Serotonin
Psilocybin
In the Treament of Depression
Depression Today
The Need for Novel Treatments
It is estimated that about 260 million of the worlds population suffer with Major Depressive Disorder (MDD) (Gukasyan N. et al, 2022). WHO reports this as 5% of the adult population worldwide. A leading cause of disability and contributor of a great proportion of the burden of disease, the financial cost of mental ill health in the UK is upwards £117.9bn. This equates to 5 per cent of UK's GDP (WHO, 2022) (McDaid D., LSE, 2022).
MDD reduces the quality of life of the sufferer, affecting all aspects and interpersonal relationships. Current treatments have variable efficacy, may take weeks to show significant symptom reduction and due to side effects many patients find it difficult to adhere to treatment plans. Risk of relapse is between 40-60% in those diagnosed with a single episode of MDD and approximately 30% of cases of MDD are categorised treatment resistant. The need for a novel approach to the treatment of depression, that is fast acting and produces sustained results over time with minimal side effects, is pertinent. (Gukasyan N. et al, 2022)
Serotonin molecule
Far from magic, the pyscho-active effects of magic mushrooms are attributed to Psilocybin and its metabolites. Psilocybin, primarily a pro-drug, is dephosphorylated by alkaline phosphatase in the liver to produce the active metabolite Psilocin which is further metabolised to psilocin-O-glucuronide. These metabolites are agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype (Serotonin) receptors (Lowe H. et al, 2021). Recent research conducted into the efficacy of psilocybin and other hallucinogenic compounds have shown promising results in the treatment of depression.
Results of two studies conducted by John Hopkin's Medicine point towards psilocybin delivering not only immediate relief from MDD but that single treatments can offer durable effects up to 12 months following a single treatment (Gukasyan N., 2022). The efficacy of this treatment beyond 12 months has yet to be investigated, however, a separate study into the use of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life threatening cancer showed sustained 'reductions in anxiety, depression, hopelessness, demoralization, and death anxiety' at 3.2 years and 4.5 year follow ups after initial treatment. In fact, in the second follow-up approximately 60–80% of participants met criteria for clinically significant responses.
Studies thus far have been on small groups but the results are very promising, both short and longer term and with regard to side effects.
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Psilocybin
Prodrug: Psilocybin molecule (top)
Active compound: Psilocin molecule (bottom)
Psilocybin
A History
Ancient Civilisations
The use of psychoactive mushrooms by indigenous people across the world dates back more than 12,000 years. They were used for medicinal and ceremonial purposes.
The First Psychedelic Renaissance
In 1957, after a piece by Gordon R. Wasson was published in LIFE magazine after he came across a tribe in Mexico utilising psychoactive mushrooms. He shared a sample with Albert Hoffmann who had previously discovered the psychoactive substance LSD. Hoffman's team isolated Psilocybin and distributed it for research purposes. The following 20 years saw psilocybin administered in clinical settings and findings began showing great promise for its therapeutic potential in depression, anxiety, alcoholism, addiction, obsessive compulsive disorder, schizophrenia and more neurological conditions
The War on Drugs
Psilocybin and other psychedelic substances began to be used recreationally sparking a global campaign, led by the American federal government under Nixon who declared a 'war on drugs'. This led to the development of policies that aimed to clamp down on not only the use and abuse of 'drugs' but also the production and distribution of such. Psilocybin has been classified a Schedule 1 substance since 1970 as per the Controlled Substances Act. This almost halted research into the therapeutic potential of psilocybin.
Return to Research
In 2011 a critical report by The Global Commission of Drug Policy stated that the "The global war on drugs has failed, with devastating consequences
for individuals and societies around the world.. fundamental reforms in national and global drug control policies are urgently needed."
Recent years have seen a return to research reigniting the hope for therapeutic agents to growing numbers of conditions that burden the the global population today
The Future
Thanks to people and organisations such as Paul Stamets, renowned mycologist, and Multidisciplinary Association for Psychedelic Studies (MAPS) the future of Psilocybin looks bright once again. For updates on the research being done on psychedelic substance as therapeutic agents, please refer to the News section.
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Psilocybe stametsii
One of the most recently discovered Psilocybin containing mushroom species; named after renowned mycologist Paul Stamets.