Background: There is interest in the potential of psychedelics as treatments for Obsessive-Compulsive and Related Disorders (OCRDs), though research in this field is still at an early stage. In this review, we examine the methodological issues present in existing research investigating the use of psychedelics in OCRDs, as a basis for improved trial design. Methods: We searched PubMed and PsycInfo for published studies and Clinicaltrial.gov for unpublished studies investigating the use of psychedelic in individuals with OCRDs. We reviewed the identified studies and described the main methodological issues undermining study outcomes. We analyzed the published selected papers using standard tools (Cochrane Risk of Bias for Non-Randomized Studies, ROBINS-I). Results: We found just two published and seven unpublished studies. Risk of bias analysis revealed a critical risk of bias, primarily related to experimental design (e.g., absence of adequate control condition), expectation bias among study participants and problems ensuring adequate blinding. The analysis of unpublished studies, although limited, identified parallel concerns, while also highlighting the implementation of promising strategies for advancing the field. Discussion: There is a shortage of unbiased evidence. Although the shortcomings in the design of the few existing studies raise important concerns, early potential efficacy justify further, well-designed research. Potential strategies, some of which already implemented in ongoing studies, to address current issues and improve the validity of future studies include the use of blinded raters and of a credible control (such as virtual reality), the choice of a lower drug dose and the inclusion of only drug-naive subjects.
