Evaluating the risk of psilocybin for the treatment of bipolar depression: A review of the research literature and published case studies

Abstract

• Despite psilocybin's apparent effectiveness in depression, people with bipolar have been excluded from all modern trials. • Epidemiological data and religious ceremony data do not provide strong evidence for excluding people with bipolar disorder from carefully designed clinical trials. • In a systematic review of the case study literature of individuals using psychedelics we found 17 cases of an adverse event possibly involving mania, five involving psilocybin, and two cases involved individuals with a likely pre-existing diagnosis of bipolar disorder. • Thus there is some reason for caution in the use of psilocybin as a treatment, but the risks may be low relative to the treatment needs of this population. Growing evidence suggests that psilocybin, the active ingredient in hallucinogenic mushrooms, can rapidly and durably improve symptoms of depression, leading to recent breakthrough status designation by the FDA and legalization for mental health treatment in some jurisdictions. Depression in bipolar disorder is associated with significant morbidity and has few effective treatments. However, there is little available scientific data on the risk of psilocybin use in people with bipolar disorder. Individuals with bipolar disorder have been excluded from modern clinical trials, out of understandable concerns of activating mania or worsening the illness course. As psilocybin becomes more available, people with these disorders will likely seek psilocybin treatment for depression and have likely already been doing so in unregulated settings. Our goal here is to summarize the known risks of psilocybin use (and similar substances) in bipolar disorder and to systematically evaluate examples of published case history data, in order to critically evaluate the relative risk of psilocybin as a treatment for bipolar depression. We found 17 cases suggesting that there is potential risk for activating a manic episode, thereby warranting caution. Nonetheless, the relative lack of systematic data or common case examples indicating risk appears to show that a cautious trial, using modern trial methods focusing on appropriate ‘set’ and ‘setting’, targeted at those lowest at risk for mania in the bipolar spectrum (e.g., bipolar 2 disorder), is very much needed, especially given the degree to which depression impacts this population.