Medical cannabinoids in children linked to more side effects, especially liver enzyme elevation and drowsiness | Research

The takeaway

A meta-analysis of 23 RCTs found medical cannabinoids in children and adolescents were associated with 3x higher withdrawals from adverse events, 1.8x more serious adverse events, and significantly elevated liver enzymes.

People interested in the safety of medical cannabis use in children, particularly for epilepsy.

5.7x higher risk of liver enzyme elevation in children

What the researchers found

Compared to control, cannabinoids in children increased risk of overall adverse events (RR 1.09), withdrawals due to AEs (RR 3.07), and serious AEs (RR 1.81). The most elevated specific risks were for liver enzyme increases (AST: RR 5.69; ALT: RR 5.67), somnolence (RR 2.28), and diarrhea (RR 1.82).

Why it matters

This is the most comprehensive safety analysis of medical cannabinoids in children to date, published in JAMA Pediatrics. As off-label cannabinoid prescribing to children grows, clinicians need evidence-based safety data to inform treatment decisions.

The numbers in context

23 RCTs, 3,612 participants (17.6% female, 57.3% male). Withdrawal from AEs: RR 3.07. Serious AEs: RR 1.81. AST elevation: RR 5.69. ALT elevation: RR 5.67. Somnolence: RR 2.28. Diarrhea: RR 1.82. Purified CBD was the most common intervention (47.8%).

How the study worked

Systematic review and meta-analysis searching MEDLINE, Embase, PsycINFO, and Cochrane Library through March 2024. Included 23 RCTs with 3,612 participants. Data pooled using random-effects models. PRISMA guidelines followed.

What this study cannot tell us

Most studies focused on epilepsy (39.1%) and chemotherapy nausea (30.4%), limiting generalizability. Heterogeneity was moderate to high for some outcomes. Half the trials included mixed adult-pediatric populations. Long-term safety data remain absent.

How to read the evidence

High-quality meta-analysis of 23 RCTs published in JAMA Pediatrics. Moderate heterogeneity and mixed adult-pediatric populations in some trials are limitations.

When this study was published

Published in 2024 with evidence searched through March 2024.

The bigger picture

Cannabinoid prescribing to children has outpaced safety evidence. This JAMA Pediatrics meta-analysis provides the first pooled safety estimates from RCTs, revealing meaningful risks, particularly liver toxicity, that clinicians and parents need to weigh against potential benefits.

Questions still open

Are the liver enzyme elevations clinically significant or just laboratory abnormalities? Does the liver toxicity risk increase with longer-term use? Are specific cannabinoid formulations safer than others in children?

Common questions

Are medical cannabinoids safe for children?

This meta-analysis found they carry meaningful risks, including 3x higher treatment dropout from side effects, nearly 6x higher liver enzyme elevation, and more than double the drowsiness compared to placebo. Benefits need to be weighed against these risks for each patient.

What were the biggest safety concerns?

Liver enzyme elevations were the most striking finding (5.7x higher risk), followed by somnolence (2.3x) and diarrhea (1.8x). The 3x higher rate of withdrawals from adverse events suggests side effects are significant enough to stop treatment in some children.

Read the original research

Cannabinoids Used for Medical Purposes in Children and Adolescents: A Systematic Review and Meta-Analysis.

JAMA pediatrics, 178(11), 1124-1135

View on PubMed ↗Publisher’s paper ↗

Citation

Chhabra, Manik; Ben-Eltriki, Mohamed; Mansell, Holly; Lê, Mê-Linh; Huntsman, Richard J; Finkelstein, Yaron; Kelly, Lauren E. (2024). Cannabinoids Used for Medical Purposes in Children and Adolescents: A Systematic Review and Meta-Analysis.. JAMA pediatrics, 178(11), 1124-1135. https://doi.org/10.1001/jamapediatrics.2024.3045