KNOW THY POISON

The Shuar tribes in Ecuador have for centuries used native plants to
induce religious intoxication and to discipline recalcitrant
children. By comparison, most North Americans know little about the
mood-altering potential of the wild vegetation around them. And those
who think they know something are often dangerously ignorant. Over a
three-week period in 1983, for example, 22 Marines wanting to get
high were hospitalized because they ate too many seeds of the
jimsonweed plant (Datura stramonium), which they found growing wild
near their base, Camp Pendleton in southern California.

A dozen seeds of jimsonweed contain about one gram of atropine, 10
grams of which can cause nausea, severe agitation, dilation of
pupils, hallucinations, headache and delirium. Tribal groups in South
America refer to datura plants as the "evil eagles." Of approximately
150 hallucinogenic plants that are routinely consumed around the
world, those with atropine have the worst reputation.

An easier way to learn about the risk posed by a substance 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% of
a group of animals is called the median effective dose. The quantity
that produces mortality in 50% 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 centres, 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.

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 adult can achieve a
relaxed affability from approximately 33 grams of ethyl alcohol, the
amount contained in 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.

In analyzing the lethality of a given psychoactive substance, the
method of absorption is a critical factor. The common routes of
consumption, from the least toxic to the most toxic (in general),
are: eating or drinking a substance, depositing it inside the
nostril, breathing or smoking it, and injecting it into a vein with a
hypodermic syringe. So, for example, smoking methamphetamine (as is
done with the popular illicit drug "crystal meth") is more dangerous
than ingesting it.

The most toxic recreational drugs, such as GHB
(gamma-hydroxybutyrate) and heroin, have a lethal dose less than 10
times their typical effective dose. The largest cluster of substances
has a lethal dose that is 10 to 20 times the effective dose: These
include cocaine, MDMA (methylenedioxymethamphetamine, often called
"ecstasy") and alcohol.

A less toxic group of substances, requiring 20 to 80 times the
effective dose to cause death, include Rohypnol (flunitrazepam or
"roofies") and mescaline (peyote cactus).

The least physiologically toxic substances, those requiring 100 to
1,000 times the effective dose to cause death, include psilocybin
mushrooms and marijuana, when ingested. (I've found no published
cases in the English language that document deaths from smoked
marijuana, so the actual lethal dose is a mystery.)

Alcohol thus ranks at the dangerous end of the toxicity spectrum. So
despite the fact that about 75% of North American adults enjoy an
occasional drink, it must be remembered that alcohol is quite toxic.
Indeed, if alcohol were a newly formulated beverage, its high
toxicity and addiction potential would surely prevent it from being
marketed as a food or drug.

Most of us have not had a life-threatening experience with alcohol.
Yet statistics show that every year about 300 people die in the
United States from an alcohol overdose -- and for at least twice that
number of overdose deaths, alcohol is considered a contributing cause.

One reason people feel comfortable with alcohol is that individuals
have reasonably good control of the quantity they consume. Certainly,
control of one's dose of alcohol is easier than with many natural or
illicit substances for which the active ingredients are not
commercially standardized.

Furthermore, alcohol is almost always consumed in a highly diluted
form. The stomach capacity of an average adult is about one litre;
therefore, a person is unlikely to overdose after drinking beer
containing 5% alcohol.

A simpleminded look at the ratio of effective to lethal doses ignores
some complications, however. Take, for example, the fact that danger
generally increases with repetitive consumption. High blood levels of
a drug, without rest periods between use, tend to heighten risk,
because the affected organs do not have sufficient time to recover.

Studies of MDMA use, for example, show that relatively small repeated
doses result in disproportionately large increases of MDMA in blood
plasma. Cocaine is the substance that induces the highest rate of
repetitive consumption as a result of mood change. Heroin and alcohol
come in second and third.

Also, the tendency of a user to take a "booster" dose prematurely is
greater with substances that require an hour or more to provide the
full psychological effect -- during the interim the user often
assumes that the original dose was not sufficiently potent. This
phenomenon routinely occurs with dextromethorphan (found in cough
medicines), GHB and MDMA.

Overdose quantities that are based on acute toxicity also do not take
into account the probability that an individual will become addicted.
This probability can be cast as a drug's capture ratio: Of the people
who sample a particular substance, what portion will become
physiologically or psychologically dependent on the drug for some
period of time? Heroin and methamphetamine are the most addictive by
this measure. Cocaine, pentobarbital (a fast-acting sedative),
nicotine and alcohol are next, followed by marijuana and possibly
caffeine. Some hallucinogens -- notably LSD, mescaline and psilocybin
- -- have little or no potential for creating dependence.

Finally, a comparison of overdose fatalities does not take into
account cognitive impairments and risky or aggressive behaviours that
sometimes follow drug use. And as most people are well aware, a
substantial proportion of violent confrontations, rapes, suicides,
automobile accidents and AIDS-related illnesses are linked to alcohol
intoxication.

Despite the health risks and social costs, consciousness-altering
chemicals have been used for centuries in almost all cultures. So it
would be unrealistic to expect that all types of recreational drug
use will suddenly cease. Self-management of these substances is
extremely difficult, yet modern Western societies have not, in
general, developed effective methods for regulating their use.

The science of toxicology may provide one step in that direction --
by helping to teach members of our society what a lot of tribal
people already know.

(Copyright) Sigma Xi, The Scientific Research Society