A Research Domain Criteria (RDoC)-Guided Dashboard to Review Psilocybin Target Domains: A Systematic Review

BACKGROUND: Preliminary results from randomized controlled studies as well as identified molecular, cellular, and circuit targets of select psychedelics (e.g., psilocybin) suggest that their effects are transdiagnostic. In this review, we exploit the Research Domain Criteria (RDoC) transdiagnostic framework, to synthesize extant literature on psilocybin. OBJECTIVE: We aimed to identify RDoC-based effects of psilocybin and vistas for future mechanistic and interventional research. METHODS: A systematic search in electronic databases (i.e., PubMed, Scopus, PsycINFO, and Web of Science) performed in January and February 2021 identified English articles published between 1990 and 2020 reporting the effects of psilocybin on mental health measures. Data from included articles were retrieved and organized according to the RDoC bio-behavioral matrix and its constituent six main domains, namely: positive valence systems, negative valence systems, cognitive systems, social processes, sensorimotor systems, and arousal and regulatory systems. RESULTS: The preponderance of research with psilocybin has differentially reported beneficial effects on positive valence systems, negative valence system, and social process domains. The data from the included studies support both short-term (23 assessments) and long-term (15 assessments) beneficial effects of psilocybin on the positive valence systems. While 12 of the extracted outcome measures suggest that psilocybin use is associated with increases in the “fear” construct of the negative valence systems domain, 19 findings show no significant effects on this construct, and seven parameters show lowered levels of the “sustained threat” construct in the long term. Thirty-four outcome measures revealed short-term alterations in the social systems’ construct namely, “perception and understanding of self,” and “social communications” as well as enhancements in “perception and understanding of others” and “affiliation and attachment”. The majority of findings related to the cognitive systems’ domain reported dyscognitive effects. There have been relatively few studies reporting outcomes of psilocybin on the remaining RDoC domains. Moreover, seven of the included studies suggest the transdiagnostic effects of psilocybin. The dashboard characterization of RDoC outcomes with psilocybin suggests beneficial effects in the measures of reward, threat, and arousal, as well as general social systems. CONCLUSIONS: Psilocybin possesses a multi-domain effectiveness. The field would benefit from highly rigorous proof-of-mechanism research to assess the effects of psilocybin using the RDoC framework. The combined effect of psilocybin with psychosocial interventions with RDoC-based outcomes is a priority therapeutic vista. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40263-022-00944-y.