Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans.

LSD increases the rate at which people learn from both rewards and punishments during a probabilistic reversal learning task, suggesting a state of heightened learning plasticity. Healthy volunteers given intravenous LSD or placebo completed a task where they had to learn which of three stimuli was most often rewarded, with the reward contingencies later reversing. Computational modeling of reinforcement learning showed that LSD primarily enhanced the reward learning rate and also elevated the punishment learning rate, while decreasing stimulus stickiness (a measure of choice repetition), indicating increased exploration. These effects point to a potential mechanism by which LSD could help revise maladaptive associations in clinical treatment.

Study at a glance

Abstract

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 incompletely understood. Here we examined how LSD affects probabilistic reversal learning (PRL) in healthy humans. Healthy volunteers received intravenous LSD (75 μg in 10 mL saline) or placebo (10 mL saline) in a within-subjects design and completed a PRL task. Participants had to learn through trial and error which of three stimuli was rewarded most of the time, and these contingencies switched in a reversal phase. Computational models of reinforcement learning (RL) were fitted to the behavioural data to assess how LSD affected the updating ('learning rates') and deployment of value representations ('reinforcement sensitivity') during choice, as well as 'stimulus stickiness' (choice repetition irrespective of reinforcement history). Raw data 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 the enhancement of the reward learning rate. The punishment learning rate was also elevated. Stimulus stickiness was decreased by LSD, reflecting heightened exploration. Reinforcement sensitivity differed by phase. Increased RL rates suggest LSD induced a state of heightened plasticity. These results indicate a potential mechanism through which revision of maladaptive associations could occur in the clinical application of LSD.