This international online study (N=759) examined the acute, subacute, and long-term effects of psychedelic drug use on cognitive performance and mental health. Participants completed cognitive tasks assessing working memory, selective attention, and visual/spatial perception, as well as questionnaires assessing mental health outcomes and quality of life. Based on self-reported substance use, participants were classified as non-users, lifetime users, and recent users. Recent users had significantly lower accuracy across all cognitive tasks, and lifetime users had the highest task accuracy without corresponding reaction time deficits. Lifetime use was not associated with long-term cognitive decline. Recent users reported more depressive and dissociative symptoms, whereas lifetime users reported lower scores. Lifetime users scored lower on psychological and social quality of life domains, indicating possible long-term psychosocial effects. These findings highlight the need to differentiate between the acute and long-term effects of psychedelics; lab-controlled, longitudinal studies are needed to enable safe clinical application.

C.A. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorder. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. C.K. received honoraria from LivaNova, Pfizer, Johnson&Johnson and AbbVie. K. H. Preller is currently and employee of Boehringer Ingelheim Switzerland. All other authors have no conflict of interest to disclose, financial or otherwise.

This study was funded in part by the Austrian Science Fund (FWF) 10.55776/KLP7307523.

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Ethics committee of the Medical University of Vienna gave ethical approval for this work (EK Nr: 1618/2021)

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