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TABLE 2.1  Landmark Discoveries Since the 1982 IOM  Report



Primary Investigators


Potent cannabinoid agonists are developed; they are the key to discovering the receptor.

M. R. Johnson and L. S. Melvin75



First conclusive evidence of specific   cannabinoid receptors.

A. Howlett and W. Devaneh36


The cannabinoid brain receptor (CB,) is cloned, its DNA sequence is identified, and its location in the brain is determined.

L. Matsuda107 and M. Herkenham


et al60


Anandamide is discovered—a naturally occurring substance in the brain that acts on cannabinoid receptors.

R. Mechoulam and W. Devane37



A cannabinoid receptor is discovered outside the brain; this receptor (CB2) is related to the brain receptor but is distinct.

S. Munro112



The first specific cannabinoid antagonist, SR 141716A, is developed.

M. Rinaldi-Carmonal32



The first cannabinoid antagonist, SR144528, that can distinguish between CB1 and CB2 receptors discovered.

M. Rinaldi-Carmona133


Basic science is the wellspring for developing new medications and is particularly important for understanding a drug that has as many effects as marijuana. Even committed advocates of the medical use of marijuana do not claim that all the effects of marijuana are desirable for every medical use. But they do claim that the combination of specific effects of marijuana enhances its medical value. An understanding of those specific effects is what basic science can provide. The multiple effects of marijuana can be singled out and studied with the goals of evaluating the medical value of marijuana and cannabinoids in specific medical conditions, as well as minimizing unwanted side effects. An understanding of the basic mechanisms through which cannabinoids affect physiology permits more strategic development of new drugs and designs for clinical trials that are most likely to yield conclusive results.

Research on cannabinoid biology offers new insights into clinical use, especially given the scarcity of clinical studies that adequately evaluate the medical value of marijuana. For example, despite the scarcity of sub-

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