Clinical Takeaway
Cannabinoids have been studied across a range of pediatric medical conditions, with available evidence drawn from both interventional trials and real-world observational data. The review captures safety and benefit findings from hundreds of studies, providing a continuously updated foundation for clinical decision-making in children under 18. Clinicians should consult this living systematic review as the most current synthesis of pediatric cannabinoid evidence before considering any therapeutic application.
#5 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, with randomized trials showing 30-50% seizure reduction in refractory epilepsy. The most common adverse effects reported across studies were somnolence, diarrhea, vomiting, and decreased appetite, occurring in more than 20% of studies reviewed.
Why This Matters Clinically
For clinicians considering cannabinoids in pediatric patients, this synthesis clarifies that the evidence base is largest for epilepsy and concentrated on CBD rather than THC or other formulations. Understanding the frequency and profile of adverse effects matters because parents and patients need realistic expectations about tolerability when making treatment decisions.
Study Snapshot
| Study Design | Living systematic review (continuously updated) of 276 studies: 84 interventional, 131 observational, 54 surveys, 7 qualitative |
| Population | Children under 18 years across multiple conditions; largest subgroups: refractory epilepsy (188,726 participants, 146 studies), cancer symptoms (208,753 participants, 30 studies), autism spectrum disorder (1,285 participants, 18 studies) |
| Intervention | Purified CBD (78.6% of interventional studies, 2-50 mg/kg/day); THC (6%, 2.5-10 mg/day); nabilone (6%, 0.5-2 mg/day); plant-derived or pharmaceutical cannabinoids |
| Primary Outcome | Safety profile and reported benefit across medical conditions in children; focus on adverse events and efficacy measures (seizure reduction for epilepsy) |
| Key Result | In RCTs, purified CBD reduced seizure frequency 30-50% in refractory epilepsy; common adverse events across >20% of studies were somnolence, diarrhea, vomiting, and decreased appetite |
Where This Paper Deserves Skepticism
This is a broad mapping exercise, not a meta-analysis with effect size pooling, so the ’30-50% seizure reduction’ finding lacks precision around confidence intervals or heterogeneity. The abstract does not specify study quality assessment methods, publication bias evaluation, or how the authors handled the wide range of outcome reporting across 276 heterogeneous studies. The bulk of participants are concentrated in epilepsy and cancer studies, meaning evidence for autism and other indications remains sparse despite being included in the headline.
Dr. Caplan’s Take
I find this systematic review useful as a landscape assessment, particularly the clear mapping of where the evidence actually sits: CBD dominates the interventional literature, seizure reduction in refractory epilepsy is the most robust signal, and the adverse event profile is manageable but real. What I don’t see here is risk stratification by age, comorbidity, or concomitant medications, which are critical for individualized prescribing. The living review model is sound in principle, but clinicians will need to drill into individual studies and RCT quality to make confident recommendations, especially outside epilepsy.
Clinical Bottom Line
CBD is the most studied cannabinoid in children and shows modest efficacy for refractory seizures, but evidence for other pediatric conditions remains limited. Somnolence, GI upset, and appetite suppression are the main tolerability concerns clinicians should counsel families about upfront.
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