The Biology of Addiction

John A. Frantz

Let us speculate about the tendency we have to become addicted to substances such as alcohol, caffeine, and cocaine. Caffeine is our primary example. Can there be any countervailing advantage associated with the ability to become addicted? Yes. Addicts tolerate fatal doses of the substances to which they are addicted without even getting sleepy. Imagine vegetarian animals surviving a drought because they become tolerant of toxic chemicals in a plant that is also surviving the drought. If there were few or no other plants to eat, addiction would be a small price to pay for the ability to thrive by eating such a plant. Opium poppies have edible leaves, tasty seeds, nutritious bulbs—and morphine throughout the plant. These principles of evolutionary biology and genetics have strong explanatory power in helping us understand the world in which we live—and in which we must survive, if we survive at all.

Soon after settling in Wisconsin in 1955, I was introduced to real coffee-drinking. A Norwegian patient asked me if he could drink coffee. He thought I was joking when I told him “Sure, just hold it to less than seventeen cups per day.” His face fell, because he drank almost twice that much. Then there was a barber who complained of headaches every Thursday for ten years. After a rather extensive get-acquainted conversation, the cause of this unusual complaint was revealed. He had not been a coffee drinker prior to marriage and finishing barber school. He drank the beverage heavily now but had never learned how to make coffee for himself. Thursday was his day off, and there was no business partner or wife to offer him coffee. He followed my advice to carry two thermoses of coffee everywhere he went on his day off, and his Thursday headaches ceased.

Headache as the withdrawal symptom of caffeine addiction is not sufficiently known. For instance, the mother of a teenage daughter once brought the young lady into my office because of a sudden onset of severe headache. The crucial information: the mother had recently told the daughter that she would have to buy her own (caffeinated) soft drinks, but the child’s allowance was insufficient to support her habit. Neither of them was aware of the connection. The headache of caffeine withdrawal is intense and not relieved by morphine in doses adequate to relieve the pain of war wounds. This is illustrated by a lady with severe abdominal pain from pancreatitis. After several days of intravenous feeding, she got a severe headache not relieved by the large doses of morphine she was receiving. A more detailed history revealed that she normally drank iced tea all day long. Intravenous caffeine relieved her headache instantly.

Decades ago I was explaining caffeine withdrawal headaches to another teenage patient. Along the way I mentioned that chocolate contains theobromine, an alkaloid differing from caffeine by only one methyl group. Despite its similarity to caffeine, I told her, theobromine is not known to be addictive. She brightened up and mentioned that when she was three, she had a puppy who ate everything that she did—including large amounts of chocolate. When she found out that dogs could be fatally poisoned by a small amount of chocolate, she wondered why her dog had never been poisoned. My explanation about caffeine must have been quite cogent, because she inferred promptly that theobromine tolerance—brought about by her dog’s having consumed slowly increasing quantities of chocolate during puppyhood—explained her pet’s survival.

This episode led me, much later, to develop my thinking about the survival of the many insects that eat poisonous food to avoid being eaten. Did we inherit addiction from a common ancestor of mammals and insects, one that had evolved the ability to eat poisonous food and store the poison without being harmed? Was that trait harmless enough that later evolution would not select against it? Apparently it was.

From 1968–1970, I served overseas in the Peace Corps. Though I wasn’t fond of tea, I drank much tea instead of water. That way I could get boiled water without creating a political episode. (Drinking Afghan tap water frequently causes dysentery in foreigners who have not grown up exposed to the many bacteria that contaminate virtually all of the local water.) Today I drink a cup of coffee only occasionally, and I dislike tea. Nonetheless, if I have one cup of coffee at lunch several days in a row, I can depend on developing a headache at about 4:00 p.m. on the first day I do not have coffee—a headache that can be relieved only by caffeine. A former addict becoming re-addicted unnaturally rapidly is called tachyphylaxis.

Presumably, addiction has sufficient benefits that it was not bred out of us. It may be pertinent that some species of insects have evolved to look like the toxic species to get a free ride. (Incidentally—and apropos of nothing in particular—small doses of caffeine are fatal to snails and slugs.)

John A. Frantz

John A. Frantz practiced medicine from 1946–2006. He taught internal medicine as a Peace Corps volunteer from 1968 to 1970.


Let us speculate about the tendency we have to become addicted to substances such as alcohol, caffeine, and cocaine. Caffeine is our primary example. Can there be any countervailing advantage associated with the ability to become addicted? Yes. Addicts tolerate fatal doses of the substances to which they are addicted without even getting sleepy. Imagine …

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