Source of the Drug
Cannabis is a highly adaptive annual plant that grows throughout temperate and tropical zones worldwide. Cannabis in the form of hemp likely originated in central Asia or near the Alai and Tian Shan mountain ranges that extend from Kyrgyzstan through Tajikistan to the China-Mongolia border. It has been a familiar agricultural crop since the beginning of civilization. Archaeologists have found evidence of hemp plant use in the late Neolithic era, dating back at least 6,000 years to the New Stone Age. Ma is the Chinese word for hemp, defined by the Merriam-Webster dictionary as a tall, widely cultivated Asian herb (Cannabis sativa) of the mulberry family with tough phloem fiber used especially for cords and ropes. It is composed of two Chinese written characters (Figure 8.1). Reference to hemp (ta ma) as a medicinal herb dates back to 2,838 B.C. in Emperor Shen Nung’s compilation of the PenTs’ao (or The Herbal), a kind of herbal standard. Emperor Nung experimented with various herbs and listed ta ma as medicinal:
FIGURE 8.1 Evolvement of the Chinese character for hemp, or ma, from the archaic chuan script (dating from 1766–1122 B.C. during the Shang Dynasty), to the contemporary cursive hsing script (emerging in the 3rd century A.D.). The ideogram is composed of the madare radical (top and left) which represents a tilted roof and is used in the characters for words such as house, shop, to live, etc. Under the “roof” are two small characters for tree which by themselves mean “small forest.” Literally, the character for hemp expresses the idea of a “small forest in or at one’s house,” or a “domestic forest.” The part beneath and to the right of the straight lines represents hemp fibers dangling from a rack. The horizontal and vertical lines represent the home in which they are drying (Abel EL. Marijuana: The First Twelve Thousand Years. Plenum Press, New York, 1980). The pictograph at the bottom combines big (ta) with ma to form the Chinese ideogram (ta ma) for psychoactive marijuana from cannabis. [Taken with permission from Koob GF, Le Moal M. Neurobiology of Addiction. Academic Press, London, 2006.]
“...ma-fen (fruits of hemp)...if taken in excess will produce hallucinations (literally ‘seeing devils’). If taken over a long term, it makes one communicate with spirits and lightens one’s body”
(Li, 1974a, b).
Hua T’o, a Chinese physician from the 2nd century A.D., used an oral preparation of cannabis called ma-fei-san (hemp-boiling compound, combined with wine) to anesthetize patients who were undergoing abdominal surgery. The Swedish botanist Carl Linnaeus named the plant Cannabis sativa in 1753. Although accounts of the etymology of the word cannabisdiffer, it may have derived from the Greek and Latin kannabis, the Assyrian kunnapu (a way to produce smoke), or perhaps the Sanskrit cana (hemp or cane). The word kan referred to hemp or cane in many ancient languages, and bis can be linked to the word aromatic. Thus, cannabis is the “fragrant cane.” The French naturalist Jean Baptiste Lamarck argued that the hemp plant grown in Europe was sufficiently different from that grown in India to be a different species. The plant grown for fiber use was called Cannabis sativa, and the plant grown for psychoactive properties was called Cannabis indica. The Russian botanist Janischevski recognized a third wild species in Asia called Cannabis ruderalis.
The relationships between an individual plant and its environment are complex and determine the representative phenotypes of the species; therefore, the genetic plasticity of Cannabis sativa enables wide phenotypic variability for adapting to diverse conditions.
Marijuana is the dry, shredded, green or brown mixture of flowers, stems, seeds, and leaves of the hemp plant Cannabis sativa. The word marijuana may have been derived from the Spanish Mariguana, one of the islands that form the Bahamas, but others have suggested it derived from the Spanish prenomes Maria (Mary) and Juana (Jane). This claim, however, has not been substantiated.
The dried mixture can be smoked like a cigarette (termed a joint) or in a pipe (bong) or in a cigar from which the tobacco has been removed (blunt). Other preparations include hash or hashish (the dried sticky resin of the flowers of the female plant) or hash oil (a sticky black liquid).
The marijuana plant contains numerous chemical species, but the active constituent mainly responsible for its pharmacological effect is (−)Δ9-6a,10a-trans-tetrahydrocannabinol, simply referred to as Δ9-THC (Box 8.1). The term cannabinoid originally referred to Δ9-THC and related phytocannabinoids of the marijuana plant Cannabis sativa with a typical 21-carbon chemical structure and any products derived from these structures. A broader definition based on pharmacology and chemistry “encompasses kindred structures, or any other compound that affects cannabinoid receptors” (Pate DW. Taxonomy of cannabinoids. In: Grotenhermen F, Russo E (eds.) Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. Haworth Integrative Healing Press, New York, 2002, pp. 15–26) or “all ligands of the cannabinoid receptor and related compounds including endogenous ligands of the receptors and a large number of synthetic cannabinoid analogs” (Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical Pharmacokinetics, 2003, (42), 327–360).
SYNOPSIS OF THE NEUROPHARMACOLOGICAL TARGETS FOR CANNABINOIDS
Cannabinoids are found in all cannabis preparations, and the principal psychoactive ingredient is Δ9-tetrahydrocannabinol (Δ9-THC). All cannabinoid drugs, both natural and synthetic, have pharmacological actions that are similar to Δ9-THC. All cannabinoids bind as direct agonists to cannabinoid receptors in the brain to produce their behavioral effects. Endogenous cannabinoids bind as agonists to cannabinoid receptors and include anandamide and 2-arachidonylglycerol (2-AG), which are widely distributed throughout the brain and have high concentrations in reward- and pain-related neurocircuits. Cannabinoids act as retrograde neuromodulators that are synthesized in postsynaptic elements of neurons as required. This occurs in response to depolarization by receptor-stimulated synthesis from membrane lipid precursors, and they are released from cells immediately after their production. The behavioral effects of cannabinoids are transduced by two transmembrane G-protein-coupled opioid receptors – cannabinoid-1 (CB1) and cannabinoid-2 (CB2) – and subsequent second-messenger gene transcription changes. The CB1 receptor is hypothesized to be largely responsible for the intoxicating effects of cannabinoids, in addition to a wide range of behavioral and physiological effects. The intoxicating effects of cannabinoids are hypothesized to be mediated by actions on cannabinoid receptors in the origin areas (ventral tegmental area) and terminal areas (nucleus accumbens) of the mesocorticolimbic dopamine system and extended amygdala (central nucleus of the amygdala, bed nucleus of the stria terminalis, and a transition zone in the shell of the nucleus accumbens). The addiction potential of cannabinoids is hypothesized to derive from powerful within-system neuroadaptations (signal transduction mechanisms) and between-system neuroadaptations (neurocircuitry changes) in the brain motivational and stress systems.
“The dried Hemp plant which has flowered, and from which the resin has not been removed, is called Gunjah. It sells from 12 annas to one rupee seer in the Calcutta bazars, and yields to alcohol twenty per 100 of resinous extract, composed of the resin (churrus) and green coloring matter (Chloro-phille). Distilled with a large quantity of water, traces of essential oil pass over, and the distilled liquor has the powerful narcotic odor of the plant. The gunjah is sold for smoking chiefly. The bundles of gunjah are about two feet long, and three inches in diameter, and contain 24 to 36 plants. The color is dusky green – the odor agreeably narcotic – the whole plant resinous and adhesive to the touch. The larger leaves and capsules without the stalks are called ‘Bangh Subjee or Sidhee.’ They are used for making an intoxicating drink, for smoking, and in the conserve or confection termed Majoon. Bang is cheaper than gunjah, and though less powerful, is sold at such a low price, that for one pice enough can be purchased to intoxicate an experienced person”
(O’Shaughnessy WB. On the preparations of the Indian hemp, or gunjah. Transactions of the Medical and Physical Society of Bengal,1838–1840, pp. 421–461).