THC, (Tetrahydrocannabinol), or more precisely its main isomer (−)-trans-Δ9-tetrahydrocannabinol ( (6aR,10aR)-delta-9-tetrahydrocannabinol), is the principal psychoactive constituent (or cannabinoid) of cannabis.
First isolated in 1964 by Israeli scientists Prof. Raphael Mechoulam and Dr. Yechiel Gaoni at the Weizmann Institute of Science. It is a water-clear glassy solid when cold, which becomes viscous and sticky if warmed. A pharmaceutical formulation of (−)-trans-Δ9-tetrahydrocannabinol, known by its Nonproprietary Name dronabinol, is available by prescription in the U.S. and Canada under the brand name Marinol.
An aromatic terpenoid, THC has a very low solubility in water, but good solubility in most organic solvents, specifically lipids and alcohols. THC, CBD, CBN, CBC, CBG and about 80 other molecules make up the phytocannabinoid family.
Like most pharmacologically-active secondary metabolites of plants, THC in Cannabis is assumed to be involved in self-defense, perhaps against herbivores. THC also possesses high UV-B absorption properties, which, it has been speculated, could protect the plant from harmful UV radiation exposure.
Tetrahydrocannabinol, along with its double bond isomers and their stereoisomers, is one of only three cannabinoids scheduled by the Convention on Psychotropic Substances (the other two are dimethylheptylpyran and parahexyl). Cannabis as a plant is scheduled by the Single Convention on Narcotic Drugs (Schedule I and IV).
THC has mild to moderate analgesic effects, and cannabis can be used to treat pain by altering transmitter release on dorsal root ganglion of the spinal cord and in the periaqueductal gray. Other effects include relaxation, alteration of visual, auditory, and olfactory senses, fatigue, and appetite stimulation. THC has marked antiemetic properties. It may acutely reduce aggression and increase aggression during withdrawal.
Due to its partial agonistic activity, THC appears to result in greater downregulation of cannabinoid receptors than endocannabinoids, further limiting its efficacy over other cannabinoids. While tolerance may limit the maximal effects of certain drugs, evidence suggests that tolerance develops irregularly for different effects with greater resistance for primary over side-effects, and may actually serve to enhance the drug’s therapeutic window. However, this form of tolerance appears to be irregular throughout mouse brain areas. THC, as well as other cannabinoids that contain a phenol group, possesses mild antioxidant activity sufficient to protect neurons against oxidative stress, such as that produced by glutamate-induced excitotoxicity.
Appetite and Taste
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.
A study in mice suggested that based on the connection between palatable food and stimulation of dopamine (DA) transmission in the shell of the nucleus accumbens (NAc), cannabis may not only stimulate taste, but possibly the hedonic (pleasure) value of food as well. The study later demonstrates habitual use of THC lessening this heightened pleasure response, indicating a possible similarity in humans. 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 palatable food, but through THC stimulation of another appetitive response as well.