Tetrahydrocannabinol, also known as THC, Δ9-THC, Δ9-tetrahydrocannabinol (delta-9-tetrahydrocannabinol), Δ¹-tetrahydrocannabinol (using an older numbering scheme), or dronabinol, is the main psychoactive substance found in the Cannabis plant. It was isolated by Raphael Mechoulam and Yechiel Gaoni from the Weizmann Institute in Rehovot, Israel in 1964. In pure form it is a glassy solid when cold and becomes viscous and sticky if warmed. THC has a very low solubility in water, but a good solubility in most organic solvents such as pure ethanol or hexane.
Its pharmacological actions are the result of its binding to the cannabinoid receptor CB1, located in the brain. The presence of these specialized receptors in the brain implied to researchers that endogenous cannabinoids were manufactured by the body, so the search began for a substance normally manufactured in the brain that binds to these receptors, the so-called natural ligand or agonist, leading to the eventual discovery of anandamide and some related compounds. This story resembles the discovery of the endogenous opiates (endorphins, enkephalins, and dynorphin), after the realization that morphine and other opiates bound to specific receptors in the brain.
Effects include: relaxation, euphoria, altered space-time perception, alteration of visual, auditory, and olfactory senses, disorientation, fatigue and appetite stimulation. It also has anti-emetic and anti-nauseant properties.
THC has a LD50 value of 1270 mg/kg (male rats), 730 mg/kg (female rats) orally (administered dissolved in sesame oil). If this were scaled up to an adult human, the lethal dose would be 2.8 ounces for a person weighing 140 lb (76 g for a 60 kg person, or over 1.4 kg (more than 3 lb) of average strength marijuana), rendering unlikely the possibility of an overdose. Studies of the distribution of the cannabinoid receptors in the brain explain why THCs toxicity is so low (i.e., the LD50 of the compound is so large): parts of the brain that control vital functions such as respiration do not have many receptors, so they are relatively unaffected even by doses larger than could ever be ingested under any normal conditions.
A number of studies indicate that THC may provide medical benefits for cancer and AIDS patients by increasing appetite and decreasing nausea, and by blocking the spread of some cancer-causing Herpes simplex viruses. It has been shown to assist some glaucoma patients by reducing pressure within the eye, and is used in the form of cannabis by a number of multiple sclerosis patients to relieve the spasms associated with their condition. Government studies indicate a variety of negative effects associated with constant, long-term use, including memory loss, depression and loss of motivation. The long-term effects of THC on humans are disputed because its status as an illegal drug almost everywhere prevents free research into the subject. The issue has become deeply politicized.
Synthetic THC, also known under the substance name dronabinol, is available as a prescription drug (under the trade name Marinol) in several countries including the USA, The Netherlands, and Germany. In the United States, Marinol is a Schedule III drug, available by prescription, considered to be non-narcotic and to have a low risk of physical or mental dependence. An analog of dronabinol, nabilone, is classified as a Schedule II controlled substance; however it is not clear if it is available commercially in the US. Efforts to get cannabis rescheduled as analogous to Marinol have not succeeded thus far. In 2005, residents of Denver, Colorado, voted by a solid margin to legalize the possession of small amounts of marijuana; however, the Denver police have stated they will follow state ordinances banning marijuana possesion. As a result of the rescheduling of Marinol from Schedule II to Schedule III, refills are now permitted for this substance. Marinol has been approved by the FDA in the treatment of anorexia of AIDS patients, as well as for refractory nausea and vomiting of patients undergoing chemotherapy.
In April 2005, Canadian authorities approved the marketing of Sativex, a mouth spray for multiple sclerosis to alleviate pain. Sativex contains tetrahydrocannabinol together with cannabidiol. It is marketed in Canada by GW Pharmaceuticals, being the first cannabis-based prescription drug in the world.
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