Showing Compound Card for Cannabidivarin (CDB000015)

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Record Information
Version1.0
Created at2020-03-19 00:35:28 UTC
Updated at2020-11-18 16:35:09 UTC
CannabisDB IDCDB000015
Secondary Accession NumbersNot Available
Cannabis Compound Identification
Common NameCannabidivarin
DescriptionCannabidivarin (CBDV) is a non-psychoactive cannabinoid found within medical Cannabis. It is one of over 100 cannabinoids identified from the Cannabis plants that can modulate the physiological activity of cannabis, or marijuana (PMID: 23408483 ). CBDV is the C3 analogue of cannabidiol (CBD). Notably, both cannabidiol and CBDV have demonstrated anticonvulsant activity in animal and human models with promising clinical trial results (PMID: 22970845 ; PMID: 25029033 ; PMID: 29290836 ; PMID: 29588939 ). Other cannabinoids with demonstrated anti-epileptic activity include Tetrahydrocannabivarin (THCV) and Δ9-tetrahydrocannabinolic acid. While the primary components of cannabis, CBD and THC, have been shown to modulate many of their physiological effects through their binding to the cannabinoid-1 (CB1) and cannabinoid-2 (CB2) receptors, the anticonvulsant cannabinoids do not interact with CB1 and CB2. The anti-epileptic activity of CBD and CBDV is thought to be modulated by their effects on transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor. TRPV1 is a member of a large family of ion channels that are involved in the onset and progression of several types of epilepsy. CBD and CBDV have been shown to dose-dependently activate and then desensitize TRPV1 as well as TRPV2 and transient receptor potential ankyrin 1 (TRPA1) channels (PMID 25029033 ; PMID: 29842819 ; PMID: 21175579 ). Desensitization of these ion channels is a potential mechanism by which these molecules cause a reduction of neuronal hyperexcitability that contributes to epileptic activity and seizures. CBDV has also been shown to inhibit the activity of diacylglycerol (DAG) lipase-α, the primary enzyme responsible for the synthesis of the endocannabinoid, 2-arachidonoylglycerol (2-AG) (PMID: 24282673 ; PMID: 14610053 ). The clinical implications of this are unclear however, as this interaction has not been shown to affect CBDV's anticonvulsant activity. CBDV is being actively developed by GW Pharmaceuticals as the experimental compound GWP42006 as it has "shown the ability to treat seizures in pre-clinical models of epilepsy with significantly fewer side effects than currently approved anti-epileptic drugs". Unfortunately, as of February 2018, GW Pharmaceuticals announced that their Phase 2a placebo-controlled study of CBDV for focal seizure did not reach its primary endpoints. They will continue to study its use in epilepsy, however, and are expanding their investigations to include its potential use in Autism Spectrum Disorder, Rett syndrome and Fragile X among others. In October 2017 CBDV was given orphan designation by the European Medicines Agency for use in Rett Syndrome and again in February 2018 for treatment of Fragile X Syndrome.
Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
ValueSource
CBDVKegg
CBDV CompoundMeSH
Chemical FormulaC19H26O2
Average Molecular Weight286.42
Monoisotopic Molecular Weight286.1933
IUPAC Name2-[(1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-en-1-yl]-5-propylbenzene-1,3-diol
Traditional Name2-[(1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-en-1-yl]-5-propylbenzene-1,3-diol
CAS Registry Number24274-48-4
SMILES
CCCC1=CC(O)=C([C@@H]2C=C(C)CC[C@H]2C(C)=C)C(O)=C1
InChI Identifier
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+/m0/s1
InChI KeyREOZWEGFPHTFEI-JKSUJKDBSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as aromatic monoterpenoids. These are monoterpenoids containing at least one aromatic ring.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassMonoterpenoids
Direct ParentAromatic monoterpenoids
Alternative Parents
Substituents
  • P-menthane monoterpenoid
  • Monocyclic monoterpenoid
  • Aromatic monoterpenoid
  • Phenylpropane
  • Resorcinol
  • 1-hydroxy-4-unsubstituted benzenoid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Benzenoid
  • Monocyclic benzene moiety
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Ontology
Not Available
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
logPNot AvailableNot Available
Predicted Properties
PropertyValueSource
logP5.13ALOGPS
logP5.44ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)9.13ChemAxon
pKa (Strongest Basic)-5.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity89.33 m³·mol⁻¹ChemAxon
Polarizability34.05 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
EI-MS/GC-MS
TypeDescriptionSplash KeyView
Predicted GC-MSCannabidivarin, 1 TMS, Predicted GC-MS Spectrum - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSCannabidivarin, 2 TMS, Predicted GC-MS Spectrum - 70eV, PositiveNot AvailableSpectrum
MS/MS
TypeDescriptionSplash KeyView
Predicted MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available2020-06-30View Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available2020-06-30View Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available2020-06-30View Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available2020-06-30View Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available2020-06-30View Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available2020-06-30View Spectrum
NMRNot Available
Pathways
Pathways
Protein Targets
Enzymes
Protein NameGene NameLocusUniprot IDDetails
Sn1-specific diacylglycerol lipase alphaDAGLA11q12.2Q9Y4D2 details
Transporters
Protein NameGene NameLocusUniprot IDDetails
Transient receptor potential cation channel subfamily V member 1TRPV117p13.2Q8NER1 details
Transient receptor potential cation channel subfamily V member 2TRPV217p11.2Q9Y5S1 details
Transient receptor potential cation channel subfamily A member 1TRPA18q13O75762 details
Metal BindingsNot Available
Receptors
Protein NameGene NameLocusUniprot IDDetails
Transient receptor potential cation channel subfamily V member 1TRPV117p13.2Q8NER1 details
Transient receptor potential cation channel subfamily V member 2TRPV217p11.2Q9Y5S1 details
Transient receptor potential cation channel subfamily A member 1TRPA18q13O75762 details
Transcriptional FactorsNot Available
Concentrations Data
Cannabis CultivarStatusValueReferenceDetails
Alien DawgDetected and Quantified0.000416 mg/g dry wt
    • David S. Wishart,...
 details
GabriolaDetected and Quantified0.000608 mg/g dry wt
    • David S. Wishart,...
 details
Island HoneyDetected and Quantified0.000508 mg/g dry wt
    • David S. Wishart,...
 details
QuadraDetected and Quantified0.00044 mg/g dry wt
    • David S. Wishart,...
 details
Sensi StarDetected and Quantified0.000491 mg/g dry wt
    • David S. Wishart,...
 details
Tangerine DreamDetected and Quantified0.000606 mg/g dry wt
    • David S. Wishart,...
 details
HMDB IDNot Available
DrugBank IDDB14050
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDC20217
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkCannabidivarin
METLIN IDNot Available
PubChem Compound11601669
PDB IDNot Available
ChEBI IDNot Available
References
General References
  1. Hill AJ, Mercier MS, Hill TD, Glyn SE, Jones NA, Yamasaki Y, Futamura T, Duncan M, Stott CG, Stephens GJ, Williams CM, Whalley BJ: Cannabidivarin is anticonvulsant in mouse and rat. Br J Pharmacol. 2012 Dec;167(8):1629-42. doi: 10.1111/j.1476-5381.2012.02207.x. [PubMed:22970845 ]
  2. Iannotti FA, Hill CL, Leo A, Alhusaini A, Soubrane C, Mazzarella E, Russo E, Whalley BJ, Di Marzo V, Stephens GJ: 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 Chem Neurosci. 2014 Nov 19;5(11):1131-41. doi: 10.1021/cn5000524. Epub 2014 Jul 29. [PubMed:25029033 ]
  3. Capasso A: Do Cannabinoids Confer Neuroprotection Against Epilepsy? An Overview. Open Neurol J. 2017 Dec 18;11:61-73. doi: 10.2174/1874205X01711010061. eCollection 2017. [PubMed:29290836 ]
  4. Morano A, Cifelli P, Nencini P, Antonilli L, Fattouch J, Ruffolo G, Roseti C, Aronica E, Limatola C, Di Bonaventura C, Palma E, Giallonardo AT: Cannabis in epilepsy: From clinical practice to basic research focusing on the possible role of cannabidivarin. Epilepsia Open. 2016 Sep 19;1(3-4):145-151. doi: 10.1002/epi4.12015. eCollection 2016 Dec. [PubMed:29588939 ]
  5. Ruzic Zecevic D, Folic M, Tantoush Z, Radovanovic M, Babic G, Jankovic SM: Investigational cannabinoids in seizure disorders, what have we learned thus far? Expert Opin Investig Drugs. 2018 Jun;27(6):535-541. doi: 10.1080/13543784.2018.1482275. Epub 2018 Jun 6. [PubMed:29842819 ]
  6. De Petrocellis L, Ligresti A, Moriello AS, Allara M, Bisogno T, Petrosino S, Stott CG, Di Marzo V: Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011 Aug;163(7):1479-94. doi: 10.1111/j.1476-5381.2010.01166.x. [PubMed:21175579 ]
  7. Amada N, Yamasaki Y, Williams CM, Whalley BJ: Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression. PeerJ. 2013 Nov 21;1:e214. doi: 10.7717/peerj.214. eCollection 2013. [PubMed:24282673 ]
  8. Bisogno T, Howell F, Williams G, Minassi A, Cascio MG, Ligresti A, Matias I, Schiano-Moriello A, Paul P, Williams EJ, Gangadharan U, Hobbs C, Di Marzo V, Doherty P: Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J Cell Biol. 2003 Nov 10;163(3):463-8. doi: 10.1083/jcb.200305129. [PubMed:14610053 ]
  9. Sharma P, Murthy P, Bharath MM: Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012 Fall;7(4):149-56. [PubMed:23408483 ]

Enzymes

Enzyme Details
1. Sn1-specific diacylglycerol lipase alpha
General function:
Involved in triglyceride lipase activity
Specific function:
Catalyzes the hydrolysis of diacylglycerol (DAG) to 2- arachidonoyl-glycerol (2-AG), the most abundant endocannabinoid in tissues. Required for axonal growth during development and for retrograde synaptic signaling at mature synapses
Gene Name:
DAGLA
Uniprot ID:
Q9Y4D2
Molecular weight:
114950.7

Transporters

Enzyme Details
1. Transient receptor potential cation channel subfamily V member 1
General function:
Involved in ion channel activity
Specific function:
Receptor-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. May be involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL
Gene Name:
TRPV1
Uniprot ID:
Q8NER1
Molecular weight:
94955.3
Enzyme Details
2. Transient receptor potential cation channel subfamily V member 2
General function:
Involved in ion channel activity
Specific function:
Calcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by IGF-I, PDGF and neuropeptide head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH
Gene Name:
TRPV2
Uniprot ID:
Q9Y5S1
Molecular weight:
85980.3
Enzyme Details
3. Transient receptor potential cation channel subfamily A member 1
General function:
Not Available
Specific function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)- tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular weight:
127485.8