Psychedelic studies in nonhuman primates: Past and future.

Research on serotonergic psychedelics in nonhuman primates (NHPs) has revealed that these drugs cause characteristic changes in both spontaneous and operant behaviors, though effects vary across studies due to differences in drugs, doses, and individual responsiveness. Some effects in NHPs mirror those in humans, such as the development of tolerance and low abuse liability, but evidence is mixed on whether psychedelics cause visual hallucinations in NHPs. NHP studies have also helped clarify mechanisms of action, connecting findings from human and rodent research. The review concludes that NHPs have potential as preclinical models for studying psychedelic effects on psychiatric conditions and suggests future research directions.

Study at a glance

Abstract

Studies of serotonergic or 'classic' psychedelics in nonhuman primates (NHPs) have provided valuable information about the drugs' effects on the brain and behavior in closely related species to humans. Psychedelics induce characteristic changes to both spontaneous and operant behaviors in NHPs, though variability exists in the different effects reported by different studies; this variability could be due to factors like differences across drugs, differences in dose ranges across studies, and inter-individual variability in drug responsiveness. Several effects of psychedelics in NHPs mirror those in humans, including development of tolerance to psychedelic effects and low abuse liability, though evidence is mixed on whether psychedelics cause visual hallucinations in NHPs. NHP studies have also examined psychedelic mechanisms of action, supporting and connecting existing findings from human and rodent studies. Here we review the knowledge gained from psychedelic research in NHPs encompassing multiple psychedelic compounds in several NHP species. We conclude by highlighting NHPs' potential to serve as preclinical models of psychedelic effects on psychiatric conditions and suggesting several directions for future research to ensure the accuracy and effectiveness of an NHP psychedelic model.