TherapeuticShroom on pixabay
TherapeuticShroom on pixabay

Boosted brain connections may explain how magic mushrooms fight depression

Embargoed until: Publicly released:
Peer-reviewed: This work was reviewed and scrutinised by relevant independent experts.

Randomised controlled trial: Subjects are randomly assigned to a test group, which receives the treatment, or a control group, which commonly receives a placebo. In 'blind' trials, participants do not know which group they are in; in ‘double blind’ trials, the experimenters do not know either. Blinding trials helps removes bias.

Experimental study: At least one thing in the experiment was changed to see if it had an impact on the subjects (often people or animals) – eg: changing the amount of time mice spend on an exercise wheel to find out what impact it has on weight loss.

People: This is a study based on research using people.

Psilocybin — a naturally occurring psychedelic found in 'magic mushrooms' — is effective for treating patients with treatment-resistant depression, according to international researchers. However, they caution that their results were achieved in a controlled environment and say that patients with depression should not attempt to self-medicate. The researchers say brain scans showed that psilocybin works by increasing the connectivity between the brain’s functional networks, an effect that was not seen in patients who received the conventional antidepressant escitalopram.

Journal/conference: Nature Medicine

Link to research (DOI): 10.1038/s41591-022-01744-z

Organisation/s: Imperial College London, UK

Funder: R.E.D. was supported by an Engineering and Physical Sciences Research Council PhD scholarship at the Imperial College London Centre for Neurotechnology (EP/L016737/1). The research was carried out at the National Institute for Health Research/Wellcome Trust Imperial Clinical Research Facility. The open-label trial was funded by a Medical Research Council clinical development scheme grant (MR/J00460X/1). The DB-RCT was funded by a private donation from the Alexander Mosley Charitable Trust, supplemented by Founders of Imperial College London’s Centre for Psychedelic Research.

Media release

From: Springer Nature

Neuroscience: Psilocybin treatment for depression increases brain connectivity

Psilocybin — a naturally occurring psychedelic — provides therapeutic responses in patients with treatment-resistant depression via increased connectivity between the brain’s functional networks, a mechanism that is not seen with the conventional antidepressant escitalopram. The findings, published in Nature Medicine, provide insights into the pathways underlying treatment-resistant depression.

Patients with depression often exhibit what is known as a ‘negative cognitive bias’, characterized by pessimism, poor cognitive flexibility, rigid thought patterns, and negative fixations about ‘self’ and the future. At least six separate clinical trials have reported improvements in depressive symptoms with psilocybin therapy. However, despite these results, the therapeutic action of psilocybin and related psychedelics is not yet fully understood.

Richard Daws and colleagues collected and analyzed brain imaging data from a sample of 59 patients participating in two clinical trials of psilocybin efficacy. The first trial included 16 patients (mean age, 42.75 years; 25% female) with treatment-resistant depression — defined as a type of major depressive disorder in which multiple courses of antidepressant treatment have not improved depressive symptoms. The second trial analyzed imaging data from 43 patients with major depressive disorder, 22 of whom received psilocybin (mean age, 44.5 years; 36% female), whereas 21 patients (mean age, 40.9 years; 29% female) received the conventional antidepressant escitalopram, and a low dose of psilocybin. Overall, the authors found that psilocybin therapy delivered a rapid, substantial and sustained antidepressant effect that was significantly greater than escitalopram. The alleviation of depression significantly correlated with an increase in the connectivity between the brain’s functional networks. These significant changes in the brain’s modular organization are reminiscent of a “carry-over” effect of psilocybin’s acute action on brain function. These changes were not observed in patients who received escitalopram.

These observations suggest that psilocybin — and possibly other psychedelics — have a novel mechanism of action relative to that of conventional antidepressants. Specifically, psilocybin therapy may alleviate depression by liberating entrenched brain networks and encouraging integrated and flexible brain functioning that is conducive to better mental health.

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