Effects of cannabidiol plus naltrexone on motivation and ethanol consumption

BACKGROUND AND PURPOSE The aim of this study was to explore if the administration of naltrexone together with cannabidiol (CBD) may improve the efficacy in reducing alcohol consumption and motivation rather than any of the drugs given separately. EXPERIMENTAL APPROACH The effects of low doses of naltrexone (0.7 mg.kg(-1), p.o.) and/or CBD (20 mg.kg(-1).day(-1), s.c.) on ethanol consumption and motivation to drink were evaluated in the oral-ethanol self-administration paradigm in C57BL/6 mice. Gene expression analyses of the opioid receptor (Oprm1) in the nucleus accumbens (NAc), tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and the 5-HT1A receptor in the dorsal raphe nucleus (DR) were carried out by real-time PCR. The role of 5-HT1A receptors in the ethanol reduction induced by the administration of CBD+naltrexone was analysed by using the 5-HT1A receptor antagonist WAY100635 (0.3 mg.kg(-1), i.p.). KEY RESULTS The administration of CBD+naltrexone significantly reduced motivation and ethanol intake in the oral self-administration procedure in a greater proportion than the drugs given alone. Only the combination of both drugs significantly reduced Oprm1, TH and 5-HT1A gene expressions in the NAc, VTA and DR respectively. Interestingly, the administration of WAY100635 significantly blocked the actions of CBD+naltrexone but had no effects by itself. CONCLUSION AND IMPLICATIONS The combination of low doses of CBD plus naltrexone were more effective than either CBD or naltrexone alone at reducing ethanol consumption and the motivation to drink. These effects appear to be mediated, at least in part, by 5-HT1A receptors.