Treatment of Fragile X Syndrome with Cannabidiol: A Case Series Study and Brief Review of the Literature.

Nicole Tartaglia,Randi Hagerman,Marcel Bonn-Miller

doi:10.1089/can.2018.0053

Abstract

Fragile X syndrome (FXS) is an X-linked dominant disorder caused by a mutation in the fragile X mental retardation 1 gene. Cannabidiol (CBD) is an exogenous phytocannabinoid with therapeutic potential for individuals with anxiety, poor sleep, and cognitive deficits, as well as populations with endocannabinoid deficiencies, such as those who suffer from FXS. The objective of this study was to provide a brief narrative review of recent literature on endocannabinoids and FXS and to present a case series describing three patients with FXS who were treated with oral CBD-enriched (CBD+) solutions. We review recent animal and human studies of endocannabinoids in FXS and present the cases of one child and two adults with FXS who were treated with various oral botanical CBD+ solutions delivering doses of 32.0 to 63.9 mg daily. Multiple experimental and clinical models of FXS combine to highlight the therapeutic potential of CBD for management of FXS. All three patients described in the case series exhibited functional benefit following the use of oral CBD+ solutions, including noticeable reductions in social avoidance and anxiety, as well as improvements in sleep, feeding, motor coordination, language skills, anxiety, and sensory processing. Two of the described patients exhibited a reemergence of a number of FXS symptoms following cessation of CBD+ treatment (e.g., anxiety), which then improved again after reintroduction of CBD+ treatment. Findings highlight the importance of exploring the therapeutic potential of CBD within the context of rigorous clinical trials.

Highlights

Fragile X syndrome (FXS) is an X-linked dominant disorder caused by the expansion of a trinucleotide repeat (CGG)n within the first exon of the fragile X mental retardation 1 (FMR1) gene, which silences the expression of the fragile X mental retardation protein (FMRP).[1]
Because the clinical abnormalities in these patients have been linked, at least in part, with dysregulation of the endocannabinoid system, we briefly review recent research characterizing the involvement of the endocannabinoid system in FXS and present the cases of three individuals with FXS who experienced functional benefit after treatment with cannabidiol (CBD)enriched (CBD+) preparations
Described are the cases of one pediatric and two adult patients with FXS for whom CBD+ treatment appears to have contributed to positive changes in anxiety and/or language skills, with no observed adverse events

Summary

Introduction

Fragile X syndrome (FXS) is an X-linked dominant disorder caused by the expansion of a trinucleotide repeat (CGG)n within the first exon of the fragile X mental retardation 1 (FMR1) gene, which silences the expression of the fragile X mental retardation protein (FMRP).[1]The absence of FMRP, an important regulator of translation of many messenger RNAs involved in synaptic plasticity,[2] leads to substantial intellectual deficits. Fragile X syndrome (FXS) is an X-linked dominant disorder caused by the expansion of a trinucleotide repeat (CGG)n within the first exon of the fragile X mental retardation 1 (FMR1) gene, which silences the expression of the fragile X mental retardation protein (FMRP).[1]. The condition has been estimated to affect *1:4000 males and 1:7000 females.[3,4,5] both sexes are susceptible, males with FXS typically exhibit more severe symptoms compared with females because the single X chromosome in males is usually fully methylated and not producing FMRP6; females typically have some. FMRP expression from the FMR1 gene on their second unaffected X chromosome.[7] Males with FXS are far more likely than females to exhibit significant intellectual and developmental disabilities (85% vs 25%).[8].

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Conclusion