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MACROSCOPE

The Toxicity of Recreational Drugs

Alcohol is more lethal than many other commonly abused substances

Robert Gable

Toxicity Profiles

The easier way to learn about the relation between the quantity of a substance taken and the resulting level of physiological impairment is through careful laboratory study. The first example of such an exercise, in 1927, used rodents. Research toxicologist John Trevan published an influential paper that reported the use of more than 900 mice to assess the lethality of, among other things, cocaine. As he and others have since found, a substance that is tolerated or even beneficial in small quantities often has harmful effects at higher levels. The amount of a substance that produces a beneficial effect in 50 percent of a group of animals is called the median effective dose. The quantity that produces mortality in 50 percent of a group of animals is termed the median lethal dose.

Laboratory tests with animals can give a general picture of the potency of a substance, but generalizing experimental results from, say, mice to humans is always suspect. Thus toxicologists also use two other sources of information. The first is survey data collected from poison-control centers, hospital emergency departments and coroners' offices. Another consists of published clinical and forensic reports of fatalities or near-fatalities.

But these sources, like animal studies, have their limitations. Simply tallying the number of people who die or who show up at emergency rooms is, by itself, meaningless because the number of such incidents will be influenced by the total number of people using a particular substance, something that is impossible to know. For example, atropine is more toxic than alcohol, but more deaths will be reported for alcohol than for atropine because so many more people get drunk than ingest jimsonweed. Furthermore, most overdose fatalities involve the use of two or more substances (usually including alcohol), situations for which the overall toxicity is largely unknown. In short: When psychoactive substances are combined, all bets are off.

How then does one gauge the relative risks of different recreational drugs? One way is to consider the ratio of effective dose to lethal dose. For example, a normally healthy 70-kilogram (154-pound) adult can achieve a relaxed affability from approximately 33 grams of ethyl alcohol. This effective dose can come from two 12-ounce beers, two 5-ounce glasses of wine or two 1.5-ounce shots of 80-proof vodka. The median lethal dose for such an adult is approximately 330 grams, the quantity contained in about 20 shots of vodka. A person who consumes that much (10 times the median effective dose), taken within a few minutes on an empty stomach, risks a lethal reaction. And plenty of people have died this way.

As far as toxicity goes, such deaths are quite telling. Indeed, autopsy reports from cases of fatal overdose (whether from alcohol or some other substance) provide key information linking death and drug consumption. But coroners are generally hard-pressed to determine the size of the dose because significant redistribution of a drug often occurs after death, typically from tissues of solid organs (such as the liver) into associated blood vessels. As a result, blood samples may show different concentrations at different times after death. Even if investigators had a valid way to measure the concentration of a lethal drug in a decedent's blood, they would still need to work backward to make a retrospective estimate of the quantity of the drug consumed. Although the approximate time of death is often known, the time the drug was taken and the rate at which it was metabolized are not so easily established. Lots of guesswork is typically involved. Obviously, people who want clean answers should not seek information from corpses.




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