Glucagon-like-peptide-1 (GLP-1)-receptor agonists have been proposed as
putative treatment for substance use disorders (SUD). The objective of this
systematic review is to characterize the effects of GLP-1-receptor agonists on
SUD-related behavioural effects of drugs, nicotine, and alcohol. The review was performed
according to Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA). A search was performed in PubMed
and EMBASE on June 16, 2018. The inclusion criteria were primary studies
investigating the use of GLP-1-receptor agonists on behavioural endpoints
related to SUD. Seventeen studies were included, investigating the effect of the
GLP-1-receptor agonists exendin-4, fluoro-exendin-4, liraglutide, AC3174 and
GLP-1 (7–36) on SUD-related behavioural effects of ethanol, cocaine,
amphetamine, and/or nicotine. All studies used rodents as subjects. Nine of the
studies dealt with ethanol, six with cocaine, two with amphetamine, and two with
nicotine. Most studies investigated acute treatment effects, finding a
significant effect in all but one experiment. A few studies investigated more
chronic effects, but only on ethanol. All the studies reported sustained
effects. Eleven studies tested more than one dose, finding a dose-related
response in ten out of thirteen experiments. Six studies report a central effect
through intra-cerebral administration or by using mice in which the central
GLP-1-receptors had been inactivated. In conclusion, a solid body of evidence
documents acute effects of GLP-1-receptor agonist treatment on behavioural
effects of alcohol, nicotine, amphetamine and cocaine. Documentation of effect
of more chronic GLP-1-receptor stimulation on these behaviours is limited.