Short- and long-term plasticity of the endocannabinoid system in neuropsychiatric and neurological disorders

The activity of the endocannabinoid system, in terms of the levels of the endocannabinoids and of cannabinoid receptors, or of the functional coupling of the latter to a biological response, undergoes to remodelling during pathological conditions. In the CNS, these changes, depending also on the nature of the disorder, can be transient or long-lasting, occur only in those tissues involved in the pathological condition and usually aim at restoring the physiological homeostasis by reducing excitotoxicity, inflammation and neuronal death. However, during chronic disorders, prolonged activation of the endocannabinoid system might also contribute to the symptoms of the pathology. Whilst acute changes of the tissue levels of the endocannabinoids reflect the “on demand” nature of their biosynthesis and release, and hence are effected mostly through regulation of the biosynthetic enzymes, chronic changes seem to be mostly due to longer-lasting alterations in the expression of anabolic and catabolic enzymes. The possibility of obtaining therapeutic advantage from endocannabinoid plasticity in neuropsychiatric and neurological disorders is discussed in this review article.