Study: Psilocybin Therapy Boosts Cognitive and Neural Flexibility in Depressed Patients

November 12, 2021

Psilocybin-assisted psychotherapy appears to increase both cognitive and neural flexibility in patients with major depressive disorder, according to new research published in Translational Psychiatry. But the findings suggest that psychedelic-induced increases in neural flexibility do not always result in cognitive improvements.

Psilocybin — the active component in so-called “magic” mushrooms — has been shown to have long-lasting and clinically significant effects on personality and mood when combined with psychotherapy. But the mechanisms behind these effects remain unclear. Researchers have proposed that psilocybin’s antidepressant effects might be the result of changes in neuroplasticity, or the brain’s ability to change structurally and functionally.

The authors of the current study were interested in examining psilocybin’s effects on two concepts related to neuroplasticity: cognitive flexibility (the ability to adaptively switch between mental processes) and neural flexibility (variability in brain activity and connectivity.)

“Many psychiatric disorders have impairments in cognitive flexibility, and during the immediate (i.e., acute) drug effects, psychedelics have been shown to increase certain measures of neural flexibility, signals in the brain thought to be involved in cognitive flexibility,” explained lead researcher Manoj Doss (@manojdoss), a postdoctoral scientist in the Center for Psychedelic and Consciousness Research at Johns Hopkins University School of Medicine.

“Some people have asserted that psychedelics enhance cognitive flexibility based on animal data that found that drugs that block the 5-HT2A receptor (the receptor activated by psychedelics) impair cognitive flexibility. However, in both animals and humans, it was recently shown that cognitive flexibility was impaired during the acute effects of psychedelics.”

“What was unclear was after the acute effects wear off but plasticity is supposedly still elevated (e.g., one week after acute psychedelic effects), are cognitive and neural flexibility enhanced by psilocybin therapy?”

Doss and his colleagues examined data from their previously published study, which found preliminary evidence that psilocybin-assisted therapy produced large reductions in depressive symptoms. The study used a wait list control condition: Thirteen participants received psilocybin treatment initially and 11 participants received the same treatment after an eight-week delay.

The treatment consisted of 18 psychotherapy sessions. During two of these sessions, psilocybin doses were administered by two clinical monitors who provided guidance and reassurance. The doses were given two weeks apart and each psilocybin session lasted approximately five hours, with the participant lying on a couch wearing eyeshades and headphones that played music, in the presence of the monitors.

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