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Med."],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S0033291722002963_sec_a1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The non-selective serotonin 2A (5-HT\n                      <jats:sub>2A<\/jats:sub>\n                      ) 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291722002963_sec_a2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Healthy volunteers received intravenous LSD (75\n                      <jats:italic>\u03bc<\/jats:italic>\n                      g 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 (\u2018learning rates\u2019) and deployment of value representations (\u2018reinforcement sensitivity\u2019) during choice, as well as \u2018stimulus stickiness\u2019 (choice repetition irrespective of reinforcement history).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291722002963_sec_a3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Raw data measures assessing sensitivity to immediate feedback (\u2018win-stay\u2019 and \u2018lose-shift\u2019 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291722002963_sec_a4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s0033291722002963","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T01:18:41Z","timestamp":1669079921000},"page":"6434-6445","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":36,"title":["Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans"],"prefix":"10.1017","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-5405","authenticated-orcid":false,"given":"Jonathan W.","family":"Kanen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5508-1421","authenticated-orcid":false,"given":"Mojtaba","family":"Rostami Kandroodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8751-5167","authenticated-orcid":false,"given":"Rudolf N.","family":"Cardinal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0642-5977","authenticated-orcid":false,"given":"Trevor W.","family":"Robbins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Nutt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6062-7150","authenticated-orcid":false,"given":"Robin L.","family":"Carhart-Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7039-5130","authenticated-orcid":false,"given":"Hanneke E. 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