Clinical Trials of Cannabidiol for Substance Use Disorders: Outcome Measures, Surrogate Endpoints, and Biomarkers

Abstract

Background: Cannabidiol (CBD) is a cannabinoid of potential interest for the treatment of substance use disorders. Our aim was to review the outcome measures, surrogate endpoints, and biomarkers in published and ongoing randomized clinical trials.Methods: We conducted a search in PubMed, Web of Science, PMC, PsycINFO, EMBASE, CENTRAL Cochrane Library, “clinicalTrials.gov,” “clinicaltrialsregister.eu,” and “anzctr.org.au” for published and ongoing studies. Inclusion criteria were randomized clinical trials (RCTs) examining the use of CBD alone or in association with other cannabinoids, in all substance use disorders. The included studies were analyzed in detail and their qualities assessed by a standardized tool (CONSORT 2010). A short description of excluded studies, consisting in controlled short-term or single administration in non-treatment-seeking drug users, is provided.Findings: The screening retrieved 207 published studies, including only 3 RCTs in cannabis use disorder. Furthermore, 12 excluded studies in cannabis, tobacco, and opioid use disorders are described.Interpretation: Primary outcomes were validated withdrawal symptoms scales and drug use reduction in the three RCTs. In the short-term or crossover studies, the outcome measures were visual analog scales for subjective states; self-rated scales for withdrawal, craving, anxiety, or psychotomimetic symptoms; and laboratory tasks of drug-induced craving, effort expenditure, attentional bias for substance, impulsivity, or anxiety to serve as surrogate endpoints for treatment efficacy. Of note, ongoing studies are now adding peripheral biomarkers of the endocannabinoid system status to predict treatment response.Conclusion: The outcome measures and biomarkers assessed in the ongoing CBD trials for substance use disorders are improving.

Therapeutic Potential of Cannabis, Cannabidiol, and Cannabinoid-Based Pharmaceuticals

“…Cannabis has been proposed to augment medication-assisted treatments such as methadone and buprenorphine. In particular, the noneuphorigenic cannabinoid CBD is viewed as having potential therapeutic use for the treatment of opioid use disorder (OUD); unfortunately, to date, only short pilot studies have been conducted, and therefore the effectiveness of this treatment remains unclear [138]. However, another recent study found that daily cannabis use was associated with lower opioid use during treatment of OUD [139].…”

Effects of combined cannabidiol (CBD) and hops (Humulus lupulus) terpene extract treatment on RAW 264.7 macrophage viability and inflammatory markers

“…This study aimed to explore the potential application of a combined formulation of cannabidiol and secondary metabolites from either C. sativa or H. lupulus extracts for long-term treatment of inflammatory diseases. CBD alone has already shown promising results in the treatment of several inflammatory diseases, including inflammatory skin conditions [ 6 , 48 – 50 ], inflammatory bowel disease [ 51 ], type 1 diabetes [ 52 ], and osteoarthritis [ 53 ]. However, its therapeutic potential still requires further investigations to improve cellular availability and to further identify other phytochemicals that contribute to the previously mentioned “entourage effect”, which potentially strengthen its effect on cellular targets [ 54 , 55 ].…”

Cannabidiol as a Harm Reduction Strategy for People Who Use Drugs: A Rapid Review

“…31,32,46 Additionally, as there is currently no evidence on the impact of CBD on methamphetamine use and current treatments are limited in efficacy, this is also a worthwhile future direction. High Karimi-Haghighi et al 30 2 2 0 2 2 2 10 Moderate Kudrich et al 31 2 2 2 2 2 2 12 High Legare et al 32 2 1 1 2 2 2 10 Moderate Morel et al 38 2 2 2 2 2 2 12 High Navarrete et al 9 2 2 2 2 2 2 12 High Pauli et al 39 2 2 0 2 2 2 10 Moderate Sloan et al 43 2 2 0 2 2 2 10 Moderate Spanagel 44 2 1 0 2 2 2 9 Moderate Wiese and Wilson-Poe 46 1 0 0 2 2 2 7 Low…”