Background: Gamma-hydroxybutyrate (GHB or sodium oxybate) is both an exogenous and endogenous
molecule with neuromodulator properties. In the United States, GHB is an approved drug for the treatment of narcolepsy
and narcolepsy with cataplexy in adults. In some European Union countries, sodium oxybate is applied for the
treatment of opioid and alcohol withdrawal.
Objective: The aim of the present review was to describe the state of art of the pre-clinical research and the clinical
evidence related to GHB used alone or in combination with other treatments in alcohol withdrawal syndrome and
alcohol abstinence maintenance.
Method: Internationally published pre-clinical findings and clinical studies investigating the effects of GHB on alcohol
withdrawal syndrome and alcohol abstinence maintenance were collected and described considering seven clinical
studies involving GHB in the treatment of alcohol withdrawal abstinence and five clinical studies involving GHB
in the treatment of alcohol abstinence maintenance. Furthermore, GHB pharmacology and characteristics of abuse
were briefly detailed.
Results: Clinical evidence indicates that GHB is effective in reducing symptoms of alcohol withdrawal syndrome
and produces beneficial effects comparable to those of benzodiazepines or chlometiazole. GHB proved effective in
increasing alcohol abstinence maintenance and in reducing alcohol craving, but it did not show any influence in
relapses of heavy drinkers when given alone. Conversely, it seems to be effective in reducing relapses in alcohol
dependent patients when given in combination with naltrexone and escitalopram.
Conclusion: Despite this bunch of evidence, studies are still limited and investigations including a larger number of
patients are needed. In addition, some safety concerns, such as insufficiency against hallucinations in alcohol withdrawal
and potential development of GHB dependence have to be more investigated.