Transdermal CBD Gel Showed Long-Term Safety in Children With Fragile X Syndrome | Research

The takeaway

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.

Parents of children with Fragile X syndrome, developmental pediatricians, CBD researchers

28 months of safe transdermal CBD use in children with Fragile X

What the researchers 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.

Why it 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 numbers in context

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 the study worked

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.

What this study cannot 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.

How to read the evidence

Moderate: large open-label extension with long follow-up, but lacks a control group for behavioral outcomes

When this study was published

Published in 2025 with data cut January 2024

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.

Questions still open

Will the behavioral improvements hold up in controlled trials? How does transdermal delivery compare to oral CBD? Would different doses produce better behavioral outcomes?

Common 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.

Read the original research

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

View on PubMed ↗Publisher’s paper ↗

Citation

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