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Richi

Tetrahydrocannabinol, also known as THC, is the main psychoactive substance found in the Cannabis plant; and additionally so in a variety of other plants. 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 good solubility in most organic solvents such as butane or hexane. As in the case of nicotine and caffeine, THC's most likely function in Cannabis is to protect the plant from herbivores or pathogens THC also possesses high UV-B (280-315 nm) absorption properties, protecting the plant from harmful radiation.

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. Additionally, it has been shown that cannabinoids, through a presently-unknown mechanism, activate endogenous opioid pathways via the μ1 opioid receptor, precipitating a dopamine release in the nucleus accumbens. This effect can be suppressed by the CB1 cannabinoid receptor antagonist rimonabant (SR141716A) or the opioid receptor antagonist naloxone.

THC has analgesic effects that, even at low doses, causes a "high", thus leading to the fact that medical cannabis can be used to treat pain. The mechanism for analgesic effects caused directly by THC or other cannabinoid agonists is not fully elucidated. Other effects include: relaxation; euphoria; altered space-time perception; alteration of visual, auditory, and olfactory senses; disorientation; fatigue; and appetite stimulation related to CB1 receptor activity in the central nervous system.

THC has an active metabolite, 11-Hydroxy-THC which may also play a role in the analgesic and recreational effects of the herb.

According to the Merck Index, 12th edition, 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 LD50 would be between approximately 50 and 86 g for a 68 kg (150 lb) female or male person respectively. This would be equivalent to 1-1.8 kg of cannabis with a 5% THC content (roughly average) taken orally. There has never been a documented fatality from marijuana or THC overdose. Absorption is limited by serum lipids which can become saturated with THC, thus the inherent solubility may mitigate toxicity.

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. There are no known reports of death caused by THC.

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