Summary: New preclinical research shows that cannabidiol (CBD) and the diabetes drug metformin reduce core behavioural difficulties in mouse models of Fragile X syndrome and Phelan-McDermid syndrome. Both genetic conditions are frequently associated with autism spectrum disorder and present challenges such as delayed speech, impaired social interaction, and repetitive behaviours. In these experiments, early or sustained treatment with CBD or metformin improved communication-like vocalisations, social behaviours and repetitive actions in mice, while producing few observable side effects. Ongoing clinical trials in people will determine whether these findings translate to human patients.
Key Facts:
- Behavioral improvements: In mouse models, CBD and metformin reduced repetitive behaviours, improved social interaction, and lessened impaired vocalisations that model speech delay.
- Favourable safety profile: Both drugs are already approved for other uses, can be administered long term, and have relatively few side effects in clinical practice.
- Clinical trials in progress: Multiple groups are conducting early-stage patient studies to evaluate metformin and CBD for Fragile X syndrome and related conditions.
Source: FENS
Researchers presented these findings at the FENS Forum 2024. The work, led by Dr Ilse Gantois of McGill University, examined how two existing medications — cannabidiol (CBD), a non‑psychoactive compound derived from cannabis, and metformin, a widely used treatment for type 2 diabetes — affect neurodevelopmental traits in established mouse models of Fragile X syndrome and Phelan‑McDermid syndrome.
Fragile X syndrome and Phelan‑McDermid syndrome are genetic neurodevelopmental disorders with high rates of autism spectrum features, including speech delay, difficulties with social communication and restricted, repetitive behaviours. Current treatments for people with these conditions typically focus on managing epilepsy, anxiety or aggression, and many commonly prescribed drugs carry significant side effects. Dr Gantois and her team framed their work around the need for safer, lifelong treatment options that target core behavioural challenges.
In earlier studies, the team demonstrated that metformin produced benefits in adult Fragile X mouse models. In the new experiments they extended treatment to newborn mice. Metformin corrected a specific biochemical imbalance in the developing brain that contributes to the disorder and prevented key behavioural abnormalities from emerging. Treated mice showed fewer high‑pitch ultrasonic vocalisations—an established proxy for impaired speech in rodents—and a reduction in repetitive grooming behaviour. Comparable improvements were observed when metformin was tested in mice modelling Phelan‑McDermid syndrome, with additional gains in measures of learning and memory.
CBD was administered beginning three weeks after birth in mice bred to represent young children. By adulthood, mice treated with CBD displayed repetitive and social behaviours that were indistinguishable from control animals, indicating normalization of those traits. Similar positive outcomes were found for CBD in the Phelan‑McDermid models. The research group is now investigating the neural mechanisms and molecular interactions through which CBD exerts these behavioural effects, to better understand why and how the compound can influence developmentally regulated circuits.
Because both metformin and CBD are already approved for other medical uses and are known to be tolerable for long‑term administration, their repurposing offers a promising translational path. Several independent teams in Canada and the United States have moved forward with early‑phase clinical trials, enrolling patients to evaluate safety, dosing and preliminary efficacy for Fragile X syndrome. These clinical studies will be essential to establish whether the behavioural benefits seen in mice can be replicated in children and adults with these genetic disorders.
Dr Gantois noted the motivation behind the work: many families affected by Fragile X and Phelan‑McDermid syndromes seek treatments that improve daily life and developmental outcomes with minimal harm. Using validated mouse models allows detailed examination of brain changes, identification of underlying causes, and systematic testing of candidate therapies. While translation from mice to humans always requires caution—mouse neurobiology differs from human neurobiology—the behavioural parallels provide a valuable starting point for clinical investigation.
Professor Richard Roche, chair of the FENS Forum communication committee and Deputy Head of the Department of Psychology at Maynooth University (not involved in the study), emphasized the need for continued research: understanding mechanisms in these genetic conditions and assessing potential treatments in clinical settings are both critical to improving outcomes. Mouse models offer a controlled way to probe mechanisms and prioritise interventions for human trials.
About this CBD and Autism research news
Author: Kerry Noble
Source: FENS
Contact: Kerry Noble – FENS
Image: The image is credited to Neuroscience News
Original Research: The findings were presented at FENS Forum 2024