Synthetic Spirits: Can we use science to reduce the harms of alcohol?
Alcohol is the oldest of all recreational drugs. While its psychological complications have long been known, only in the past century have its medical complications, such as liver cirrhosis, cardiovascular disease, and cancers, become recognized.
In many Western countries these medical problems have increased at an alarming rate. In the United Kingdom, for example, the death rate from liver disease has risen 500% over the past 40 years. It is predicted that, within a decade, liver disease will overtake cardiovascular disease as the leading cause of death in the UK. For these reasons, a recent systematic assessment of drug-related health hazards in the UK scored alcohol as the worst drug overall (Nutt et al., Lancet, 376:1558-66, 2010).
These facts raise two questions: why is alcohol so widely available if it is so toxic and what can we do about it? The answer to the first question appears to be partly due to the fact that many people (and governments) take an ostrich-like view of the health hazards of alcohol. This attitude is compounded by the argument (probably false) that, at low doses and in some populations, alcohol may, in fact, have certain health benefits. Both attitudes belie the facts.
If alcohol were invented today and subjected to current safety-of-use assessments, it would fail badly. Ethanol, the active ingredient, is toxic itself, which is why it is used to protect food from microbial infections and to sterilize skin. An amount only three times higher than a common intoxicating dose leads to death in naive users. And there is no antidote. Moreover, ethanol is converted to acetaldehyde as part of its elimination process. This is a highly toxic substance that in effect pickles the liver and other organs of regular drinkers.
So what can we do about it? I think it is time to use the now-considerable knowledge of the neuropsychopharmacology of alcohol to develop safer, alternative intoxicants whose effects can be reversed by antidotes. A prime target of alcohol in the brain is the GABA-A receptor. Alcohol enhances the actions of the endogenous neurotransmitter GABA, which regulates the major inhibitory system in the brain. Since GABA-A receptors are found on most neurons, alcohol has a wide range of effects.
Other drugs that enhance GABA at this receptor mimic the relaxing, antianxiety effects of alcohol. The best examples are the benzodiazepines, which enhance GABA action. Drinkers report that agonists at benzodiazepine receptors behave just like alcohol And there exist potent and effective antagonist/antidotes, which are currently clinically available.
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