The pharmacological effects of cannabis have been exploited for over 4800 years for recreational, medicinal, or religious purposes.
However, it is less than 100 years since the chemicals in cannabis responsible for the production of some of its effects and the pharmacological actions of some of these chemicals were identified.
Particularly noteworthy advances have been the discovery that cannabis is the source of a family of at least 104 compounds now known as phytocannabinoids, that one of these compounds is delta-9-tetrahydrocannabinol (THC), and that this is the main psychoactive constituent of cannabis.
No less important was the elucidation of the chemical structure of THC, its chemical synthesis, its pharmacological characterization, and the discovery in the late 1980s that it produces many of its effects by activating a G protein-coupled receptor now known as the cannabinoid CB1 receptor.
Importantly, these major findings were followed by the discovery in the early 1990s first, that our tissues produce chemicals called endocannabinoids that activate this receptor, second that another cannabinoid receptor, the CB2 receptor, is also activated by both THC and endocannabinoids, and third that this “endocannabinoid system” of cannabinoid receptors and endogenous agonists modulates the unwanted symptoms or even the progression of a number of disorders, often in an “autoprotective” manner.
It is also noteworthy that two drugs subsequently found to activate the CB1 receptor were first licensed as medicines a few years before the discovery of this receptor. These are nabilone (Cesamet®), a THC-like synthetic cannabinoid that is not present in cannabis, and synthetic THC, known as dronabinol (Marinol®).
The discovery of the endocannabinoid system reinvigorated the interest of scientists, clinicians, research funders, and pharmaceutical companies in cannabis and cannabinoids. So too did a growing number of reports in the 1990s, for example, in the press, of the beneficial effects of self-medicating with cannabis, particularly for multiple sclerosis.
It is clear that significant progress has already been made in our understanding both of how cannabis and some of its constituents produce beneficial or harmful effects in the brain or in other organs and tissues, and of how some of the beneficial effects can be exploited therapeutically with acceptable benefit-to-risk ratios.
However, it is also clear that there are still numerous important needs that have yet to be met, just two of which being the need to characterize the pharmacology of the many phytocannabinoid and nonphytocannabinoid constituents of cannabis more completely, and the need to identify and then exploit the best new therapeutic applications for cannabis-based medicines.
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