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Well, most of us have experienced the wonderful feeling of the dreaded hangover. How does it work exactly? I imagine it has something to do with dehydration but what are the underlying mechanisms?

Extra points for explaining why mixing drinks makes it worse and why (or if) a hair of the dog (another drink) the next day can help. Someone once told me that hangovers are the first symptoms of withdrawal and if you drink (anecdotal evidence suggests that it should be the same drink as the night before, but I doubt this is true) a small amount of alcohol, the symptoms are alleviated. I don't really see how that can be true.

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up vote 7 down vote accepted

First, the hormonal and hemodynamic changes seen in hangover are distinct from those seen in alcohol withdrawal, so the advice to drink more is not good, even if some symptoms are in fact improved. See tables 2/3 in the cited review.

It appears the molecular mechanism of veisalgia (HA, a new word) is not well known.

1. acetaldehyde Part of it may be attributed to acetaldehyde but there is clearly more to it. The liver enzyme alcohol dehydrogenase 1 (ADH1) produces acetaldehyde from ethanol, and aldehyde dehydrogenase 2 (ALDH2) makes acetate from that, so the aldehyde does not exist for a long time, and is rather responsible for short-term illnesses.

2. ADH and diuresis

Hangover severity is proportional to antidiuretic hormone concentration (46). Alcohol inhibits the effect of antidiuretic hormone on the kidneys, thereby inducing diuresis that is out of proportion to the volume of fluid ingested. As blood alcohol concentration decreases and dehydration persists, the serum level of antidiuretic hormone increases, maintaining water retention in dehydrated patients with hangover. In our clinical experience, hydration attenuates but does not completely relieve hangover symptoms.

3. cytokines

The constellation of hangover symptoms (nausea, headache, diarrhea) resembles that seen in conditions related to dysregulated cytokine pathways (for example, in viral infections and after administration of interferon-alpha). Alcohol alters cytokine production through a thromboxane pathway. Levels of thromboxane B2 are elevated during experimentally induced alcohol hangover (42), and the administration of tolfenamic acid, a prostaglandin inhibitor, at the time of alcohol consumption has a small prophylactic effect in reducing hangover severity (9).

4. further substances

Congeners, the byproducts of individual alcohol preparations (which are found primarily in brandy, wine, tequila, whiskey, and other dark liquors), increase the frequency and severity of hangover (24, 39, 40). Clear liquors, such as rum, vodka, and gin, tend to cause hangover less frequently.

So there are factors that aren't even identified exactly, and these could fit the mixing of drinks observation.

There are several reviews out there, just search for hangover at Google Scholar.

Wiese, Jeffrey G., Michael G. Shlipak, and Warren S. Browner. "The alcohol hangover." Ann Intern Med 132.11 (2000): 897-902. Online at http://dionysus.psych.wisc.edu/lit/topics/Hangover/WieseJ2000a.pdf

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Thanks for the comprehensive answer, I would have accepted it earlier but I was holding out in case anyone could explain the mixing drinks thang. –  terdon Nov 28 '12 at 15:10
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