapy, creative activity, and spiritual development. I will present my own model of the nature and function of spontaneous imagery narratives; this model incorporates both previous and new views,and uses imagery from a variety of religious traditions to depict the creative psychophysiological and spiritual processes involved. One new hypothesis that ayahuasca research clearly supports is an ancient idea placed in a newcontent: that creative human activities are a blending of deliberative thought processes and spontaneous experiencing.

The Ethnopharmacology of Ayahuasca

Ethnopharmacology is a relatively new science that studies the cultural aspects of substances (plants, animals, minerals) and their biological characteristics and activities. While investigating and identifying compounds and the various uses they have in indigenous and non-indigenous groups, this science is also involved in studying the bio-activity of these materials. Ethnopharmacology is connected with other ethno-sciences, especially ethnobotany, which studies the uses of plants by human groups and their chemical and biological aspects.

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