Endocannabinoid signaling in reward and addiction: From homeostasis to pathology

Abstract

The endogenous cannabinoid system is an important regulatory system involved in physiological homeostasis. Endocannabinoid signaling is known to modulate neural development, immune function, metabolism, synaptic plasticity, and emotional state. Accumulating evidence also implicates brain endocannabinoid signaling in the processing of natural and drug-induced reward states and dysregulated endocannabinoid signaling in the etiology of aberrant reward function and drug addiction. In this chapter, we discuss the influence of endocannabinoid signaling on the rewarding and motivational effects of natural rewards such as food, sex, and social interaction, as well as evidence demonstrating an endocannabinoid influence in the rewarding effects of abused drugs. The effects of long-term drug consumption on endocannabinoid signaling are discussed, along with evidence that the resultant dysregulation of endocannabinoid function contributes to various aspects of drug dependence and addiction including physical symptoms of drug withdrawal, increased stress responsivity, negative affective states, dysregulated synaptic plasticity, dysregulated extinction of drug-related memories, relapse to drug taking, and impaired cognitive function. Lastly, consideration is given to the role for dysregulated endocannabinoid signaling in pathological food reward and eating disorders.