Cannabidivarin (CBDv)

What is CBDV?

By Dr. Bonni Goldstein, MD

Cannabinoid receptors

• CBDV does not bind to cannabinoid receptors (?) CB2 interaction?
• As we learn more about this cannabinoid, the question mark above may change.
• One 2007 study discussed the potential binding of CBDV to CB2 receptor.

Endocannabinoid interaction

• CBDV blocks DAGL, the enzyme involved in 2-ag synthesis.
• If 2-ag is blocked, we don’t make as much.

TRP channels

• CBDV activates TrpA1, TrpV1, TrpV2
• TrpV1 thought to be important for anti-convulsive effects
• CBDV also blocks TrpM8 channel, involved in cancer growth

GPR55

• CBDV weakly blocks receptor, involved in pain, inflammation, seizures and energy metabolism

GABA receptors

• CBDV recovered GABA-A receptor “rundown”, which is a phenomenon associated with drug resistant epilepsy.

Supporting research

• Case reports-Morano et al., 2016 seizure reduction with homemade CBDV rich preparation. https://pubmed.ncbi.nlm.nih.gov/29588939/
• Multiple animal studies reporting anti-convulsant effects of CBDV
  • https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/j.1476-5381.2012.02207.x
  • https://peerj.com/articles/214/#fig-5
  • Huizenga et al,. 2019
• Clinical trial of purified CBDv in adults with poorly controlled focal seizures, failed to reach primary endpoint
  • Placebo response, single compound vs whole plant
  • Evidence reported use of isolate
  • Hard to know why this clinical trial failed

Rett Syndrome

• Chronic treatment with CBDV- Vigili Et al, 2018
• Link to Zamberletti, 2018 article.
• Reported mice w/ genetic defect when given CBDV, rescued social deficits, improved motor coordination and brain waves, led to study in human children
  • Efficacy and safety of CBDV treatment of epilepsy in girls w/ Rett syndrome: A Phase 1 clinical trial
  • 5 girls w/ Rett syndrome and drug-resistant epilepsy treated w/ CBDV in phase 1 trial
  • Dosing from 2.5mg/kg/day up to 10mg/kg/day
  • Remarkable results-79% reduction of seizures
  • 3/5 having 75% reduction of seizures.
  • This corresponds to overall seizure reduction from 32 to 7.2 seizures/month
  • CBDV APPEARS TO BE WELL TOLERATED WITH NO SERIOUS SIDE EFFECTS, sedation and drooling were one reported side effect

Autism

• Link to 2021 Zamberletti article.
• CBDV treatment ameliorates autism-like behaviors and restores hippocampal…Would it reverse or prevent autism-like behaviors?
• Animal model looked at reversing and preventing ASD like behavior in rats exposed to Valproic acid prenatally (model of ASD).
• In symptomatic rats, improvements in social impairments, social novelty preferences, short terms memory deficits, repetitive behaviors, hyperlocomotion.
• CBDV prevented all of the above.
• CBDV also found pre-natal valproic acid exposure had significant effects on ECS, CB1 receptor, FAAH, MAGL levels and triggered neuroinflammation. All alterations were restored after CBDV treatment.
• Autism trial in humans are now in progress, safety/tolerability of CBDV in children and young adults with ASD.

Neuropathic Pain

• Patent acquired in 2018 for other cannabinoids in a mouse model of pain.
• CBDV (as well as CBG/THCv) was effective at reducing pain (better than CBD) for both thermal hyperalgesia and mechanical allodynia.

Prader-Willi Syndrome

• CBDV vs placebo in children and adults up to age 30 with Prader-Willi
• Eating fixation, irritability, repetitive/disruptive behaviors, intense persistent hunger and food pre-occupation and sleep disturbances.
• Currently this study is in the recruiting phase
• CBDV may help with mood, sleep and food regulation.

Dr. Bonni’s Suggestion on what to look for in product

• Look for whole plant CBDV, Full spectrum.
• Not a fan of isolate but her patients are already on lots of cannabis and by adding in extra cannabinoids, they are still getting whole plant spectrum.
• Side effects:
  • Sedation, drooling (possibly)
• Some products have added ingredients which some patients may have issues with, take for example, peppermint may trigger seizures in some patients.
• No mixing with other products as this can make it difficult to determine where the unwanted side effects are coming from.
• She wants cannabis, oil and that is it!

Reference

Goldstein, B. (2022, September 1). What is CBDV? [Video file]. Retrieved from https://www.youtube.com/watch?v=4OAeGC5464Q