Alcohol use disorder is associated with several mental, physical, and social problems. Its treatment is difficult and often requires a combination of pharmacological and behavioural therapy. The brain histaminergic system, one of the wake-active systems that controls whole-brain activity, operates through three neuronal GPCRs. The histamine H-3 receptor (Hrh3), which is expressed in many brain areas involved in alcohol drinking and alcohol reward, can be targeted with a number of drugs developed initially for cognitive disorders and/or disorders related to sleep, wakefulness, and alertness. In all rodent alcohol drinking models tested so far, H-3 receptor antagonists have reduced alcohol drinking and alcohol-induced place preference and cue-induced alcohol reinstatement. Several H-3 receptor antagonists tested and found to be safe for humans could be subjected to clinical tests to treat alcohol use disorder. Preference should be given to short-acting drugs to avoid the sleep problems associated with the wake-maintaining effects of the drugs. Linked Articles This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.3/issuetoc

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