Alcohol use disorders (AUDs) constitute the most common form of substance abuse. The development of AUDs involves repeated alcohol use leading to tolerance, alcohol withdrawal syndrome, and physical and psychological dependence, with loss of ability to control excessive drinking.

How does DHM help with hangovers?

Currently, there is no effective therapeutic agent for AUDs without major side effects. Dihydromyricetin (DHM; 1 mg/kg, i.p. injection), a flavonoid component of herbal medicines, counteracted acute alcohol (EtOH) intoxication, and also withdrawal signs in rats including tolerance, increased anxiety, and seizure susceptibility; DHM greatly reduced EtOH consumption in an intermittent voluntary EtOH intake paradigm in rats.

GABAA receptors (GABAARs) are major targets of acute and chronic EtOH actions on the brain. At the cellular levels, DHM (1μM) antagonized both acute EtOH-induced potentiation of GABAARs and EtOH exposure/withdrawal-induced GABAAR plasticity, including alterations in the responsiveness of extrasynaptic and postsynaptic GABAARs to acute EtOH and, most importantly, increases in GABAAR α4 subunit expression in the hippocampus and cultured neurons.

What is DHM good for?

DHM anti-alcohol effects on both behavior and CNS neurons were antagonized by flumazenil (10 mg/kg in vivo; 10 μM in vitro), the benzodiazepine (BZ) antagonist. DHM competitively inhibited BZ-site [3H]flunitrazepam binding (IC50, 4.36 μM), suggesting DHM interaction with EtOH involves the BZ sites on GABAARs.

In summary, we determined DHM’s anti-alcoholic effects on animal models and determined a major molecular target and cellular mechanism of DHM for counteracting alcohol intoxication and dependence. We demonstrated pharmacological properties of DHM consistent with those expected to underlie the successful medical treatment of AUDs; therefore DHM is a therapeutic candidate.

Conclusion

In addition to enhancing alcohol clearance and alcohol metabolic enzymes, DHM has a direct and complex interaction with GABA-A receptors that likely accounts for many of its anti-alcohol effects. DHM counteracts acute alcohol intoxication and helps to reduce alcohol withdrawal symptoms.

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