CBDV (Cannabidivarin): Epilepsy, Autism and What the Trials Found

Most minor cannabinoids arrive with big claims and a handful of mouse studies. CBDV is different. A pharmaceutical company took it into a 162-patient epilepsy trial. A children’s hospital gave it to girls with Rett syndrome and watched seizures fall by about 80 percent. A London imaging group showed that a single dose changes brain chemistry in autistic adults, and a placebo-controlled autism trial remains listed as recruiting. That is a real research record. It also includes a trial that did not beat placebo, a seizure result from five patients with no control group, and brain scans that have not yet been tied to how anyone feels or behaves. This article walks through all of it.

What Is CBDV and Where Does It Come From?

CBDV has the same two-ring skeleton as CBD. The difference is the tail: CBD carries a five-carbon (pentyl) side chain, CBDV a three-carbon (propyl) one. That small change is why it belongs to the “varin” family alongside THCV, which our THCV and other varin cannabinoids article covers.

The plant does not make CBDV by trimming CBD. Labeling studies show the three-carbon cannabinoids come from a separate biosynthetic route that starts with a shorter building block, and the resulting precursor, cannabigerovarinic acid (CBGVA), is accepted by the same enzymes that turn CBGA into THCA, CBDA and CBCA.^[1] So the plant makes cannabidivarinic acid (CBDVA) first, and heat or time converts it to CBDV, exactly as CBDA becomes CBD. Our acidic cannabinoids profile explains that step. CBDVA is not inert, either: in a cell assay it blocked T-type calcium channels, a target of some anti-seizure drugs.^[2]

Most cannabis contains very little CBDV. In a Dutch survey of eleven medicinal cannabis varieties, only one had a measurable amount, about 1.5 mg per gram, and the authors noted the long-standing hypothesis that the enzymes behind propyl cannabinoids trace back to Cannabis indica populations rather than C. sativa.^[3] Breeders have since produced CBDV-rich lines, so the compound is no longer rare in the way it was a decade ago.

How Does CBDV Work?

Its anticonvulsant effects do not appear to depend on CB1, the receptor principally responsible for THC’s characteristic high. When University of Reading researchers tested CBDV-rich extracts in mouse and rat seizure models, the anti-seizure effect held even when CB1 was blocked.^[4] That fits what the trials saw later: participants reported diarrhea, nausea and sleepiness, not intoxication.^[5] Our endocannabinoid system pillar explains why a cannabinoid can be active without touching CB1.

The best-supported mechanism involves TRP channels, the sensory ion channels better known for detecting heat and chili. In cells, CBDV activates and then rapidly desensitizes TRPV1, with similar effects on TRPV2 and TRPA1, and in rat hippocampal slices it shortened and shrank the bursts of electrical activity that model a seizure. Blocking TRPV1 did not fully cancel that effect, so TRPV1 is part of the story, not all of it.^[6] An earlier screen by the same Italian group found that CBDV, like most neutral cannabinoids, potently activates TRPV2.^[7]

In animals the anticonvulsant record is broad. Purified CBDV protected mice against electroshock and sound-triggered seizures and rats against the chemical convulsant pentylenetetrazole; it did not stop pilocarpine seizures alone but did when combined with valproate or phenobarbital, and it did not impair motor function.^[8] That body of work helped support GW Pharmaceuticals’ decision to take it into people.

What Happened in the Epilepsy Trial?

GW’s compound, coded GWP42006, went into a Phase 2 trial of 162 adults whose focal seizures were not controlled by their existing medication. Half took CBDV, titrated up to 800 mg twice a day, and half took placebo for eight weeks. Seizures fell 40.5 percent on CBDV and 37.7 percent on placebo. The difference was not significant (p = 0.648), and no seizure subtype or secondary outcome separated the groups either.^[5] GW announced the miss in February 2018; the full paper appeared in 2021.

Two things stand out. First, a 40 percent reduction looks substantial in isolation, and the authors argued that a pharmacological response may have been obscured by the unusually large placebo improvement. But because CBDV did not separate from placebo, the trial cannot establish how much, if any, of that reduction came from the drug. Second, the trial was reasonably large for an early CBDV study, although treatment lasted only eight weeks, and it used a dose far above anything in a consumer product. CBDV was reasonably tolerated: 72.8 percent of the CBDV group had at least one adverse event against 48.1 percent on placebo, mostly digestive upset and sleepiness, and three CBDV participants (versus one on placebo) had liver enzyme elevations more than three times the upper limit of normal, none meeting the criteria for drug-induced liver injury.^[5] We found no later placebo-controlled epilepsy trial of CBDV in adults, from GW, from Jazz Pharmaceuticals, which acquired GW in 2021, or from anyone else.

Rett Syndrome: Five Girls, Big Numbers

Rett syndrome is a severe genetic disorder, almost always in girls, caused by mutations in the MECP2 gene; drug-resistant seizures are common. In mice carrying the same mutation, chronic CBDV eased behavioral deficits and brain atrophy,^[9] and a second study found that five weeks of CBDV fully restored recognition memory, normalized brain growth factors, and delayed, though only temporarily, the motor decline.^[10]

The human study that followed is the most striking CBDV result on record, and the easiest to over-read. Australian clinicians gave five girls with Rett syndrome and drug-resistant epilepsy, median age 12.6, CBDV titrated to about 10 mg per kilogram per day. The study reported a median seizure reduction of 79 percent; overall monthly seizure frequency fell from 32 to 7.2. All five improved, three by more than 75 percent, and four were able to reduce their other anti-seizure drugs. Sleepiness and drooling were the side effects clearly tied to the drug.^[11] There was no placebo group. The authors themselves wrote that a larger Phase 2 trial would be needed to test whether the result is real, and the epilepsy trial above is the reminder of why: its placebo arm cut seizures by 38 percent.

A small American program points the same way. In a 2018 conference abstract, five children with autism and drug-resistant epilepsy received CBDV under an expanded-access protocol; two became seizure-free and one improved by 70 percent, and caregivers reported gains in communication and social engagement.^[12] Again, no control group.

What About Autism?

The autism work comes from two directions: brain imaging in adults at King’s College London, and a treatment trial in children in New York.

The London team gave 34 adults, 17 of them autistic, a single 600 mg dose of CBDV or placebo and scanned them with magnetic resonance spectroscopy. CBDV raised a marker of glutamate signaling in the basal ganglia in both groups; it did not change GABA.^[13] A second scan session in 28 men used functional MRI and found that the striatal over-connectivity typical of the autistic participants shifted toward the neurotypical pattern after CBDV.^[14] Both are mechanism studies. They show the drug reaches the brain and nudges systems that are different in autism, which is why they matter. They do not show that anyone’s symptoms changed, the samples were small, and the connectivity study enrolled only men. The authors say so.

The treatment trial is Eric Hollander’s at Montefiore Medical Center: 100 children and adolescents with autism, randomized to CBDV at 10 mg per kilogram per day or placebo for twelve weeks, with irritability as the primary outcome. The registry still lists the study as recruiting, with completion estimated for February 2027, although its last formal status verification was in October 2025. As of October 2026, no results had been posted or published.^[15] The question is being asked properly; the answer is not in yet.

Where Else Has CBDV Been Tested in People?

Once more, and it did not work. A Berlin group ran a placebo-controlled crossover trial of CBDV at 400 mg a day in 32 people with HIV-associated nerve pain. Pain was slightly higher on CBDV than on placebo, not significantly so, and the authors concluded the compound was safe but not a meaningful pain treatment.^[16] It is a small study, but it is the only one, and it points the wrong way.

What Is Still Only in the Lab?

Everything else. In a mouse model of Duchenne muscular dystrophy, CBDV and CBD at 60 mg per kilogram prevented the loss of movement, reduced inflammation and restored autophagy, the cellular cleanup process that fails in dystrophic muscle.^[17] In mice with chemically induced colitis it reduced intestinal inflammation, and in gut biopsies from children with ulcerative colitis it reduced inflammatory signaling in the dish.^[18] Those are good reasons to keep studying it. None has reached a patient.

One lab finding runs the other way. Austrian toxicologists reported that low concentrations of CBD and CBDV caused DNA damage and chromosomal abnormalities in human-derived cell lines.^[19] A cell result does not establish a risk in people. The short clinical studies did not reveal a major safety signal, but they were neither long enough nor designed to evaluate genotoxicity or long-term cancer risk. It still belongs on the list, because “non-intoxicating” is not the same as “inert.” For a full map of the preclinical work, the 2021 review by the Insubria group that did much of the Rett research is the best single source.^[20]

Can You Buy CBDV?

Yes. It is sold as a hemp-derived isolate and as an ingredient in oils and gummies, usually alongside CBD, and in the United States it falls under the 2018 hemp definition when it comes from plants at or below 0.3 percent THC. That definition narrows on December 11, 2026, when the federal hemp redefinition takes effect; check our acidic cannabinoids profile for the details and the Congressional Research Service for the current statutory text.^[21] No CBDV product is FDA-approved for any use.

Two practical points. The trial doses were hundreds of milligrams a day for adults, and roughly 10 mg per kilogram for children; compare that with the CBDV figure on a product’s certificate of analysis before assuming you are taking anything like a studied dose. And if the interest is seizures, in a child or an adult, this is a conversation for the neurologist, not a supplement decision. CBDV has been studied mainly as an add-on to existing anti-seizure medication, and some participants changed their other drugs during treatment.^[11] Its interaction profile is not sufficiently established for unsupervised use.

The Bottom Line

CBDV is a cannabinoid with real pharmacology, a solid animal record for seizures, and one of the more clinically studied minor cannabinoids. The placebo-controlled epilepsy trial did not beat placebo, and the one pain trial did not either. The Rett syndrome and autism-with-epilepsy results are the most exciting numbers in this article and the least secure, because nothing was compared against them. The imaging work shows that CBDV does something measurable in the autistic brain, while an ongoing placebo-controlled trial is testing whether those biological effects translate into symptom improvement. Until it reports, CBDV is a promising compound with an open question, and that is a better place than most minor cannabinoids can claim.

References

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2. Udoh M, Bladen C, Heblinski M, et al. The anticonvulsant phytocannabinoids CBGVA and CBDVA inhibit recombinant T-type channels. Frontiers in Pharmacology. 2022.
3. Fischedick JT, Hazekamp A, Erkelens T, et al. Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes. Phytochemistry. 2010;71(17–18):2058–2073.
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6. Iannotti FA, Hill CL, Leo A, et al. Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chemical Neuroscience. 2014.
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8. Hill AJ, Mercier MS, Hill TDM, et al. Cannabidivarin is anticonvulsant in mouse and rat. British Journal of Pharmacology. 2012;167(8):1629–1642.
9. Vigli D, Cosentino L, Raggi C, Laviola G, Woolley-Roberts M, De Filippis B. Chronic treatment with the phytocannabinoid cannabidivarin (CBDV) rescues behavioural alterations and brain atrophy in a mouse model of Rett syndrome. Neuropharmacology. 2018.
10. Zamberletti E, Gabaglio M, Piscitelli F, et al. Cannabidivarin completely rescues cognitive deficits and delays neurological and motor defects in male Mecp2 mutant mice. Journal of Psychopharmacology. 2019;33(7):894–907.
11. Hurley EN, et al. The efficacy and safety of cannabidivarin treatment on epilepsy in girls with Rett syndrome: a phase I clinical trial. Epilepsia. 2022.
12. Barnes G, Sullivan J, Sears L, Qiu X, VanLanding K. Safety and tolerability of GWP42006 (CBDV) in subjects with drug resistant epilepsy and autism. American Epilepsy Society Annual Meeting, 2018; abstract 3.288.
13. Pretzsch CM, Voinescu B, Lythgoe D, et al. Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without autism spectrum disorder (ASD): a single dose trial during magnetic resonance spectroscopy. Translational Psychiatry. 2019;9:313.
14. Pretzsch CM, Floris DL, Voinescu B, et al. Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin. Molecular Autism. 2021;12:49.
15. Montefiore Medical Center. Cannabidivarin (CBDV) vs. placebo in children with autism spectrum disorder (ASD). ClinicalTrials.gov identifier NCT03202303; record updated October 2025, accessed October 2026.
16. Eibach L, Scheffel S, Cardebring M, et al. Cannabidivarin for HIV-associated neuropathic pain: a randomized, blinded, controlled clinical trial. Clinical Pharmacology & Therapeutics. 2021;109(4):1055–1062.
17. Iannotti FA, Pagano E, Moriello AS, et al. Effects of non-euphoric plant cannabinoids on muscle quality and performance of dystrophic mdx mice. British Journal of Pharmacology. 2019;176(10):1568–1584.
18. Pagano E, Romano B, Iannotti FA, et al. The non-euphoric phytocannabinoid cannabidivarin counteracts intestinal inflammation in mice and cytokine expression in biopsies from UC pediatric patients. Pharmacological Research. 2020.
19. Russo C, Ferk F, Mišík M, et al. Low doses of widely consumed cannabinoids (cannabidiol and cannabidivarin) cause DNA damage and chromosomal aberrations in human-derived cells. Archives of Toxicology. 2019.
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21. Congressional Research Service. Changes to the statutory definition of hemp and implications for agricultural policy. In Focus IF13136, updated September 28, 2026.

Editor’s note: This article was originally published on September 19, 2021, by Lisa Rennie. In October 2026 the editors rewrote it to cover the completed clinical trials, the Rett syndrome and autism research, and the trials still under way, and merged an earlier 2017 article on CBDV and epilepsy into it. This article is for information only and is not medical advice.

Reviewed by Chana Frenkel, Ph.D.

Last updated October 2026 · Originally published September 19, 2021.