Exploring the therapeutic potential of psychedelics: Fear extinction mechanisms and amygdala modulation

Abstract

Classical psychedelics are increasingly receiving attention as potential therapeutic agents for treating post-traumatic stress disorder (PTSD). Research has explored various classical psychedelics in the context of fear learning, recall, and extinction in rodents. We provide an overview of the reported effects of these substances on behavioral responses to learned fear. The amygdala complex, a key brain region involved in fear learning and extinction, plays a central role in these processes. We discuss how psychedelics interact with various cell types in the amygdala and propose which neural circuits may be essential for the observed fear-suppressing effects following psychedelic administration in rodents. The rodent amygdala has functional homology with the human amygdala. Thus, insights gained from preclinical studies can inform the design and implementation of clinical trials for psychedelic-assisted psychotherapy for PTSD. Finally, we stress the importance of considering compound-specific pharmacology and the acute duration of action as key factors in guiding the future direction of this field.