De Wit’s work bridges a gap between research into how drugs affect animals and how they influence humans. (Photography by Jason Smith)

Sobriety tests

Harriet de Wit studies drug use in humans to better prevent and treat addiction.

Houseplants and travel photos dot the shelves in Harriet de Wit’s office, where she greets a visitor and beckons toward a comfy leather couch. “Tea? Water?” she asks, holding a ceramic mug ringed with cartoon cats.

Drinks served, de Wit settles into a large leather chair, ankles crossed. Beside her looms a tall bookshelf crammed with textbooks and manuals on drug abuse. Among the titles: The Wiley-Blackwell Handbook of Addiction Psychopharmacology, a 782-page tome she recently coedited.

For more than three decades, de Wit’s Chicago laboratory has researched the effects that commonly abused drugs, both legal and illegal, have on the human body and mind. Asked about her work, she pauses and says,“We need to be a bit careful in presenting what we do to the world.” That’s because rather than using animals like much drug research does, her lab relies on healthy human volunteers, all of whom undergo extensive medical and psychological testing before they participate in a study. Depending on the experiment, a subject might consume a substance such as caffeine, alcohol, nicotine, MDMA (“ecstasy”), or THC, the active ingredient in marijuana.

It’s research that’s prone to sensationalism, says de Wit, the principal investigator on several projects funded by the National Institutes of Health. “The first thing many ask is, ‘You mean, you give drugs to people?’”

Yes, she does. But her research questions are sober minded. Why are some people more likely to abuse drugs and alcohol than others? What environmental triggers can lead to relapse? What genetic factors put an individual more at risk for dependency? She’s also currently doing a nondrug study about the genetic basis of impulsive behaviors, which can be risk factors for drug taking. Unraveling the underlying mechanisms, de Wit says, can lead to more effective prevention of and treatment for addiction.    

The Human Behavioral Pharmacology Laboratory recruits potential volunteers with Craigslist ads. Participants are typically between the ages of 18 and 35, or at least 21 for studies involving alcohol. An online survey eliminates anyone taking medications or with above- or below-average body weight. Individuals who make the cut visit the lab to take detailed psychiatric and personality questionnaires and undergo a screening interview designed to rule out anyone with serious anxiety, depression, or other psychiatric issues.

As a final step, volunteers review their medical history with a nurse and have a complete physical exam as well as an electrocardiogram. A psychiatrist then reviews all the materials and approves or declines the applicant.

When an approved volunteer arrives for a study, lab assistants take a blood-alcohol measure and urine sample to make sure the person hasn’t been using drugs. Depending on the experiment, the subject might complete a computerized questionnaire about their emotional state, then repeat the same questionnaire, along with physiological tests, at regular intervals to track a drug’s effect. Volunteers, who generally receive the lowest possible doses known to produce behavioral or mood-altering effects, are carefully monitored throughout each multihour session, which they spend in a small room equipped with a computer, movies, and magazines to help pass the time. No one leaves the lab until they are sober.

De Wit’s work bridges a gap between studies that investigate how drugs affect animals and how they influence humans. With rats, experimenters have long measured how much reward the animal experiences from a drug by testing for what’s known as place preference. The rodent is put in a large chamber divided into two parts. On one side, the animal repeatedly receives a commonly abused drug. On the other, it receives a placebo. When the divider is removed, rats typically hang out on the side where they got the drugs, signaling their preference. 

De Wit and longtime colleague Emma Childs, an assistant professor and research associate, wanted to see if the place conditioning principle, which had never been studied in humans, held across species. “Drug users often form very strong positive associations with places where they use drugs,” such as bars or parties, de Wit explains.

To test the theory, the researchers had subjects visit the lab six times, each time being escorted to one of two rooms. Both are nearly identical, furnished with a leather couch, computer, and pile of magazines you’d find in any doctor’s office. A Monet landscape decorates otherwise plain walls.

Unaware of what substance they’re consuming, subjects receive a small amount of alcohol—dosage is determined by gender and body weight—in one room and a placebo in the other. On a seventh and final session, subjects are asked which space they preferred. Most opted for the room where they received the alcohol.

Of course, kicking a drug habit isn’t as simple as avoiding a particular environment. Withdrawal symptoms often trigger relapse. Less understood, however, is why some drug users resume old behavior long after withdrawal pangs subside.

One culprit is a phenomenon known as incubation. In a 2011 study, de Wit and her colleagues discovered that smokers who abstained from nicotine and then were exposed to reminders—photos of people smoking, the scent of smoke, the act of holding a lit cigarette—were more likely to experience cravings the longer they had been away from cigarettes.

It’s a finding with real-world repercussions. “We tend to think with substance-abuse treatment that if you put people in an inpatient unit, away from all their cues,” de Wit says, “the longer they’re in treatment, the better.” In fact, that may foster an incubation period in which cravings grow more intense. “Taking people away from all their cues isn’t necessarily going to improve their situation,” de Wit adds. “But showing them cues along the way might actually immunize them.”

Such discoveries reiterate her lab’s ultimate aim: paving the way toward more insightful and informed treatments.