Psychedelics and Evidence-based Psychotherapy A Systematic Review with Recommendations for Advancing Psychedelic Therapy Research

The present systematic review aimed to document, summarize, and constructively critique the current landscape of psychological interventions currently in use in modern psychedelic drug trials. The evidence base indicates large variability in psychological interventions used across trials, the lack of appropriate study designs to disentangle the effect of the psychological component as distinct from or in interaction with the drug or drug expectancy effect, and no clear inference on the optimal or necessary psychological treatment components to be paired with a psychedelic for any indication. We offer the following recommendations to guide research in this area. First, it will be helpful to determine the efficacy of the psychological component (if not already established) apart from any participant expectancy for or receipt of drug to eliminate the influence of drug expectancy and drug effects, respectively. These currently taint existing findings from clinical trials of psychedelic compounds with inactive placebo, active placebo, or low -dose comparator arms. Whether efficacious as a standalone treatment or not, further testing of the psychological component in interaction with an active drug can then be conducted with this important knowledge in hand. Second, experimental designs that unravel the relative contributions of PAT components are necessary to better inform treatment development, particularly in the case where researchers choose to incorporate EBTs into PAT. The optimal approach from a regulatory, treatment development, and treatment dissemination framework is to determine what is essential versus incremental versus nonincremental in optimizing therapeutic outcomes for patients, which can be most readily accomplished through rigorous validation of the incremental benefit of added components. Third, comparative efficacy and mechanism -focused trials will help to inform on how and why certain EBT components may enhance therapeutic outcomes, how such enhancements occur, and better substantiate the evidence base for novel PAT -specific psychological approaches with purported active ingredients. In aggregate, extensive foundational work needs to be undertaken to best understand how to combine psychedelics with psychotherapeutic interventions for optimal therapeutic outcomes.