Cannabidivarin (CBDV) Versus Placebo in Children with Autism Spectrum Disorder (ASD)
Abstract
There is a clear unmet need for new therapeutics to treat irritability in children with autism spectrum disorder (ASD) that do not have the metabolic and weight adverse event profiles of the currently approved treatments. Cannabidivarin (CBDV) is a nonpsychoactive phytocannabinoid and a safe variant of Cannabidiol (CBD). It has no appreciable tetrahydrocannabinol (THC) (less than 0.01%), has been shown to have no impact on weight or metabolism, and improves both social and cognitive functioning in animal models. The Centers for Disease Control and Prevention currently estimates 1 in 68 children have ASD. ASD is characterized by deficits in social communication, irritability, repetitive behaviors, impulsivity, temper tantrums, and high caregiver burden. Currently, the only Food and Drug Administration (FDA)-approved medications for symptoms of ASD are aripiprazole and risperidone, both of which are indicated for irritability in pediatric ASD. These medications are effective but are associated with considerable side effects. The anticonvulsant divalproex sodium (valproate/VPA) also significantly reduces irritability and repetitive behaviors in individuals with ASD. Although VPA is efficacious for pediatric epilepsy and some symptoms of ASD, it also has significant side effects, including weight gain, sedation and nausea. CBDV, like VPA, is also effective in the treatment of pediatric epilepsy, and ASD animal studies demonstrate potential mechanisms for treatment with CBDV, including potential therapeutic effects on repetitive behaviors, irritability, sociability, and quality of life, as well as the capacity to reduce inflammation. This proposal addresses the Fiscal Year 2016 Autism Research Program Area of Interest relating to the development of novel pharmacological treatments for ASD. We aim to compare CBDV vs. placebo on changes in irritability in 100 children aged 5 to 18 years with ASD after 12 weeks of treatment. Additionally, we will also look at changes in repetitive behaviors, social communication, quality of life, and adaptive behavior. Our protocol addresses any ethical issues related to the use of a cannabis-related study drug. It is important to note that CBDV has no psychoactive properties and negligible amounts of THC (less than 0.01%), making it preferable to CBD. The use of the CBDV compound, instead of other cannabis-related compounds, thus decreases the risk of it showing up on a urine drug test and protects older subjects who may need drug testing for employment or school. If families are concerned, the study team will provide documentation that the subject is in a research study using a cannabis-related compound that has no psychoactive effects. Additionally, we will exclude patients with a history of cannabis usage or who test positive for delta9-THC at screening or baseline. Data suggest that individuals with ASD have lower rates of drug and alcohol use and misuse than other psychiatric populations, with no greater use than expected in the general population. Clinicians will continuously monitor patients for substance abuse throughout the trial during discussions with the family and patient. There is an urgent need to develop new medications to treat the core symptoms of ASD. Current FDA-approved treatments only target the associated symptoms of irritability and aggression and have significant adverse weight and metabolic effects. CBDV has the potential to be a valuable therapeutic agent for individuals with ASD by virtue of its anti-inflammatory, antioxidative, neuroprotective, anti-anxiety and anticonvulsant properties. With its effects on multiple mechanisms known to be dysfunctional in the ASD population and low side effect profile, CBDV is a promising treatment that needs further exploration in this population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710253
Entities
People
- Eric Hollander
Organizations
- Albert Einstein College of Medicine
- United States Army