Also Known As: Marinol, Tetrahydrocannabinol
Tetrahydrocannabinol, also known as delta-9-tetrahydrocannabinol (Î”9-THC), or dronabinol, is the principal psychoactive constituent of the cannabis plant. First isolated in 1964, in its pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed. An aromatic terpenoid, THC has a very low solubility in water, but good solubility in most organic solvents, specifically lipids and alcohols.
Like most pharmacologically-active secondary metabolites of plants, THC in cannabis is assumed to be involved in self-defense, perhaps against herbivores but as of now it is still unknown. However, it is known that female cannabis plants produce THC in the absence of males. THC also possesses high UV-B (280-315 nm) absorption properties, which, it has been speculated, could protect the plant from harmful UV radiation exposure.
It has long been known that in humans, cannabis increases appetite and consumption of food. The mechanism for appetite stimulation in subjects is believed to result from activity in the gastro-hypothalamic axis. CB1 activity in the hunger centers in the hypothalamus increases the palatability of food when levels of a hunger hormone ghrelin increase prior to consuming a meal. After chyme is passed into the duodenum, signaling hormones such as cholecystokinin and leptin are released, causing reduction in gastric emptying and transmission of satiety signals to the hypothalamus. Cannabinoid activity is reduced through the satiety signals induced by leptin release.
Based on the connection between palatable food and stimulation of dopamine (DA) transmission in the shell of the nucleus accumbens (NAc), it has been suggested that cannabis does not only stimulate taste, but possibly the hedonic value of food. A taste-reactivity paradigm in mice was used to investigate the influence of THC on DA release in the NAc upon application of sucrose or quinine solutions. THC application was found to enhance DA release in the NAc from sucrose, but not quinine, in a dose-dependent manner. This effect was enhanced with sweeter solution, which correlated with an increase the researchers' hedonic-behavior assessment as well. The mechanism behind this effect was elucidated by application of rimonabant, a CB1 receptor inverse agonist, known to reduce intake of food or sweet solutions. However, the same DA enhancement effect was not found upon repeated application of sucrose, suggesting that the DA response undergoes habituation. The inconsistency between DA habituation and enduring appetite observed after THC application suggests that cannabis-induced appetite stimulation is not only mediated by enhanced pleasure from platable food, but through THC stimulation of another appetitive response as well.