FEB/MAR 2006
Volume 12 - No. 1
Research Activities at a Featured Program
SRNT Newsletter
February/March 2006, Volume 12, Number 1
Research Activities at a Featured Program:
The University of Massachusetts Medical School's
Research into the Origins of Nicotine Dependence
Since joining GASP (i.e., Group Against Smoking Pollution, now called the Tobacco Control Resource Center,http://www.tobacco.neu.edu/) in the 1970's, I have been involved in advocacy on the political side of tobacco control, non-smokers' rights, litigation against cigarette manufacturers, curtailing the sale of tobacco to minors, and ridding the world of Joe Camel and other tobacco advertising. Beyond helping my patients quit, I had little interest in the medical aspects of nicotine dependence until ten years ago when one of my teenage patients told me that her attempts to quit smoking had failed. I found this remarkable because she had been smoking for only a few weeks, and I had been taught that dependence developed very slowly.
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University of Massachusetts |
A search for the beginning
As a physician, I wanted to learn how nicotine dependence begins. What are its first symptoms? How quickly does it develop? How many cigarettes does it take? With help and guidance from my colleagues Judith Savageau, Judith Ockene, Lori Pbert, and Kenneth Fletcher at the University of Massachusetts Medical School, I made the transition from policy research to clinical research. Over the past ten years, we have amassed data on the origins of dependence from 20,000 adolescent interviews.
A loss of autonomy
Contemporary definitions and measures of nicotine dependence, with their focus on the end-stage of this process, were ill-suited to the challenge of identifying its birth. In fact, the field's reluctance to stray from the DSM definition of dependence has been a constant obstacle to our progress. Fortunately, the concept of lost autonomy, which is central to all definitions of addiction, has been very useful. I have proposed that dependence begins with the loss of full autonomy, i.e., when quitting first requires effort or involves discomfort. We developed a tool to measure autonomy, the Hooked on Nicotine Checklist, and Robert Wellman at Fitchburg State College has established its reliability and validity in both adolescents and adults by administering it to thousands of smokers in a half-dozen studies. Investigators around the world are now measuring autonomy; to my knowledge, the HONC is in use in about two-dozen studies in eight languages. Please visit the HONC website for more information: http://fmchapps.umassmed.edu/honc
What we have learned from measuring autonomy
- Youth typically lose full autonomy over tobacco within days to weeks of initiating intermittent smoking, although some are more resilient.
- When autonomy is lost, the average rate of consumption is two cigarettes, one day per week.
- The loss of autonomy precedes daily smoking two-thirds of the time.
- Even prior to the onset of daily smoking, many smokers fail at quitting.
- The development of a single symptom of diminished autonomy is perhaps the strongest predictor of continued smoking.
- The loss of autonomy is incremental, growing symptom by symptom, faster in girls than in boys.
- Diminished autonomy is distributed over a continuous spectrum of severity. Smokers populate every point on the HONC scale from 0 to 10 in a unimodal bell-shaped distribution with a mean of 7 for all adult smokers and 3 for chippers.
- Smoking one cigarette can relieve withdrawal symptoms for days in both adolescent and adult intermittent smokers; it is not necessary to maintain nicotine levels in the blood.
- Daily cigarette consumption correlates strongly with the severity of diminished autonomy in novice smokers, but quite poorly in long-term smokers.
- In comparison to adults, youth have a far greater number of symptoms of diminished autonomy than would be expected based on how much they smoke.
Dissecting lost autonomy
Our data and theoretical models suggest that three factors contribute to lost autonomy: craving, withdrawal symptoms, and psychological dependence. In collaboration with Jennifer O'Loughlin and her colleagues at McGill University in Quebec, we are developing an instrument that will measure these factors individually. We hope that improving the resolution of our measure will allow us to delve a little deeper into the onset of dependence.
Social smokers
Now that we understand that dependence typically begins prior to daily smoking, we are taking a closer look at adult "social smokers." They confirm what we have heard from youth: many experience withdrawal if they go more than a day or two between cigarettes.
Does the process of addiction begin with the first cigarette?
After learning that the rapid onset of lost autonomy is the rule, I turned to the neuroscience literature to see what a few doses of nicotine could do to the brain. Prior to our clinical studies, nobody had seriously considered that nicotine dependence could begin with a few doses; neuroscientists typically exposed animals to doses equivalent to heavy smoking. Based on our data, I suggested to Ted Slotkin that he study the effects of very low intermittent doses of nicotine, equivalent to smoking a cigarette or two. His team at Duke University detected a significant increase in nicotinic acetylcholine receptors in the rat hippocampus in response to just four small doses of nicotine administered over two days. Although the functional significance of receptor up-regulation is unknown, this experiment showed that even brief, low-dose exposures to nicotine cause rapid adaptations in brain chemistry.
A theoretical model of nicotine dependence
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Joseph DiFranza and Robert Wellman |
Why focus on the beginning?
I believe that efforts to improve the effectiveness of smoking cessation therapies have been frustrated by our ignorance of how nicotine causes addiction: how it starts, how it is maintained, and how it resolves. Many suppositions about nicotine dependence have proven false. My goal is to understand the mechanisms driving nicotine dependence and then to use that knowledge to design targeted pharmacological and behavioral therapies.
About the Author: Joseph DiFranza is Professor of Family Medicine and Community Health at the University of Massachusetts Medical School.