Effect of CBD on the Brain

February 13, 2025 updated by: Francois Corbin, Université de Sherbrooke

Effect of CBD on the GABAergic System in Patients with Fragile X Syndrome.

This proposal 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). Although most individuals with FXS have moderate to severe intellectual disability (ID), caregivers are mainly concerned about aggressive behavior and anxiety problems, hallmark features of the condition. Concurrent lines of evidence suggest that targeting the endocannabinoid (eCB) system by administration of cannabidiol (CBD) could upregulate GABAergic functions and correct inhibitory deficits presumed responsible for the neuropsychiatric phenotype of FXS. However, the eCB system and its effect on the brain remains unexplored in FXS patients. This clinical trial aims to define the therapeutic relevance of the eCB system for FXS using a multimodal neuroimaging approach to finely characterize the acute effects of oral CBD on the principal inhibitory neurotransmitter system (GABA) in a large cohort of FXS patients.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

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

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

Yes

Description

Inclusion Criteria:

Eligibility criteria for FXS participants will include:

  • age between 7 and 55 years, molecular diagnosis of FXS,
  • intelligence quotient (IQ) <70,
  • aberrant behavior questionnaire score (ABC-C) > 20,
  • <3 psychoactive drugs, drug stable for > 3 months.

Eligibility criteria for the control group:

  • 18 and 55 years old,
  • be in good general health, with no history of neurological or psychiatric disorders.

Eligibility Criteria for all Participants:

  • A minimum weight of 60 kg;
  • no history of liver problems (A complete blood profile to measure liver enzyme levels (bilirubin, aspartate aminotransferase (AST), argininosuccinate lyase (ASL), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)) will be obtained before randomization for all participants).

Exclusion Criteria:

  • The presence of an absolute contraindication to the use of TMS and MRI / MRS (ie presence of metal in the head).
  • Individuals with ALT / ASL levels greater than 3 times the upper normal baseline, or if bilirubin exceeds 2 times the upper baseline,

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CBD first
A single dose of CBD dose administered followed by a dose of placebo 3 weeks later.
Drug: CBD Oral Solution (eCBD system Target)
Participants receive orally 6 ml of CBD Oral Solution (100 mg / ml; 60 mg / kg; max 600 mg of CBD) followed by 6 ml of a placebo composed of the inactive ingredients of CBD Oral Solution 3 weeks later.
Drug: Placebo
Participants receive orally 6 ml of a placebo composed of the inactive ingredients of CBD Oral Solution followed by 6 ml of Oral CBD Solution (100 mg / ml; 60 mg / kg; max 600 mg of CBD)
Experimental: Placebo first
A single dose of placebo dose administered followed by a dose of CBD 3 weeks later.
Drug: CBD Oral Solution (eCBD system Target)
Participants receive orally 6 ml of CBD Oral Solution (100 mg / ml; 60 mg / kg; max 600 mg of CBD) followed by 6 ml of a placebo composed of the inactive ingredients of CBD Oral Solution 3 weeks later.
Drug: Placebo
Participants receive orally 6 ml of a placebo composed of the inactive ingredients of CBD Oral Solution followed by 6 ml of Oral CBD Solution (100 mg / ml; 60 mg / kg; max 600 mg of CBD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Short Intracortical Inhibition
Time Frame: Comparison between pre and 2 hours post administration of Oral CBD solution and placebo
Transcranial Magnetic Stimulation (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)
Comparison between pre and 2 hours post administration of Oral CBD solution and placebo

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracortical Facilitation
Time Frame: Comparison between pre and 2 hours post administration of Oral CBD solution and placebo
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).
Comparison between pre and 2 hours post administration of Oral CBD solution and placebo
Gaba concentration levels
Time Frame: Comparison between pre and 2 hours post administration of Oral CBD solution and placebo
Estimation of GABA concentrations in the brain from magnetic resonance spectroscopy (MRS)
Comparison between pre and 2 hours post administration of Oral CBD solution and placebo

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 (Estimated)

May 1, 2025

Primary Completion (Estimated)

December 15, 2027

Study Completion (Estimated)

December 15, 2027

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)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 13, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-3424
  • 236114 (Other Identifier: Health Canada)
  • 202010PJT-451514 (Other Grant/Funding Number: Canadian Institutes of Health Research)

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.

Subscribe