The non-selective serotonin 2A (5-HT2A) receptor agonist lysergic acid diethylamide (LSD) holds promise as a treatment for some psychiatric disorders. Psychedelic drugs such as LSD have been suggested to have therapeutic actions through their effects on learning. The behavioural effects of LSD in humans, however, remain largely unexplored. Here we examined how LSD affects probabilistic reversal learning in healthy humans. Conventional measures assessing sensitivity to immediate feedback ("win-stay" and "lose-shift" probabilities) were unaffected, whereas LSD increased the impact of the strength of initial learning on perseveration. Computational modelling revealed that the most pronounced effect of LSD was enhancement of the reward learning rate. The punishment learning rate was also elevated. Increased reinforcement learning rates suggest LSD induced a state of heightened plasticity. These results indicate a potential mechanism through which revision of maladaptive associations could occur.
bioRxiv Subject Collection: Neuroscience