Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: A systematic review of clinical and preclinical evidence.

Catherine Kelly; Bart J Cooley; Lilith Zeng; Tristan Hurzeler; Victoria Manning; Gavan P McNally; Joshua Watt; Paul S Haber; Kirsten C Morley

doi:10.1016/j.neubiorev.2026.106911

PubMed · 42600962

Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: A systematic review of clinical and preclinical evidence.

Catherine Kelly·Bart J Cooley·Lilith Zeng·Tristan Hurzeler·Victoria Manning·Gavan P McNally·Joshua Watt·Paul S Haber·Kirsten C Morley

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Abstract

Psychedelic agents induce a window of heightened neuroplasticity that extends beyond acute intoxication, during which neural circuits are more amenable to change. This period may facilitate changes in cognition relevant to the treatment of psychiatric disorders. This systematic review synthesised clinical and preclinical evidence of subacute and long-term (≥1 day) effects of classic and non-classic psychedelics on cognition. MEDLINE, EMBASE, APA PsycInfo and Web of Science were searched to identify human and animal studies investigating psychedelics and cognition (executive function, attention, decision-making). Sixty-seven (47 clinical, 20 preclinical) articles met inclusion criteria. Psilocybin demonstrated the most consistent evidence of subacute and longer-term cognitive improvement, particularly in cognitive flexibility and attention. Ketamine showed enhancement across cognitive domains, although findings were heterogeneous. LSD and DMT showed no consistent subacute changes, while MDMA was associated with transient cognitive impairments that resolved within days. Risk of bias assessments revealed selective outcome reporting, poor reporting of missing data and inadequate methodological detail, limiting the confidence of findings. Current evidence provides preliminary support for subacute changes in cognition following administration of select psychedelic agents. Cognitive improvements were more frequently seen in psychiatric populations than healthy subjects, which may reflect a remediation of existing cognitive deficit rather than enhancement above normal functioning. Adequately powered, controlled studies with standardised reporting of cognitive outcomes are required to determine the magnitude, durability and clinical relevance of psychedelic-associated cognitive change.

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Hallucinogens Humans Ketamine Animals N-Methyl-3,4-methylenedioxyamphetamine Cognition Cognitive Enhancement Decision making Executive function MDMA Psychedelic Journal Article Systematic Review Review

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Catherine Kelly, Bart J Cooley, Lilith Zeng, Tristan Hurzeler, Victoria Manning, Gavan P McNally, Joshua Watt, Paul S Haber, Kirsten C Morley. 2026-08-14. Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: A systematic review of clinical and preclinical evidence.. https://doi.org/10.1016/j.neubiorev.2026.106911

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Animals subject Cognition subject Cognitive Enhancement subject Executive Function subject Hallucinogens subject Humans subject Journal Article subject Journal Article; Systematic Review; Review resource Ketamine subject Systematic reviews study

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