Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder.
Manoj K. Doss, Michal Považan, Monica D Rosenberg, Nathan D. Sepeda, Alan K. Davis, Patrick H. Finan, Gwenn S Smith, James J Pekar, Peter B Barker, Roland R. Griffiths, Frederick S. Barrett
Translational Psychiatry November 8, 2021 DOI: 10.1038/s41398-021-01706-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label study Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Patients with major depressive disorder |
| Intervention | Psilocybin therapy |
| Duration | At least 4 weeks post-treatment |
| Topics | Neuroplasticity Psychedelic-assisted therapy Depression Psilocybin |
| Keywords | Psilocybin therapy Psychedelic treatment Psilocybin treatment Mushroom therapy Cognitive flexibility Mental agility Neural flexibility Brain adaptability Cognitive enhancement Brain flexibility Major depression Depression treatment Mental well-being Psychiatric care Mental health Mood disorder Neuroscience research Brain imaging Neural connections Brain science Neurological study Brain function |
| Citations | 343 |
| Key points | Psilocybin therapy increased cognitive flexibility for at least four weeks, but greater increases in neural flexibility between the ACC and PCC were associated with less improvement in cognitive flexibility. |
Abstract
Psilocybin has shown promise for the treatment of mood disorders, which are often accompanied by cognitive dysfunction including cognitive rigidity. Recent studies have proposed neuropsychoplastogenic effects as mechanisms underlying the enduring therapeutic effects of psilocybin. In an open-label study of 24 patients with major depressive disorder, we tested the enduring effects of psilocybin therapy on cognitive flexibility (perseverative errors on a set-shifting task), neural flexibility (dynamics of functional connectivity or dFC via functional magnetic resonance imaging), and neurometabolite concentrations (via magnetic resonance spectroscopy) in brain regions supporting cognitive flexibility and implicated in acute psilocybin effects (e.g., the anterior cingulate cortex, or ACC). Psilocybin therapy increased cognitive flexibility for at least 4 weeks post-treatment, though these improvements were not correlated with the previously reported antidepressant effects. One week after psilocybin therapy, glutamate and N-acetylaspartate concentrations were decreased in the ACC, and dFC was increased between the ACC and the posterior cingulate cortex (PCC). Surprisingly, greater increases in dFC between the ACC and PCC were associated with less improvement in cognitive flexibility after psilocybin therapy. Connectome-based predictive modeling demonstrated that baseline dFC emanating from the ACC predicted improvements in cognitive flexibility. In these models, greater baseline dFC was associated with better baseline cognitive flexibility but less improvement in cognitive flexibility. These findings suggest a nuanced relationship between cognitive and neural flexibility. Whereas some enduring increases in neural dynamics may allow for shifting out of a maladaptively rigid state, larger persisting increases in neural dynamics may be of less benefit to psilocybin therapy.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
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Psilocybin therapy increased cognitive flexibility for at least four weeks, but greater increases in neural flexibility between the ACC and PCC were associated with less improvement in cognitive flexibility.
Synthesized
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Psilocybin therapy increased cognitive flexibility for at least four weeks, but greater increases in neural flexibility between the ACC and PCC were associated with less improvement in cognitive flexibility.
Synthesized
Comparable studies
Other non-randomized and open-label trials on psilocybin and psychedelic-assisted therapy, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Patients with severe, unipolar, treatment-resistant major depression | 2017 | Open-label trial | n = 20 |
| HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. Cancer patients with a DSM-5 depressive disorder (major depressive disorder or... | 2023 | Open-label feasibility and safety pilot study | n = 12 |
| Group psychedelic therapy: empirical estimates of cost-savings and improved access Adults with PTSD or major depressive disorder eligible for psychedelic-assisted therapy... | 2023 | Comparative cost analysis using trial data and published estimates | |
| Increased low-frequency brain responses to music after psilocybin therapy for depression. Patients with treatment-resistant depression | 2023 | Open-label trial | n = 19 |
| Group format psychedelic-assisted therapy interventions: Observations and impressions from the HOPE trial Patients with a DSM-5 depressive disorder associated with a cancer diagnosis | 2023 | Open-label feasibility and safety pilot study |