Identification
- Generic Name
- Tetrahydrocannabivarin
- DrugBank Accession Number
- DB11755
- Background
Tetrahydrocannabivarin (THCV) is a propyl analogue of tetrahydrocannabinol (Δ9-THC), one of the primary pharmacological components of Medical Cannabis. Δ9-THC is currently available in several synthetic forms, including Dronabinol, while purified or isolated THCV is not approved for any medical uses and is not available as any marketed products. As a major phytocannabinoid, however, THCV is accessible within Medical Cannabis along with other identified cannabinoids including Cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), cannabivarin (CBV), and Cannabidivarin (CBDV).
THCV is one of four cannabinoids with identified potential as anticonvulsant agents, which also includes Δ9-tetrahydrocannabinolic acid, Cannabidiol (CBD), and Cannabidivarin (CBDV) 11.
Although THCV possesses an almost identical structure to Δ9-THC (varying only by the length of its lipophilic alkyl chain), it has different molecular targets and pharmacological profile 1. Compared to THC which demonstrates its effects through weak partial agonist activity of both endocannabinoid receptors Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R), THCV acts as a CB1 antagonist and a partial agonist of CB2 2. Further evidence has also shown that THCV acts as an agonist of GPR55 and l-α-lysophosphatidylinositol (LPI) 3. Beyond the endocannabinoid system, THCV has also been reported to activate 5HT1A receptors to produce an antipsychotic effect that has therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia 4. Furthermore, THCV interacts with different transient receptor potential (TRP) channels including TRPV2, which may contribute to the analgesic, anti-inflammatory and anti-cancer effects of cannabinoids and Cannabis extracts 5. It has also shown antiepileptiform and anticonvulsant properties, that suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states such as untreatable epilepsy 10.
Cannabinoid receptors are utilized endogenously by the body through the endocannabinoid system, which includes a group of lipid proteins, enzymes, and receptors that are involved in many physiological processes. Through its modulation of neurotransmitter release, the endocannabinoid system regulates cognition, pain sensation, appetite, memory, sleep, immune function, and mood among many others. These effects are largely mediated through two members of the G-protein coupled receptor family, cannabinoid receptors 1 and 2 (CB1 and CB2)6. CB1 receptors are found in both the central and peripheral nervous systems, with the majority of receptors localized to the hippocampus and amygdala of the brain. Physiological effects of using cannabis make sense in the context of its receptor activity as the hippocampus and amygdala are primarily involved with regulation of memory, fear, and emotion. In contrast, CB2 receptors are mainly found peripherally in immune cells, lymphoid tissue, and peripheral nerve terminals 7.
Reliably studying the effects of Cannabis (and of THCV) is complicated by the numerous other compounds that Cannabis contains such as terpenes, flavonoids, phenols, amino acids, and fatty acids among many others that have the potential to modulate the plant's pharmacological effect 8,9.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Tetrahydrocannabivarin (DB11755)
- Weight
- Average: 286.415
Monoisotopic: 286.193280077 - Chemical Formula
- C19H26O2
- Synonyms
- THCV
- External IDs
- GWP-42004
- GWP42004
- O-4394
Pharmacology
- Indication
THCV does not currently have any FDA, Health Canada, or EMA approved indications.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Compared to THC which demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, THCV acts as a CB1 antagonist and a partial agonist of CB2 2. Further evidence has also shown that THCV acts as an agonist of GPR55 and l-α-lysophosphatidylinositol (LPI) 3. Beyond the endocannabinoid system, THCV has also been reported to activate 5HT1A receptors to produce an antipsychotic effect that has therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia 4. Furthermore, THCV interacts with different transient receptor potential (TRP) channels including TRPV1, which may contribute to the analgesic, anti-inflammatory and anti-cancer effects of cannabinoids and Cannabis extracts 5.
- Mechanism of action
Target Actions Organism ACannabinoid receptor 1 antagonistHumans AG-protein coupled receptor 55 partial agonistHumans A5-hydroxytryptamine receptor 1A agonistHumans ATransient receptor potential cation channel subfamily V member 2 agonistHumans ATransient receptor potential cation channel subfamily M member 8 antagonistHumans ATransient receptor potential cation channel subfamily A member 1 agonistHumans UCannabinoid receptor 2 partial agonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Tetrahydrocannabivarin is combined with 1,2-Benzodiazepine. Acebutolol Tetrahydrocannabivarin may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of hypertension can be increased when Aceclofenac is combined with Tetrahydrocannabivarin. Acemetacin The risk or severity of hypertension can be increased when Tetrahydrocannabivarin is combined with Acemetacin. Acenocoumarol The risk or severity of adverse effects can be increased when Tetrahydrocannabivarin is combined with Acenocoumarol. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 2,2-dimethyl-1-benzopyrans. These are organic compounds containing a 1-benzopyran moiety that carries two methyl groups at the 2-position.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzopyrans
- Sub Class
- 1-benzopyrans
- Direct Parent
- 2,2-dimethyl-1-benzopyrans
- Alternative Parents
- Alkyl aryl ethers / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Oxacyclic compounds / Hydrocarbon derivatives
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / 2,2-dimethyl-1-benzopyran / Alkyl aryl ether / Aromatic heteropolycyclic compound / Benzenoid / Ether / Hydrocarbon derivative / Organic oxygen compound / Organooxygen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- I5YE3I47D8
- CAS number
- 31262-37-0
- InChI Key
- ZROLHBHDLIHEMS-HUUCEWRRSA-N
- InChI
- InChI=1S/C19H26O2/c1-5-6-13-10-16(20)18-14-9-12(2)7-8-15(14)19(3,4)21-17(18)11-13/h9-11,14-15,20H,5-8H2,1-4H3/t14-,15-/m1/s1
- IUPAC Name
- (6aR,10aR)-6,6,9-trimethyl-3-propyl-6H,6aH,7H,8H,10aH-benzo[c]isochromen-1-ol
- SMILES
- CCCC1=CC(O)=C2[C@@H]3C=C(C)CC[C@H]3C(C)(C)OC2=C1
References
- General References
- Morales P, Hurst DP, Reggio PH: Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. [Article]
- Pertwee RG: The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008 Jan;153(2):199-215. doi: 10.1038/sj.bjp.0707442. Epub 2007 Sep 10. [Article]
- Anavi-Goffer S, Baillie G, Irving AJ, Gertsch J, Greig IR, Pertwee RG, Ross RA: Modulation of L-alpha-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids. J Biol Chem. 2012 Jan 2;287(1):91-104. doi: 10.1074/jbc.M111.296020. Epub 2011 Oct 25. [Article]
- Cascio MG, Zamberletti E, Marini P, Parolaro D, Pertwee RG: The phytocannabinoid, Delta(9)-tetrahydrocannabivarin, can act through 5-HT(1)A receptors to produce antipsychotic effects. Br J Pharmacol. 2015 Mar;172(5):1305-18. doi: 10.1111/bph.13000. [Article]
- 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. [Article]
- Zou S, Kumar U: Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018 Mar 13;19(3). pii: ijms19030833. doi: 10.3390/ijms19030833. [Article]
- Kaur R, Ambwani SR, Singh S: Endocannabinoid System: A Multi-Facet Therapeutic Target. Curr Clin Pharmacol. 2016;11(2):110-7. [Article]
- Pollastro F, Minassi A, Fresu LG: Cannabis Phenolics and their Bioactivities. Curr Med Chem. 2018;25(10):1160-1185. doi: 10.2174/0929867324666170810164636. [Article]
- Baron EP: Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been .... Headache. 2015 Jun;55(6):885-916. doi: 10.1111/head.12570. Epub 2015 May 25. [Article]
- Hill AJ, Weston SE, Jones NA, Smith I, Bevan SA, Williamson EM, Stephens GJ, Williams CM, Whalley BJ: Delta(9)-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. Epilepsia. 2010 Aug;51(8):1522-32. doi: 10.1111/j.1528-1167.2010.02523.x. Epub 2010 Feb 26. [Article]
- 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 6:1-7. doi: 10.1080/13543784.2018.1482275. [Article]
- External Links
- PubChem Compound
- 93147
- PubChem Substance
- 347828110
- ChemSpider
- 84092
- ChEMBL
- CHEMBL2387541
- ZINC
- ZINC000005649505
- PDBe Ligand
- I8E
- Wikipedia
- Tetrahydrocannabivarin
- PDB Entries
- 8sp8
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Dyslipidemia / Type 2 Diabetes Mellitus 1 2 Completed Treatment Type 2 Diabetes Mellitus 1 2 Terminated Treatment Schizophrenia 1 0 Completed Treatment High Cholesterol / Hyperglycemia / Obesity, Morbid / Syndrome, Metabolic 1 0 Recruiting Treatment Androgenetic Alopecia (AGA) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0089 mg/mL ALOGPS logP 6.08 ALOGPS logP 5.06 Chemaxon logS -4.5 ALOGPS pKa (Strongest Acidic) 9.34 Chemaxon pKa (Strongest Basic) -4.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 29.46 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 87.53 m3·mol-1 Chemaxon Polarizability 34.7 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0290000000-360d1820113e71fa5dcf Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0090000000-bd288c50f076de66e17f Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0390000000-f8aba349c9f90a424f93 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0090000000-c1ebf6a1ece5a9c9cd93 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0f7a-3960000000-117750901c719ae33e14 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0frf-0090000000-6ec7f1e5e71cad470628 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 183.2987327 predictedDarkChem Lite v0.1.0 [M-H]- 182.24178 predictedDeepCCS 1.0 (2019) [M+H]+ 184.6167327 predictedDarkChem Lite v0.1.0 [M+H]+ 184.61516 predictedDeepCCS 1.0 (2019) [M+Na]+ 183.1137327 predictedDarkChem Lite v0.1.0 [M+Na]+ 191.77634 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Drug binding
- Specific Function
- Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered l...
- Gene Name
- CNR1
- Uniprot ID
- P21554
- Uniprot Name
- Cannabinoid receptor 1
- Molecular Weight
- 52857.365 Da
References
- Morales P, Hurst DP, Reggio PH: Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Partial agonist
- General Function
- G-protein coupled receptor activity
- Specific Function
- May be involved in hyperalgesia associated with inflammatory and neuropathic pain (By similarity). Receptor for L-alpha-lysophosphatidylinositol (LPI). LPI induces Ca(2+) release from intracellular...
- Gene Name
- GPR55
- Uniprot ID
- Q9Y2T6
- Uniprot Name
- G-protein coupled receptor 55
- Molecular Weight
- 36637.12 Da
References
- Morales P, Hurst DP, Reggio PH: Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. [Article]
- Anavi-Goffer S, Baillie G, Irving AJ, Gertsch J, Greig IR, Pertwee RG, Ross RA: Modulation of L-alpha-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids. J Biol Chem. 2012 Jan 2;287(1):91-104. doi: 10.1074/jbc.M111.296020. Epub 2011 Oct 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
- Gene Name
- HTR1A
- Uniprot ID
- P08908
- Uniprot Name
- 5-hydroxytryptamine receptor 1A
- Molecular Weight
- 46106.335 Da
References
- Morales P, Hurst DP, Reggio PH: Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. [Article]
- Cascio MG, Zamberletti E, Marini P, Parolaro D, Pertwee RG: The phytocannabinoid, Delta(9)-tetrahydrocannabivarin, can act through 5-HT(1)A receptors to produce antipsychotic effects. Br J Pharmacol. 2015 Mar;172(5):1305-18. doi: 10.1111/bph.13000. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General 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.
- Specific Function
- Calcium channel activity
- Gene Name
- TRPV2
- Uniprot ID
- Q9Y5S1
- Uniprot Name
- Transient receptor potential cation channel subfamily V member 2
- Molecular Weight
- 85980.335 Da
References
- Morales P, Hurst DP, Reggio PH: Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Calcium channel activity
- Specific Function
- Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalypto...
- Gene Name
- TRPM8
- Uniprot ID
- Q7Z2W7
- Uniprot Name
- Transient receptor potential cation channel subfamily M member 8
- Molecular Weight
- 127684.035 Da
References
- Morales P, Hurst DP, Reggio PH: Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Temperature-gated cation channel activity
- Specific Function
- Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in t...
- Gene Name
- TRPA1
- Uniprot ID
- O75762
- Uniprot Name
- Transient receptor potential cation channel subfamily A member 1
- Molecular Weight
- 127499.88 Da
References
- Morales P, Hurst DP, Reggio PH: Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Partial agonist
- General Function
- Cannabinoid receptor activity
- Specific Function
- Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and b...
- Gene Name
- CNR2
- Uniprot ID
- P34972
- Uniprot Name
- Cannabinoid receptor 2
- Molecular Weight
- 39680.275 Da
References
- Morales P, Hurst DP, Reggio PH: Molecular Targets of the Phytocannabinoids: A Complex Picture. Prog Chem Org Nat Prod. 2017;103:103-131. doi: 10.1007/978-3-319-45541-9_4. [Article]
Drug created at October 20, 2016 20:45 / Updated at June 12, 2020 16:53