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.
Frontiers in Pharmacology
November 2, 2018
Adam D. G. Hampshire, Christopher Timmermann, Christopher Timmermann et al.
422 citations
Psychological well-being increased two weeks after a psychedelic experience and remained elevated at four weeks. Higher ratings of a 'mystical-type experience' positively influenced this change in well-being, while 'challenging experience' and 'visual effects' did not. Having 'clear intentions' for the experience fostered mystical-type experiences. A positive 'set' and recreational intentions reduced the likelihood of a challenging experience. The trait 'absorption' and higher drug doses amplified all aspects of the acute experience. Baseline traits had the strongest effect on well-being change, underscoring the importance of extra-pharmacological factors in shaping responses to psychedelics.
Trends Cogn Sci
February 3, 2023
Manesh Girn, Fernando E. Rosas, Richard E. Daws et al.
76 citations
Psychedelics reduce the functional segregation of large-scale brain networks, but findings have been largely inconsistent. A complexity-science perspective that emphasizes the distributed, interactional, and dynamic nature of brain function may explain these inconsistencies. The authors propose that psychedelics induce a mode of brain function that is more dynamically flexible, diverse, integrated, and tuned for information sharing, consistent with greater criticality. This 'meta' perspective can unify past findings and guide intuitions toward compelling mechanistic models.
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.
May 10, 2022
Robin Carhart‐Harris, Richard E. Daws, David Nutt
preprint
The authors respond to a critique of their earlier work that questioned whether psilocybin truly opens depressed minds. They address the skeptic's arguments, defending their original evidence and conclusions about psilocybin's effects on depression. The response clarifies methodological points and reaffirms the potential of psilocybin as a treatment for depression, while acknowledging the need for further research to address lingering doubts.