Masthay Jamie C, Kwan Alex C, Chang Steve W C
Department of Psychology, Yale University, New Haven, CT, USA.
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Mol Psychiatry. 2025 Sep 12. doi: 10.1038/s41380-025-03240-5.
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.
对非人类灵长类动物（NHPs）进行的血清素能或“经典”迷幻药研究，为这些药物对与人类亲缘关系密切的物种的大脑和行为的影响提供了有价值的信息。迷幻药会引起非人类灵长类动物自发行为和操作性行为的特征性变化，不过不同研究报告的不同效应存在差异；这种差异可能归因于药物差异、不同研究剂量范围的差异以及药物反应性的个体间差异等因素。迷幻药在非人类灵长类动物身上产生的几种效应与在人类身上的效应相似，包括对迷幻效果产生耐受性以及低滥用倾向，不过关于迷幻药是否会在非人类灵长类动物身上引发视觉幻觉，证据并不一致。非人类灵长类动物研究还探究了迷幻药的作用机制，支持并联系了来自人类和啮齿动物研究的现有发现。在此，我们回顾从非人类灵长类动物迷幻药研究中获得的知识，这些研究涵盖了几种非人类灵长类动物物种中的多种迷幻化合物。我们通过强调非人类灵长类动物作为迷幻药对精神疾病影响的临床前模型的潜力，并提出未来研究的几个方向来确保非人类灵长类动物迷幻药模型的准确性和有效性来得出结论。
