Cannabinoids discovery

After the discovery of specific endocannabinoid receptors, the amount of scientific literature quickly rose and not only new potential indications were established, but also the mechanisms for the already known effects were clarified. Although the most prominent effect of C. sativa is clearly related to THC and its activity at the CBl receptor, most other natural cannabinoids are not active there. Today two other natural cannabinoids CBD and THCV are the focus of medicinal research. 

Before the discovery of specific cannabinoid receptors, the term cannabinoid was used to describe the biologically active constituents of the Cannabis sativa plant, including A -THC (67), cannabidiol (68) and their analogues and derivatives, many of which have characteristic pharmacological effects. 

Martin and co-workers [196] have also published on the discovery and SAR of pyrazole cannabinoids as described in the CBi agonist section. The analogues were tested for CBi receptor binding affinity and in a battery of in... 

The advent of synthetic cannabimimetics with a high degree of enantioselectivity (Johnson, 1986 Little, 1988) paved the road for the identification of specific cannabinoid binding sites in rat brain (Devane, 1988). This discovery marked the onset of a revolution in the understanding of cannabinoid biology. 

The discovery of the cannabinoid receptors and their G-protein-coupled nature strongly suggested the existence of endogenous cannabimimetic... 

Since the discovery of anandamide in 1992, a number of studies have examined its pharmacological properties. Although its roles are still elusive, a plethora of data supports the initial postulate that anandamide is the major endogenous cannabinoid ligand. As mentioned earlier, anandamide binds to CB1 from brain preparations and displaces various well-... 

With the discovery of anandamide and 2-arachidonyl glycerol as two new families of endocannabinoids, cannabinoid research has taken major... 

Johnson MR, Melvin LS, The discovery of nonclassical cannabinoid analgesics. In Mechoulam C, ed. Cannabinoids as Therapeutic Agents. Boca Raton, FL CRC Press, 1986 121-145. 

Martin BR, Mechoulam R, Razdan RK. Discovery and characterization of endogenous cannabinoids. Life Sci 1999 65 573-595. 

Pertwee RG. Pharmacological, physiological and clinical implications of the discovery of cannabinoid receptors. In Pertwee RG, ed. Cannabinoid Receptors. New York Academic Press, 1995a 69-83. 

Pertwee RG. Cannabinoid receptor ligands clinical and neuropharmaco-logical considerations, relevant to future drug discovery and development. Exp Opin Invest Drugs 2000 9 1-19. 

Marijuana and hashish are derivatives of the cannabis sativa plant. Although cannabinoids have been used for centuries for recreational and therapeutic purposes, dramatic advances in cannabinoid neurobiology have occurred since 1990 [34-37]. This is attributable to the cloning of cannabinoid receptors and the discovery of endogenous cannabinoids, termed endocannabinoids. 

A number of pharmaceutical companies are working to develop drugs that will block the marijuana high sought by the world s estimated 144 million regular marijuana users. In 1988, researchers identified the receptors in the brain to which the marijuana molecule attaches. Named Cannabinoid Receptor l (CBl), it became the site of intensive scientific research, subsequently leading to the discovery that the brain naturally produces several compounds that fit the CBl receptors. One of these natural compounds was named anandamide from ananda, the Sanskrit word for bliss. ... 

Analogous to the discovery of the endogenous opiates and opiate receptors, the discovery of cannabinoid receptors in 1988 suggested the presence of endogenous cannabimimetic compounds. In 1992 anandamine—the ethanolamide of arachidonic acid was purified from porcine brain and shown to behave... 

That of mediators of signals is an area open to discovery. Endogenous cannabinoids are an example. Putatively involved in important functions with cannabinoid receptors on nerve cells, they remain elusive, however (Christie 2001). 

Nevertheless and despite the widely illegal recreational use of cannabis the effects of cannabinoids on the brain still are under active investigation. The discovery of neuronal receptor proteins for cannabinoids and the existence of endogenous cannabinoid substances (Sullivan, 2000) are the most important milestones to date. 

Some naturally occurring neurotransmitters may be similar to drugs we use. For example, it is well known that the brain makes its own morphine (i.e., beta endorphin), and its own marijuana (i.e., anandamide). The brain may even make its own antidepressants, it own anxiolytics, and its own hallucinogens. Drugs often mimic the brain s natural neurotransmitters. Often, drugs are discovered prior to the natural neurotransmitter. Thus, we knew about morphine before the discovery of beta-endorphin marijuana before the discovery of cannabinoid receptors and anandamide the benzodiazepines diazepam (Valium) and alprazolam (Xanax) before the discovery of benzodiazepine receptors and the antidepressants amitriptyline (Elavil) and fluoxetine (Prozac) before the discovery of the serotonin transporter site. This un-... 

Analogous to the discovery of endogenous opiates, isolation of cannabinoid receptors provided the appropriate tool to isolate an endogenous cannabimimetic eicosanoid, anandamide, from porcine... 

A cannabinoid is a type of chemical compound concentrated in the resin of the cannabis plant. THC is the only cannabinoid that is highly psychoactive and present in large amounts in cannabis. Until recently, there has been little information on precisely how THC acts on the brain, which cells are affected by THC, or even what general areas of the brain are most affected by it. All this changed in the 1980s and 1990s with the discovery of specific cannabinoid receptors—Cannabinoid receptor 1 (CB1) and Cannabinoid receptor 2 (CB2). 

There are two features of the cannabinoids which may ultimately be of therapeutic importance. THC lowers intraocular pressure, which may be of benefit in the treatment of glaucoma. There is also evidence that THC is a moderately effective antiemetic agent. Such a discovery has led to the development of nabilone, a synthetic cannabinoid, as an antiemetic agent, but its use is limited because of the dysphoria, depersonalization, memory disturbance and other effects which are associated with the cannabinoids. Whether the bronchodilator action of THC will ever find therapeutic application in the treatment of asthma remains an open question. 

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