Towards the Use of Whole Natural Products in Psychedelic Research and Therapy: Synergy, Multi-Target Profiles, and Beyond

Interest in psychoactive plants like ayahuasca and Psilocybe mushrooms for clinical use has grown. An emerging drug discovery trend, polypharmacology, suggests that drugs acting on multiple targets may be safer and more effective than highly selective ones, especially for complex conditions such as mental health and neurodegenerative diseases. Natural products often contain multiple interacting compounds that produce synergistic effects. This chapter advocates using whole natural products rather than isolated compounds, combining psychedelic-assisted therapy with polypharmacology.

Study at a glance

Abstract

Interest in psychoactive ethnobotanicals such as ayahuasca or Psilocybe mushrooms for clinical uses has increased over the last two decades. While clinical and experimental approaches have focused on using isolated compounds of interest (such as psilocybin), an emerging trend in drug discovery involves a more comprehensive approach. The polypharmacology paradigm, as it has been named, suggests that promiscuous drugs could be safer and more effective than highly selective ones. This is especially relevant with regards to complex diseases, like most mental health problems and neurodegenerative diseases, and for natural products, including psychoactive ethnobotanicals. Natural products not only show a multi-target profile, but they also contain several compounds capable of interacting with one another and producing synergistic effects. In this chapter, the use of whole natural products instead of isolated compounds is suggested in support of combining two recent paradigms: psychedelicassisted therapy on the one side and polypharmacology on the other.