A Brief History of Cannabinoid Research
As early as 5,000 years ago Cannabis was noted for its effects on the central nervous system[1]. This often manifested in the form of pain relief, appetite stimulation, and sedation (Iverson 2000). Medicinal Cannabis preparations were widely used in western medicine during the 19th century. At the time it was no secret that pharmaceutical preparations of Cannabis were variable. As the active ingredient was not known, quality control was virtually impossible, and this is in part why the plant fell out of use.
During the Victorian era, many plants were extracted for their unique properties, namely alkaloids. These plant chemists were successful because the alkaloids they were targeting are water soluble organic bases that form crystalline solids when combined with acids. Among the medicinal compounds isolated in the 19th century were quinine, morphine, and cocaine. These were major advances in plant chemistry. The molecules on the cannabis plant, however, are almost completely insoluble in water. The chemical nature of cannabinoids prevented early Victorian scientists from making efficient extracts of these polar compounds. The active ingredient, THC, wasn’t isolated and identified until 1964.
In the 1990s, researchers made discoveries essential for the establishment of the cannabinoid research field. By the end of the decade scientists discovered two distinct cannabinoid receptors (i.e., CB1 and CB2), isolated endogenous cannabinoids (e.g.,Anandamide and 2-Arachidonylglycerol), synthesized a cadre of ligands, and generated cannabinoid receptor knockout mice (Matsuda 1990, Gerard 1990, Zimmer 1999). Efforts to identify and clone the CB1 receptor also demonstrate that the CB1 receptor is one of the most abundant proteins in the brain. Thus, cannabinoid receptors became an attractive target for drug development. The availability of synthetic THC and novel analogs has allowed researchers to begin characterizing the role of this neuronal G-protein coupled receptor. The sum of all knowledge on how cannabinoid receptors and their ligands work together in mammals is referred to as the endocannabinoid system.
Footnote:
[1] Evidence for the medicinal use of Cannabis goes back to the emperor Chen Nung (the father of Chinese agriculture), a discoverer of medicinal plants, and also taught his people how to cultivate grains. Chen Nung is believed to be the author of the oldest known Chinese pharmacopoeia, in which, he writes about the medical use of Cannabis for rheumatism, menstrual fatigue, malaria, constipation, and absentmindedness.
