Classical Herbal Drugs of Abuse 1931 Cannabis and Tetrahydrocannabinol

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Cannabis is derived from Cannabis sativa, an herbaceous annual plant. The species C. sativa can be divided into the following subspecies and varieties: C. sativa var. sativa, C. sativa var. spontanea, C. sativa spp. indica, C. sativa var. indica, and C. sativa var. kafiristanica [6, 7]. The plant is highly recognizable: the leaves are typically separated into five or more serrated leaflets. The stem of the plant is extremely fibrous and is therefore a popular source of fabric fiber.

Cannabis is reported to have been first used by the Chinese in 2737 BCE. It was also known on the Indian subcontinent and the Arabian Peninsula well before the birth of Christ as an herbal remedy. The remains of cannabis seeds discovered in Germany date to 500 BCE. Cannabis was used as an antimalarial and antirheumatic drug, a narcotic, an aphrodisiac, a carminative, and as a remedy to treat nausea and headache.

Sinsemilla is a seedless, more potent form produced from the unfertilized flowering tops of female cannabis plants, often found in the USA [8]. Other forms of cannabis include Thai sticks, hashish (resin), and oil (hash oil). Modern names used to describe cannabis include "weed," "grass," "dope," "dagga," and "pot."

The most interesting compounds contained in cannabis are the cannabinoids, a group of at least 66 substances [9]. The most psychoactive cannabinoid in cannabis is A9-tetrahydrocannabinol (THC). The chemical structure of THC (1) is shown in Fig. 19.1.

The cannabis plant is dioecious, with male and female flowers borne on separate plants. The female plant is more robust with larger flowers and, importantly, contains a higher THC content. All parts of the plant contain THC including flowers, leaves, seeds, and stalks. Oil is produced from the seeds and flower heads.

The plants prefer a warm humid climate, although it will grow in most climates. However, indoor and glasshouse cultivation are required for the cooler climates.

Cannabis is used mainly by smoking in the form of cigarettes (joints) or using cold-water pipes (bongs). It can also be made into "cookies" and eaten. Heat is essential to activate procannabinoids to THC.

THC increases the heart rate, blood pressure, and body temperature. More importantly, smoking THC produces a range of cognitive and psychomotor effects associated with a transient euphoric effect that is usually perceived as a "high." Short term memory loss can occur particularly with repeated use.

The cannabinoids are ligands of the cannabinoid G-protein coupled receptors. Evidence for the existence of a human cannabinoid receptor was found in the mid-1980s, and the CBi receptor was confirmed by cloning in 1990. A second cannabinoid receptor, the CB2 receptor, was confirmed by cloning in 1993 [10]. The CB1 receptor is predominantly found at central and peripheral nerve terminals, whereas the CB2 receptor is mainly distributed in immune cells [9].

With the discovery of cannabinoid receptors, the question arose as to whether these receptors had endogenous ligands or whether they were targets only for THC and other plant cannabinoids. The first endogenous cannabinoid was described in 1992. The substance was identified as arachidonoyl ethanolamide and named anandamide. So far, five endogenous cannabinoid receptor agonists have been described [10].

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