Tetrahydrocannabivarin (THCV, THV, O-4394, GWP42004) is a homologue of

tetrahydrocannabinol Tetrahydrocannabinol (THC) 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'' ...

(THC) having a propyl (3-carbon) side chain instead of a pentyl (5-carbon) group on the molecule, which makes it produce very different effects from THC.

Natural occurrence

THCV is prevalent in certain central Asian and southern African strains of ''Cannabis''.

Chemistry

Similar to

THC Tetrahydrocannabinol (THC) 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'' ...

, THCV has 7 possible

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...

isomers In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

and 30

stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...

s (see: Tetrahydrocannabinol#Isomerism). The alternative isomer Δ⁸-THCV is known as a synthetic compound with a code number of O-4395, but it is not known to have been isolated from ''

Cannabis ''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 ...

'' plant material. D8THCV_structure

]

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 India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...

Nepal Nepal (; ne, नेपाल ), formerly the Federal Democratic Republic of Nepal ( ne, सङ्घीय लोकतान्त्रिक गणतन्त्र नेपाल ), is a landlocked country in South Asia. It is mai ...

, Thailand,

Afghanistan Afghanistan, officially the Islamic Emirate of Afghanistan,; prs, امارت اسلامی افغانستان is a landlocked country located at the crossroads of Central Asia and South Asia. Referred to as the Heart of Asia, it is bordere ...

, and

Pakistan Pakistan ( ur, ), officially the Islamic Republic of Pakistan ( ur, , label=none), is a country in South Asia. It is the world's List of countries and dependencies by population, fifth-most populous country, with a population of almost 24 ...

, as well as southern and western Africa. THCV levels up to 53.7% of total cannabinoids have been reported. THCV is a

cannabinoid receptor type 1 Cannabinoid receptor type 1 (CB1), also known as cannabinoid receptor 1, is a G protein-coupled cannabinoid receptor that in humans is encoded by the ''CNR1'' gene. The human CB1 receptor is expressed in the peripheral nervous system and central ...

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

or, at higher doses, a CB₁ receptor agonist and

cannabinoid receptor type 2 The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the ''CNR2'' gene. It is closely related to the cannabinoid receptor type 1 (CB1), which is la ...

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...

. Δ⁸-THCV has also been shown to be a CB₁ antagonist. Both papers describing the antagonistic properties of THCV were demonstrated in

murine The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families excep ...

models. THCV is an

of THC at CB₁ receptors and lessens the psychoactive effects of THC.

Biosynthesis

Unlike

cannabidiol Cannabidiol (CBD) is a phytocannabinoid discovered in 1940. It is one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. , clinical research on CBD incl ...

(CBD), and

cannabichromene Cannabichromene (CBC), also called cannabichrome, cannanbichromene, pentylcannabichromene or cannabinochromene, is an anti-inflammatory which may contribute to the pain-killing effect of cannabis. It is one of the hundreds of cannabinoids found i ...

(CBC), THCV doesn't begin as

cannabigerolic acid Cannabigerolic acid (CBGA) is the acidic form of cannabigerol (CBG). It is a dihydroxybenzoic acid and olivetolic acid in which the hydrogen at position 3 is substituted by a geranyl group. It is a biosynthetic precursor to Delta-9-tetrahydroc ...

(CBGA). Instead of combining with

olivetolic acid Olivetolic acid is an organic compound that is an intermediate in the biosynthetic pathway of the cannabinoids in ''Cannabis sativa ''Cannabis sativa'' is an annual herbaceous flowering plant indigenous to Eastern Asia, but now of cosmopoli ...

to create CBGA,

geranyl pyrophosphate Geranyl pyrophosphate (GPP), also known as geranyl diphosphate (GDP), is the pyrophosphate ester of the terpenoid geraniol. Its salts are colorless. It is a precursor to many natural products. Occurrence GPP is an intermediate in the isoprenoid ...

joins with divarinolic acid, which has two fewer carbon atoms. The result is

cannabigerovarin acid Cannabigerovarin (CBGV), the propyl homolog of cannabigerol (CBG), is a cannabinoid present in ''Cannabis''. There is no observation related to the psychoactive or psychotropic effects of CBGV when consumed or inhaled. The possible benefits of ...

(CBGVA). Once CBGVA is created, the process continues exactly the same as it would for THC. CBGVA is broken down to

tetrahydrocannabivarin carboxylic acid Tetrahydrocannabivarin (THCV, THV, O-4394, GWP42004) is a homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of a pentyl (5-carbon) group on the molecule, which makes it produce very different effects from THC. ...

(THCVA) by the enzyme

THCV synthase Tetrahydrocannabivarin (THCV, THV, O-4394, GWP42004) is a homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of a pentyl (5-carbon) group on the molecule, which makes it produce very different effects from THC. ...

. At that point, THCVA can be

decarboxylated Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is t ...

with heat or UV light to create THCV.

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.

GW Pharmaceuticals GW Pharmaceuticals is a British pharmaceutics company known for its multiple sclerosis treatment product nabiximols (brand name, Sativex) which was the first natural cannabis plant derivative to gain market approval in any country. Another cannab ...

is studying plant-derived tetrahydrocannabivarin (as GWP42004) for type 2 diabetes in addition to

metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...

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.

Legal status

It is not scheduled by

Convention on Psychotropic Substances The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as #Amphetamine-type stimulants, amphetamine-type stimulants, barbiturates, benzodiazepines, and Psychedelic drug, psychede ...

. In the United States, THCV is not specifically listed as a

Schedule I drug The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...

, but "Marijuana Extract" is. THCV could be considered an analog of THC, in which case, sales or possession intended for human consumption could be prosecuted under the

Federal Analog Act The Federal Analogue Act, , is a section of the United States Controlled Substances Act passed in 1986 which allows any chemical "substantially similar" to a controlled substance listed in Controlled Substances Act#Schedule I controlled substance ...

United States

THCV is not scheduled at the federal level so long as it is not derived from the cannabis plant in the United States.§1308.11 Schedule I.
section (d) Hallucinogenic substances part (33) The

2018 United States farm bill The 2018 farm bill or Agriculture Improvement Act of 2018 is an enacted United States farm bill that reauthorized $867 billion for many expenditures approved in the prior farm bill (the Agricultural Act of 2014). The bill was passed by the Senat ...

legalized the production and sale of THCV if it is derived from hemp compliant with the farm bill.

References

External links

Erowid
Compounds found in ''Cannabis sativa'' {{Cannabinoidergics Phytocannabinoids CB1 receptor antagonists Terpeno-phenolic compounds Benzochromenes