A Mapping Literature Review of Medical Cannabis Clinical Outcomes and Quality of Evidence in Approved Conditions in the United States, from 2016 to 2019

Background: Medical cannabis is available to patients by physician order in two-thirds of the United States (U.S.) as of 2020, but remains classified as an illicit substance by federal law. States that permit medical cannabis ordered by a physician typically require a diagnosed medical condition that is considered qualifying by respective state law. Objectives: To identify and map the most recently (2016-2019) published clinical and scientific literature across approved conditions for medical cannabis, and to evaluate the quality of identified recent systematic reviews. Methods: Literature search was conducted from five databases (PubMed, Embase, Web of Science, Cochrane, and ClinicalTrials.gov), with expansion and update from the National Academies of Sciences, Engineering, and Medicine’s (NASEM) comprehensive evidence review through 2016 of the health effects of cannabis on several conditions. Following consultation with experts and stakeholders, 11 conditions were identified for evidence evaluation: amyotrophic lateral sclerosis (ALS), autism, cancer, chronic pain, Crohn’s disease, epilepsy, glaucoma, HIV/AIDS, multiple sclerosis (MS), Parkinson’s disease, and posttraumatic stress disorder (PTSD). The following exclusion criteria were imposed: preclinical focus, non-English language, abstracts only, editorials/commentary, case studies/series, and non-U.S. study setting. Data extracted from studies included: study design type, outcome, intervention, sample size, study setting, and reported effect size. Studies classified as systematic reviews with or without meta-analysis were graded using the AMSTAR-2 tool by two raters to evaluate the quality of evidence, with additional raters to resolve cases of evidence grade disagreement. Results: A total of 438 studies were included after screening. Five completed randomized controlled trials (RCTs) were identified, and an additional 11 trials were ongoing, and 1 terminated. Cancer, chronic pain, and epilepsy were the most researched topic areas, representing more than two-thirds of all reviewed studies. The quality of evidence assessment for each condition suggests that few high-quality systematic reviews are available for most conditions, with the exceptions of MS, epilepsy, and chronic pain. In those areas, findings on chronic pain are mostly in alignment with the previous literature, suggesting that cannabis or cannabinoids are potentially beneficial in treating chronic neuropathic pain. In epilepsy, findings suggest that cannabidiol is potentially effective in reducing seizures in pediatric patients with drug-resistant Dravet and Lennox-Gastaut syndromes. In MS, recent high-quality systematic reviews did not include new RCTs, and are therefore not substantially expanding the evidence base. In sum, the most recent clinical evidence suggests that for most of the conditions assessed, we identified few studies of substantial rigor and quality to contribute to the evidence base. However, there are some conditions for which significant evidence suggests that select dosage forms and routes of administration likely have favorable risk-benefit ratios (i.e., epilepsy and chronic pain), with the higher quality of evidence for epilepsy driven by FDA-approved formulations for cannabis-based seizure treatments. Conclusion: The body of evidence for medical cannabis requires more rigorous evaluation before consideration as a treatment option for many conditions and evidence necessary to inform policy and treatment guidelines is currently insufficient for many conditions.