The muopioid system has a key role in hedonic and motivational processes critical to substance addiction. However, existing muopioid antagonists havehad limited success as anti-addiction treatments. GSK1521498 is a selective and potent muopioid antagonist being developed for the treatment of overeating and substance addictions. In this study, 28 healthy participants were administered single doses of GSK1521498 20 mg, ethanol 0.5 g/kg body weight, or both in combination, in a double blind placebo controlled four-way crossover design. The primary objective was to determine the risk ofsignificant adverse pharmacodynamic and pharmacokinetic (PK) interactions. The effects of GSK1521498 on hedonic and consummatory responses to alcohol and the attentional processing of alcohol-related stimuli, and their modulation by the OPRM1 A118G polymorphism were also explored.GSK1521498 20 mg was well tolerated alone and in combination with ethanol. There were mild transient effects of GSK1521498 on alertness and mood that were greater when it was combined with ethanol. These effects were not of clinical significance. There were no effects of GSK1521498 on reactiontime, hedonic or consummatory responses. These findings provide encouraging safety and PK data to support continued development of GSK1521498 for the treatment of alcohol addiction.