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It will come as no news to addicted smokers that quitting is unpleasant.
But if knowledge is power, it may strengthen smokers in the agony of withdrawal to learn that according to a new study published in the May 7 Nature, the brain-or, more precisely, the brain of an addicted rat-undergoes a dramatic decrease in the capacity to experience pleasure during nicotine withdrawal comparable to what occurs during withdrawal from other abusable drugs, including alcohol, heroin, and cocaine.
There has been an explosion of research on nicotine in recent years, but prior studies have focused on the physical, rather than emotional, aspects of withdrawal, observed principal author Athina Markou, Ph.D., who conducted the study ("Dramatic decreases in brain reward function during nicotine withdrawal") with colleagues at the Scripps Research Institute in La Jolla, Calif. Markou spoke with Psychiatric News.
"This is an animal model of the emotional effects of nicotine withdrawal," she said. It is the affective aspects of withdrawal, rather than the more readily observed physical symptoms, that stimulate craving and drive a return to drug use, she believes.
John Hughes, M.D., chair of the APA Task Force on Nicotine Dependence, concurs with Markou's hypothesis about the role of emotions in driving relapse.
"I think the major impact is that we as physicians often focus on the physical sequelae of withdrawal such as seizure and tremors," said Hughes. "But to the patient what's important is how they feel, their depression, and their irritability." The role of nicotine withdrawal syndrome in driving relapse has been minimized because clinicians, observing relatively minor physical symptoms of withdrawal, have failed to appreciate the severity of emotional symptoms, said Hughes.
"The corollary to that is that what may be causing relapse is not the physical symptoms but the emotional symptoms. So this animal model may be tapping into more clinically relevant issues than prior studies that looked at seizures and so forth." As a clinician, said Hughes, he is impressed that the study found the emotional impact of nicotine withdrawal comparable with that of other major drugs of abuse.
In this study, rats were implanted with a pump that administered a dose of nicotine equivalent to smoking 30 cigarettes daily. At the same time, they were implanted with electrodes that allowed them to stimulate a pleasure center in the brain. The authors' working hypothesis was that if nicotine withdrawal produced a decrease in the capacity to experience pleasure, the rats would work harder, stimulating the pleasure center more frequently during withdrawal, and this is, in fact, what happened.
Although withdrawal triggers numerous changes, the only variable measured for this study was anhedonia, diminished capacity to experience pleasure, Markou explained. The authors have developed a more extensive model of the emotional effects of withdrawal that cuts across the diagnostic categories of the DSM-IV, she noted. The broader model includes not only anhedonia, which is one of the negative symptoms of schizophrenia, but "dysphoria" and other affective states symptomatic of depression.
The model may prove clinically relevant in that 49 percent of people diagnosed with depression and 88 percent of those diagnosed with schizophrenia smoke cigarettes, according to Markou. This compares with about 30 percent of the general population. Smoking may be a form of "self-medication," she said. In withdrawal, self-medication simply means using a drug to ease withdrawal symptoms. But the more interesting concept of self-medication is that people may discover, through experimentation, that certain drugs or combinations of drugs ease the affective distress of certain syndromal or subsyndromal psychiatric disorders, she commented.
"Knowing what I know, if I were a psychiatrist I would pay more attention to affective symptomatology and treat it with whatever it takes," she said. For smokers struggling to quit, it is important that they understand that "when they wake up in the morning, their cranky mood" is symptomatic of nicotine withdrawal. It may be essential to success for clinicians to treat any comorbid disorders as well as the symptoms directly caused by withdrawal, she observed.
APA's Hughes said that he has found that people in nicotine withdrawal "look [psychiatrically] like people seen in a psychiatric outpatient clinic. When people say quitting makes life less pleasurable," that is really a layperson's way of expressing what this study describes.
The research was funded by the National Institute on Drug Abuse (NIDA) and Novartis Pharma of Basel, Switzerland.