CBDV Reverses Neurological Symptoms in Mouse Model for Autism
CBDV is the latest extract to get the ‘go’ signal to move into phase 2 clinical trials. Researchers are looking to find out if humans with ASD will respond as well as mice to CBDV treatment.
Over the past decade, a large amount of new knowledge has been generated about the etiology of autism spectrum disorder (ASD), including a genetic link (which now explains 10-20% of cases), and a presumed epigenetic link, which is the result of gene-environment interactions.
Despite such great progress, the core symptoms of ASD remain untreatable. The most common approach to treatment, by pharmaceuticals, consists of anti-psychotics and selective serotonin reuptake inhibitors (SSRIs). Although these may alleviate irritability and aggressive behaviour, they are not effective in relieving the core ASD symptoms.
Autism and the Endocannabinoid System
An interesting finding regarding the etiology of ASD is that the endocannabinoid balance is affected, particularly in the presence of other comorbidities, such as: seizures, sleep disturbances and anxiety. The discovery of this connection resulted in several investigations into the potential use of exogenous cannabinoids (cannabis medicine) as a treatment strategy for ASD.
Although the use of medicinal cannabis in pediatric populations remains controversial, pharmaceutical companies have turned towards cannabis extracts, featuring combinations of cannabinoids, or specific cannabinoids preparations.
New York Trial to Test CBDV Therapy
Indeed, a clinical trial has been initiated in Bronx, NY, and is expected to start in the very near future (October 2018) to examine therapeutic benefits of the cannabinoid, cannabivarin (CBDV), a closely related cousin of CBD. It is a phase 2, randomized, double-blind, placebo-controlled study where the primary outcome measure will be improvement in irritability and secondary measures will include repetitive behavior, social withdrawal and quality of life.
For a pharmaceutical compound to enter a phase 2 trial, substantial pre-clinical evidence must exist to highlight its therapeutic potential. Indeed, CBDV has been evaluated in a mouse model of neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms.
Several physiological processes at the level of the brain are impaired in the mouse model and are regulated by the endocannabinoid system. These include: social behaviour , anxiety and stress response and motor control. Additionally, other neuropsychiatric disorders have also been characterized by deranged endocannabinoid system : anxiety, depression, Fragile X syndrome, schizophrenia.
Researchers found that two-week treatment with CBDV injections improved most aspects of the disorder. These include general health, social behaviour and the motor skills.
These mice also had reduced brain weight, and CBDV treatment reversed that!
Interestingly, different doses produced different effects. For example, 2 and 20 mg/kg dose was most beneficial for correcting the social deficits, whereas 20 and 100 mg/kg doses were most beneficial for general health aspects and motor coordination. Overall, the authors highlight that 20mg/kg dose was the most influential on the overall symptomatology. These varying results with different doses is not unusual, since similar trends have been encountered with CBD, and were explained by the involvement of different molecular pathways.
When considering the myriad of symptoms involved in ASD (anxiety, sleep disturbances, cognitive disturbances), it is tempting to speculate that indeed, CBD and the structurally related CDBV are likely to be therapeutically beneficial because substantial evidence exists to support this. For example, CBD has been shown to relieve PTSD symptoms, which include sleep disturbances and anxiety. As well, a pre-clinical study found that sustained CBD treatment reversed the cognitive deficits in an Alzheimer’s disease mouse model. Additionally, one case series discovered that CBD treatment may actually lead to improvement in the quality of sleep in Parkinson’s disease.
Indeed, the initiation of CBDV clinical trial is most exciting, and extremely timely since it is estimated that 1 in 59 children in US by the age of 8 meets the ASD criteria.