Homologue of tetrahydrocannabinol
Tetrahydrocannabivarin
Routes of administration
Oral ,
smoked ,
inhaled
ATC code
Legal status
US : Unscheduled
Also legal in UK, Canada and Netherlands
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 )
Formula C 19 H 26 O 2
Molar mass 286.415 g·mol−1 3D model (
JSmol )
CCCC1=CC2=C(C3C=C(CCC3C(O2)(C)C)C)C(=C1)O
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
Y Key:ZROLHBHDLIHEMS-HUUCEWRRSA-N
Y
N Y
(what is this?)
(verify)
Tetrahydrocannabivarin (THCV , THV , O-4394 , GWP42004 ) 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 .
[1] THCV was studied by
Roger Adams as early as 1942.
[2]
Natural occurrence
THCV is prevalent in certain central Asian and southern African strains of Cannabis .
[3]
[4]
Chemistry
Similar to
THC , THCV has 7 possible
double bond
isomers and 30
stereoisomers (see:
Tetrahydrocannabinol#Isomerism ). The alternative isomer Δ8 -THCV is known as a synthetic compound with a code number of O-4395,
[5] but it is not known to have been isolated from
Cannabis plant material.
O-4395 (Δ8 -THCV), 31262-38-1
[1]
Description
Plants with elevated levels of propyl cannabinoids (including THCV) have been found in populations of Cannabis sativa L. ssp. indica (= Cannabis indica Lam.) from China,
India ,
Nepal , Thailand,
Afghanistan , and
Pakistan , as well as southern and western Africa. THCV levels up to 20% of total cannabinoids have been reported.
[2]
THCV is a
cannabinoid receptor type 1
antagonist or, at higher doses, a CB1 receptor agonist and
cannabinoid receptor type 2
partial agonist .
[6] Δ8 -THCV has also been shown to be a CB1 antagonist.
[7] Both papers describing the antagonistic properties of THCV were demonstrated in
murine models. THCV is an
antagonist of THC at CB1 receptors and lessens the psychoactive effects of THC.
[8]
THCV also acts as an agonist of
GPR55 and
l-α-lysophosphatidylinositol (LPI), and beyond the
endocannabinoid system , THCV also activate
5-HT1A receptors to produce an
antipsychotic effect, that has shown therapeutic potential for ameliorating some of the negative,
cognitive and positive symptoms of
schizophrenia . THCV furthermore 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 . It has also shown
anti-epileptiform and
anticonvulsant properties, that suggest possible therapeutic application in the treatment of
pathophysiologic hyperexcitability states such as untreatable epilepsy.
[9]
THCV is found to inhibit the activity of both
fatty acid amide hydrolase (FAAH) and
monoacyl glycerol lipase (MGL), even at micromolar concentrations, and thereby able to inhibit the
hydrolysis of the endocannabinoids
anandamide (AEA:
C 22
H 37
NO 2 ; 20:
4 ,
ω-6 ) besides other
N -acylethanolamines and
2-Arachidonoylglycerol (2-AG: C23 H38 O4 ; 20:4, ω-6), respectively, therefore, it can also act as an indirect agonist at the
cannabinoid receptors , by enhancing the activity of the
endocannabinoid system (ECS).
[10]
[11]
Biosynthesis
Unlike
THC ,
cannabidiol (CBD), and
cannabichromene (CBC), THCV doesn't begin as
cannabigerolic acid (CBGA). Instead of combining with
olivetolic acid to create CBGA,
geranyl pyrophosphate joins with
divarinolic acid , which has two fewer carbon atoms. The result is
cannabigerovarin acid (CBGVA). Once CBGVA is created, the process continues exactly the same as it would for THC. CBGVA is broken down to
tetrahydrocannabivarin carboxylic acid (THCVA) by the enzyme
THCV synthase . At that point, THCVA can be
decarboxylated with heat or UV light to create THCV.
[12]
Research
Reducing blood sugar
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 to
metformin .
[14] [
better source needed ]
Appetite control
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]
Pancreatic cancer
THCV has been demonstrated to show anti-cancer properties in vitro on PANC-1, AsPc-1, HPAF-II, and MiaPaCa-2 cell lines. There is no record of research on in vivo models
[16] [
better source needed ]
Energy and Motivation
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.
[17]
[18] [
better source needed ]
Legal status
It is not scheduled by
Convention on Psychotropic Substances . [
citation needed ]
United States
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.
[19]
The
2018 United States farm bill legalized the production and sale of THCV if it is derived from hemp compliant with the farm bill.
[20] [
non-primary source needed ]
See also
References
^ 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 .
^
^ 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. Retrieved 2023-06-30 .
^ 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). Retrieved 2022-07-07 .
^ 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 .
^ Tesfatsion T, Collins A, Ramirez G, Mzannar Y, Khan H, Aboukameel O, et al. (2022). "Antineoplastic Properties of THCV, HHC and their anti-Proliferative effects on HPAF-II, MIA-paca2, Aspc-1, and PANC-1 PDAC Pancreatic Cell Lines". ChemRxiv .
doi :
10.26434/chemrxiv-2022-v4zqc-v2 .
^ Phylos.
"Phylos® and People Science® Announce Results of IRB-Backed Controlled Research Study on the Energizing Effects of THCV" . www.prnewswire.com . Retrieved 2024-03-10 .
^
"THCV Efficacy Study_ Abstract and Method [C142-202402-001] (1).pdf" . Google Docs . Retrieved 2024-03-10 .
^
"§1308.11 Schedule I. section (d) Hallucinogenic substances part (33)" . Drug Enforcement Agency . U.S. Department of Justice. Archived from
the original on 2009-08-27.
^
"Summary of H.R. 2 (115th): Agriculture Improvement Act of 2018" . GovTrack.
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