Psilocybin (O-phosphoryl-4hydroxy-N, N-dimethyltryptamine) and its active metabolite psilocin (4-hydroxy-N, N-dimethyltryptamine) are the main psychoactive components of psychedelic mushrooms. In the central nervous system, psilocin acts as an agonist of serotonergic 5-HT1A and 5-HT2A/C receptors, leading to altered states of consciousness in humans (Tyls et al., 2014). Psilocybin doses of 0.04–0.43 mg/kg cause alterations in perception, cognition, and emotions, while also eliciting long-term changes in well-being and mood in both healthy and psychiatric subjects (Dos Santos et al., 2016; Kor?ák et al., 2019; Barrett et al., 2020). These long-lasting positive changes lead to an exploration of the therapeutic potential of psychedelics as well as the mechanisms underlying this potential. Because of its general safety, intermediate duration of action, and therapeutic potential in several neuropsychiatric disorders, psilocybin is currently the most intensely studied psychedelic in clinical trials (Sewell et al., 2006; Grob et al., 2011; Stebelska, 2013; Dos Santos, 2014).
Overall, there has been an increasing preclinical (Catlow et al., 2013; Baumeister et al., 2014) and clinical (Carhart-Harris et al., 2016; Bogenschutz and Ross, 2018) evidence for the antidepressant potential of psilocybin. Although exact mechanisms are currently unknown, it is generally believed to be attributed to either a direct action on 5-HT receptors or the psychological effects of acute intoxication (Carhart-Harris and Goodwin, 2017). It has been shown that serotonergic psychedelics including psilocybin via 5-HT2A receptors promote neuroplasticity (Ly et al., 2018), a fundamental mechanism of neuronal adaptation that is disrupted in depression (Carhart-Harris and Goodwin, 2017) and restored by antidepressant treatments including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) or electroconvulsive therapy (ECT) (Hayley and Littlejohn, 2013).
https://www.frontiersin.org/articles/10.3389/fphar.2020.602590/full
