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stantive clinical data, basic science has made it clear that cannabinoids can affect pain transmission and, specifically, that cannabinoids interact with the brain's endogenous opioid system, an important system for the medical treatment of pain (see chapter 4).

The cellular machinery that underlies the response of the body and brain to cannabinoids involves an intricate interplay of different systems. This chapter reviews the components of that machinery with enough detail to permit the reader to compare what is known about basic biology with the medical uses proposed for marijuana. For some readers that will be too much detail. Those readers who do not wish to read the entire chapter should, nonetheless, be mindful of the following key points in this chapter:

·      The most far reaching of the recent advances in cannabinoid biology are the identification of two types of cannabinoid receptors (CB₁ and CB₂) and of anandamide, a substance naturally produced by the body that acts at the cannabinoid receptor and has effects similar to those of THC. The CB₁ receptor is found primarily in the brain and mediates the psychological effects of THC. The CB₂ receptor is associated with the immune system; its role remains unclear.

·      The physiological roles of the brain cannabinoid system in humans are the subject of much active research and are not fully known; however, cannabinoids likely have a natural role in pain modulation, control of movement, and memory.

·      Animal research has shown that the potential for cannabinoid dependence exists, and cannabinoid withdrawal symptoms can be observed. However, both appear to be mild compared to dependence and withdrawal seen with other drugs.

·      Basic research in cannabinoid biology has revealed a variety of cellular pathways through which potentially therapeutic drugs could act on the cannabinoid system. In addition to the known cannabinoids, such drugs might include chemical derivatives of plantderived cannabinoids or of endogenous cannabinoids such as anandamide but would also include noncannabinoid drugs that act on the cannabinoid system.

This chapter summarizes the basics of cannabinoid biology—as known today. It thus provides a scientific basis for interpreting claims founded on anecdotes and for evaluating the clinical studies of marijuana presented in chapter 4.