Prevalence of Gastrointestinal Adverse Events of Therapeutic Cannabinoids in Children: A Systematic Review and...

Introduction: The endocannabinoid system plays a crucial role in gastrointestinal homeostasis; although some gastrointestinal adverse events have been reported with therapeutic cannabinoids in children, the complete profile of gastrointestinal adverse events in the pediatric population remains unknown. Through a systematic review and meta-analysis, we aimed to identify the prevalence of gastrointestinal adverse events from therapeutic cannabinoids in children. Materials and Methods: A literature search of OVID MEDLINE, EMBASE, CINAHL, Web of Science, and The Cochrane Library was performed from inception to May 19, 2023. Selected studies included randomized controlled trials, retrospective cohort studies, uncontrolled before-after studies, and observational retrospective studies in English, French, or Spanish that reported gastrointestinal adverse events in the pediatric population under therapeutic cannabinoid interventions. The study was registered with PROSPERO and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. A random-effects model was used to pool and analyze the extracted data. Extracted data included the presence of adverse gastrointestinal events by analyzing the type of cannabinoid, duration of treatment, dosage, and type of study. A subgroup meta-analysis was also performed, focusing on patients' conditions. Results: Twenty-five studies were included, comprising 1,201 pediatric patients receiving therapeutic cannabinoids, of whom 451 experienced gastrointestinal adverse events, representing a cumulative prevalence of 33.91% (95% confidence interval [CI]: 21.49% to 49.04%). Interventional studies reported a higher prevalence of GI adverse events (47.36%; 95% CI: 31% to 64%) compared with observational studies (17.6%; 95% CI: 8.5% to 32.7%). As most studies focused on patients with epilepsy, a subanalysis was performed within this population, revealing that patients with Dravet syndrome had a higher prevalence of diarrhea compared with other types of epilepsy (21.75%; 95% CI: 8.52% to 45.34% vs. 5.95%; 95% CI: 3.11% to 11.1%). Discussion: This systematic review and meta-analysis showed a high prevalence of gastrointestinal adverse events in children receiving therapeutic cannabinoids, with some populations, such as those with Dravet syndrome, being at higher risk than others. With the increased public discourse of cannabinoids being "natural" and mistakenly equating them as "risk-free," this information can help clinicians educate patients and the broader public on the adverse effects profile of these treatments.