ABSTRACT
The endogenous cannabinoids are molecules synthesized by animals, from insects to mammals, that generate effects similar to those produced by marijuana (Figure 25.1).1 The generic name of these molecules, known as endocannabinoids, derives from the scientific name of marijuana (Cannabis sativa) and its more abundant natural components, the cannabinoids. There are several endogenous cannabinoids produced by the brain, and other molecules that have cannabinoid-like activity, although they do not bind to the cannabinoid receptor (Table 25.1). Oleamide is an example of a molecule that binds to the CB1 and CB2 receptors only at high concentrations,2 and thus is considered to be an atypical or weak endocannabinoid. All these molecules are lipids and differ from the classic neurotransmitters in several ways. For example, classic neurotransmitters such as catecholamines or acetylcholine are synthesized and stored in synaptic vesicles from which they are released as a result of neuron depolarization. Endocannabinoids, instead, are synthesized from membrane lipid precursors and released immediately thereafter, as a response to activation of membrane receptors. They are not, therefore, stored at any point during or after synthesis. In addition, their transmission is retrograde3 (Figure 25.2). All in all, the most fascinating aspect of these molecules is the potential physiological processes they might regulate in normal subjects, one of which is the sleep-waking cycle.
