Psilocybin-Assisted Therapy as an Alternative Intervention for Treatment-Resistant Depression in Healthcare Workers

Psilocybin, a naturally occurring psychedelic compound and 5-HT2A (serotonergic) receptor agonist, has recently gained attention for its potential therapeutic benefits in individuals with TRD. A landmark study published in The New England Journal of Medicine demonstrated that a single dose of psilocybin reduced depressive symptoms in patients with treatment-resistant depression, with sustained improvements noted weeks after treatment (Goodwin et al., 2022). Further, recent research involving frontline healthcare workers during the COVID-19 pandemic 3 found psilocybin therapy to be effective in alleviating symptoms of depression and burnout (Back et al., 2024). These findings suggest psilocybin therapy may offer a novel and potentially transformative approach for managing TRD, particularly in populations exposed to chronic occupational stress. This paper will explore the efficacy of psilocybin-assisted therapy as an alternative intervention for healthcare workers with TRD and will make several policy and practice recommendations to establish equitable and safe implementation in clinical practice.