Endogenous conversion of alcohol to norepinephrine and epinephrine may contribute to hangover

Several theoretical publications have suggested that there may be a novel biosynthetic pathway or pathways that transform alcohol (ethanol) into the catecholaminergic neurotransmitters dopamine, (NE), and epinephrine (EPI). A recent empirical, high-resolution mass spectrometry study in mice found that ethanol indeed boosts hippocampal NE in a molecularly selective manner, where such NE could be converted to EPI. The current publication puts forth a new but related hypothesis: boosting of NE and EPI by ethanol may play an important role in the alcohol-related hangover (AH). Aversive symptoms of AH such as fatigue, headache, dry mouth, nausea, elevated blood pressure, sweating, sensitivity to light and sound, anxiety, irritability, dehydration, and disrupted sleep, may all be partially related to elevated NE and EPI, both in the brain and in the periphery. Some of these symptoms have previously been associated with noradrenergic or adrenergic signaling. If conversion of ethanol to these two catecholamines really is a prominent factor in AH, then noradrenergic transmission reducing drugs such as clonidine, guanfacine, propranolol, and prazosin may have therapeutic properties in this condition. Lastly, if consumption of excessive amounts of alcohol can result in dangerously high levels of NE and EPI through acute biosynthesis, this could play a role in alcohol poisoning and its potential lethality.