CURRENT STATE OF PSILOCYBIN-ASSISTED THERAPY IN MOOD DISORDERS.

Psychedelics are currently undergoing a scientific renaissance, with modern studies investigating therapeutic efficacy of psychedelic-assisted therapy in a range of psychiatric conditions. In particular, psilocybin-assisted therapy (PAT) has been suggested to have positive effects on patients suffering from depression and psychiatric distress associated with life-threatening disease - contexts with growing needs for alternative treatments - in a therapeutic setting involving fewer doses and less important adverse effect compared to that of classic psychotrope administration. Psychedelics are partial agonists of the serotonin 2A (5-HT2A) G protein-coupled receptors, whose activation likely mediates the acute psychoactive effects. Furthermore, psychedelics seem to induce a hyper-plastic state which allows for adaptation of inflexible pathological thinking patterns. Post-acutely, they are suggested to induce rapid, robust and sustained neuroplasticity. Eight clinical PAT trials have been conducted between January 1st 2001 and March 31st 2023 and are reviewed here. Five of them evaluate the effect on depressive symptomatology in an otherwise general population. The other three evaluate effect on depression and anxiety in patients suffering from somatic life-threatening disease. The studies reviewed here show that PAT is safe and feasible to administer in current clinical models. Preliminary efficacy shows significant improvements in depressive and anxious symptomatology which are immediate and partially sustained. One study comparing PAT to selective serotonergic reuptake inhibitors showed no significant difference of efficacy between the two treatments. Preliminary results regarding efficacy of PAT on mood disorders are promising, but further research is warranted for stronger inferences, with a particular focus on larger, multicentric studies, more diverse populations and a stronger control for expectancy and unblinding.