Screening the receptorome for plant-based psychoactive compounds.

Psychoactive plants and their derivatives have long been used for spiritual, therapeutic, and recreational purposes, and they have also advanced understanding of neurochemical processes and central nervous system diseases. G-protein coupled receptors (GPCRs) are the most common molecular targets for psychoactive drugs, and the receptorome—the portion of the genome encoding ligand reception—comprises over 8% of the human genome, offering many possible targets. A systematic, comprehensive study is needed to identify novel active psychoactive plant-based compounds and their molecular targets. This work describes a high-throughput screening system for psychoactive compounds against the receptorome, using Salvia divinorum and Banisteriopsis caapi as examples where the system identified each compound's molecular target.

Study at a glance

Abstract

Throughout time, humans have used psychoactive plants and plant-derived products for spiritual, therapeutic and recreational purposes. Furthermore, the investigation of psychoactive plants such as Cannabis sativa (marijuana), Nicotiana tabacum (tobacco) and analogues of psychoactive plant derivatives such as lysergic acid diethylamide (LSD) have provided insight into our understanding of neurochemical processes and diseases of the CNS. Currently, many of these compounds are being used to treat a variety of diseases, such as depression and anxiety in the case of Piper methysticum Kava Kava (Martin et al., 2002; Singh and Singh, 2002). G-protein coupled receptors (GPCRs) are the most common molecular target for both psychoactive drugs and pharmaceuticals. The "receptorome" (that portion of the genome encoding ligand reception) encompasses more than 8% of the human genome (Roth et al., 2004) and as such provides a large number of possible targets for psychoactive drug interactions. A systematic, comprehensive study is necessary to identify novel active psychoactive plant-based compounds and the molecular targets of known compounds. Herein we describe the development of a high throughput system (HTS) to screen psychoactive compounds against the receptorome and present two examples (Salvia divinorum, the "magic mint" hallucinogen and Banisteriopsis caapi, the main component of Ayahuasca, a psychoactive beverage) where HTS enabled the identification of the molecular target of each compound.