Psilocybin use in bipolar disorder: A comprehensive review

Bipolar disorder (BD) is a severe and persistent mental disorder characterized by recurrent mood episodes, with BD depression accounting for most of the illness burden. Although the mainstay treatment of BD consists of pharmacotherapy with mood stabilizers and atypical antipsychotics, a large proportion of patients with BD depression do not respond to adequate trials of medications. In addition, these medications can be associated with multiple, often significant adverse effects, highlighting the need for novel therapeutic agents that are acceptable, effective and safe for patients.

We performed a comprehensive narrative review on the use of psilocybin in BD, with a focus on clinical outcomes.

Two small clinical trials show that psilocybin combined with psychotherapy was safe and effective for the treatment of BDII depression with large treatment effects. No serious adverse events, including treatment-emergent mania/hypomania or increased suicidality, were reported in both trials. However, other studies have raised concerns about the safety of psilocybin in BD patients, including the development or worsening of manic symptoms, sleep disruptions and anxiety. Overall, the majority of BD patients believe that psilocybin could benefit their mental health problems, but their experiences varied depending on several contextual factors, such as polysubstance use, psilocybin dose, solo versus social experiences and pre-psilocybin sleep deprivation.

Despite its promising potential, the efficacy and safety of psilocybin in the treatment of BD depression remain unclear, and future research is essential to clarify its therapeutic value in BD.