The role of glucagon-like peptide 1 (GLP-1) in addictive disorders

Abstract

Drug, alcohol and tobacco use disorders are a global burden affecting millions of people. Despite decades of research, treatment options are sparse or missing, and relapse rates are high. Glucagon-like peptide 1 (GLP-1) is released in the small intestine, promotes blood glucose homeostasis, slows gastric emptying and reduces appetite. GLP-1 receptor agonists approved for treating Type 2 diabetes mellitus and obesity have received attention as a potential anti-addiction treatment. Studies in rodents and non-human primates have demonstrated a reduction in intake of alcohol and drugs of abuse, and clinical trials have been initiated to investigate whether the preclinical findings can be translated to patients. This review will give an overview of current findings and discuss the possible mechanisms of action. We suggest that effects of GLP-1 in alcohol and substance use disorders is mediated centrally, at least partly through dopamine signalling, but precise mechanisms are still to be uncovered. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.

Keywords: GLP-1; addiction; alcohol; alcohol use disorder; amphetamine; cocaine; dopamine; glucagon-like peptide-1; nicotine; opioids; substance use disorder; tobacco.

Conflict of interest statement

A.F.‐J. has received an unrestricted research grant from Novo Nordisk A/S to investigate the effects of GLP‐1 receptor stimulation on metabolic disturbances and weight gain in antipsychotic‐treated patients with schizophrenia. There is no other possible conflicts of interest, for the remaining authors.

© 2021 The British Pharmacological Society.

Figures

FIGURE 1

Effects of glucagon‐like peptide 1 (GLP‐1) receptor stimulation on alcohol reward‐related behaviours in preclinical models. CPP, conditioned place preference; DHipp, dorsal hippocampus; ex‐4, exenatide; ex‐9, exendin 9–39; LDTg, laterodorsal tegmental nucleus; LH, lateral hypothalamus; NAc, nucleus accumbens; NAcs, nucleus accumbens shell; NTS, nucleus tractus solitarius; VTA, ventral tegmental area

FIGURE 2

Effects of glucagon‐like peptide 1 (GLP‐1) receptor stimulation in various substance reward‐related behaviours in preclinical models. CPP, conditioned place preference; LS, lateral septum; NAc, nucleus accumbens; NTS, nucleus tractus solitarius; VTA, ventral tegmental area