Chinese tree extract stops rats getting drunk

For hardened drinkers, it sounds too good to be true: a natural substance that keeps them sober no matter how much they drink, neutralises hangovers and eventually breaks the cycle of alcohol addiction.

Alcoholism is a huge problem globally, killing 2.5 million people a year according to the World Health Organization. There has been serious research recently looking for drugs that stop people drinking, or at least encourage them to drink less.

Extracts of a Chinese variety of the oriental raisin tree (Hovenia dulcis) could be the answer. The extracts have been used for 500 years to treat hangovers in China. Now dihydromyricetin (DHM), a component of the extract, has proved its worth as an intoxication blocker in a series of experiments on boozing rats. It works by preventing alcohol from having its usual intoxicating effects on the brain, however much is in blood.

Soon, a preparation containing DHM will be tested for the first time in people. "I would give it to problem drinkers who can't resist going to the pub and drinking," says pharmacologist Jing Liang of the University of California, Los Angeles, who led the research team.

"DHM will reduce the degree of drunkenness for the amount of alcohol drunk and will definitely reduce the hangover symptoms," says Liang. "In time, it will reduce their desire for alcohol."

Too drunk to stand

Liang first tested whether DHM blocks the clumsiness and loss of coordination caused by drinking too much. To do this, she measured how long it took for treated rats to right themselves after being laid on their backs in a V-shaped cradle.

After she injected rats' abdomens with a dose of alcohol proportionate to the amount a human would get from downing 15 to 20 beers in 2 hours by a human, they took about 70 minutes, on average, to right themselves. However, when an injection of the same amount of booze included a milligram of DHM per kilogram of rat body weight, the animals recovered their composure within just 5?minutes.

DHM also stopped rats in a maze from behaving in ways resembling anxiety and hangovers. Rats given heavy doses of alcohol cowered away in corners of the maze, whereas those given the extract with their alcohol behaved normally and were as inquisitive as rats given no alcohol at all, exploring the more open corridors of the maze.

Finally, DHM appeared to discourage rats from boozing when they had a free choice between drinking a sweetened solution of alcohol or sweetened water. Over a period of three months, rats will normally get addicted to increasing volumes of the hard stuff. Rats given DHM, though, drank no more than about a quarter of the amount that the "boozers" eventually built up to. Moreover, boozy rats that had worked up to the higher levels suddenly dropped down to a moderate intake when given DHM after seven weeks.

All the benefits of DHM were lost instantly when Liang also gave the rats a drug called flumazenil, which is known to block receptors in the brain for a neurotransmitter called gamma aminobutyric acid (GABA). According to Liang, this proved that DHM works by stopping alcohol from accessing the same receptors. This, she says, explains why DHM kept the rats sober even when they had huge amounts of alcohol in their blood.

Good idea?

"This supports other data that GABA receptors are key in the actions of alcohol and that targeting this interaction is a viable approach to reducing alcohol intake," says David Nutt of Imperial College London, former head of the British government's advisory committee on drugs. "Let's hope it's safe to use in humans."

Other alcohol experts fear that the availability of a "sobriety pill" could encourage more, not less drinking. Markus Heilig, clinical director of the US National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, says that Roche abandoned development of a similar compound called Ro15-4513. "There was a lot of philosophical worry that an 'alcohol antidote' would entice people to consume alcohol and then count on being able to terminate the intoxicating effects on demand," says Heilig.

Ro15-4513 caused serious side effects, including anxiety and convulsions. Liang says there is no sign that DHM carries similar side effects.

Journal reference: The Journal of Neuroscience, DOI: 10.1523/jneurosci.4639-11.2012

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