Source: Treves N, Mor N, Allegaert K, et al. Efficacy and safety of medical cannabinoids in children: a systematic review and meta-analysis. Sci Rep. 2021;11(1):23462; doi:10.1038/s41598-021-02770-6Investigators from multiple institutions conducted a systematic review and meta-analysis to assess the efficacy and safety of medical cannabinoids (MC) in children. Studies in which the efficacy and safety of MCs and placebo or other pharmacotherapy were compared in patients ≤18 years old were selected for review. Outcomes of interest included seizure reduction in children treated with cannabidiol (CBD) or CBD-containing products, reduction in vomiting and retching events in patients with chemotherapy induced nausea and vomiting treated with nabilone (synthetic D-9-Tetrahydrocannabinol [THC]), and adverse events in children receiving MCs such as decreased appetite, gastrointestinal hyperactivity (eg, vomiting, diarrhea, nausea, upset stomach), serious adverse events, adverse mental events, infections, and pyrexia. Seizure reduction was assessed as a 50% reduction in seizure rate from baseline, reported seizure events, and Caregiver Global Impression of Change (CGIC). A variety of statistical tests applicable to meta-analysis were used to compare outcomes in children treated with MCs or comparison treatment.Data from 8 studies were included in the review. Of these, 5 studies reported outcomes on seizure control: 3 evaluated CBD treatment for children with Dravet syndrome and 2 studies using CBD-THC extracts for other conditions. Overall, MCs were associated with an increase in achieving 50% reduction in seizures (RR, 1.69; 95% CI, 1.20, 2.36), and a significant reduction in seizure events (RR, 0.59; 95% CI, 0.36, 0.97); however, a statistically significant reduction in seizure events was observed only in studies evaluating pure CBD treatment and not in those assessing CBD-THC extracts. A significant improvement in CGIC scores was associated with MCs in these studies. Similarly, in 2 studies with a total of 48 participants, nabilone was found to be superior to conventional treatment (prochlorperazine or domperidone) as an anti-emetic in children receiving chemotherapy (difference in means, -11.5; P <0.001).There were 6 studies, including 513 patients, in which serious adverse events were assessed; a non-significant increase associated with MCs was found (RR, 1.59; 95% CI, 0.85, 2.98). Treatment with CBD in doses of 20 mg/kg was associated with decreased appetite (RR, 2.40; 95% CI, 1.39, 4.15, compared to placebo), but the overall risk associated with predominant CBD treatments was of borderline significance (RR, 2.10; 95% CI, 0.96, 4.62). CBD treatment also was associated with an increased risk of gastrointestinal hyperactivity (RR, 2.30; 95% CI, 1.28, 4.12). A statistically significant increase in adverse mental events was found in 4 of 8 studies. There was no statistically significant increase in risk of infections or pyrexia associated with MC use.The authors conclude that MCs are effective in the treatment of some conditions in children but may be associated with an increased risk of adverse events.Dr Candee has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The results of the current study build upon a prior systematic review from 2017 that was centered largely around the use of medical cannabinoids for Dravet syndrome, a rare drug-resistant epilepsy, which showed limited and low-quality evidence in support of the use of MC in children and adolescents.1 Beyond the addition of 3 more years of studies from which to choose, the current review is more comprehensive and stringent in its selection criteria, with investigators reaching out to authors for any missing data and combing through the references of any eligible studies to ensure inclusiveness. While the results of more recent studies support the safety and efficacy of long-term use of CBD for the treatment of epilepsy in children, the current study is the first of its kind to focus more broadly on treatment with MCs in the pediatric population.2,3The current study is, however, also thereby limited in its scope, as it includes MCs used for a variety of medical purposes (eg, epilepsy, severe behavioral problems, chemotherapy-induced nausea and vomiting, spasticity, and autism). This reduces the applicability of the findings. Furthermore, the precise outcomes for each data subset (based on pharmacological mechanism or organ system) were not defined during the study design phase but rather during the data extraction process. The observational nature of the study and limited size are weaknesses as well.Medical CBD is effective in reducing seizures in children with Dravet syndrome, and naboline (synthetic THC) decreases vomiting in patients treated with chemotherapy. Safety concerns related to MC use in children include adverse mental events. (See AAP Grand Rounds. 2021;46[4]:40.)4
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