Alcohol use disorders (AUDs) are among the most prevalent substance use disorders. According to the World Health Organization, AUDs have the highest morbidity and mortality burden worldwide (2.5 million deaths every year) and are associated with wide-reaching social problems.
Disulfiram, oral naltrexone, injectable naltrexone, and acamprosate are FDA-approved for alcohol dependence. These medications are primarily used to prevent post-detoxification relapse. Several new treatment strategies using older medications and new medications may be effective on the basis of preclinical and/or clinical data.
In this review, we discuss the established medications as well as experimental therapeutic options that may emerge as future medications for alcohol intoxication, withdrawal, and/or long-term abstinence maintenance or harm-reduced drinking.
Alcohol intoxication
Alcohol intoxication describes the acute effects of alcohol ingestion: clinical symptoms are close-ly correlated with blood alcohol levels. The subjective effects of alcohol in amounts consistent with alcohol intoxication are likely due to alcohol’s effects on glutamatergic and γ-aminobutyric acid (GABAergic) neurotransmission.1,2 These effects include stimulatory effects such as euphoria (“ascending limb” symptoms that predominate when blood alcohol levels are rising in early intoxication) and sedative effects (“descending limb” symptoms that predominate when blood alcohol levels are falling in later intoxication).
At present, there are no treatments to reduce the intoxicating effects of alcohol. Recently, dihydromyricetin, a flavonoid from the herb Hovenia dulcis that has been reported for more than a millennium as an antihangover treatment in traditional Chinese medicine, showed anti-intoxication and withdrawal effects in rats. These effects are mediated via the benzodiazepine site of the GABAA receptor.3 Although mitigating alcohol’s intoxicating effects has not been an active area of investigation to date, such treatments could be very useful in reducing the rewarding effects of intoxication.
Alcohol withdrawal syndrome
Compared with withdrawal syndrome from other substances, alcohol withdrawal syndrome is associated with the highest mortality. Repeated and prolonged alcohol intake can induce tolerance, and abrupt drinking cessation can lead to irritability, tremor, insomnia/anxiety, diaphoresis, vital sign instability (eg, tachycardia, elevated blood pressure), seizures, alcoholic hallucinosis, delirium, and death. Alcohol withdrawal may result from overactivation of the glutamatergic system with concomitant understimulation of the GABAergic system in the absence of alcohol.
As GABAA receptor agonists, benzodiazepines remain the standard of care in the treatment of alcohol withdrawal syndrome, especially to reduce the risk of seizures.4 There appears to be no statistically significant difference in the efficacy, safety, or tolerability of individual benzodiazepines, although some reports indicate that long-acting chlordiazepoxide is the preferred oral agent. The best predictor of a complicated alcohol withdrawal syndrome (eg, seizures, delirium tremens) is a past history of complicated withdrawal.
