This Month in Psychopharmacology

Psilocybin Therapy Increases Cognitive And Neural Flexibility In Patients With Major Depressive Disorder

Psilocybin therapy has shown promise in treating major depressive disorder (MDD) and other psychiatric illnesses. However, the cognitive and neural mechanisms underlying its enduring efficacy is poorly understood. An open-label study examined the enduring effects of psilocybin therapy (1 and 4 weeks post-treatment) on the cognitive and neural flexibility (measured with the Penn Conditional Exclusion Test [PCET] and dynamic functional connectivity [dFC], respectively) of adults with MDD. Data from 24 patients indicated that psilocybin treatment (a moderately high dose session of 20 mg/70 kg and a high dose session of 30 mg/70 kg separated by approximately 1.6 weeks) plus therapy resulted in a significant reduction of depression symptoms from baseline to 1 and 4 weeks post-treatment. Likewise, there was significant improvement in cognitive flexibility from baseline to 1 to 4 weeks post-treatment. Changes in depression symptoms and cognitive flexibility were not significantly correlated. Psilocybin therapy also generally increased dFC across the brain in a nonlinear fashion. Larger pre- to post-treatment increases in dFC between the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC), regions involved in cognitive flexibility and psychedelic treatment response, were associated with less improvement in cognitive flexibility. These findings suggest that although neural flexibility could be critical during the acute effects of psychedelic treatment to permit the exploration of novel cognitive states, persistent increases in neural flexibility could become destabilizing. Greater baseline dFC of the ACC was also associated with less improvement in cognitive flexibility; therefore, patients with lower baseline neural flexibility may be more likely to benefit from psilocybin therapy. Overall, psilocybin therapy may improve cognitive flexibility in MDD, but its association with neural flexibility is complex and requires further investigation.


Doss MK et al. Transl Psychiatry 2021;11(1):574. Abstract

For more information:

NEI Psychopharm YouTube Channel
Don't You Want Psychedelic Drugs (Psychedelic-Assisted Psychotherapy)
Encore Presentation
Hot Topics! The Latest in Psychopharmacology for Major Depressive Disorder
CME/CE Credit: 1.0 | Expires: September 25, 2024
NEI Podcast: PsychopharmaStahlogy Show
Episode 98 - Now You See It, Now You Don’t: The Power of Psychedelic-Assisted Psychotherapy
Encore Presentation
Out of the Pipeline: What Next? Optimizing Outcomes for Treatment-Resistant Depression

CME credits: 1.25 | Expires: November 8, 2023