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Tetrahydrocannabinol, also known as THC, Δ-THC, Δ-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.

Pharmacology

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, 2 arachidonyl glyceride (2-AG) and other 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.

THC has analgesic effects even at low doses that do not cause a "high", and cannabis was once commonly used to treat pain. Other 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 properties.

Toxicity

THC has a LD₅₀ value of 1270 mg/kg (male rats) and 730 mg/kg (female rats) administered orally dissolved in sesame oil.

If this were scaled up to an adult human, the lethal dose would be between approximately 50 and 86 g for a 68 kg (150 lb) person. This would be equivalent to 1-1.8 kg of marijuana with a 5% THC content (roughly average) taken orally (much more if smoked). It is important to note, however, that toxicity studies in animal models do not necessarily correlate to human toxicity. THC receptor distribution in the rat CNS is different than that of humans, meaning that there is the significant possibility that toxicity in humans varies from the published animal LD50 studies. There has never been a documented fatality from marijuana or THC overdose.

Studies of the distribution of the cannabinoid receptors in the brain explain why THC's 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.

Research

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. Studies also indicate a variety of negative effects associated with constant, long-term use, including short-term memory loss, and depression. The long-term effects of THC on humans have been disputed because its status as an illegal drug almost everywhere prevents free research into the subject. The issue has become deeply politicized.

Preliminary research on synthetic THC has been conducted on patients with Tourette syndrome. Animal studies suggested that Marinol and nicotine could be used as an effective adjunct to neuroleptic drugs in treating TS. Research on twelve patients showed that Marinol reduced tics with no significant adverse effects. A six-week controlled study on 24 patients showed the patients taking Marinol had a significant reduction in tic severity without serious adverse effects. Seven patients dropped out or had to be excluded from the study, but only one due to adverse side-effects. More significant reduction in tic severity was reported with longer treatment. No detrimental effects on cognitive functioning, and a trend towards improvement in cognitive functioning was reported during and after treatment. Marinol's usefulness as a treatment for TS cannot be determined until/unless longer controlled studies on larger samples are undertaken. PMID 2567480 PMID 11951146 PMID 12716250 PMID 12589392

Synthetic THC

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; it is available commercially in the US under the trade name Cesamet, manufactured by Lilly. Efforts to get cannabis rescheduled as analogous to Marinol have not succeeded thus far. 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.

See also

• Cannabinoids
  • HU-210
• Medical cannabis
• War on Drugs
• Cannabis
• THC Ministry
• Cannabis rescheduling in the United States
• Cannabidiol, an isomer of THC
• Psychoactive drug
• Health issues and the effects of cannabis

External links

• Scientific American Marijuana research
• THC-pharm, a German producer of THC for pharmacies.
• Erowid Compounds found in Cannabis sativa.
• Machinery of the "marijuana munchies"

• Cannabinoids
• Schedule I controlled substances