Written by Jonny Woodall
You may or may not be familiar with changing laws surrounding psychedelics around the world, but it seems that collective efforts by researchers, scientists & psychedelic activists are bringing in major changes in the west with the decriminalisation and in some cases even legalisation of the therapeutic use of psychoactive plant & fungi as medicine.
One of the most exciting areas of research and legislative developments is on the use of psilocybin to treat major depressive disorder (MDD) and treatment resistant depression [i]. Depression is the number one cause of disability in the world with approximately 300 million people affected. Costing an annual $210 billion dollars to the global economy [ii] with an estimated 10% to 30% considered treatment-resistant to pharmaceutical antidepressants [iii], MDD is a growing problem that requires healthcare systems to consider new methods of help.
This much needed help is looking like it is found within one of nature’s most magical gifts, the humble psychedelic mushroom. In recent decades ethnobotanists have discovered that the use of mushrooms for religious, healing and divinatory experiences spans across multiple indigenous cultures. From a herbalist’s point of view, what unites all of the global distribution of psychedelic mushrooms is the collection of potent neuro-active metabolites that inhabit each mushroom. Psilocybin being one of these inherent metabolites of particular interest to scientists, researchers and psychiatry.
Psilocybin is a naturally occurring tryptamine alkaloid discovered within the hundred plus species of psychedelic mushrooms occurring in many of the temperate or tropical climates of the world. Most commonly referenced as being an isolated constituent within the fungi genus of Psilocybe [iv],psilocybin is just one constituent within a cocktail of potent compounds found within psychoactive mushrooms. Other constituents found within the Psilocybe genus include the alkaloid psilocin and a range of beta-carbolines including harmane and harmine. Both of which are potent inhibitors of monoamine oxidase enzyme [v].
The average psilocybin content within the psilocybe species is about 1%. Meaning one gram of mushrooms provides approximately 10mg of psilocybin [vi]. A number of modern human trials using psilocybin to treat depression follow the guide of 20mg-30mg psilocybin per 70kg of human body weight [vii].
Like many psychoactive compounds, psilocybin exerts its effect on the nervous system via the 5-HT2A receptor. This is the same receptor targeted by selective serotonin reuptake inhibitor (SSRI) anti-depressant drugs. The difference is that psilocybin works as an agonist of the receptor, thereby producing a different and a potentially much more profound psychoactive reaction than SSRI.
The traditional view taken by governments of the world is one of great caution and criminality when considering the cultivation, possession, consumption and/or prescription of psilocybin containing mushrooms. The majority of countries around the world have legislation that makes it illegal to pick, grow, possess and consume psilocybin containing mushrooms. After many decades of protest by indigenous communities, scientists and organisations such as the Multi-disciplinary Association for Psychedelic Studies (MAPS) endlessly campaigning for the safe and legal use of psilocybin containing mushrooms we can now see a positive momentum of change across the western world.
In November 2019 the United States Food and Drug Administration granted the Usona Institute ‘Breakthrough Therapy’ designation to conduct clinical trials on the use of psilocybin for treating MDD [viii]. This phase 2 trial involving 80 participants is due to finish in Spring 2021 [ix] with results most likely showing psilocybin can produce sustained and substantial decreases in symptoms of anxiety and depression. These healing effects have been shown before in sporadic trials with some even reporting sustained improvements in depressive symptoms following a single high dose treatment of psilocybin at the 6 month follow-up for almost 80% of the participants involved [x].
In 2016 the Beckley Foundation, based in London (UK) published results from a trial that involved 12 patients with moderate to severe, treatment resistant depression [xi]. After prescribing two dosages (10mg and 25mg, seven days apart) in a supportive setting, 67% of patients were depression free one week after treatment. 42% were still in remission three months later. These results are revolutionary when compared to conventional pharmaceutical options. Similar research has also been explored with other plant based psychedelic treatments for depression such as Ayahuasca [xii].
Given the current conventional medical paradigm of patenting medicines, the trials involving psilocybin for depression remains in this exploratory stage. It could be that in years to come as more evidence emerges on how therapeutic isolated psilocybin can be, that we see a global distribution of this treatment. This does however bring up the question as to how taking isolated psilocybin on its own as a patented medicine compares to using the whole mushroom as found in the wild or through cultivation. This is a debate that has gone on for many decades between herbalists, pharmacists and scientists. The discussion of reductionism versus holism.
Many users of psilocybin containing mushrooms consume the whole mushroom on its own without considering the legal situation or cost of attaining a pharmaceutical isolate of psilocybin. This is all with the backdrop of the growing movement towards drug decriminalisation moving through the world, particularly the U.S.
In November 2020 the state of Oregon went further than decriminalisation and became the first state in the U.S to pass legislation that legalised the medicinal use of psilocybin [xiii]. At the moment this doesn’t mean that whole psilocybin containing mushrooms can be openly sold at dispensaries like cannabis is, but it does mean they are drafting proposals for how and which treatment centres can provide psilocybin for those who wish to explore this method of treatment. This may follow other examples around the world, such as Holland, where Psilocybin mushrooms in the form of truffles are offered as a tool for healing and self-development [xiv].
It is forecasted that as more research on psilocybin is produced and the evidence-base is enhanced, then it is inevitable that more parts of the world will follow the path that medicinal cannabis has taken. Fewer prosecutions and ‘turning a blind eye’ to decriminalisation, to legalisation for medical treatment, and finally to potential legal cultivation, possession and consumption.
It remains to be seen how this movement of research, science, recreational use and overall discussion will lead us to. Each individual country will decide on the path they decide to take but it finally feels like the healing role of our more misunderstood plant and fungi allies is finally being acknowledged.
- Davis, A. K. Barrett, F. S. May, D. G. et al. (2020) Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder – A Randomized Clinical Trial, JAMA Psychiatry, 10.1001/jamapsychiatry.2020.3285
- Greenberg, P. E. Fournier, A. A. Sisitsky, T. Pike, C. T. Kessler, R. C. (2015) The Economic Burden of Adults with Major Depressive Disorder in the United States (2005 and 2010), Journal of Clinicla Psychiatry, Feb;76(2): p. 155-162.
- Nemeroff, C. B. (2007) Prevalence and Management of Treatment-Resistant Depression, Journal of Clinical Psychiatry, 68 Suppl 8: p. 17-25.
- Peredy, T. Bradford, H. (2014) Mushroom, Psilocybin, Encyclopaedia of Toxicology (Third Edition), p. 418-419.
- Blei, F. Dorner, S. Fricke, J. Baldeweg, F. Trottman, F. Komor, A. Meyer, F. Hertwick, C. Hoffmeister, D. (2019) Simultaneous Production of Psilocybin and a Cocktail of β‐Carboline Monoamine Oxidase Inhibitors in “Magic” Mushrooms, Chemistry – A European Journal, Vol. 26 (3) p. 729.734.
- Griffiths, R. R. Johnson, M. W. Carducci, M. A. et al. (2016) Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial, The Journal of Psychopharmacology, Dec;30(12): p. 1181-1197.
- Carhart-Harris, R. L. Bolstridge, M. Rucker, J. Day, C. M. J. Erritzoe, D. Kaelen, M. et al. (2016) Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study, Lancet Psychiatry, May 17.
- Jimenez-Garrido, D. F. Gomez-Sousa, M. Ona, G. Dos Santos, R. G. Hallak, J. E. C. Alcazar-Corcoles, M. A. Bouso, J. C. (2020) Effects of Ayahuasca on mental health and quality of life in naïve user: a longitudinal and cross-sectional study combination, Scientific Reports 10, 4075.