Cannabinoids as a Treatment for Fragile X Syndrome

Devin Binder, MD, PhD
Principal Investigator

Patricia Salgado Pirbhoy, PhD
Co-Principal Investigator

University of California, Riverside

2021 Grant Funding: $90,000

University Total Funding: $608,000

Summary

Many people with Fragile X syndrome are hyper-sensitive to sights and sounds, and Electroencephalography (EEG) studies show that there are abnormalities in brain circuits. EEG studies show similar changes in Fragile X mice. So the team will use EEG tests in mice to find which drugs best reduce hypersensitivity. They can then easily move on to human EEG-based clinical trials. What they learn will tell us much more about why people with Fragile X are hypersensitive – and which drugs could best help them.

The Science

By Devin Binder MD, PhD

Many individuals with Fragile X syndrome (FXS) experience exaggerated responses to sensory stimuli. Unfortunately, the underlying mechanisms involved in this hyperarousal state are poorly understood. Human electroencephalography (EEG) studies in human patients with FXS point to changes in neural circuit-level functioning and have identified neural biomarkers that are associated with hyper-responses to auditory stimuili and cortical hyperexcitability. These EEG biomarkers are also found in the mouse model of FXS. Our laboratory has recently characterized these neural biomarkers with a 30-channel multielectrode array (MEA) system providing the opportunity to evaluate electrocortical activity and responses to sound in a manner that can be easily translated to human EEG-based clinical trials. Most importantly, these biomarkers provide the opportunity to test candidate pharmacological interventions targeting the endocannabinoid (eCB) system objectively by exploring the effects of these drugs on electrocortical activity.

As the popularity of cannabis grows in the public due to the overpromotion of clinical studies or personal anecdotes, many families are turning toward cannabis or cannabis related products to treat their children with FXS and autism spectrum disorder (ASD). However, there has been limited research on the effects of cannabis or modulators of the endocannabinoid system (endogenous cannabis system) in FXS. Our goal is to assess two potential treatment strategies to target the endocannabinoid system to ameliorate auditory hypersensitivity and cortical hyperexcitability. In one approach, we will inhibit cannabinoid receptors to test the hypothesis that excessive eCB signaling underlies FXS pathophysiology. In the second approach, we will enhance endocannabinoid ligand levels, specifically, anandamide (AEA), which has been identified as a key modulator following cannabidiol (CBD) treatments. These studies will help determine the most effective treatment strategy for auditory hypersensitivity and cortical hyperexcitability as well as help guide improvements in endocannabinoid system-mediated therapies.

Global Leader in Fragile X Research

FRAXA-funded researchers around the world are leading the way towards effective treatments and ultimately a cure.

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Global Leader in Fragile X Research

FRAXA-funded researchers around the world are leading the way towards effective treatments and ultimately a cure.

Explore Current Research Grants
Help Fund the Cure