Tuesday, February 10, 2009
How Brain Science Began
Civilization’s debt to opium.
The history of brain science probably began about 4,000 B.C., somewhere in Sumeria, when human beings first discovered the extraordinary effects of the unripened seed pods of the poppy plant. Modern neuroscience owes a great debt of gratitude to this tame-looking plant drug and its sticky, incredibly potent byproduct called opium. Neuropharmacology—the study of the action of drugs on the nervous system—would never have advanced so quickly without it.
Historically, the emphasis has been on opium’s cash value, not its value to science. A trade staple on the Silk Route for centuries, opium was very nearly the perfect business. The present-day drug companies, known collectively as Big Pharma, are not the first capitalists in the world to exert an unprecedented grip on drug retailing.
From roughly 1720 to the late 1800s, the merchants of the British East India Company ran a brisk and lucrative opium business with the Oriental “heathens.” In 1839, the British went to war with China to maintain unlimited trading rights. The British won the war, retained the right to market opium in the Orient, and picked up the island of Hong Kong in the bargain.
Opium’s effects are concentrated at specific receptor sites, while alcohol’s range of action is more diffuse. Nonetheless, the two drugs have similar effects along the limbic reward pathway. Morphine comes right from the source, isolated from the crude opium resin found on Papaver somniferum—the opium poppy. Morphine is known as a “pure mu agonist,” meaning it locks securely into the “mu” subset of endorphin receptors, and activates them. This alters the transmission of pain messages, and induces a contented, euphoric state of relaxation. Codeine, another natural painkiller, is found in opium in very small concentrations. Most medical codeine is synthesized from morphine.
The body’s own opiates are referred to as endogenous opioids. Endorphins and enkephalins are interchangeable terms for these chains of amino acids. An important mechanism of action in this process is morphine’s inhibitive effect on GABA. By inhibiting the inhibitor, so to speak, neurotransmitter levels increase down the line, particularly in the nucleus accumbens. Hence, feelings of pleasure.
Alcohol stimulates the mu receptor as well, so we are back to the same basic chain of limbic activation triggered by drinking. GABA is the bridge that connects the alcohol high and the heroin high.
Rapid cellular tolerance is the hallmark of opiate addiction. Brain cells quickly become less responsive to the same doses of the drug. “The body’s natural enkephalins are not addicting because they are destroyed rapidly by peptide-degrading enzymes as soon as they act at opiate receptors,” writes Solomon Snyder. “Therefore, they are never in contact with receptors long enough to promote tolerance…. As analgesics, the enkephalin derivatives developed by drug companies have not been superior to morphine, or even as good as morphine.” Even the brain’s own morphine is not as good as morphine. Nothing is as good as morphine.
Recent evidence for the heritability of opiate addiction looks strong. “Harvard did some really superb studies using a huge cohort of military recruits in the U.S. Army,” according to Mary Jeanne Kreek, a specialist in opiate addiction at Rockefeller University in New York. “Heroin addiction has even a larger heritable component than any of the other addictions, so that up to 54% of heroin addictions seem to be on a genetic basis or a heritable basis.” Estimates of alcohol’s heritability generally run to 40 or 50 per cent.
--Excerpted from The Chemical Carousel: What Science Tells Us About Beating Addiction. (Spring 2009).