Psychedelics may enhance cognitive flexibility, but findings are mixed, with some studies showing impairment. This review proposes that acute effects of psychedelics boost learning from reward receipt, which can lead to perseveration, while post-acute effects enhance learning from reward omission, counteracting that perseveration. Different serotonin receptor subtypes (5-HT2C, 5-HT2A, 5-HT1A) may support these distinct learning processes. This hypothesis explains when psychedelics improve flexible decision-making and why insights reached under their influence can be held strongly, and it suggests strategies to reduce maladaptive belief formation.
Depression symptoms improved over time in patients receiving five ketamine infusions, with faster initial improvement that slowed later. Higher scores on the Adverse Childhood Experiences (ACE) survey were linked to greater symptom reduction, regardless of whether patients received ketamine-assisted therapy or infusions alone. Younger adults showed a stronger response to infusions alone compared to ketamine-assisted therapy, while older adults showed the opposite pattern. The association between higher ACE scores and greater symptom reduction was particularly pronounced in younger adults and reversed in older adults. These findings suggest ketamine may offer a targeted benefit for people with early life stress, especially younger adults.