TL;DR: The pharmacological mechanisms for the putative reduction in recidivism to alcohol and cocaine misuse are suggested and inhibition of dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) and the dopamine transporter is suggested.
Abstract: Ayahuasca is a hallucinogenic botanical mixture originating in the Amazon area where it is used ritually, but is now being taken globally. The 2 main constituents of ayahuasca are N,N-dimethyltryptamine (DMT), a hallucinogen, and harmine, a monoamine oxidase inhibitor (MAOI) which attenuates the breakdown of DMT, which would otherwise be broken down very quickly after oral consumption. Recent developments in ayahuasca use include the sale of these compounds on the internet and the substitution of related botanical (anahuasca) or synthetic (pharmahuasca) compounds to achieve the same desired hallucinogenic effects. One intriguing result of ayahuasca use appears to be improved mental health and a reduction in recidivism to alternate (alcohol, cocaine) drug use. In this review we discuss the pharmacology of ayahuasca, with a focus on harmine, and suggest pharmacological mechanisms for the putative reduction in recidivism to alcohol and cocaine misuse. These pharmacological mechanisms include MAOI, effects at 5-HT2A and imidazoline receptors and inhibition of dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) and the dopamine transporter. We also speculate on the therapeutic potential of harmine in other CNS conditions.
TL;DR: In this paper, a transformational psychotherapy framework is introduced that outlines how ayahuasca could be used to support sustainable transformation, highlighting the challenges of intercultural knowledge transfer, and various adaptogenic effects of Ayahuasca including effects on body, brain, and mental functioning.
Abstract: While psychoactive drugs such as ketamine and psilocybin have been researched extensively in the past decades, scientific interest in ayahuasca has just started to grow, due to its potential therapeutic benefits. Beyond its traditional indigenous and mestizo use in the Amazon, ayahuasca is currently spreading all over the world as an alternative plant medicine in various ritualistic contexts. This rapid dissemination coincides with the observational evidence that ayahuasca facilitates transformational processes with beneficial health outcomes. However, more empirical research is needed to move beyond anecdotal evidence and further verify therapeutic efficacy and biomechanisms of ayahuasca under controlled conditions. The objective of this chapter is to outline future possibilities of ayahuasca-assisted therapies based on the biomedical literature on psychedelics and other contexts in which ayahuasca is used to support health and wellbeing. First, psychedelic medicines will be contrasted with standard psychopharmaceuticals as a novel treatment option that necessitates a paradigm shift from substitution- to transformation-based therapy. Second, various adaptogenic effects of ayahuasca will be reviewed, including effects on body, brain, and mental functioning. Third, a novel transformational psychotherapy framework will be introduced that outlines how ayahuasca could be used to support sustainable transformation. Finally, future research directions of developing pharmahuasca applications in clinical settings will be contrasted with traditional and indigenous contexts of ayahuasca use, highlighting the challenges of intercultural knowledge transfer.