Blast from the Past: Revisiting the Significance of Therapeutic Potential of Psilocybin

Research on the therapeutic potential of psychedelic drugs fell into a hiatus in the past decades until scientists from the United States, Switzerland, and Germany began its revival, exploring its biochemical and physiologic effects in combination with psychotherapy. In the 1950s to the mid-1960s, tens of thousands of patients are estimated to have been treated by psychedelic drugs such as psilocybin because of its unique potency, but its therapeutic promise was eclipsed by countercultural movements (Carhart-Harris, & Goodwin, 2017). Psilocybin, a naturally occurring plant alkaloid found in Psilocybe genus of mushrooms, popularly known as “magic mushrooms” may have been used for healing purposes for many years, (Carhart-Harris et al., 2016), but its pharmacodynamic significance needs high-quality clinical trials to earn medical justification. COMPASS Pathways was recently approved by the US Food and Drug Administration (FDA) for a clinical trial of psilocybin therapy for treatment-resistant depression (TRD).  A life sciences company with the primary intent of accelerating patient access to evidence-based innovation in mental health, COMPASS Pathways will springboard landmark trials across North America and Europe, including the UK and other countries, after regulatory approvals. Phase III studies will be dependent upon the success of these trials.

Globally, the burden of the high prevalence of TRD in the primary care setting justifies the need for a more clinician-led proactive approach to improving the outcome of patient management. While the 2016 study of Carhart-Harris et al. provides preliminary support for safety and efficacy of psilocybin for treatment of TRD, the study highlighted the importance of further trials with a more rigorous design. However, the lack of single definition of what constitutes ‘treatment resistance’ as noted by Thomas et al. (2013), made it critical to stratify research participants based on treatment resistance in association to non-adherence to medication, treatment resistance attributable to failure to respond after antidepressant medication to the more complex medication non-response classification systems. The FDA approval for COMPASS Pathways to conduct a Phase IIb trial will help amplify current knowledge on the effect of psilocybin on depression. Major depression has been ranked by the World Health Organization (WHO) as the fourth leading contributor to the global burden of disease and is expected to be top of the ranking by 2030 (Erritzoe et al., 2018). According to  George Goldsmith, COMPASS Pathways Chairman/Co-founder, and Ekaterina Malievskaia, Chief Medical Officer/Co-founder, the collaborative effort among scientists, clinicians, patient representatives and regulators from Europe and North America will give us evidence-based understanding of the efficacy of psilocybin therapy, as well as assess the safety and positive outcome of this new approach. The study will be the largest psychoactive care clinical trial following numerous academic early reviews on psilocybin’s pharmacodynamic and pharmacokinetic promise in improving the management outcome of TRD. Completion of COMPASS Pathways studies will raise awareness on the safety and efficacy of this novel protocol that could be benefited by patients with depression who failed to respond with either cognitive psychotherapy or medication. Removing psychological defenses as the original rationale of using psychedelic drugs in combination with psychotherapy, endorses the findings of Watts et al. (2017) on the increased amygdala (right amygdala) responses suggestive to positive mood effects and alleviation of depressive symptoms of psychedelics (Roseman et al., 2017). The continued focus on therapeutic interventions with evidence-based alternative strategies is critical in easing the socio-economic burden and improving the prognosis of TRD.



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