According to the 2018 WHO Global Report, about 3.3 million deaths (5.3% of all deaths), were attributable to alcohol consumption in 2016. There are significant sex differences in the proportion of global deaths attributable to alcohol, 7.6% of deaths among males and 4.0% of deaths among females were attributable to alcohol.

Overall, 133 million disability-adjusted life years, or 5.1% of the global burden of disease and injury, were attributable to alcohol consumption. There is also a wide geographical variation in the proportion of alcohol-attributable deaths, with the highest alcohol-attributable fractions reported in the WHO European Region.

Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, cancer, diabetes mellitus, alcohol use disorders (AUDs), unipolar depressive disorders, epilepsy, hypertensive heart disease, ischemic heart disease, ischemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and foetal alcohol syndrome .

Despite intensive research, the neurobiological substrates responsible for AUDs are still poorly understood.

Ethanol is a small amphiphilic molecule which can bind to numerous sites in the central nervous system, such as cell membranes and their receptors. For example, ethanol was shown to inhibit NMDA-mediated glutamatergic transmission and to potentiate GABAergic inhibitory currents. Ethanol was also shown to increase dopamine (DA) release in rat nucleus accumbens, a property which is shared by most drugs abused by humans, such as psychostimulants and opiates.

Also like psychostimulants and opiates, ethanol can trigger in rodents a locomotor response that increases with repeated injections, especially in DBA/2J or Swiss (CD1) mice. This phenomenon, called behavioural sensitization, is thought to play a critical role in the development of drug-taking and drug-seeking behaviours.

The pharmacological treatment of alcohol dependence is a major challenge in public health. The exiting pharmacopoeia has therefore developed around substitution products, for which the main therapeutic objective is to limit the physical symptoms induced by withdrawal. However, there are few if any substances that aim to counteract the states of psychic dependence, i.e. the irrepressible need (or craving) for alcohol. This state of psychic dependence is much more robust and is generally the cause of relapses.

Several pharmacological treatments have been proposed for the treatment of alcohol dependence.

Naltrexone, an opiate antagonist, has been tested in clinical trials. Studies have shown that it reduces alcohol consumption, the relapse rate and the desire to drink, especially in the case of severe alcoholization. Unfortunately, its use is limited due to its gastrointestinal side effects (nausea, vomiting and loss of appetite).

Mention may also be made of the use of naltrindole, a δ-opiate receptor antagonist, which has shown some efficacy in animal models.

The use of acamprosate has also been considered. Although its mechanism of action has not been elucidated fully, there is good deal of evidence suggesting that acamprosate acts by modulation of glutamatergic transmission. The molecule would appear to be effective, at least in the treatment of withdrawal symptoms. Its efficacy with respect to craving for alcohol is still under discussion.

Serotonergic antidepressants have also been used. Therapeutic trials based on the serotonin reuptake inhibitors have given variable results, and clinical studies have not demonstrated any real efficacy.

Benzodiazepines are effective when used at the time of withdrawal. Long-term efficacy is controversial, especially as patients follow this type of treatment for long periods to combat symptoms of abstinence such as anxiety and insomnia. There is the question of the benefit/risk ratio of replacing one product of abuse with another, in a patient who is already susceptible to the phenomenon of dependence.

Last but not least, disulfiram is an aversion drug, used since 1940. When it is taken simultaneously with alcohol, this product triggers unpleasant effects such as nausea, vomiting, an increase in blood pressure and heart rate.

Addictive properties of drugs of misuse are generally considered to be mediated by an increased release of DA in the ventral striatum.

However, some experiments indicated an implication of α1b-adrenergic receptors in behavioural responses to psychostimulants and opiates. DA release induced in the ventral striatum by morphine (20 mg/kg) was completely blocked by drug2 (1 mg/kg), an α1-adrenergic antagonist. However, morphine-induced increases in DA release in the ventral striatum were found to be similar in mice deleted for the α1b-adrenergic receptor (α1b-AR KO) and in wild-type (WT) mice, suggesting the presence of a compensatory mechanism.

This acute morphine-evoked DA release was completely blocked in α1b-AR KO mice by SR46349B (1 mg/kg), a 5-HT2A antagonist. SR46349B also completely blocked, in α1b-AR KO mice, the locomotor response and the development of behavioural sensitization to morphine (20 mg/kg) and D-amphetamine (2 mg/kg). Accordingly, the concomitant blockade of 5-HT2A and α1b-adrenergic receptors in WT mice entirely blocked acute locomotor responses, but also the development of behavioural sensitization to morphine, D-amphetamine or cocaine (10 mg/kg).

Inhibitory effects of each antagonist on locomotor responses to morphine or D-amphetamine were more than additive (160%) in naive WT mice but not in those sensitized to either drug. Because of these latter data and the possible compensation by 5-HT2A receptors for the genetic deletion of α1b-adrenergic receptors, the existence of a functional link between these receptors could be postulated.