Studies of Cannabinoid-Based Products in ClinicalTrials.gov: A Scoping Review.

Abstract

<h4>Background and objectives</h4>There is increased interest in using cannabinoid-based products for therapeutic purposes. Because of unique regulatory challenges associated with these products, understanding the state of current research is critical to inform future research. The objective of this review was to survey the characteristics of registered studies on ClinicalTrials.gov that describe using cannabinoid-based products as an intervention.<h4>Methods</h4>The scoping review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist and guidance. Eligible studies registered on ClinicalTrials.gov that used cannabinoid-based products as an intervention included those using approved drugs, compounds (nonapproved drugs/extracts with defined phytocannabinoid content), cannabis (whole cannabis products), and hemp (hemp-derived products and products without defined cannabinoid content). Data were extracted on October 1, 2023, using queries, and a relational database was built. Stratification categories included intervention, disease state, study phase, number of participants, study duration, sponsor, and chronological trends. Statistical analyses were descriptive.<h4>Results</h4>Of 2428 identified records, 879 interventions from 825 unique (non-duplicated) studies were eligible for analysis. Of the 879 eligible for analysis, studies included drugs (n = 287 [32.7%]), compounds (n = 383 [43.6%]), cannabis (n = 178 [20.3%]), and hemp (n = 31 [3.5%]). The most common Medical Subject Headings categories were psychological disorders (n = 170 [20.6%]), pathological conditions-signs and symptoms (n = 153 [18.5%]), nervous system diseases (n = 127 [15.4%]), substance use disorders (n = 97 [11.7%]), and studies in healthy volunteers (n = 77 [9.3%]). Of the 825 unique studies, 521 (63.2%) were early phase 1 to phase 2/3, 103 (12.5%) phase 3, and 40 (4.8%) phase 4; 161 studies (19.5%) were not assigned a phase, including observational and expanded access studies. Sponsors of studies included academic institutions/hospitals (582 studies [70.5%]), pharmaceutical companies/commercial entities (221 [26.8%]), government (21 [2.5%]), and an individual (1 [0.1%]). Most studies (n = 447/825 [54.2%]) had < 50 participants. Mean and median enrollment for studies that provided data (n = 816) were 104 and 41 participants (IQR, 1-81), respectively. Mean and median study duration with applicable data (n = 808) were 837 and 717 days (IQR, 366-1117), respectively. The number of submitted studies per period increased over time (2013 or earlier, n = 168; 2014-2018, n = 220; 2019 and after, n = 437).<h4>Conclusion</h4>Registered studies on ClinicalTrials.gov using cannabinoid-based interventions were typically phase 2, randomized, and small (< 50 participants). The results of this review highlight the diverse nature of clinical studies across disease states and reinforce the need for larger, placebo-controlled studies of cannabinoid-based interventions.