Review examines psychedelic mechanisms across species

The review brings together evidence and concepts from evolutionary biology, molecular pharmacology, comparative neuroscience and computational psychiatry to examine how serotonergic psychedelics affect receptors, neural plasticity, circuits and therapeutic outcomes. It uses predictive processing and the Relaxed Beliefs Under Psychedelics (REBUS) framework to discuss how these drugs may temporarily alter hierarchical inference.

Comparisons across species, from invertebrates to non-human primates, suggest that receptor pharmacology may be conserved while circuit organization differs. The authors therefore frame animal models as complementary tools for studying molecular, cellular and computational mechanisms, not as direct proxies for human hallucinatory experience. They also discuss preclinical and emerging translational evidence that biased receptor signaling and non-hallucinogenic psychoplastogens might separate plasticity-related effects from hallucinations. The review presents a conceptual framework; it does not establish clinical efficacy or support changes to treatment practice.