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 (NTX) 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 NTX (0.7 mg/kg; p.o.) and/or CBD (20 mg/kg/day; 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 μ opioid receptor (Oprm1) in the nucleus accumbens (NAc), tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and serotonin 1A receptor (5-HT_1A ) in the dorsal raphe nucleus (DR) were carried out by real-time polymerase chain reaction. The role of 5-HT_1A on the ethanol reduction induced by the administration of CBD + NTX was analysed by using the 5-HT_1A receptor antagonist WAY100635 (0.3 mg/kg, i.p.).

KEY RESULTS:

The administration of CBD + NTX 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-HT_1A gene expressions in the NAc, VTA and DR, respectively. Interestingly, the administration of WAY100635 significantly blocked the actions of CBD + NTX but had no effects by itself.

CONCLUSION AND IMPLICATIONS:

The combination of low doses of CBD plus NTX resulted more effective to reduce ethanol consumption and motivation to drink. These effects, appears to be mediated, at least in part, by 5-HT_1A receptors.

This article is protected by copyright. All rights reserved.