Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans.
Jonathan W. Kanen, Qiang Luo, Mojtaba Rostami Kandroodi, Rudolf N. Cardinal, Trevor W Robbins, David Nutt, Robin Carhart-Harris, Hanneke E.m. den Ouden
Psychological Medicine October 1, 2023 DOI: 10.1017/s0033291722002963 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subjects experimental design Peer reviewed |
|---|---|
| Population | Healthy humans |
| Intervention | LSD |
| Dose | 75 μg in 10 mL saline |
| Topics | LSD Serotonin |
| Keywords | 5-ht2a Cognitive flexibility Computational modeling Probabilistic reversal learning Reinforcement learning Psychedelics hallucinogens Entheogens Neuroscience brain research Neural science Neurobiology |
| Citations | 44 |
| Key findings | LSD enhanced the reward learning rate and elevated the punishment learning rate, while decreasing stimulus stickiness, indicating heightened learning plasticity and exploration. |
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.
Comparable studies
Other experimental studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neural correlates of the LSD experience revealed by multimodal neuroimaging. Human participants | 2016 | Experimental study | |
| Crystal structure of an LSD-bound human serotonin receptor | 2017 | Experimental study with structural biology and molecular dynamics simulations | |
| Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Midbrain neurons containing serotonin | 1968 | Experimental study | |
| Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain | 2017 | Experimental study | |
| LSD-Assisted Psychotherapy in Patients with Terminal Cancer Cancer patients | 1973 | Experimental study | n = 60 |
Citations in the library
Cited by 32
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
- Canalization and plasticity in psychopathology Neuropharmacology December 27, 2022
- Therapeutic mechanisms of psychedelics and entactogens. Neuropsychopharmacology July 24, 2023
- Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective Frontiers in Psychiatry December 17, 2021
- Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications. Brain Sciences January 25, 2025
and 27 more in the library
Cites 38
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
and 33 more in the library