Tetrahydrocannabinol
Tetrahydrocannabinol (THC) is a cannabinoid found in cannabis.[9] It is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Its chemical formula C21H30O2 includes compounds,[10] the term THC usually refers to the delta-9-THC isomer with chemical name (−)-trans-Δ9-tetrahydrocannabinol. It is a colorless oil.
"THC" redirects here. For other uses, see THC (disambiguation).Clinical data
Marinol, Syndros
(6aR,10aR)-delta-9-Tetrahydrocannabinol; (−)-trans-Δ9-Tetrahydrocannabinol; THC
- US FDA: Dronabinol
Physical: Low
Psychological: Low–moderate
Relatively low: 9%
Oral, local/topical, transdermal, sublingual, inhaled
- AU: Unscheduled: ACT, Schedule 8 (Controlled Drug)
- BR: Dronabinol: A3; THC <30mg/ml: A3; others: F2 (prohibited).[1]
- CA: Unscheduled
- DE: Dronabinol: Anlage III, Δ9-THC: II, other isomers and their stereochemical variants: I. (Does not apply to THC as part of cannabis, which is regulated separately, see Cannabis (drug))
- UK: Class B
- US: Schedule II as Syndros, and Schedule III as Marinol[2]
- UN: Psychotropic Schedule I /II
10–35% (inhalation), 6–20% (oral)[3]
Mostly hepatic by CYP2C[3]
1.6–59 h,[3] 25–36 h (orally administered dronabinol)
65–80% (feces), 20–35% (urine) as acid metabolites[3]
C21H30O2
314.469 g·mol−1
−152° (ethanol)
0.0028 mg/mL (23 °C)[8]
Overdose[edit]
The median lethal dose of THC in humans is not fully known as there is conflicting evidence. A 1972 study gave up to 9000 mg/kg of THC to dogs and monkeys without any lethal effects. Some rats died within 72 hours after a dose of up to 3600 mg/kg.[16] A 2014 case study based on the toxicology reports and relative testimony in two separate cases gave the median lethal dose in humans at 30 mg/kg (2.1 grams THC for a person who weighs 70 kg; 154 lb; 11 stone), observing cardiovascular death in the one otherwise healthy subject of the two cases studied.[17] A different 1972 study gave the median lethal dose for intravenous THC in mice and rats at 30–40 mg/kg.[18]
Interactions[edit]
Formal drug–drug interaction studies with THC have not been conducted and are limited.[19][20] The elimination half-life of the barbiturate pentobarbital has been found to increase by 4 hours when concomitantly administered with oral THC.[19]
Chemistry[edit]
Solubility[edit]
As with many aromatic terpenoids, THC has a very low solubility in water, but good solubility in lipids and most organic solvents, specifically hydrocarbons and alcohols.[8]
Total synthesis[edit]
A total synthesis of the compound was reported in 1965; that procedure called for the intramolecular alkyl lithium attack on a starting carbonyl to form the fused rings, and a tosyl chloride mediated formation of the ether.[35]
Biological function[edit]
As a phytochemical, THC is assumed to be involved in the plant's evolutionary adaptation against insect predation, ultraviolet light, and environmental stress.[36][37][38]
Biosynthesis[edit]
In the Cannabis plant, THC occurs mainly as tetrahydrocannabinolic acid (THCA, 2-COOH-THC). Geranyl pyrophosphate and olivetolic acid react, catalysed by an enzyme to produce cannabigerolic acid,[39] which is cyclized by the enzyme THC acid synthase to give THCA. Over time, or when heated, THCA is decarboxylated, producing THC. The pathway for THCA biosynthesis is similar to that which produces the bitter acid humulone in hops.[40][41] It can also be produced in genetically modified yeast.[42]