Chapter 33 - Medical use of cannabidiol in fragile X syndrome

Abstract

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the most common single gene cause of autism spectrum disorder (ASD). It is caused by a full mutation (>200 CGG repeats) that is typically methylated, thereby turning off transcription in the FMR1 gene, leading to the absence or deficiency of the FMR1 protein (FMRP). FMRP is a regulator of translation for hundreds of mRNAs from other genes that are often associated with ASD. In the absence of FMRP, there is dysregulation of multiple pathways involved in synaptic plasticity, ionic channel homeostasis, and the balance of inhibitory and excitatory pathways. FMRP also regulates the endocannabinoid system (ECS), and this has led to treatment studies of cannabidiol (CBD) in animal studies and in patients with FXS. The most recent trials of a topical CBD preparation have demonstrated significant efficacy in anxiety and in behavioral problems for those with FXS. This chapter reviews the clinical and molecular phenotype for FXS and associated disorders and the studies utilizing CBD in patients with FXS.