Molecular Pathways of the Therapeutic Effects of Ayahuasca, a Botanical Psychedelic and Potential Rapid-Acting Antidepressant

Biomolecules  – November 02, 2022

Source: OpenAlex

Summary

Ayahuasca, a traditional hallucinogen, shows encouraging potential as an antidepressant. Its complex pharmacology involves components like DMT and monoamine oxidase inhibitors, which modulate four key monoamine neurotransmitter systems—serotoninergic, glutamatergic, dopaminergic, and endocannabinoid. Evidence suggests these substances also influence three specific targets, impacting Neurotransmitter Receptor Influence on Behavior. Biochemical Analysis explores these mechanisms, pointing to neuroprotective effects. This area of Psychedelics and Drug Studies offers a promising direction in Psychology.

Abstract

Ayahuasca is a psychoactive brew traditionally used in indigenous and religious rituals and ceremonies in South America for its therapeutic, psychedelic, and entheogenic effects. It is usually prepared by lengthy boiling of the leaves of the bush Psychotria viridis and the mashed stalks of the vine Banisteriopsis caapi in water. The former contains the classical psychedelic N,N-dimethyltryptamine (DMT), which is thought to be the main psychoactive alkaloid present in the brew. The latter serves as a source for β-carbolines, known for their monoamine oxidase-inhibiting (MAOI) properties. Recent preliminary research has provided encouraging results investigating ayahuasca’s therapeutic potential, especially regarding its antidepressant effects. On a molecular level, pre-clinical and clinical evidence points to a complex pharmacological profile conveyed by the brew, including modulation of serotoninergic, glutamatergic, dopaminergic, and endocannabinoid systems. Its substances also interact with the vesicular monoamine transporter (VMAT), trace amine-associated receptor 1 (TAAR1), and sigma-1 receptors. Furthermore, ayahuasca’s components also seem to modulate levels of inflammatory and neurotrophic factors beneficially. On a biological level, this translates into neuroprotective and neuroplastic effects. Here we review the current knowledge regarding these molecular interactions and how they relate to the possible antidepressant effects ayahuasca seems to produce.

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