Psilocybin dose linked to brain changes lasting a month

A single strong dose of psilocybin was associated with measurable changes in brain activity and possible structural changes that lasted up to a month, according to researchers at UC San Francisco and Imperial College London. The findings may help explain why the psychedelic compound in magic mushrooms has shown promise in studies of depression, anxiety and addiction, even though this study involved healthy adults without diagnosed mental health conditions.

The study, published in Nature Communications, examined 28 volunteers who had not previously used a psychedelic. UCSF said the design let researchers compare a very low 1 mg dose, treated as a placebo, with a later 25 mg dose that can produce a strong psychedelic experience.

Researchers measured brain activity, brain connectivity, psychological insight, well-being and cognitive performance before dosing, during the peak effects and in follow-up testing. They used EEG to record electrical activity during the experience, functional MRI to assess brain activity, and diffusion tensor imaging to examine brain connections.

More varied brain activity

The team focused on brain “entropy,” a measure of how varied and unpredictable neural activity is. UCSF said EEG readings showed increased entropy within 60 minutes after the 25 mg dose, suggesting the brain was producing and processing a wider range of information during the psychedelic state.

Participants with larger entropy increases in the minutes and hours after psilocybin were more likely to report stronger psychological insight the following day, according to the researchers. Those insight reports were then associated with greater improvements in well-being one month later.

“Psychedelic means ‘psyche-revealing,’ or making the psyche visible,” said senior author Robin Carhart-Harris, the Ralph Metzner Distinguished Professor of Neurology at UCSF. “Our data shows that such experiences of psychological insight relate to an entropic quality of brain activity and how both are involved in causing subsequent improvements in mental health.”

Carhart-Harris said the results suggest that the subjective psychedelic experience, along with its brain activity patterns, is a key part of how psychedelic therapy may work.

Signs of longer-lasting change

One month after the 25 mg dose, diffusion tensor imaging showed signs that neural tracts were denser and had greater integrity, UCSF reported. The researchers said the pattern ran opposite to changes often associated with aging, when neural tracts tend to become more diffuse.

The team cautioned that more research is needed to determine what those imaging findings mean. UCSF described the result as an early indication that psychedelics may leave detectable brain changes beyond the acute drug effect.

The day after the 25 mg dose, 27 of the 28 volunteers described it as the single most unusual state of consciousness they had experienced, according to UCSF. The remaining participant placed it among the five most unusual experiences of their life.

Participants reported more psychological insight after the 25 mg dose than after the 1 mg dose. Well-being scores also improved two and four weeks after the higher dose, including responses to statements about optimism and coping with problems, UCSF said.

One month later, participants also scored better on a measure of cognitive flexibility, which tests the ability to adjust thinking in response to new information. First author Taylor Lyons, a research associate at Imperial College London, said psilocybin appeared to loosen rigid patterns of brain activity and help people revise entrenched patterns of thought.

The researchers said the work could help guide future psilocybin treatment studies in patients. One possible goal would be finding a dose that produces enough brain entropy to support meaningful insight without making the experience more intense than needed.

This story draws on original reporting from ScienceDaily.