Efficacy and safety of medical cannabinoids in children: a systematic review and meta-analysis

Abstract

Despite the increased use of medical cannabinoids, the efficacy and safety of the treatment among children remain uncertain. The objective was to study the efficacy and safety of medical cannabinoids in children. The search included studies through 11-May-2020. Selection criteria included studies evaluating efficacy and safety outcomes of medical cannabinoids (tetrahydrocannabinol, cannabidiol and other cannabis derivatives) versus control in children, independently assessed by two reviewers. Eight studies were included, all of which are randomized controlled trials. Cannabidiol is associated with 50% reduction in seizures rate (Relative Risk (RR) = 1.69, 95% CI [1.20-2.36]) and caregiver global impression of change (Median Estimated difference = (- 1), 95%CI [- 1.39-(- 0.60)]) in Dravet syndrome, compared to placebo. While cannabidiol was associated with a reduction in reported seizure events (RR = 0.59, 95% CI [0.36-0.97]), no association was found in products contained also tetrahydrocannabinol (RR = 1.35, 95% CI [0.46-4.03]). Higher dose of cannabidiol was associated with decreased appetite (RR = 2.40, 95% CI [1.39-4.15]). A qualitative assessment suggests that medical cannabinoids might be associated with adverse mental events. In conclusion, cannabidiol is associated with clinical improvement in Dravet syndrome. However, cannabidiol is also associated with decreased appetite. Adverse mental events were reported as well, however, more research should be performed to assess well this outcome.

Figure 1

Efficacy in convulsions reduction during medical cannabinoids treatment. (a) Meta-analysis: 50% reduction in seizures in CBD treatment vs. Placebo (p-value = 0.002). (b) Meta-analysis: reported seizures events in medical cannabinoids vs. Placebo (p-value = 0.24). (c) Meta-analysis: reported seizures events in CBD products vs. Placebo (p-value = 0.04). (d) Meta-analysis: reported seizures events in CBD: THC mixed products vs. Placebo (p-value = 0.58).

Figure 2

(a) Analysis of CGIC median measurement. Median estimated difference = (− 1), CI [− 11.39, − 0.60] (p-value < 0.001). (b) Box plot of CGIC assessment: Devinsky 2017 (left) and Miller 2020 (right), Dots mark outliers.

Figure 3

Serious adverse events in medical cannabis treatment. (a) Meta-analysis: serious adverse events in medical cannabinoids treatment (p-value = 0.14). (b) Trial seqaential analysis of serious adverse events in medical cannabinoids treatment, yielding information size of 1,768 participants for reaching statistical significance. Current evidence suggests p-value = 0.12 based on trial sequential analysis calculation.

Figure 4

Decreased appetite in CBD treatments and other gastrointestinal events in medical cannabinoids treatment. (a) Meta-analysis: decreased appetite events in CBD treatment vs. Placebo (p-value = 0.06). (b) Network Meta-analysis: decreased appetite events in three doses of CBD treatment vs. Placebo (Aran et al. was excluded since only the mean dosage was reported and for most participants the goal dosage 10 mg/kg was not achieved). (c) Meta-analysis: Gastrointesitnal hyperactivity events in medical cannabinoids treatment vs. Placebo (p-value = 0.07). (d) Meta-analysis: Gastrointesitnal hyperactivity events in CBD treatment vs. Placebo (p-value = 0.005). (e) Meta-analysis: Gastrointesitnal hyperactivity events in CBD: THC mixed products vs. Placebo (p-value = 0.88).