Medical Cannabis in Pediatrics: Evidence-Based Endocannabinoid Research and Clinical Trials
Clinical Takeaway
Cannabinoids have been studied across a range of pediatric medical conditions, with evidence drawn from interventional trials, observational studies, and surveys. The current body of research supports cautious clinical consideration of cannabinoids in children, particularly for conditions like refractory epilepsy, where pharmaceutical formulations have the strongest evidence. Safety and efficacy data remain an active area of investigation, and clinicians should rely on peer-reviewed findings rather than anecdotal reports when evaluating treatment options for pediatric patients.
#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
This living systematic review of 276 studies found that purified CBD is the most studied cannabinoid in children (in 66 interventional trials), with evidence suggesting 30-50% seizure reduction in refractory epilepsy. The most common adverse events reported across studies were somnolence, diarrhea, vomiting, and decreased appetite, occurring in more than 20% of studies.
Why This Matters Clinically
Clinicians managing children with refractory epilepsy, cancer symptoms, or autism spectrum disorder increasingly encounter patient or parent requests for cannabinoid therapy. This review maps what evidence actually exists (and what gaps remain) to help inform risk-benefit conversations and identify which conditions have the most robust data.
Study Snapshot
| Study Design | Living systematic review of 276 studies (84 interventional, 131 observational, 54 surveys, 7 qualitative); searched MEDLINE, Embase, PsycInfo, Cochrane Library from inception through April 2023 |
| Population | Children under 18 years receiving plant-derived or pharmaceutical cannabinoids for medical conditions; largest indication was refractory epilepsy (146 studies, 188,726 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) |
| Primary Outcome | Safety profile and reported benefit data across medical indications; seizure frequency reduction was primary outcome in epilepsy studies |
| Key Result | Purified CBD associated with 30-50% seizure frequency reduction in refractory epilepsy; somnolence, diarrhea, vomiting, and decreased appetite reported in >20% of studies |
Where This Paper Deserves Skepticism
This is a map of the literature, not a meta-analysis with pooled estimates, so the 30-50% seizure reduction figure lacks confidence intervals and likely reflects heterogeneous study quality and designs. The abstract does not specify how many of these 276 studies were randomized controlled trials versus open-label case series, which dramatically affects evidence strength for each indication. Notably, cancer studies (n=30) enrolled 208,753 participants but the abstract provides no efficacy or safety data for this group, raising questions about what was actually found. The funding source and potential for publication bias are not mentioned. Generalizability is unclear because inclusion of observational and survey data without quality ratings may inflate the apparent evidence base.
Dr. Caplan’s Take
I find this systematic review valuable as a landscape assessment rather than a definitive efficacy statement. The refractory epilepsy data (particularly with purified CBD) is the most developed, with reasonable sample sizes and RCT representation, though 30-50% seizure reduction sits in the modest range and doesn’t tell us who benefits versus who doesn’t. For autism and cancer indications, we’re essentially looking at early-phase observations rather than confirmed therapeutic effects. The adverse event profile is reassuring in relative terms (somnolence and GI effects are manageable), but we need more structured safety monitoring in children, especially around long-term effects on developing brain and metabolic function. This review will help clinicians calibrate expectations when families bring cannabinoid questions to the table.
Clinical Bottom Line
Purified CBD has the most evidence for refractory epilepsy in children (30-50% seizure reduction), but autism and cancer indications remain preliminary. Common adverse effects are mild but frequent (somnolence, diarrhea, vomiting, reduced appetite), and clinicians should counsel families that evidence quality varies widely by indication.
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