# Clinical Data on Transdermal CBD Gel Safety in Fragile X > **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637) > **Publisher:** CED Clinic (https://cedclinic.com) > **Canonical URL:** https://cedclinic.com/transdermal-cannabidiol-gel-safety-fragile-x-syndrome/ > **Published:** 2026-04-15T14:22:43-04:00 | **Last Modified / Clinically Audited:** 2026-09-28T11:01:30-04:00 > **Clinical Summary:** Explore transdermal cannabidiol gel safety in Fragile X syndrome with clinical data on tolerability and long-term use in pediatric patients. --- #### Clinical Takeaway Transdermal cannabidiol gel (ZYN002) is being studied long-term in children and adolescents with Fragile X syndrome, targeting [behavioral symptoms](https://cedclinic.com/cannabis-palliative-care-alzheimers-efficacy/) linked to dysregulated endocannabinoid signaling. Interim data from this open-label extension trial are evaluating the ongoing safety and tolerability profile of synthetic CBD delivered through the skin. Results from this study will help clarify whether transdermal CBD can be used sustainably in a pediatric population with a complex neurodevelopmental condition. ### #23 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. **Citation:** 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](https://cedclinic.com/medical-cannabis-gilles-de-la-tourette-syndrome-experience/). 2025. PMID: 41254489. **Study type:** Journal Article, Randomized Controlled Trial  |  **Topic area:** Cannabidiol  |  **CED Score:** 10 Design: 5 Journal: 0 N: 2 Recency: 2 Pop: 2 Human: 1 Risk: -2 **Quality Gate Alerts:** - Preclinical only **Methodological Considerations:** - Open-label design — placebo effect not excluded **Abstract:** BACKGROUND: Dysregulated endocannabinoid signaling is involved in Fragile X syndrome (FXS), suggesting a potential role for the endocannabinoid signaling modulator, cannabidiol, in treatment. ZYN002 is a synthetic cannabidiol that has been uniquely formulated as a gel for transdermal delivery and is currently under investigation for the treatment of behavioral symptoms associated with FXS. DESIGN: ZYN2-CL-017 is an ongoing, long-term, open-label extension (OLE) safety trial of ZYN002 in patients with FXS. We are enrolling patients from past and current ZYN002 [clinical trials](https://cedclinic.com/endocannabinoid-system-emotional-memory-ptsd-treatment/) to evaluate the safety and tolerability of ZYN002 in patients with FXS. METHODS: Primary safety assessments were conducted in patients who enrolled into the OLE from 2 completed ZYN002 trials. Secondary analyses, conducted in a subgroup enrolled from a completed placebo-controlled trial of ZYN002, included the FXS-specific Aberrant Behavior Checklist-Community Social Avoidance and Irritability subscales (ABC-CFXS SA and ABC-CFXS Irr, examined change from baseline of the randomized study) and the Caregiver Global Impression of Change (CaGI-C, examined change from baseline of the OLE), in which caregivers were asked to rate the change in their child’s overall behavior. RESULTS: At the time of this interim analysis data cut (January 31, 2024), 240 patients had been enrolled from 2 completed ZYN002 trials. Mean age at entry to the OLE was 9.7 years (range 3-17 years), and the majority were male (76.3%) and White (80.4%). Mean exposure to ZYN002 during the initial trials and OLE was 28 months. Treatment-related [adverse events](https://cedclinic.com/cbd-endocrine-effects-gynecomastia-risk-safety/) (AEs) were reported in 12.9% of patients; the most common (6.7% of patients) was short-term application site pain. The highest degree of skin irritation reported by investigators was moderate erythema in 7 patients (2.9%). In the secondary analysis cohort (n=196 evaluable patients), patients demonstrated clinically meaningful changes in ABC-CFXS SA, ABC-CFXS Irr, and CaGI-C scor  |   |  [View on PubMed ↗](https://pubmed.ncbi.nlm.nih.gov/41254489/)[Full Text ↗](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12625530/)[DOI ↗](https://doi.org/10.1186/s11689-025-09657-x) [https://cedclinic.com/contact/](https://cedclinic.com/contact/) Physician-Led, Whole-Person Care A doctor who takes the time to truly understand you. Personal care that starts with listening and is guided by experience and ingenuity. 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[Read More](https://cedclinic.com/transdermal-cannabidiol-gel-fragile-x-syndrome-safety/) [Phase 2 Open-Label INSPIRE Trial on Transdermal CBD Gel in 22q11.2 Deletion Syndrome](https://cedclinic.com/transdermal-cannabidiol-gel-children-inspire-trial/) Insights from the INSPIRE trial assessing transdermal CBD gel safety and effectiveness in children with 22q11.2 deletion syndrome. [Explore Trial](https://cedclinic.com/transdermal-cannabidiol-gel-children-inspire-trial/) [Endocannabinoid System & Child Autism Risk: New Evidence](https://cedclinic.com/peripregnancy-cannabis-exposure-autism-risk-new-evidence/) New research on the endocannabinoid system's role in child autism risk and implications for cannabinoid therapies. [Learn More](https://cedclinic.com/peripregnancy-cannabis-exposure-autism-risk-new-evidence/) Have thoughts on this? 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