The Tolerance Effect: How Drinking May Have Really Killed Amy Winehouse - TIME

Amy Winehouse died of alcohol poisoning, according to a British coroner's inquest released Wednesday. The singer had a blood level of alcohol five times the legal limit for driving at the time of her "death by misadventure," the report said.  But the ultimate cause of her death may have been ignorance:  Winehouse was likely unaware of the potentially fatal change in alcohol tolerance that follows a period of sobriety.

By all accounts, the soulful singer had been sober for about a month, before relapsing in the days leading up to her death. Police recovered three empty vodka bottles in the London apartment where her body was found. Winehouse had been prescribed a sedative to mitigate withdrawal symptoms, but no other drugs were found in her body when she died, and the coroner ruled that drugs did not contribute to her death.

Given Winehouse's well-known history of excess, it's probably safe to assume that she had in the past consumed the same amount of alcohol that killed her, likely without experiencing much more than passing out and waking up with a hangover. So why was it different this time?

It may have been due to Winehouse's recent abstinence. Winehouse had almost certainly built up tolerance to alcohol while she was drinking, then lost it during her few weeks of sobriety. Tolerance develops in part because the brain is a very conservative organ. When drugs push certain brain systems in one direction, other systems try to balance out the effect by pulling them back the opposite way.

That means that the same dose of a drug will over time produce a smaller effect. And this increasingly unsatisfying experience prompts addicts to take more and more. Over time, users need extreme doses to get the same high.

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This is precisely why doctors can't always determine whether any given dose of a drug is "lethal," and coroners may not be able to establish whether it could be the cause of death. Heroin addicts often take doses that would kill 10 non-addicted people, and they can do it without even feeling high or suffering any impairment. (Indeed, methadone maintenance treatment is based on the fact that a steady, regular dose of a substance produces such predictable tolerance that it does not impair cognitive functioning or skills like driving.)

Significant periods of abstinence, however, can eliminate or dramatically reduce tolerance. If you needed 10 drinks to get drunk before you quit alcohol, then you might slug them down before you realize how much stronger the effects are now. It's possible that in Winehouse's case, such a mistake was deadly.

Research shows that one of the highest risk periods for overdose is in the first days of relapse, immediately following a period of abstinence. That's true whether the substance involved is alcohol, opioids like heroin or — as is often the case — a mixture of multiple drugs. This aspect of shifting tolerance is an important cause of overdose death.

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Obviously, it's safest to avoid becoming an addict or alcoholic in the first place — and if you do become addicted, it's certainly best to avoid relapsing. But relapse doesn't have to be deadly. Awareness of the problem of tolerance can at least give people a chance to reduce the risk of overdose, so that they can hopefully return to recovery. If you do relapse, be mindful that the dose you took the day before you quit may now be deadly.

R.I.P., Amy Winehouse.

Maia Szalavitz is a health writer at TIME.com. Find her on Twitter at @maiasz. You can also continue the discussion on TIME Healthland's Facebook page and on Twitter at @TIMEHealthland.