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.
The participants underwent brain scans approximately four weeks before the first psilocybin session and one week after the second psilocybin session. They also completed a measure of cognitive flexibility known as the Penn Conditional Exclusion Test.
The researchers found that cognitive flexibility was improved one week after psilocybin therapy and dynamic functional connectivity was increased between the posterior cingulate cortex and anterior cingulate cortex, brain regions known to support cognitive flexibility. Doss and his colleagues said that “it is possible that enhancements in cognitive and neural flexibility may open a window of plasticity during which improvements can be facilitated (e.g., with supportive psychotherapy), though this remains speculative.”
But the findings also indicated there is a complicated relationship between cognitive and neural flexibility. Greater increases in neural flexibility were actually associated with less improvements in cognitive flexibility.
“Cognitive flexibility and neural flexibility are increased one week after psilocybin therapy, but there’s not a one-to-one mapping between these cognitive and neural processes,” Doss told PsyPost. “That is, neural flexibility does seem to support cognitive flexibility up to an extent, but too much neural flexibility might not be adaptive, like in the case of poor attention or schizophrenia.”
The study, as with all research, includes some other caveats as well.
“It was an open-label design, and like most psychedelic studies, the sample was relatively small,” Doss explained. “Also, these were patients with major depressive disorder, so these findings might not hold up in a psychiatrically healthy sample or even a different psychiatric disorder.”
“Unfortunately, most psychedelic studies are based on the same datasets (i.e., the same datasets with tweaks in the analysis), so although it may seem like lots of new information is coming out, they’re just retellings of the same stories,” Doss added. “This is one new piece of the puzzle, but the effects should be replicated in independent datasets.”
The study, “Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder“, was authored by 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, and Frederick S. Barrett.
