A team of scientific researchers is currently conducting animal experiments to study how CBD interacts with the brains of mice, aiming to better understand how the drug affects their behavior.

This new animal study highlights the possible benefits of CBD (cannabidiol) and the diabetes drug metformin in the treatment of behavioural disorders.

According to the study presented at the Federation of European Neuroscience Societies (FENS) Forum 2024, research on mouse models of Fragile X syndrome and Phelan-McDermid syndrome has shown that treatment with cannabidiol (CBD) and the diabetes drug metformin can alleviate difficulties with behavioural disorders.

Fragile X syndrome and Phelan-McDermid syndrome are two genetic disorders that cause various neurodevelopmental difficulties throughout life. Both conditions can easily lead to autism spectrum disorders, including delayed language skills, social difficulties and repetitive behaviours.

The study was presented by Dr Ilse Gantois from McGill University in Montreal, Canada, who explains, ‘Several medications are currently available for the treatment of depression, anxiety, epilepsy, and aggression in people with Fragile X Syndrome, however, most of these medications have many side effects. Similarly, for Phelan McDermid syndrome, current treatments focus on epilepsy and anxiety. Current research on this disorder is very limited.’

‘Throughout my career, I have often met parents of children with Fragile X Syndrome and listened to how they struggle to help their children lead more comfortable lives. So, with my experience in behavioural neuroscience, I wanted to find safe treatments to improve behavioural disorders in children with these conditions.’

Metformin is the most commonly used drug to treat type 2 diabetes. In previous studies, Dr Gantois and colleagues have successfully used metformin to treat adult mice that were bred to be models of fragile X syndrome. Now, the researchers have tested metformin in newborn mice that were bred to be models of fragile X syndrome.

This study shows that metformin corrects biochemical differences in the brains of the mice that lead to the condition. The researchers also found that metformin prevented the young mice from developing speech disorders (which manifested as very sharp squeaks in the mice) and repetitive behaviours (which manifested as excessive grooming).

The team also used metformin in mice simulating Phelan-McDermid syndrome, and again found that they reduced speech impairment and repetitive behaviours, and improved the mice's impaired learning and memory behaviours.

Dr Gantois and her colleagues administered CBD to mice that had been bred to model Fragile X syndrome from three weeks after birth. when the mice reached adulthood, their repetitive behaviours and social behaviours were the same as those of the control mice. The researchers found similar improvements when they treated mice simulating Phelan-McDermid syndrome with CBD.

The team is currently studying the interaction of CBD in the mouse brain to better understand why the drug affects behaviour in this way.

It is known that several other research groups in Canada and the United States are currently conducting patient trials of metformin and CBD in Fragile X syndrome.

Dr Gantois said, ‘The results of this study and clinical trial could have a major impact on behavioural disorders in patients with Fragile X syndrome and Phelan-McDermid syndrome. The major strength of these studies is that we are using medications that are approved for lifetime use with minimal side effects. Taken at an early age, these medications can ultimately improve language delays, social interactions and repetitive behaviours in these developmental conditions.

Dr Gantois noted, ‘Using mouse models allows a detailed look at what is happening in the brain to determine the underlying causes of these diseases and to study the effects of behaviour and targeted drugs. Of course, the mouse brain is not the same as the human brain, but we can often translate the mouse behaviours we study into human behaviours.’

The researchers are also looking at the effects of these drugs on mouse models of other autism spectrum disorder-related disorders to see if they could have wider uses.

Professor Richard Roche is Chair of the Communications Committee of the Neuroscience Forum of the Federation of European Neuroscience Societies (FENS) and Associate Head of the Department of Psychology at Maynooth University, Maynooth, County Kildare, Ireland (who was not involved in this study).

Professor Roach commented, ‘More research is needed to help us understand disorders such as Fragile X Syndrome and Phelan-McDermid Syndrome and to find out how we can treat these developmental disorders to give children a better chance of happiness in life. Mouse research models of these disorders provide us with an important window into the mechanisms that occur within the brain so that we can investigate the possible benefits of new therapies.