Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: A systematic review of clinical and preclinical evidence
Kelly et al. (2026) systematically reviewed clinical and preclinical evidence on subacute and long-term (≥1 day) changes in cognitive functioning following administration of classic psychedelics, MDMA and ketamine. The review included 67 studies (47 clinical and 20 preclinical) examining domains including executive function, attention and decision-making.
Psilocybin: strongest and most consistent evidence of cognitive improvement, particularly cognitive flexibility and attention.
Ketamine: evidence of cognitive enhancement across domains, but heterogeneous.
LSD/DMT: no consistent subacute cognitive effects.
MDMA: transient cognitive impairments, reported to resolve within days.
Psychiatric populations: improvements appeared more frequently than in healthy participants, potentially reflecting remediation of cognitive deficits rather than enhancement.
Overall: evidence is promising but preliminary, and it is too early to make firm claims about the magnitude or durability of cognitive benefits.
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.
Kelly, C., Cooley, B. J., Zeng, L., Hurzeler, T., Manning, V., McNally, G. P., Watt, J., Haber, P. S., & Morley, K. C. (2026). Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: A systematic review of clinical and preclinical evidence. Neuroscience & Biobehavioral Reviews, 106911. Read Paper
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