Ethnopharmacology and the development of psychoactive drugs: are the fruits too high or have we been clumsy?

In spite the prominent role of natural products in the history of psychopharmacology, and the unquestionable need for more effective drugs for treating mental disorders, new plant-derived psychoactive drugs are lacking. The advantages of natural products over synthetic ones in the interaction with biological targets of therapeutic interest has been documented. A higher hit rate of ethnopharmacology-driven plant collections over those guided by biodiversity and/or chemotaxonomy is acknowledged in screening programs. Scientific journals focusing on the biological evaluation of plant species used in traditional medical systems often conclude that the data is coherent with the reported use. This presentation investigates possible reasons to explain the meager results of ethnopharmacology-driven leads in the development of psychoactive drugs. Ethnopharmacology studies on Psychotria colorata, Ptycophetalum olacoides, the monoterpene linalool, and the indole alkaloid alstonine are used to illustrate methodological issues relevant to question in place. The collection of relevant clinical data in the field, phytochemical and pharmacological specificities to study ethnomedicines, the scarcity of accumulated knowledge on promising species, and the issues of reproducibility and translational values of experimental models are discussed. The identification and potential solutions for bottlenecks, as well as the development of adequate conservation and benefit sharing policies, will be instrumental to foster the discovery of innovative psychoactive drugs from traditional knowledge.