Nat Med
April 11, 2022
Richard E. Daws, Christopher Timmermann, Bruna Giribaldi et al.
432 citations
Psilocybin therapy produces rapid and sustained antidepressant effects that correlate with a global increase in brain network integration. In two clinical trials, one open-label in treatment-resistant depression and one double-blind randomized controlled trial comparing psilocybin with escitalopram in major depressive disorder, functional MRI showed that psilocybin reduced brain network modularity, making higher-order functional networks more interconnected and flexible. The antidepressant response to escitalopram was milder, with no changes in brain network organization. These consistent efficacy-related brain changes across both studies suggest that psilocybin's antidepressant mechanism involves global increases in brain network integration.
Journal of Psychopharmacology
March 9, 2021
Otto Simonsson, James D. Sexton, Peter S. Hendricks
75 citations
People who have used a classic psychedelic at least once in their lifetime report better overall health and are less likely to be overweight or obese, based on data from over 171,000 U.S. adults. The study also found a trend toward lower odds of having a heart condition or cancer in the past year among those who had used a classic psychedelic. The findings suggest that classic psychedelics may be linked to better physical health, but the authors note that further research is needed to determine whether the relationship is causal and to explore possible mechanisms.
Frontiers in Psychiatry
February 11, 2020
James D. Sexton, Charles D. Nichols, Peter S. Hendricks
45 citations
Lifetime use of classic tryptamine psychedelics is linked to lower odds of past-month psychological distress and past-year suicidal thinking, while lifetime use of novel phenethylamines is linked to higher odds of past-year suicidal thinking and planning. These findings, from a large nationally representative U.S. survey, suggest that classic tryptamines may hold greater therapeutic potential than novel phenethylamines, which may pose risks for harm. No significant associations were found for other psychedelic classes.
Journal of psychopharmacology (Oxford, England)
September 1, 2019
James D. Sexton, Michael S Crawford, Noah W Sweat et al.
33 citations
Novel psychedelics, such as 2C-B, 2C-I, and 2C-E, are used by a very small fraction of the U.S. adult population (0.12%). Users tend to be younger, male, White, more educated but with lower income, and almost all have also used classic psychedelics. Compared to those who have used only classic psychedelics, people who have used novel psychedelics are more likely to report past-year suicidal thinking and planning, though novel psychedelic use alone is not associated with psychological distress or suicidality. The findings suggest novel psychedelics may differ from classic psychedelics in their mental health associations, but more research is needed.
Research Square
May 20, 2021
Richard E. Daws, Christopher Timmerman, Bruna Giribaldi et al.
11 citations
Across two clinical trials, psilocybin therapy produced robust antidepressant effects that were linked to a decrease in brain network modularity measured by resting-state fMRI. In an open-label study of 16 adults with treatment-resistant depression, Beck Depression Inventory scores dropped sharply at one week and six months, and the reduction in network modularity one day after treatment correlated with clinical improvement at six months. In a double-blind randomized trial of 43 adults with major depressive disorder, the psilocybin arm showed superior antidepressant effects at two and six weeks compared with escitalopram, and improvements correlated with decreased modularity. These convergent findings suggest that psilocybin therapy may work by reducing the brain's network modularity.