Clinical Takeaway
Cannabinoids have been studied across a wide range of pediatric medical conditions, with the current evidence base drawing from hundreds of studies including clinical trials and real-world observational data. The research reflects meaningful variability in study design, cannabinoid formulations, and patient populations, making direct comparisons difficult. Safety and efficacy conclusions remain condition-specific, and clinical decisions should be guided by the strongest available evidence for each individual indication.
#4 Cannabinoids for Medical Purposes in Children: A Living Systematic Review.
Citation: Chhabra Manik et al.. Cannabinoids for Medical Purposes in Children: A Living Systematic Review.. Acta paediatrica (Oslo, Norway : 1992). 2025. PMID: 40437694.
Design: 5 Journal: 0 N: 2 Recency: 2 Pop: 3 Human: 1 Risk: 0
Methodological Considerations:
- Small sample — underpowered for subgroup analysis
Abstract: AIM: We developed a living systematic review (LSR) that will continuously map the safety and reported benefit data related to cannabinoid use for medical purposes in children. METHODS: MEDLINE, Embase, PsycInfo, and the Cochrane Library were searched from inception to April 2023. Studies involving at least one child < 18 years who was administered plant-derived or pharmaceutical cannabinoids as an intervention or treatment for medical conditions were included. RESULTS: Of 37 189 identified citations, 276 studies were included: 84 interventional, 131 observational, 54 surveys, and 7 qualitative studies. Among interventional and observational studies, common indications for cannabinoids in children were refractory epilepsy (n = 146 studies, 188 726 participants), cancer and cancer symptoms (n = 30 studies, 208 753 participants), and autism spectrum disorder (n = 18 studies, 1285 participants). Common cannabinoids identified in interventional studies were purified cannabidiol (CBD) (78.6%, n = 66 studies, 5235 participants) with dose range of 2-50 mg/kg/day, tetrahydrocannabinol (6%, n = 5 studies, 148 participants) with dose range of 2.5-10 mg/day (max dose of tetrahydrocannabinol in nabiximols 32.4 mg) and nabilone (6%, n = 5 studies, 267 participants) with dose range of 0.5-2 mg/day. In randomised controlled trials, purified cannabidiol was reported to reduce seizure frequency ranging between 30% and 50%. Common adverse events (> 20% studies) in studies enrolling children were somnolence, diarrhoea, vomiting, and decreased appetite. CONCLUSION: These findings will continue to be updated to inform practice and reveal knowledge gaps for future research.
What This Study Teaches Us
A living systematic review of 276 studies found that purified CBD is the most commonly studied cannabinoid in children, showing a 30-50% reduction in seizure frequency in randomized trials for refractory epilepsy. Common adverse effects across pediatric studies include somnolence, diarrhea, vomiting, and decreased appetite, occurring in over 20% of studies.
Why This Matters Clinically
Clinicians are increasingly asked by families about cannabinoids for children with refractory epilepsy, cancer symptoms, and autism. This map of the current evidence base helps distinguish where we have actual trial data (seizures) versus observational reports (autism, cancer), and clarifies what side effects to counsel families about upfront.
Study Snapshot
| Study Design | Living systematic review (ongoing, updated continuously). Included 84 interventional, 131 observational, 54 survey, and 7 qualitative studies from inception through April 2023. |
| Population | Children under 18 years across 276 studies. Largest groups: refractory epilepsy (146 studies, 188,726 participants), cancer/cancer symptoms (30 studies, 208,753 participants), autism spectrum disorder (18 studies, 1,285 participants). |
| Intervention | Purified CBD (78.6% of interventional studies, 2-50 mg/kg/day), THC (6%, 2.5-10 mg/day), and nabilone (6%, 0.5-2 mg/day). Studies examined plant-derived or pharmaceutical cannabinoids. |
| Primary Outcome | Safety profile and reported benefit across medical indications. RCT subset assessed seizure reduction for epilepsy. |
| Key Result | In RCTs, purified CBD reduced seizure frequency by 30-50%. Somnolence, diarrhea, vomiting, and decreased appetite reported in over 20% of pediatric studies. |
Where This Paper Deserves Skepticism
The abstract conflates interventional trials (most rigorous) with observational and survey data, making it hard to judge strength of evidence by indication. The huge participant numbers for cancer (208,753) and epilepsy (188,726) likely reflect database retrospectives or passive data collection rather than controlled trials, which waters down the apparent evidence. The abstract doesn’t specify how many of the 276 studies were actually RCTs versus observational, nor does it clarify whether the reported seizure reductions came from the same CBD formulation (Epidiolex) or heterogeneous preparations, which matters for clinical translation.
Dr. Caplan’s Take
I find this systematic review useful for what it does well: cataloging the landscape of cannabinoid research in children and flagging that most of the clinical work has been in refractory epilepsy. The 30-50% seizure reduction figure aligns with what we see in practice with purified CBD, though that reflects enriched RCT populations, not all children. What troubles me is the heterogeneity hidden in the numbers. Autism has 18 studies but only 1,285 total participants and no seizure endpoint to anchor on. Cancer symptom studies are even more scattered. The adverse event profile looks like what I counsel families about, but aggregating across indications and formulations obscures whether somnolence in an epilepsy child on polypharmacy is the same safety signal as in a cancer child. This is a helpful resource for point-of-care searching, not a substitute for critically reading the underlying trials.
Clinical Bottom Line
Purified CBD has the strongest evidence base for refractory epilepsy in children (30-50% seizure reduction in RCTs). For other indications like autism and cancer symptoms, evidence remains largely observational, and clinicians should counsel families that somnolence, GI upset, and appetite changes are common and should be monitored.
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