Effect of CANnabidiol on Anxiety and GABAergic Function in Individuals With Fragile-X Syndrome (CANAX)

August 25, 2026 updated by: Francois Corbin, Université de Sherbrooke
This study focuses on the therapeutic relevance of the endocannabinoid (eCB) system for the treatment of Fragile-X syndrome (FXS), the primary hereditary cause of autism spectrum disorder (ASD). Most individuals with FXS have moderate to severe intellectual disability (ID), and caregivers are mainly concerned about aggressive behavior and anxiety problems. Since FXS individuals have a normal lifespan, the overall lifetime cost for the Canadian society of a single case is estimated at $1.2 to $4.7 millions reaching $18 billions for all FXS cases. There is no cure for FXS, as all clinical trials so far have been unsuccessful.FXS is caused by transcriptional silencing of the Fragile X mental retardation protein (FMR1) gene, making FXS a simple model to study ASD and ID pathophysiological mechanisms. Of those, neuronal hyperexcitability is largely recognized as a core deficit in FXS, and a critical therapeutic target for the disorder. Using transcranial magnetic stimulation (TMS) in FXS patients, our team provided the first direct evidence of Gamma-aminobutyric acid (GABA) receptor a (GABAa) dysfunctions in humans with this disorder and showed that this inhibitory deficit is linked with cortical hyperexcitability (PMID: 31748507). Concurrent lines of evidence suggest that stimulation of the endocannabinoid (eCB) system with the administration of Cannabidiol (CBD) could upregulate GABAergic function and correct inhibitory deficits presumed responsible for the neuropsychiatric phenotype of FXS. CBD has been shown to increase GABA concentration levels in the brains of healthy individuals, an effect that could help correct the hyperexcitability typically found in FXS. Thus, this trial aims to define the therapeutic potential of the eCB system for FXS, by measuring the impacts of oral CBD administration on the principal inhibitory neurotransmitter system of FXS patients, and the severity of the clinical phenotype.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Quebec
      • Sherbrooke, Quebec, Canada, J1H5N4
        • Recruiting
        • Universite de Sherbrooke, CHUS Research Center
        • Contact:
        • Contact:
          • Amanda Andrews, B.A.
          • Phone Number: 819-346-1110
        • Principal Investigator:
          • Jean-Francois Lepage, Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Molecular diagnosis of FXS
  • Age 7 to 40 inclusively
  • Overall ABC-C score > 20
  • Taking up to 3 psychoactive drugs
  • No therapeutic change for the last 3 months

Exclusion Criteria:

  • Taking valproic acid
  • Taking clobazam
  • History of liver problems
  • aspartate aminotransferase (AST) or alanine transaminase (ALT), > 3 times the reference values
  • Bilirubin > 2 times the reference values
  • Absolute contraindication to the use of TMS and MRI (e.g. presence of metal in the body), will also be considered as an exclusion criterion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CBD First
Participants will start with CBD to stimulate the eCB for 12 weeks, undergo an 8-week washout period, and then receive a 12-week placebo.
Drug: CBD Oral Solution
Participants will start with oral CBD dose of 5 mg/kg/day for two weeks and then increase to 10 mg/kg/day.
Drug: Placebo
Participants will receive a dose of a placebo composed of the inactive ingredients of CBD of the same volume as the CBD Oral Solution.
Experimental: Placebo First
Participants will start with a placebo for 12 weeks, undergo an 8-week washout period, and then receive a 12-week CBD to stimulate the eCB system.
Drug: CBD Oral Solution
Participants will start with oral CBD dose of 5 mg/kg/day for two weeks and then increase to 10 mg/kg/day.
Drug: Placebo
Participants will receive a dose of a placebo composed of the inactive ingredients of CBD of the same volume as the CBD Oral Solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Impact of Oral CBD Solution anxiety.
Time Frame: At baseline, 12 weeks, 20 weeks, and 32 weeks
Caregivers will complete The Anxiety, Depression, and Mood Scale (ADAMS). The ADAMS consists of 29 items on a 4-point scale from 0 (behavior have not occurred or is not a problem) to 3 (behavior occurs a lot, or is a severe problem). It evaluates emotional disturbances along five dimensions: mania/hyperactivity, depressed mood, social avoidance, general anxiety, and obsessive behavior.
At baseline, 12 weeks, 20 weeks, and 32 weeks
Impact of Oral CBD Solution on disruptive behavior
Time Frame: At baseline, 12 weeks, 20 weeks, and 32 weeks

Caregivers will complete the Aberrant Behavior Checklist-Community Fragile-X (ABC-C FX). The ABC-C FX has 55 items and is subdivided into explores 6 subdomains: irritability, hyperactivity, lethargy/withdrawal, stereotypy, inappropriate speech, and social avoidance. Higher scores reflect higher aberrant behavior.

ABC-C FX is considered the gold standard for assessing behavioral changes in clinical trials in FXS.
At baseline, 12 weeks, 20 weeks, and 32 weeks
Impact of Oral CBD Solution on Behavioral Inhibition
Time Frame: At baseline, 12 weeks, 20 weeks, and 32 weeks
Participants will complete the NIH Toolbox Cognitive Battery Flanker Task, a behavioral inhibition task validated in FXS. Global scores range from 0 to 10 and are algorithmically defined using accuracy and reaction time. Higher scores reflect better performance.
At baseline, 12 weeks, 20 weeks, and 32 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Impact of Oral CBD Solution on intracortical inhibition
Time Frame: At baseline, 12 weeks, 20 weeks, and 32 weeks
TMS-derived measure of Intracortical inhibition: The degree of decrease of peak-to-peak motor evoked potential (MEP) amplitude induced by the administration of a conditioning stimulus (set at 70% of resting motor threshold) 2-4 ms before the test stimulus (stimulation intensity required to produce an MEP of 1 millivolt (mV), approximately 120% of resting motor threshold)
At baseline, 12 weeks, 20 weeks, and 32 weeks
Impact of Oral CBD Solution on intracortical facilitation
Time Frame: At baseline, 12 weeks, 20 weeks, and 32 weeks
Transcranial magnetic stimulation (TMS) -derived measure of Intracortical facilitation: The degree of increase of peak-to-peak motor evoked potential (MEP) amplitude induced by the administration of a conditioning stimulus (set at 80% of resting motor threshold) 12-24 ms before the test stimulus (stimulation intensity required to produce an MEP of 1 mV, approximately 120% of resting motor threshold).
At baseline, 12 weeks, 20 weeks, and 32 weeks
Impact of Oral CBD Solution on
Time Frame: At baseline, 12 weeks, 20 weeks, and 32 weeks
Estimation of GABA concentrations in the brain from magnetic resonance spectroscopy
At baseline, 12 weeks, 20 weeks, and 32 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Université de Sherbrooke

Collaborators

Canadian Institutes of Health Research (CIHR)
Centre de recherche du Centre hospitalier universitaire de Sherbrooke
Jazz Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2025

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

January 26, 2024

First Submitted That Met QC Criteria

February 7, 2024

First Posted (Actual)

February 15, 2024

Study Record Updates

Last Update Posted (Actual)

August 28, 2026

Last Update Submitted That Met QC Criteria

August 25, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-4527
  • 202010PJT-451514 (Other Grant/Funding Number: Canadian Institutes of Health Research)
  • 275882 (Other Identifier: Health Canada)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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