Led by investigators from the University of California, San Francisco, and Imperial College London’s Centre for Psychedelic Research, the findings come from a new analysis of brain scans of almost 60 patients with resistant depression treated with psilocybin.
Thomas Angus/Imperial College London
Dr. Robin Carhart-Harris
“Not much is known about the changes in brain function after psychedelic experience. There has been much more research done on the acute brain action of psychedelics, but there is very little on the postacute or subacute changes in brain function,” study investigator Robin Carhart-Harris, PhD, former head of the Imperial Centre for Psychedelic Research and now director of the Neuroscape psychedelics division at UCSF, and senior author of the study, told this news organization.
“This research is a major advance because it is showing replication across two datasets with different designs. One in which the scanning is done 1 day after intervention and the other one when the posttreatment scanning is done 3 weeks after the second of two psilocybin therapy sessions,” Dr. Carhart-Harris added.
The study was published online in Nature Medicine.
A disruptor?
Psilocybin is one of a number of psychedelics under investigation as a potential therapy for psychiatric disorders. In the last 15 years, at least six separate clinical trials have reported impressive improvements in depressive symptoms with psilocybin therapy. Several studies have tested a synthesized a form of the drug to treat patients with depression and anxiety – with promising results.
However, the therapeutic action of psilocybin and other serotonergic psychedelics is still not completely understood, although it is known that they affect 5-HT2A receptors and are hypothesized to briefly disrupt these connections, allowing them to reform in new ways in the days and weeks following treatment.
This research assessed the subacute impact of psilocybin on brain function in two clinical trials of depression:
The first trial was an open-label trial of oral psilocybin in patients with treatment-resistant depression.
Patients had baseline clinical assessment and resting-state functional MRI, followed by fixed-order “low” (10 mg) and “high” (25 mg) psilocybin therapy dosing days separated by 1 week. Of the 19 patients recruited, 3 were excluded as a result of excessive fMRI head motion. The team confirmed an antidepressant effect of psilocybin in 16 patients via reduced questionnaire scores from baseline.
Brain network modularity was significantly reduced 1 day after psilocybin therapy in 10 of 16 participants (mean difference, –0.29; t15, 2.87; 95% confidence interval, 0.07-0.50; P = .012; d = 0.72). This result implies an increase in functional connectivity between the brain’s main intrinsic networks.
Pre- vs posttreatment change in modularity significantly correlated with change in Beck Depression Inventory (BDI) score at 6 months, relative to baseline (r14 = 0.54, 95% CI, 0.14-0.78, P = .033). Results imply that decreased brain modularity 1 day after psilocybin therapy relates to long-term improvements in symptom severity.