Cannabidivarin

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Cannabidivarin
Cannabidivarin.svg
Cannabidivarin molecule ball.png
Clinical data
ATC code
  • none
Identifiers
  • 2-((1S,6S)-3-methyl-6-(prop-1-en-2-yl)
    cyclohex-2-enyl)-5-propylbenzene-1,3-diol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.236.933 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H26O2
Molar mass 286.415 g·mol−1
3D model (JSmol)
  • C=C(C)[C@H]2CCC(\C)=C/[C@@H]2c1c(O)cc(CCC)cc1O
  • InChI=1S/C19H26O2/c1-5-6-14-10-17(20)19(18(21)11-14)16-9-13(4)7-8-15(16)12(2)3/h9-11,15-16,20-21H,2,5-8H2,1,3-4H3/t15-,16+/m1/s1 Yes check.svgY
  • Key:REOZWEGFPHTFEI-CVEARBPZSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Cannabidivarin (CBDV, GWP42006) is a non-intoxicating psychoactive cannabinoid found in Cannabis . It is a homolog (chemistry) of cannabidiol (CBD), with the side-chain shortened by two methylene bridges (CH2 units).

Contents

Although cannabidivarin (CBDV) is usually a minor constituent of the cannabinoid profile, enhanced levels of CBDV have been reported in feral populations of C. indica ( = C. sativa ssp. indica var. kafiristanica) from northwest India, and in hashish from Nepal. [1] [2] [3]

CBDV demonstrated anticonvulsant in rodent models in a single published study. [4] It was identified for the first time in 1969 by Vollner et al. [5]

Similarly to CBD, it has seven double bond isomers and 30 stereoisomers (see: Cannabidiol#Isomerism). It is not scheduled by Convention on Psychotropic Substances. It is being actively developed by GW Pharmaceuticals (as GWP42006) [6] because of a demonstrated neurochemical pathway for previously observed anti-epileptic and anti-convulsive action. [7] GW has begun several Phase-2 trials for adult epilepsy, [8] for childhood epilepsy and for Prader-Willi Syndrome. [9] [10]

See also

Related Research Articles

<i>Cannabis</i> Genus of flowering plants

Cannabis is a genus of flowering plants in the family Cannabaceae. The number of species within the genus is disputed. Three species may be recognized: Cannabis sativa, C. indica, and C. ruderalis. Alternatively, C. ruderalis may be included within C. sativa, or all three may be treated as subspecies of C. sativa, or C. sativa may be accepted as a single undivided species. The genus is widely accepted as being indigenous to and originating from Asia.

<span class="mw-page-title-main">Tetrahydrocannabinol</span> Psychoactive component of cannabis

Tetrahydrocannabinol (THC) is a cannabinoid found in cannabis. It is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term THC usually refers to the delta-9-THC isomer with chemical name (−)-trans9-tetrahydrocannabinol. It is a colorless oil.

<span class="mw-page-title-main">Cannabinoid</span> Compounds found in cannabis

Cannabinoids are several structural classes of compounds found in the cannabis plant primarily and most animal organisms or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoactive compound in cannabis. Cannabidiol (CBD) is also a major constituent of temperate cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea.

<i>Cannabis sativa</i> Plant species

Cannabis sativa is an annual herbaceous flowering plant. The species was first classified by Carl Linnaeus in 1753. The specific epithet sativa means 'cultivated'. Indigenous to Eastern Asia, the plant is now of cosmopolitan distribution due to widespread cultivation. It has been cultivated throughout recorded history and used as a source of industrial fiber, seed oil, food, and medicine. It is also used as a recreational drug and for religious and spiritual purposes.

<span class="mw-page-title-main">Cannabinol</span> Naturally-occurring cannabinoid

Cannabinol (CBN) is a mildly psychoactive phytocannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. This activity at CB1 and CB2 receptors constitutes interaction of CBN with the endocannabinoid system (ECS).

<span class="mw-page-title-main">Cannabidiol</span> Phytocannabinoid discovered in 1940

Cannabidiol (CBD) is a phytocannabinoid, one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. Medically, it is an anticonvulsant used to treat multiple forms of epilepsy. It was discovered in 1940 and, as of 2022, clinical research on CBD included studies related to the treatment of anxiety, addiction, psychosis, movement disorders, and pain, but there is insufficient high-quality evidence that CBD is effective for these conditions. CBD is sold as an herbal dietary supplement and promoted with yet unproven claims of particular therapeutic effects.

<span class="mw-page-title-main">Tetrahydrocannabivarin</span> Homologue of tetrahydrocannabinol

Tetrahydrocannabivarin is a homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of pentyl (5-carbon), making it non-psychoactive in lower doses. It has been shown to exhibit neuroprotective activity, appetite suppression, glycemic control and reduced side effects compared to THC, making it a potential treatment for management of obesity and diabetes. THCV was studied by Roger Adams as early as 1942.

<span class="mw-page-title-main">Cannabivarin</span> Chemical compound

Cannabivarin (CBV), also known as cannabivarol, is considered a non-psychoactive cannabinoid — it does not produce the euphoric side effects found in THC. Minor amounts of CBV are found in the hemp plant Cannabis sativa. It is an analog of cannabinol (CBN) with the side chain shortened by two methylene bridges (-CH2-). CBV is an oxidation product of tetrahydrocannabivarin (THCV, THV).

<i>Cannabis indica</i> Species of plant

Cannabis indica is an annual plant species in the family Cannabaceae indigenous to the Hindu Kush mountains of Southern Asia. The plant produces large amounts of tetrahydrocannabinol (THC) and tetrahydrocannabivarin (THCV), with total cannabinoid levels being as high as 53.7%. It is now widely grown in China, India, Nepal, Thailand, Afghanistan, and Pakistan, as well as southern and western Africa, and is cultivated for purposes including hashish in India. The high concentrations of THC or THCV provide euphoric effects making it popular for use for several purposes such as recreational drugs, clinical research drugs and the potential of Cannabis or selected constituents for new drug research or being used in alternative medicine, among many others.

<i>Cannabis ruderalis</i> Species of plant

Cannabis ruderalis is a variety, subspecies, or species of Cannabis native to Central and Eastern Europe and Russia. It contains a relatively low quantity of psychoactive compound tetrahydrocannabinol (THC) and does not require photoperiod to blossom. Some scholars accept C. ruderalis as its own species due to its unique traits and phenotypes which distinguish it from C. indica and C. sativa; others debate whether ruderalis is a subspecies under C. sativa.

<span class="mw-page-title-main">Geoffrey Guy</span>

Geoffrey William Guy is a British pharmacologist, physician, businessman and academic, who co-founded GW Pharmaceuticals and has developed treatments using compounds found in cannabis, which are the first cannabis-based medicines approved by and available on the British National Health Service (NHS).

<i>Cannabis</i> strain Plant varieties of Cannabis sativa L., pure or hybrid

Cannabis strains is a popular name to refer to plant varieties of the monospecific genus Cannabis sativa L.. They are either pure or hybrid varieties of the plant, which encompasses various sub-species C. sativa, C. indica, and C. ruderalis.

<span class="mw-page-title-main">Dronabinol</span> Generic name of Δ9-THC in medicine

Dronabinol, sold under the brand names Marinol and Syndros, is the generic name for the molecule of delta-9-tetrahydrocannabinol (THC) in the pharmaceutical context. It has indications as an appetite stimulant, antiemetic, and sleep apnea reliever and is approved by the U.S. FDA as safe and effective for HIV/AIDS-induced anorexia and chemotherapy-induced nausea and vomiting.

The entourage effect is a hypothesis that cannabis compounds other than tetrahydrocannabinol (THC) act synergistically with it to modulate the overall psychoactive effects of the plant.

<span class="mw-page-title-main">CBD-DMH</span> Chemical compound with cannabinoid effects

Cannabidiol-dimethylheptyl (CBD-DMH or DMH-CBD) is a synthetic homologue of cannabidiol where the pentyl chain has been replaced by a dimethylheptyl chain. Several isomers of this compound are known. The most commonly used isomer in research is (−)-CBD-DMH, which has the same stereochemistry as natural cannabidiol, and a 1,1-dimethylheptyl side chain. This compound is not psychoactive and acts primarily as an anandamide reuptake inhibitor, but is more potent than cannabidiol as an anticonvulsant and has around the same potency as an antiinflammatory. Unexpectedly the “unnatural” enantiomer (+)-CBD-DMH, which has reversed stereochemistry from cannabidiol, was found to be a directly acting cannabinoid receptor agonist with a Ki of 17.4nM at CB1 and 211nM at CB2, and produces typical cannabinoid effects in animal studies, as does its 7-OH derivative.

<span class="mw-page-title-main">Medical cannabis research</span> Medical research on using cannabis

Medical cannabis research includes any medical research on using cannabis. The earliest systematic studies of physiological effects of cannabis-derived chemical were conducted in the 1920's. The level or research activity in this area remained relatively low and constant until 1966, when a 10-fold increase in publication activity occurred within 10 years. After the adoption of the Convention on Psychotropic Substances in 1971 there was a drop in research publishing, which continued till ca. 1987. Since then, cannabis research has been continuously on the rise. There is no apparent inflection point is 2013, when Uruguay "became the first country in the world to fully regulate its marijuana market, from production to consumption and distribution." Since then a large number of countries enacted policies on medical cannabis research, and there are substantial differences between such policies in different countries.

<span class="mw-page-title-main">8,9-Dihydrocannabidiol</span> Chemical compound

8,9-Dihydrocannabidiol is a synthetic cannabinoid that is closely related to cannabidiol (CBD) itself. that was first synthesized by Alexander R. Todd in 1940 derived from the catalytic hydrogenation of cannabidiol.

<span class="mw-page-title-main">7-Hydroxycannabidiol</span> Chemical compound

7-Hydroxycannabidiol (7-OH-CBD) is an active metabolite of cannabidiol, generated in the body from cannabidiol by the action of the enzyme CYP2C19. While methods have been developed for its synthetic production, and measurement of levels in the body following consumption of cannabidiol, its pharmacology has been relatively little studied, though it has been found to possess similar anticonvulsant effects to cannabidiol itself, as well as lowering blood triglyceride levels. Like its precursor CBD, it is not known to exhibit any psychoactive effects on the body and is known to counter the psychoactive effects of THC if it is present at the same time. This mode of action in 2015 was discovered to be at least contributing in part by being a non competitive negative allosteric modulator of the Cannabinoid receptor type 1.

<span class="mw-page-title-main">Hexahydrocannabinol</span> Hydrogenated derivative of THC

Hexahydrocannabinol (HHC) is a hydrogenated derivative of tetrahydrocannabinol (THC). It is a naturally occurring phytocannabinoid that has rarely been identified as a trace component in Cannabis sativa, but can also be produced synthetically by firstly acid cyclization of cannabidiol and then hydrogenation of tetrahydrocannabinol. The synthesis and bioactivity of HHC was first reported in 1940 by Roger Adams.

Cannabinoids are compounds found in the cannabis plant or synthetic compounds that can interact with the endocannabinoid system. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (Delta-9-THC), the primary intoxicating compound in cannabis. Cannabidiol (CBD) is another major constituent of some cannabis plants. Conversion of CBD to THC can occur when CBD is heated to temperatures between 250–300 °C, potentially leading to its partial transformation into THC.

References

  1. Turner CE, Cheng PC, Lewis GS, Russell MH, Sharma GK (1979). "Constituents of Cannabis sativa XV: Botanical and chemical profile of Indian variants". Planta Medica. 37 (3): 217–25. doi:10.1055/s-0028-1097331. S2CID   83483599.
  2. Hillig KW, Mahlberg PG (June 2004). "A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae)". American Journal of Botany. 91 (6): 966–975. doi: 10.3732/ajb.91.6.966 . PMID   21653452.
  3. Merkus FW (August 1971). "Cannabivarin and tetrahydrocannabivarin, two new constituents of hashish". Nature. 232 (5312): 579–580. Bibcode:1971Natur.232..579M. doi:10.1038/232579a0. PMID   4937510. S2CID   4219797.
  4. Hill AJ, Mercier MS, Hill TD, Glyn SE, Jones NA, Yamasaki Y, et al. (December 2012). "Cannabidivarin is anticonvulsant in mouse and rat". British Journal of Pharmacology. 167 (8): 1629–1642. doi:10.1111/j.1476-5381.2012.02207.x. PMC   3525866 . PMID   22970845.
  5. Vollner L, Bieniek D, Korte F (January 1969). "[Hashish. XX. Cannabidivarin, a new hashish constituent]". Tetrahedron Letters. 10 (3): 145–147. doi:10.1016/S0040-4039(01)87494-3. PMID   5778489.
  6. "GW Pharmaceuticals Announces Preliminary Results of Phase 2a Study for its Pipeline Compound GWP42006". GW Pharmaceuticals. 21 February 2018. Retrieved 28 May 2019.
  7. Amada N, Yamasaki Y, Williams CM, Whalley BJ (2013). "Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression". PeerJ. 1: e214. doi: 10.7717/peerj.214 . PMC   3840466 . PMID   24282673.
  8. "GW Pharmaceuticals Initiates Phase 2 Clinical Study of Cannabidivarin (CBDV) in Epilepsy" (Press release). GW Pharmaceuticals. May 6, 2015. Retrieved November 10, 2015.
  9. "GW Pharma Press release". Archived from the original on 2015-11-21.
  10. "NSW advice to practitioners on Medical Cannabis trials" (PDF). Archived from the original (PDF) on 2015-11-21.