Homologue of tetrahydrocannabinol
Pharmaceutical compound
Tetrahydrocannabivarin Clinical data Routes of Oral ,smoked ,inhaled ATC code Legal status Legal status US: Also legal in UK, Canada and Netherlands Identifiers 6,6,9-Trimethyl-3-propyl-6a,7,8,10a-tetrahydro-6H -benzo[c]chromen-1-ol
CAS Number PubChem CID IUPHAR/BPS ChemSpider UNII CompTox Dashboard (EPA) Chemical and physical data Formula C 19 H 26 O 2 Molar mass −1 3D model (JSmol ) 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
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Tetrahydrocannabivarin (THCV ,THV ,O-4394 ,GWP42004 ) is ahomologue oftetrahydrocannabinol (THC) having apropyl (3-carbon) side chain instead ofpentyl (5-carbon), making it non-psychoactive in lower doses. It has been shown to exhibitneuroprotective activity ,appetite suppression ,glycemic control and reducedside effects compared to THC, making it a potential treatment for management ofobesity anddiabetes .[ 1] Roger Adams as early as 1942.[ 2]
THCV is prevalent in certain central Asian and southern African strains ofCannabis .[ 3] [ 4]
Similar toTHC , THCV has 7 possibledouble bond isomers and 30stereoisomers (see:Tetrahydrocannabinol#Isomerism ). The alternative isomer Δ8 -THCV is known as a synthetic compound with a code number of O-4395,[ 5] Cannabis
The chemical structure of (Δ8 -THCV), a synthetic analog of THCV. Other names include O-4395, CAS 31262-38-1[1]
Plants with elevated levels of propyl cannabinoids (including THCV) have been found in populations ofCannabis sativa L. ssp.indica (=Cannabis indica Lam.) from China,India ,Nepal , Thailand,Afghanistan , andPakistan , as well as southern and western Africa. THCV levels up to 20% of total cannabinoids have been reported.[2]
THCV is acannabinoid receptor type 1 antagonist or, at higher doses, a CB1 receptor agonist andcannabinoid receptor type 2 partial agonist .[ 6] 8 -THCV has also been shown to be a CB1 antagonist.[ 7] murine models. THCV is anantagonist of THC at CB1 receptors and lessens the psychoactive effects of THC.[ 8]
THCV also acts as an agonist ofGPR55 andl-α-lysophosphatidylinositol (LPI), and beyond theendocannabinoid system , THCV also activate5-HT1A receptors to produce anantipsychotic effect, that has shown therapeutic potential for ameliorating some of the negative,cognitive and positive symptoms ofschizophrenia . THCV furthermore interacts with differenttransient receptor potential (TRP) channels includingTRPV2 , which may contribute to theanalgesic ,anti-inflammatory andanti-cancer effects ofcannabinoids andCannabis extracts . It has also shownanti-epileptiform andanticonvulsant properties, that suggest possible therapeutic application in the treatment ofpathophysiologic hyperexcitability states such as untreatable epilepsy.[ 9]
THCV is found to inhibit the activity of bothfatty acid amide hydrolase (FAAH) andmonoacyl glycerol lipase (MGL), even at micromolar concentrations, and thereby able to inhibit thehydrolysis of the endocannabinoidsanandamide (AEA:C 22 H 37 NO 2 ; 20:4 ,ω-6 ) besides otherN -acylethanolamines2-Arachidonoylglycerol (2-AG: C23 H38 O4 ; 20:4, ω-6), respectively, therefore, it can also act as an indirect agonist at thecannabinoid receptors , by enhancing the activity of theendocannabinoid system (ECS).[ 10] [ 11]
UnlikeTHC ,cannabidiol (CBD), andcannabichromene (CBC), THCV doesn't begin ascannabigerolic acid (CBGA). Instead of combining witholivetolic acid to create CBGA,geranyl pyrophosphate joins withdivarinolic acid , which has two fewer carbon atoms. The result iscannabigerovarin acid (CBGVA). Once CBGVA is created, the process continues exactly the same as it would for THC. CBGVA is broken down totetrahydrocannabivarin carboxylic acid (THCVA) by the enzymeTHCV synthase . At that point, THCVA can bedecarboxylated with heat or UV light to create THCV.[ 12]
Reducing blood sugar [ edit ] THCV is a new potential treatment against obesity-associated glucose intolerance with pharmacology different from that of CB1 inverse agonists/antagonists.[ 13] GW Pharmaceuticals is studying plant-derived tetrahydrocannabivarin (as GWP42004) for type 2 diabetes in addition tometformin .[ 14] [better source needed
THC increases appetite, which is sometimes referred to as "the munchies." THC acts as a CB1 agonist. As a CB1 antagonist,THCV has been shown to reduce appetite in murine models.[ 15]
Energy and motivation [ edit ] A 2:1 ratio of naturally derived THCV to THC extract has been demonstrated to show energizing and motivating effects in a double blind placebo clinical study which relied on a self-reported user survey for results.[ 16] [ 17] [better source needed
It is not scheduled byConvention on Psychotropic Substances .[citation needed
THCV is not scheduled at the federal level so long as it is not derived from cannabis varieties that produce more than .3% THC on a dry weight basis in the United States.[ 18]
The2018 United States farm bill legalized the production and sale of THCV if it is derived from hemp compliant with the farm bill.[ 19] [non-primary source needed
^ Abioye A, Ayodele O, Marinkovic A, Patidar R, Akinwekomi A, Sanyaolu A (January 2020)."Δ9-Tetrahydrocannabivarin (THCV): a commentary on potential therapeutic benefit for the management of obesity and diabetes" .Journal of Cannabis Research .2 (1): 6.doi :10.1186/s42238-020-0016-7 PMC 7819335 PMID 33526143 . ^ Adams R, Loewe S, Smith CM, McPhee WD (1942)."Tetrahydrocannabinol Homologs and Analogs with Marihuana Activity. XIII1 " Journal of the American Chemical Society .64 (3):694– 697.doi :10.1021/ja01255a061 . ^ Baker PB, Gough TA, Taylor BJ (1980)."Illicitly imported Cannabis products: some physical and chemical features indicative of their origin" .Bulletin on Narcotics .32 (2):31– 40.PMID 6907024 . ^ Hillig KW, Mahlberg PG (June 2004)."A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae)" .American Journal of Botany .91 (6):966– 75.doi :10.3732/ajb.91.6.966 PMID 21653452 . ^ Brown NK, Harvey DJ (April 1988). "In vivo metabolism of the n-propyl homologues of delta-8- and delta-9-tetrahydrocannabinol in the mouse".Biomedical & Environmental Mass Spectrometry .15 (7):403– 10.doi :10.1002/bms.1200150708 .PMID 2839261 . ^ Pertwee RG (January 2008)."The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin" .British Journal of Pharmacology .153 (2):199– 215.doi :10.1038/sj.bjp.0707442 .PMC 2219532 PMID 17828291 . ^ Pertwee RG, Thomas A, Stevenson LA, Ross RA, Varvel SA, Lichtman AH, et al. (March 2007)."The psychoactive plant cannabinoid, Delta9-tetrahydrocannabinol, is antagonized by Delta8- and Delta9-tetrahydrocannabivarin in mice in vivo" .British Journal of Pharmacology .150 (5):586– 94.doi :10.1038/sj.bjp.0707124 .PMC 2189766 PMID 17245367 . ^ Thomas A, Stevenson LA, Wease KN, Price MR, Baillie G, Ross RA, et al. (December 2005)."Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist" .British Journal of Pharmacology .146 (7):917– 26.doi :10.1038/sj.bjp.0706414 .PMC 1751228 PMID 16205722 . ^ "Tetrahydrocannabivarin" .PubChem . U.S. National Library of Medicine. Retrieved2023-06-30 .^ McPartland JM, Duncan M, Di Marzo V, Pertwee RG (February 2015)."Are cannabidiol and Δ(9) -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review" .British Journal of Pharmacology .172 (3):737– 753.doi :10.1111/bph.12944 .PMC 4301686 PMID 25257544 . ^ Jadoon KA (2013-09-13)."Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study" .Diabetes Care .39 (10). ^ Walsh KB, McKinney AE, Holmes AE (29 November 2021)."Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses" .Frontiers in Pharmacology .12 777804.doi :10.3389/fphar.2021.777804 PMC 8669157 PMID 34916950 . ^ Wargent ET, Zaibi MS, Silvestri C, Hislop DC, Stocker CJ, Stott CG, et al. (May 2013)."The cannabinoid Δ(9)-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity" .Nutrition & Diabetes .3 (5): e68.doi :10.1038/nutd.2013.9 .PMC 3671751 PMID 23712280 . ^ GW Pharmaceuticals plc (2014-03-17)."GW Pharmaceuticals Provides Update on Cannabinoid Pipeline" .GlobeNewswire News Room (Press release). Retrieved2022-07-07 . ^ Riedel G, Fadda P, McKillop-Smith S, Pertwee RG, Platt B, Robinson L (2009)."Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice" .British Journal of Pharmacology .156 (7):1154– 1166.doi :10.1111/j.1476-5381.2008.00107.x .PMC 2697695 PMID 19378378 . ^ Phylos."Phylos® and People Science® Announce Results of IRB-Backed Controlled Research Study on the Energizing Effects of THCV" .www.prnewswire.com . Retrieved2024-03-10 . ^ "THCV Efficacy Study_ Abstract and Method [C142-202402-001] (1).pdf" .Google Docs . Retrieved2024-03-10 .^ "§1308.11 Schedule I. section (d) Hallucinogenic substances part (33)" .Drug Enforcement Agency . U.S. Department of Justice. Archived fromthe original on 2009-08-27.^ "Summary of H.R. 2 (115th): Agriculture Improvement Act of 2018" . GovTrack.Erowid Compounds found inCannabis sativa
Phytocannabinoids comparison )
Cannabibutols Cannabichromenes Cannabicyclols Cannabidiols Cannabielsoins Cannabigerols Cannabiphorols Cannabinols Cannabitriols Cannabivarins Delta-3-tetrahydrocannabinols Delta-4-tetrahydrocannabinols Delta-7-tetrahydrocannabinols Delta-8-tetrahydrocannabinols Delta-9-tetrahydrocannabinols Delta-10-Tetrahydrocannabinols Delta-11-Tetrahydrocannabinols Miscellaneous cannabinoids Active metabolites
Endocannabinoids Synthetic
Classical cannabinoids Non-classical Adamantoylindoles Benzimidazoles Benzoylindoles Cyclohexylphenols Eicosanoids Indazole-3- Indole-3-carboxamides Indole-3-carboxylates Naphthoylindazoles Naphthoylindoles Naphthoylpyrroles Naphthylmethylindenes Naphthylmethylindoles Phenylacetylindoles Pyrazolecarboxamides Tetramethylcyclo- Tetramethylcyclo- Others
Allosteric CBR Tooltip Cannabinoid receptor ligands Endocannabinoid (inactivation inhibitors) Anticannabinoids (antagonists/inverse
Receptor (ligands )
CB1 Tooltip Cannabinoid receptor type 1
Agonists(abridged,full list ) Inverse agonists Antagonists
CB2 Tooltip Cannabinoid receptor type 2
Agonists 2-AG 2-AGE (noladin ether) 3,3'-Diindolylmethane 4-O-Methylhonokiol α-Amyrin · β-Amyrin A-796,260 A-834,735 A-836,339 AM-1172 AM-1221 AM-1235 AM-1241 AM-2232 Anandamide AZ-11713908 Cannabinol Caryophyllene CB-13 CBS-0550 CP 55,940 GW-405,833 (L-768,242) GW-842,166X HU-308 JTE 7-31 JWH-007 JWH-015 JWH-018 JWH-73 JWH-133 L-759,633 L-759,656 Lenabasum (anabasum) Magnolol MDA-19 Nabitan NADA Olorinab (APD-371) PF-03550096 S-444,823 SER-601 Serinolamide A UR-144 Tedalinab THC (dronabinol) THCV Tetrahydromagnolol Virodhamine Antagonists
NAGly GPR18)
GPR55
GPR119
Transporter (modulators )
eCBTs Tooltip Endocannabinoid transporter
Enzyme (modulators)
Others Others: 2-PG (directly potentiates activity of 2-AG at CB1 receptor) ARN-272 (FAAH-like anandamide transporter inhibitor)
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