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

Ayahuasca, a hallucinogenic beverage used in Amazonian ethnomedicine and shamanism, has a unique pharmacology relying on the oral activity of N,N-dimethyltryptamine (DMT), which is normally degraded by monoamine oxidase (MAO) but becomes active when MAO is inhibited by beta-carboline alkaloids. The beverage has long been integrated into mestizo folk medicine and is used as a sacrament by syncretic churches in Brazil, some of which have expanded to the United States. A biomedical study of the Uñiao do Vegetal church suggested therapeutic applications for alcoholism and substance abuse, while clinical studies in Spain showed safety in healthy adults but did not clarify therapeutic uses. The article outlines regulatory and methodological challenges to clinical investigation in the United States, including unclear legal status and variable composition.

Study at a glance

Abstract

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 beta-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.