Psychedelics Do Not Always Enhance Cognitive Flexibility: The Potential Role of Time-Varying Effects on Reward Learning Processes

Psychedelics don’t always increase cognitive flexibility.

The paper challenges the relatively common idea that psychedelics generally make people more cognitively flexible.

The authors reviewed evidence on two major forms of cognitive flexibility:

• Reversal learning — learning that a previously rewarded choice is no longer correct and changing behaviour accordingly.

• Set-shifting — switching from one rule or attentional strategy to another.

Across animal and human studies, psychedelic effects were mixed. Some studies showed improved flexibility, some showed impairments, and others found no significant effect. Kosted et al. (2026) argue that psychedelics do not uniformly enhance cognitive flexibility; instead, their effects may vary over time, with acute psychedelic states potentially strengthening learning from reward receipt and promoting perseveration, while post-acute effects may enhance learning from reward omission and facilitate behavioural updating. Why psychedelics might sometimes increase cognitive flexibility and sometimes do the opposite, the paper's answer is essentially: the brain may be learning differently depending on when you test it and what kind of feedback it receives.

Abstract

Although research on psychedelics (hallucinogenic serotonin 2A or 5-HT2A agonists) has shown initial promise in ameliorating a range of psychiatric conditions, the mechanisms by which psychedelics promote therapeutic benefits have yet to be elucidated. Researchers have posited enhancements in cognitive flexibility as a transdiagnostic mechanism through which psychedelics could disrupt repetitive, maladaptive thoughts and/or behavioral patterns and induce insights.

However, the acute and post-acute effects of psychedelics on cognitive flexibility have been mixed, including several cases in which cognitive flexibility is impaired. Here, we review the acute and post-acute effects of psychedelics on cognitive flexibility, specifically reversal learning and set-shifting, and propose that time-varying effects on learning from reward receipt and reward omission can account for these mixed findings.

The synthesized evidence suggests that the acute effects of psychedelics may especially enhance learning from reward receipt that can become difficult to overcome, thereby leading to perseveration. In contrast, enhancements in learning from reward omission may become more prominent post-acutely and can counteract such perseveration. Whereas 5-HT2C activation appears to especially support learning from reward receipt, 5-HT2A and 5-HT1A activation may be more important for learning from reward omission.

We end with proposing how different learning systems could support these two forms of learning, recommendations for future work, and implications for psychedelic therapy. Together, our hypothesis accounts for conditions in which psychedelics enhance flexible decision-making and why insights reached on psychedelics may be held so strongly, and it informs strategies to potentially minimize the formation of maladaptive beliefs.

Kosted R, Doss MK, Donegan JJ, Cisler JM, Fonzo GA. Psychedelics do not always enhance cognitive flexibility: The potential role of time-varying effects on reward learning processes. Neurosci Biobehav Rev. 2026 Sep;188:106788. doi: 10.1016/j.neubiorev.2026.106788. Epub 2026 May 30. PMID: 42219133; PMCID: PMC13331243. Read Paper

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