2 - How cannabis works in the brain

Summary

Important advances have been made in the past decade in understanding how cannabis affects the brain. As with morphine 20 years earlier, research on the psychopharmacology of a plant-derived drug led to the discovery of a naturally occurring cannabinoid system in the brain, whose functions are only now beginning to be understood. This chapter will review what is known about the interactions of cannabis with the cannabinoid system in the brain and how the drug affects psychomotor, cognitive, perceptual and appetitive functions. There is also speculation on what brain mechanisms may underly the intoxicant effects of cannabis, and a review of its addictive properties.

Cannabinoid receptors

In Chapter 1 the identification of Δ⁹-tetrahydrocannabinol (THC) was reviewed as the principal active component in the complex mixture of cannabinoids present in extracts of the plant Cannabis sativa, and the discovery of a series of naturally occurring endogenous cannabinoids (endocannabinoids), of which anandamide has so far been most intensively studied, was outlined. A series of synthetic cannabinoids – some of which are more potent and more water-soluble than THC – is also available (Pertwee, 1999) (Fig. 2.1). All of these compounds act as agonists at the CB₁ cannabinoid receptor (Matsuda et al., 1990), which is the only one known to be expressed in the brain. A second cannabinoid receptor, CB₂, is expressed only in peripheral tissues, principally in the immune system (Munro et al., 1993; Felder and Glass, 1998; Pertwee, 1999).