STUDIES ON PSILOCYBIN AND DEPRESSION
Psilocybin, a naturally-occurring psychedelic compound found in certain ‘magic’ mushrooms, is being studied as a potential treatment for treatment-resistant depression (TRD). TRD is a type of depression that does not respond to traditional treatments. About 100 million people in the world suffer with treatment-resistant depression, which means they have not responded to at least two anti-depressant treatments for their major depressive disorder.
Studies in recent years have shown that psilocybin may have promise as a treatment for TRD, having reported improvements in depressive symptoms, including in those with terminal illness, after psilocybin-assisted psychotherapy (Griffiths et al. 2016; Ross et al. 2016; Grob et al. 2011; Carhart-Harris et al. 2016).
In 2022, the largest trial to date - a multicentre clinical trial led by COMPASS Pathways across 22 international sites, including the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and South London and Maudsley NHS Foundation Trust - found that a single 25mg dose of psilocybin, alongside psychological support, had a significantly greater impact in reducing symptoms of depression in participants with TRD in the weeks following the trial than a lower, 1mg dose.
Published in the New England Journal of Medicine, the trial also involved designing and delivering one of the largest training programmes for therapists to provide psychological support alongside psilocybin in research settings. A therapy manual was developed to enable the standardisation of the psychological support across sites and therapists around the world.
Psilocybin works by binding to serotonin receptors in the brain, which leads to changes in brain activity and the release of neurotransmitters that play a role in mood regulation. This is similar to how traditional anti-depressants – selective seratonin re-uptake inhbitors or SSRIs – work. However, psilocybin may have a more rapid and sustained effect on symptoms without ‘numbing’ patients to the full range of emotion and experience.
Another proposed mechanism of action of psilocybin in treating depression is its ability to increase neuroplasticity, or the ability of the brain to adapt and change, a vital tool for wellbeing in a world that is by natrue ever-changing and unpredictable. Depression – along with other conditions including OCD and eating disorders - is often characterised by repetitive or obsessiely rigid thought patterns, and a lack of capacity to see other perspectives or ways of being. Psilocybin – along with some other psychedelics - appears to ‘dissolve’ some of these rigid connections, returning our brain to a more primitive, child-like, ‘entropic’ state (so named by Carhartt-Harris et al., 2014, in the journal Frontiers in Human Neuroscience) free of entrenched beliefs, filters, ideals and expectations, where new neural connections can be made between parts of the brain that do not usually communicate. This can create a significant shift in perspective in a short space of time.
Further research is needed to fully understand the safety and efficacy of psilocybin as a treatment for TRD, and to determine optimal dosing and administration protocols in a therapeutic setting, since some trials have reported adverse effects – including increased anxiety and paranoia – in some participants.
Thus a 2022 trial - Single-dose psilocybin-assisted therapy in major depressive disorder: A placebo-controlled, double-blind, randomised clinical trial - published in the Journal of Clinical Medicine, set out explore whether moderate doses could have as much impact, along with psychotherapeutic support, as higher doses or two-dose protocols (as well as a placebo group). In summary, the results do suggest that a single, moderate dose of psilocybin may be as efficacious in reducing depressive symptoms as the repeated and higher doses administered in previous studies while at the same time inducing less adverse events - the intervention was well-tolerated by all participants. Nevertheless, the study-leaders called for further trials.
In addition to its potential benefits for TRD, psilocybin is also being studied for the treatment of other mental health conditions such as anxiety, PTSD, and addiction.
Psilocybin is still a controlled substance in many parts of the world, including the UK, and not yet widely available as a clinical treatment option, as governments approach these research findings with caution. However, de-regulation is gathering pace, particularly in a number of US states, such as Colorado and California, and many biotech start-ups are rushing to patent synthetic forms of psilocybin and other substances in anticipation of widespread therapeutic use. Nevertheless, always be cautious and do your research.
