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Understanding How Age and Sex Factor in Drug Addiction

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Now a professor of pharmacology at the Duke University School of Medicine, Cynthia Kuhn, has spent most of her career researching the effects of licit and illicit drugs. | Duke University

Cynthia Kuhn’s switch from geology to psychopharmacology began with a bummer. In the 1960s, Kuhn was an undergraduate at Stanford, and as she puts it, “obsessed with volcanoes,” which was a rare pursuit for women back then. So rare, in fact, that when it came time to do her required summer fieldwork, Kuhn was the only woman signed up. Not willing to send her into the field “with the boys,” Kuhn’s supervisor barred her from going on the trip, effectively extinguishing her dreams of volcanology. Ever resilient and inquisitive, Kuhn soon found a new obsession, one that was a sign of the times.

“It was the ’60s. I wasn’t much of a drug taker, but I was fascinated that there could be a chemical substance that could make you see things that weren’t there,” explains Kuhn. “So I went to graduate school to study LSD [lysergic acid diethylamide].” 

The 66-year-old Kuhn, who was awarded an AAAS Fellowship last year, is now a professor of pharmacology at the Duke University School of Medicine where she primarily researches the neurotransmitters dopamine, norepinephrine, and serotonin, and the various drugs that interact with them. Kuhn ended up not focusing her research on the hallucinogen LSD, but the list of licit and illicit drugs that have passed through her lab is impressive, ranging from the dance party drug Ecstasy to subtler mood-altering substances such as marijuana and the antidepressant Prozac. But for most of Kuhn’s career, her work has revolved around the stimulants amphetamine and cocaine, and the neurotransmitter dopamine.

“Dopamine is key to getting addiction started,” says Kuhn. “We know that stimulants like cocaine and amphetamine make dopamine go up as part of their primary pharmacologic action, but other drugs also interact with dopamine.”

When she began her study in the 1960s, not much was know about the connection between dopamine and addiction. That’s changed. Dopamine—part of what is commonly called the brain’s reward system—is now understood to be linked to multiple forms of addiction including to drugs such as marijuana and alcohol, which don’t have as direct a link to the neurotransmitter. Because cocaine and amphetamine have that direct link, they are ideal for studying not only addiction, but also how the brain uses dopamine. Kuhn’s research has revealed that different brain types use dopamine differently, strongly suggesting that factors such as sex and age can play significant roles in addiction.

One of Kuhn’s major contributions to the field has been to show that the brains of males and females have different amounts of dopamine and, thus, different susceptibilities to addiction.

“There is evidence that once females start taking a drug they establish that addiction more quickly than males,” said Kuhn.

According to Kuhn’s and others’ research, the reason for this addiction disparity has to do with how dopamine interacts with the sex hormones estrogen and testosterone. In multiple studies using rats, Kuhn and her colleagues have observed that estrogen appears to encourage a larger amount of dopamine in the brain, while testosterone lowers it. The reason is reproduction. During ovulation, estrogen levels in females go up along with dopamine, a process that encourages females to find mates.

“In the lab, I like to joke that dopamine is the only reason a male rat ever gets laid,” says Kuhn. “And this [dopamine estrogen connection] seems to explain why females respond more when you give them amphetamine or cocaine. This is true of humans and of rats.”

Kuhn is quick to point out that one shouldn’t draw too many conclusions when comparing studies in rats with those in humans, noting that there are multiple social and biological factors behind addiction.

“Addiction in women is strongly linked to abuse. We can’t model in rodents the terrible things humans do to each other,” says Kuhn.

Another large piece of Kuhn’s work has looked at how age can create disparities in addiction as well. In numerous studies, again using rats, Kuhn found that younger subjects were more sensitive and less able to develop tolerance to drugs ranging from THC, the psychoactive compound found in marijuana, to cocaine.

In 1998 Kuhn co-authored a book for the general public, “Buzzed: The Straight Facts About the Most Abused Drugs from Alcohol to Ecstasy.” Kuhn sees the book, now in its fourth edition, as part of larger effort on her part to inform the general public about the neuroscience of drugs and addiction.

Drug laws and policies, says Kuhn, frequently lack good science. Kuhn asserts that criminalizing drug use instead of recognizing the biological and social foundations of addiction is ultimately harmful. But this student of the ’60s is also quick to point out that society should not go the opposite route without adequate research, pointing to Oregon, Colorado, and Washington state’s legalization of marijuana as examples of liberal policies that are also lacking a foundation in good science.

 “Something I’ve learned over the years studying a lot of different drugs, is none are completely innocuous,” said Kuhn.

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<p>Now a professor of pharmacology at the Duke University School of Medicine, Cynthia Kuhn, has spent most of her career researching the effects of licit and illicit drugs. | Duke University</p>
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Nathan Gilles