Medical Cannabinoid CBDV: Autism May Have a Cure!

Oct 14, 2021

There are more than 130 cannabinoids in plant cannabis. Two of the most important cannabinoids are THC (tetrahydrocannabinol) and CBD (cannabidiol), and the ingredient introduced today is another cannabinoid with medicial use-- CBDV (subcannabidiol).
Medical Cannabinoid CBDV has been evaluated as a potential treatment for certain mood and behavioral disorders, such as RETT syndrome (RETT) and autism spectrum disorders (ASD). "ASD mouse models demonstrate potential therapeutic mechanisms for CBDV, including potential therapeutic effects on repetitive behavior, irritability, sociability, quality of life, and reduction of inflammation," as the study shows.
According to domestic hospital diagnosis statistics, the incidence of autism is 2‰ ~ 3‰, among which true autism accounts for less than 0.2% and pseudoautism accounts for more than 99.8%. Pseudo-autism was divided into six categories: 70 percent with very low courage, 30 percent with hyperarousal, 15 percent with Asperger's syndrome, 30 percent with weak language skills, 10 percent with poor observation and perception, 6 percent with delayed brain development, and 5 percent with no known cause. Some children had more than two problems.
The disease usually starts within 36 months and is mainly manifested by three core symptoms: social interaction disorder, communication disorder, narrow interests and rigid and repetitive behavior, and there is no specific drug treatment at present.    

CBDV for autism
Last month, clinical data published in the journal Molecular Autism showed that CBDV could modulate the brain chemical circuits of people with autism. An international team of researchers from Germany, Spain, the Netherlands and the United Kingdom assessed the administration of CBDV versus placebo in a group of men with ASD.
The researchers conclude: "A single dose of CBDV is sufficient to alter atypical FC (functional connectivity) in the striatum in the mature brain of autistic patients to patterns originally found in neural models. But further research is needed to determine whether striatal heart rate regulation is associated with changes in ASD symptoms."
Recently several observational trials have documented behavioral improvements in ASD patients who received cannabis extracts.
On 22 April 2021, the University of Insubia in Italy published a research paper on the therapeutic potential of cannabinoids for epilepsy and autism disorders. The following is the abstract: https://www.sciencedirect.com/science/article/abs/pii/S0163725821000802
Pharmacokinetic studies of Medical Cannabinoid CBDV are still scarce. Most pharmacokinetic studies have been conducted on CBD, and results obtained in general have been extended to CBDV, mainly because of structural similarities between the two compounds.
CBDV is a highly lipid soluble compound with a distribution volume of 32l/kg and can rapidly cross the blood-brain barrier. Only one single phase 1 study assessed the pharmacokinetic characteristics of CBDV orally (25-800 mg per day for 5 days) or intravenously (a single infusion of 5 mg) in healthy volunteers.
The drug is well tolerated by both routes and rapidly metabolized in the liver. However, after oral ADMINISTRATION of CBDV, the low solubility of CBDV in water leads to unstable gastrointestinal absorption, resulting in poor bioavailability and pharmacokinetic changes. It has been suggested that oral lipid preparations developed through nanotechnology could be a useful tool to solve this problem in the future, to improve the bioavailability of oral preparations for clinical use.
In addition, CBDV strongly binds to plasma proteins and exhibits a very high first pass metabolism (directly metabolized by the liver) in the liver, further reducing its oral bioavailability by an estimated less than 10%.
In the liver, major first-stage reactions include hydroxylation oxidation and decarboxylation, operated by a series of cytochrome P450(CYP450) isoenzymes, particularly CYP3A4, CYP2C9 and CYP2C19, as well as CYP1A1, CYP1A2, CYP2C9, CYP2D6 and CYP3A5.
Glucoaldehyde acidification by UDP-glucuronic acid transferases (UGTs) is the major second-stage reaction of CBD, and it is suggested that CBDV may have a similar mechanism, namely UGT1A7, UGT1A9 and UGT2B7 are the most important enzymes. CBD and CBDV have elimination half-lives between 18 and 32 hours and can be administered clinically once or twice daily.
Finally, CBDV, like CBD, is a potent inhibitor of most CYP450 enzymes. Studies have shown that CBD and CBDV have inhibitory effects on CYP1A1, but CBD has a stronger inhibitory effect. CBD is also an effective inhibitor of CYP3A4, CYP2C19 and CYP2D6, which play an important role in the metabolism of several exogenous substances.
 However, some of these effects occur at concentrations that are not clinically relevant. The ability of CBDV and CBD to interfere with CYP450 may increase the likelihood of pharmacokinetic interactions with other therapeutic agents, including antiepileptic drugs (AED).

Pleiotropic effects of CBDV on receptor and enzyme
Despite the small number of studies, the preclinical results collected so far raise the interesting possibility that CBDV may represent a promising compound for the treatment of epilepsy and ASD. However, these preclinical findings sometimes do not translate to the clinic.
One possible explanation for this difference is the poor pharmacokinetic curve of post-oral CBDV, which highlights the need for new and more effective oral formulations. On the other hand, both epilepsy and ASD are highly heterogeneous diseases, so CBDV may only be effective in specific subpopulations of patients."
Hopefully, there will be more and more clinical trials of Medical cannabinoid CBDV in the future, bringing light to millions of people with autism and social phobia.

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