Transdermal CBD Gel Showed Long-Term Safety in Children With Fragile X Syndrome
An interim analysis of 240 children and adolescents with Fragile X syndrome found transdermal CBD gel was well tolerated over an average of 28 months, with the most common side effect being mild application site pain.
Quick Facts
What This Study Found
Over a mean exposure of 28 months, treatment-related adverse events occurred in 12.9% of patients, with application site pain being most common (6.7%). The worst skin reaction was moderate redness in 2.9%. Secondary analyses showed clinically meaningful improvements in social avoidance, irritability, and overall behavior as rated by caregivers.
Key Numbers
240 patients enrolled. Mean age 9.7 years. 76.3% male. Mean exposure 28 months. Treatment-related AEs: 12.9%. Application site pain: 6.7%. Moderate erythema: 2.9%. Clinically meaningful improvements in social avoidance, irritability, and caregiver global impression.
How They Did This
Interim analysis of an ongoing open-label extension safety trial (ZYN2-CL-017) of transdermal CBD gel (ZYN002) in 240 patients with Fragile X syndrome enrolled from two completed clinical trials. Mean age 9.7 years, 76.3% male. Safety was the primary outcome.
Why This Research Matters
Fragile X syndrome has limited treatment options for behavioral symptoms. Long-term safety data for CBD in this pediatric population is essential for clinical development, and the behavioral improvements suggest potential efficacy.
The Bigger Picture
Transdermal CBD delivery avoids first-pass liver metabolism, potentially reducing side effects. The long-term safety profile in children is encouraging for a population with few treatment options for behavioral symptoms.
What This Study Doesn't Tell Us
Open-label design without a control group in the extension phase. Cannot separate drug effects from natural maturation or placebo effects for behavioral measures. Predominantly White male sample.
Questions This Raises
- ?Will the behavioral improvements hold up in controlled trials?
- ?How does transdermal delivery compare to oral CBD?
- ?Would different doses produce better behavioral outcomes?
Trust & Context
- Key Stat:
- 28 months of safe transdermal CBD use in children with Fragile X
- Evidence Grade:
- Moderate: large open-label extension with long follow-up, but lacks a control group for behavioral outcomes
- Study Age:
- Published in 2025 with data cut January 2024
- Original Title:
- Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study.
- Published In:
- Journal of neurodevelopmental disorders, 17(1), 69 (2025)
- Authors:
- Berry-Kravis, Elizabeth, Hagerman, Randi, Cohen, Jonathan(2), Budimirovic, Dejan, Buchanan, Caroline B, Silove, Natalie, Tich, Nancy, Thibodeau, Anthony, Dobbins, Thomas, Sebree, Terri, O'Quinn, Stephen, Albers, David S, Bzdek, Kristen G, Nomikos, George, Budur, Kumar
- Database ID:
- RTHC-06057
Evidence Hierarchy
Participants are randomly assigned to treatment or placebo groups to test cause and effect.
What do these levels mean? →Frequently Asked Questions
Is CBD safe for children with Fragile X syndrome?
This interim analysis of 240 patients over an average of 28 months found the transdermal CBD gel was generally well tolerated. Treatment-related side effects occurred in 12.9%, mostly mild application site pain. No serious safety concerns emerged.
Did the CBD help with behavior?
Secondary analyses showed clinically meaningful improvements in social avoidance, irritability, and overall behavior. However, without a placebo comparison in this extension phase, these improvements cannot be definitively attributed to the CBD treatment.
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Cite This Study
https://rethinkthc.com/research/RTHC-06057APA
Berry-Kravis, Elizabeth; Hagerman, Randi; Cohen, Jonathan; Budimirovic, Dejan; Buchanan, Caroline B; Silove, Natalie; Tich, Nancy; Thibodeau, Anthony; Dobbins, Thomas; Sebree, Terri; O'Quinn, Stephen; Albers, David S; Bzdek, Kristen G; Nomikos, George; Budur, Kumar. (2025). Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study.. Journal of neurodevelopmental disorders, 17(1), 69. https://doi.org/10.1186/s11689-025-09657-x
MLA
Berry-Kravis, Elizabeth, et al. "Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study.." Journal of neurodevelopmental disorders, 2025. https://doi.org/10.1186/s11689-025-09657-x
RethinkTHC
RethinkTHC Research Database. "Long-term safety and tolerability of transdermal cannabidiol..." RTHC-06057. Retrieved from https://rethinkthc.com/research/berry-kravis-2025-longterm-safety-and-tolerability
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.