As clinical trials and research into the use of psychedelics as therapeutic interventions for complex mental health conditions like treatment-resistant depression (TRD) continue, late-stage clinical trials continue to deliver consistently positive and promising outcomes. Despite the overwhelming evidence, we do not yet fully understand how psilocybin facilitates positive changes in the brain. The recently published results of a small study aim to offer insights.
A group of researchers recently in London conducted a series of advanced brain imaging studies to explore the effects of psilocybin on the different brain regions of patients with TRD. The results published in the Nature Medicine journal reinforced existing findings on the viability of psilocybin as a treatment for TRD but most notably also offered a potential visual representation of the brain activities involved in the positive outcomes.
Researchers performed brain imaging studies of patients taking part in two separate psilocybin for depression trials. They scanned the brains of the participants before and after treatments.
The larger study which involved a double-blind randomized controlled trial sponsored by the Imperial Colledge of London included 43 participants with severe depression. All patients were told that they were receiving an unknown dose of psilocybin. The participants were assigned to one of two study groups: group A received 25mg of psilocybin followed by 3 weeks of daily placebo capsules while group B received 1mg of psilocybin (presumed inactive) followed by 3 weeks of daily 10mg dose of escitalopram (a common anti-depressant). Both groups were then administered the same initial dose of psilocybin (25mg for group A and 1mg for group B) followed by 3 weeks of daily placebo capsules (group A) or 3 weeks of daily 20mg escitalopram capsules (group B). All participants received an fMRI scan of their brain one day before the initial dose and at the end of the second 3-week period.
The smaller study involved an open-label trial that included 16 participants with TRD who were administered a small (10mg) and large (25mg) dose of psilocybin one week apart followed by assessments conducted one day and 6-months after the second dose. fMRI scans were performed one day before the first and one day after the second doses.
In both groups, the brain scans appeared to validate the follow-up reports. Participants in group A of the larger study reported rapid and sustained improvements in depressive symptoms over the course of the 3-weeks following administration of psilocybin and their brain scans captured a significant uptake in neural activity resembling a healthy brain. In contrast, participants in group B reported mild improvements only and their brain scans continued to demonstrate reduced neural activity associated with depression, pessimism, and negative feedback loop.
Similarly, the participants in the open-label study reported significant and lasting improvements following the two psilocybin administrations, and their brain scans demonstrated a reduction in brain activity associated with depression and uptake in activity associated with enhanced cognitive flexibility.
Source: Nature Medicine
To measure brain activity associated with depressive symptoms, researchers utilized a methodology that measured "brain network modularity" and "global network integration" by monitoring connectivity across the brain’s main intrinsic networks, most notably the Default Mode Network (DMN). Past neuroimaging research has consistently demonstrated a link between DMN overactivity and symptoms of depression. In addition, other higher-order brain networks associated with cognitive control such as the executive network (EN) and salience network (SN) have been implicated in depression.
While these findings are incredibly encouraging, studies of larger scope and size are needed to further explore and validate these assumptions and findings. With that said, the significantly positive and long-lasting effects of psilocybin on depression offer a unique and extremely promising option for the millions who suffer from depression. It is not inconceivable that in the coming decade psilocybin therapies can become the preferred mode of treatment for depressive disorders.
