Chronic effects of cannabinoid drugs on monoaminergic systems and the role of endocannabinoids and cannabinoid receptors in human brain disorders

Abstract

The endocannabinoid system and cannabinoid (CB) receptors participate in the regulation of a variety of psychiatric and neurological disorders through a functional coupling with the monoaminergic systems in the brain. Norepinephrine, serotonin (5-HT) and dopamine systems are modulated via inhibitory CB 1 receptors by direct or indirect effects. The repeated stimulation of CB 1 receptors (and receptor desensitization) can lead to the induction of tolerance on the activity of monoaminergic systems. The chronic administration of CB drugs can also alter the function of presynaptic inhibitory monoamine autoreceptors and heteroreceptors and thus modulate the final effects on these systems. The functional interactions between endocannabinoids, CB receptors, and monoaminergic systems suggest a potential role for CB receptor signaling in the pathophysiology and treatment of various psychiatric and neurological disorders, including drug addiction, which are discussed on evidence from postmortem and living human brain studies.