A popular adulterant in South American street drugs makes cocaine more addictive in rats
Many people perceive cocaine as one of the most intense stimulant drugs available: It’s illegal, highly addictive and dangerous. Caffeine, in contrast, is the kinder, cuddlier stimulant. It’s legal, has mild effects and in forms such as coffee, it might even be good for your health.
But caffeine in combination with cocaine is another story. In South America, drug distributors have started “cutting” their cocaine with caffeine. This cheaper substitute might, at first glance, seem to make the cocaine less potent. After all, there’s less of the drug there. But new data shows that when combined, cocaine and caffeine make a heck of a drug.
Coca paste is a popular form of cocaine in South American countries. A smoked form of cocaine, coca paste is the intermediate product in the extraction process used to get pure cocaine out of coca leaves. Because it is smoked, the cocaine in the coca paste hits the brain very quickly, making the drug highly addictive, explains Jose Prieto, a neurochemist at the Biological Research Institute Clemente Stable in Montevideo, Uruguay.
Much of the time, Coca paste isn’t acting alone, however. In a 2011 study published in Behavioral Brain Research, Prieto and his colleagues examined the contents of coca paste from police seizures. “Nearly 80 percent of the coca paste samples” were adulterated, Prieto says, “most with caffeine.” Caffeine adulteration ranged from 1 to 15 percent of the drug volume.
Prieto and his group began to wonder just what the caffeine might be adding to the already addictive effects of cocaine. They administered some of the seized drugs to rats. When given cocaine, rats will generally race around as the drug increases their motor activity. But when given coca paste contaminated with 10 percent caffeine, the rats ran around much more than with cocaine alone.
This increase has implications for its addictive potential as well. When animals receive cocaine repeatedly over a period of days, their initial running response will intensify. This early sensitization process can contribute to future addiction. When rats got cocaine and caffeine together, they ran more, and this effect sensitized, meaning that over several days, they ran farther and farther, much more than with cocaine alone. The effect also happened faster. Cocaine sensitization usually takes five days, but with caffeine added in, it took only three. The scientists published their findings May 14 in The American Journal on Addictions.
While activity in a cage is one thing, it doesn’t show whether added caffeine might make cocaine more rewarding or addictive. Prieto teamed up with Valentina Valentini, a neuroscientist at the University of Cagliari in Italy, to find out how caffeine might affect cocaine’s addictive potential. They implanted catheters into a group of rats, and trained them to administer their own saline, caffeine, cocaine or cocaine/caffeine combined.
Rats given either caffeine or saline never really learned to self-administer the drugs. “It was expected,” Valentini says. “We know that caffeine is a stimulant, but not an addictive drug.” But rats given cocaine or cocaine/caffeine in combination quickly picked up the task.
Then, the scientists changed the game. They introduced the rats to a progressive test. Where the animals previously had to poke a trigger only once to receive the drug, they next had to poke three times, then five, then eight. Each dose costs more and more effort, until finally the animals give up. This is a measurement of how motivated a rat might be to obtain a particular drug.
Cocaine itself made the animals work, but cocaine and caffeine together proved a lot more motivating. “It was pretty impressive,” Prieto says. Valentini and Prieto presented their work at the Society for Neuroscience meeting in Chicago on October 18.
Cutting coca paste with caffeine means dealers get more for their money. “It’s cheap, [and] easy to get,” says Valentini. “Maybe this can explain in part why the adulteration with caffeine can increase drug-seeking behavior in people who are dependent.” Valentini suspects that the caffeine is acting as a “cue,” something the rat (or human) experiences as a signal that cocaine is there and a high is nigh.
This means cutting cocaine with the cheaper caffeine isn’t just money-saving, it’s also money-making. “It’s a win-win for the pusher, it’s a win-win for the cartel,” says John Bruno, a neuropsychopharmacologist at Ohio State University in Columbus. The new study “took on a real-world issue.”
How is the caffeine enhancing cocaine’s effects? That’s the next question. Cocaine acts by blocking the recycling of the chemical messenger dopamine. Dopamine quickly builds up in the spaces between cells, dramatically enhancing its effects and leading to powerful feelings of reward.
Caffeine, however, does not impact dopamine. It acts on the receptor chemical messenger adenosine, blocking adenosine’s actions and keeping us awake. “It could be modulating the dopamine,” says Valentini. But what exactly caffeine is doing to give that cocaine a little extra buzz remains to be seen.