Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges
This study (2004) discusses ayahuasca as a possible therapeutic agent and details the challenges that need to be overcome for clinical studies utilizing ayahuasca in the United States to become viable.
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 h-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.
Research Summary of 'Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges'
Introduction
Ayahuasca is a traditional Amazonian psychoactive brew prepared from Banisteriopsis caapi together with DMT-containing admixture plants such as Psychotria viridis. Its unique pharmacology depends on h-carboline alkaloids in B. caapi that inhibit monoamine oxidase A (MAO-A), permitting the normally orally inactive hallucinogen N,N-dimethyltryptamine (DMT) to reach the brain. Use ranges from indigenous shamanic and mestizo ethnomedicine to contemporary syncretic religious practices in Brazil and rising recreational and ritual use internationally. Legal status is ambiguous in some jurisdictions because DMT is a Schedule I substance despite source plants themselves not being explicitly scheduled in many places. Mckenna sets out to review the botany, chemistry, pharmacology, and available biomedical data on ayahuasca, to summarise key clinical investigations (notably a biomedical field study of long-term users, the so-called Hoasca Project), and to discuss the regulatory and methodological challenges that must be addressed before standardised clinical trials—particularly in the United States—can proceed. The paper also proposes a stepwise pathway for preclinical work and clinical development under an Investigational New Drug (IND) framework.
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McKenna, D. J. (2004). Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacology & Therapeutics, 102(2), 111-129. https://doi.org/10.1016/j.pharmthera.2004.03.002
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