The Effect of Psychedelics on Associative Learning: a Systematic Review

Psychedelics are emerging as potential treatments for neuropsychiatric conditions, with evidence suggesting a single administration can lead to enduring behavioural changes. While the underlying putative mechanism(s) remain unclear, there is evidence supporting altered learning as a key candidate. This systematic review examined studies assessing the effects of psychedelics on associative learning in humans and animals. Electronic databases were searched until 02/02/2026 for studies investigating differences in learning after classical psychedelic administration. 62 studies were included (2 human studies). Classical and operant conditioning paradigms were employed, including fear extinction, conditioned avoidance, conditioned place preference and reversal learning. Studies assessed acute and post-acute effects, however repeated dosing paradigms often obscured this distinction. There was heterogeneity in study designs, paradigms, drug administration timings and doses, and behavioural effects appeared to be influenced by dose, timing, training intensity, and sex. The evidence reviewed suggests that psychedelic administration enhances associative learning in animals across paradigms, although findings were not consistent. Possible mechanisms identified spanned levels of explanation including computational (prediction error sensitivity), neuropharmacological (serotonin receptor agonism), and cellular/subcellular (structural plasticity). Learning enhancements extend into the post-acute phase of psychedelic action and appear to depend on environmental engagement during this window. Studies suggest that psychedelics enhance associative learning in animals; however, while human studies demonstrate altered cognitive flexibility and learning-related processes, direct evidence of enhanced associative learning remains limited. Understanding whether a period of enhanced learning follows the psychedelic experience may have implications for psychedelic-assisted psychotherapy, where behavioural changes must generalise and persist beyond the drug-induced state.