Abstinence Makes the Heart Grow Fonder

full_ashtrayThe common wisdom about kicking an addiction is to “isolate and conquer.” People trying to give up smoking, or coffee, or something more serious, are usually advised to stay away from reminders of their drug, such as other people smoking, the smell of coffee, or other cues that might remind them of their habit. Taken to its extreme, this isolation policy is the backbone of inpatient drug treatment programs, which remove an addict from their environment and away from addiction “triggers” for 30 days or more. At the hospital, addicts can safely pass through withdrawal symptoms, receive psychiatric care, and return to society equipped to resist the siren call of their vice.

However, research in animals throws a wrench into that theory of addiction treatment. In animals taught to hit a lever to receive addictive substances such as cocaine, heroin, or sucrose, an extended period of abstinence away from drug-related cues produces an unintended effect. Rather than decreasing the animals’ response to the cues (which in the world of a rat’s cage is usually a light or a sound rather than an ashtray or a syringe), longer periods of abstinence inspire a more robust and energetic “relapse” of lever-pressing.

This “incubation effect” suggests that the longer addicts stay away from their drug, the more likely they are to succumb to a relapse when they see or smell a drug-related trigger. But that idea had not been translated from rats to humans until an experiment performed by Gillinder Bedi and colleagues in the laboratory of Harriet de Wit, professor of psychiatry at the University of Chicago Medical Center. Published last month in the journal Biological Psychiatry, the experiment shows the first evidence that incubation of drug cues also occurs in humans. Further, their results suggest that current treatments for addiction may miss, or even run counter to, an important cause of relapse.

“Many factors contribute to relapse,” de Wit said. “One is the presence of withdrawal symptoms, the other is just the immediate difficulty of removing a habit that you had. But there might be this other factor, incubation, that grows over time without dissipating, at least for weeks or perhaps months.”

In Bedi’s experiment, cigarette smokers were paid $30 a day to abstain from smoking for as long as 35 days. As testament to the allure of nicotine, only half of the subjects recruited for the study reached their smoke-free target despite the financial rewards, de Wit said. The participants who did successfully abstain until their goal (7, 14, or 35 days) returned to the lab where they were exposed to either smoking-related cues (pictures of people smoking, lit cigarettes, ashtrays, etc.) or neutral cues or a matched show of neutral, non-smoking cues. To enhance the sensory experience, subjects held a lit cigarette while viewing the smoking cues or a pencil during the neutral session. Before and after the cues, subjects completed surveys to report how strongly they craved cigarettes.

Before the slide show sessions, participants reported expected, positive results of quitting: withdrawal symptoms and craving decreased with the more days since their last cigarette. But after viewing the parade of cigarette-related images, the opposite effect was observed. Subjects assigned to the group that abstained from smoking for a longer period of time (35 days) reported more cue-driven craving compared to those who only abstained for 7 or 14 days.

That looks a lot like the incubation effect seen in rats, and according to de Wit, may actually be an even more impressive effect than what was seen in animal studies. Whereas rats can be kept totally isolated from drug cues for as long as necessary, the subjects in Bedi’s study were presumably exposed to some smoking-related cues – friends smoking, cigarettes in movies, etc. – during a typical day of their paid abstinence. Yet in the laboratory, the cues still held the power to spark craving, and this craving increased with the number of days of abstinence. In a further surprise, most subjects returned to their smoking habits after their part in the research was finished, regardless of how long they had abstained from smoking for the study.

“I think one of the really interesting things is that almost everybody goes back to smoking, even after a month of not smoking,” de Wit said. “You would think if they could go drug-free for a month it would be pretty easy to stay quit after that, and yet they went back.”

The results suggest that drug treatment programs may do well to try to reduce the incubation effect in recovering addicts, to prevent drug-related cues from undoing weeks of progress. In animals, incubation was blocked with a drug that blocks the neurotransmitter glutamate. Reducing the power of the drug cues through extinction by repeatedly exposing a person to the cues until they no longer inspire craving might also work. Either way, to counteract the lingering, long-term effect of incubation, the central strategy of addiction therapy will be have to re-examined.

“Treatment programs often think the longer the inpatient treatment and the longer you’re away from all your cues, the better, so you do 30 days of treatment when you’re not supposed to see any cigarettes or think about them. That might be exactly the wrong thing to do,” de Wit said. “It would be really important for any drug users to go back to that drug-using environment; to go back to the bar, for example. This is controversial, because experts always say to stay away from your drug-using environments. And it would be difficult, but the more they extinguish in those situations the better armed they will be to not have this phenomenon.”

[USA Today wrote about this research last month and spoke to Bedi and other smoking experts.]

About Rob Mitchum (526 Articles)

Rob Mitchum is communications manager at the Computation Institute, a joint initiative between The University of Chicago and Argonne National Laboratory.

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