Nicotine Addiction and Treatment

By Arline Kaplan ©2002 (All Rights Reserved)

While the number of current teenage smokers has steadily declined since 1997, 19% of high school seniors smoke every day and 10% smoke a half-pack of cigarettes or more, according to the Monitoring the Future Survey (Johnston et al., 2001).

Researchers from the University of Michigan’s Institute for Social Research reported that current smoking (defined as smoking one or more cigarettes during the past 30 days) has been declining in the last few years. Between 1996 and 2001, the percentage of eighth graders reporting current smoking dropped from 21% to 12.2%; among 10th graders, from 30.4% to 21.3%; and among 12th graders, from 34% to 29.5% (Johnston et al., 2001). Despite the decline, 5.5% of eighth graders, 12.2% of 10th graders and 19% of 12th graders smoke daily, and 1.2% of eighth graders, 2.2% of 10th graders and 2.8% of 12th graders use smokeless tobacco daily—clear signs of many adolescents being dependent on nicotine.

Additionally, adolescents appear to be particularly vulnerable to becoming nicotine dependent, especially at low levels of cigarette consumption and when they continue to smoke on a regular daily basis (Zickler, 2001).

Epidemiological studies by Denise Kandel, Ph.D., of Columbia University and the New York State Psychiatric Institute, show that for same numbers of cigarettes smoked, teenagers have higher dependence levels than adults. Using data from the National Household Survey on Drug Abuse, Kandel and colleagues found that the rate of nicotine dependence is higher in people younger than 25 years of age than in other age groups and that their dependence develops with less exposure to nicotine (Kandel and Chen, 2000, as cited in Zickler, 2001).

In an interview, pediatrician Eric Moolchan, M.D., director of a Teen Tobacco Addiction Treatment Research Clinic for the National Institute on Drug Abuse (NIDA), noted that unpublished laboratory data suggests teenagers have enhanced physiological responses to tobacco smoking as compared to adults. When heart rates and blood pressure are measured before and after smoking, the teenagers generally have greater increases than adults do.

Of equal concern is that behaviors established during the teenage years “tend to stick around and lead to health problems later on,” said Moolchan.

Frank Vocci, Ph.D., director of NIDA’s Division of Treatment Research and Development, noted that more than 70% of smokers start before age 19 and many continue into adulthood. The catastrophic consequences of this disorder begin to show in middle age, he said. For example, 30% of the deaths in the 35- to 69-year-old age cohort are attributed to cigarette smoking. Smokers dying in this cohort lose an average of 23 years of life.

Treatments for Adolescents

Seeking to intervene early in the addictive cycle, Moolchan is lead investigator for an intramural research project assessing the safety and therapeutic efficacy of pharmacological and psychological interventions for tobacco dependence in adolescents. Begun in 1999, the current study involves 100 young people ages 13 years to 17 years who smoke at least 11 cigarettes per day and are motivated to quit. The teenagers are self-referred; they responded to community and media ads, globally directed to the teenage population in Baltimore, Md.

Many of the teenagers are dependent on tobacco but also have a psychiatric diagnosis, particularly oppositional defiant disorder, Moolchan said. Some of them also report past symptoms of attention-deficit/hyperactivity disorder (ADHD). Moolchan believes researchers should further explore the link between the cognitive effects of nicotine and ADHD, since there may be some evidence “for the self-medication hypothesis here.”

In the teen study, two forms of nicotine replacement therapy―skin patch and gum―are being evaluated along with a cognitive behavioral therapy approach specifically designed for smoking cessation. All the teenagers receive the cognitive behavioral therapy. For evaluation of the pharmacotherapies, the teenagers are randomized to one of three groups: active patch and placebo gum; active gum and placebo patch; or placebo gum and placebo patch. The outpatient interventions are for 12 weeks. Follow-up is at six months posttreatment with a biochemical confirmation of smoking status and at one year.

For the cognitive behavioral part of the treatment, Moolchan said a variety of teen-centered methods are used, such as developing refusal skills, looking at lifestyle stressors and exploring various courses of action.

“We look more holistically at what teenagers go through and what they might be interested in,” he said, adding the teen-centered treatment approach will be described in the Journal of Child and Adolescent Substance Abuse.

“We are looking at outcomes in smoking cessation, and various outcome measures linked to that, such as point prevalence abstinence, continuous abstinence and prolonged abstinence, as measured by self-report, but also saliva cotinine (a metabolite of nicotine) and exhaled carbon monoxide,” Moolchan said. Investigators are studying dependence, craving and withdrawal issues as well.

Preliminary data indicates that about one quarter of the kids quit smoking, Moolchan said.

Besides Moolchan, several other researchers are investigating smoking cessation approaches applicable to adolescents.

“Preliminary results in adolescents are showing that this group has a more difficult time quitting than adults even though they profess a desire to quit,” NIDA’s Vocci said. “We have several researchers funded for studies in adolescents as does the National Cancer Institute with 18 investigators.”

One of the psychotherapies being investigated for use with adolescents is that of motivational interviewing. Peter M. Monti, Ph.D., director of the Center for Alcohol and Addiction Studies at Brown University in Rhode Island, received a five-year grant in 1997 to examine whether a brief, individual motivational interview followed by a booster session over the telephone one week later could be effective in changing subsequent cigarette smoking behavior in a population of adolescent smokers. The smokers are recruited from emergency rooms, as well as local high schools, the community and a pediatrician’s office.

“A secondary aim is to assess the impact of the intervention in changing cognitions and behavior that may be related to smoking cessation, including motivation to change smoking behavior, negative evaluation of smoking consequences and treatment seeking for smoking cessation,” Tracy O’Leary, Ph.D., assistant professor at Brown and director of the study, said in an interview.

A further aim of the study is to explore the applicability of specific smoking-related assessment scales (e.g., measures of nicotine dependence) for adolescents.

To determine the effectiveness of the motivational interviewing, the researchers will compare the rates of smoking and smoking quit attempts between those receiving the motivational interview intervention and a control group (those receiving brief advice to stop smoking).

A unique aspect of the study is that it includes a parent intervention. Parents complete an assessment of their own smoking behaviors, their attitudes about smoking and their levels of approval/disapproval of teen smoking. Parents whose children are in the motivational interviewing group also receive a brief intervention by telephone themselves. They learn about the elements of motivational interviewing and receive support for helping their children change their smoking behavior.

To date, O’Leary said they have recruited and conducted the assessment battery and intervention with 143 adolescent smokers. More than three-quarters of eligible parents have participated in the parent intervention. Adolescents and their parents are individually followed up at one- three- and six-months post intervention. This year, the researchers plan to complete baseline interventions and follow-up interviews and prepare the data for treatment outcome analyses and publication of study results.

Treatment Approaches for Adults

Many of the treatment approaches being investigated for adolescents have been used successfully with adults. The U.S. Centers for Disease Control and Prevention reported that an estimated 47 million adults in the United States are current smokers; 68% want to quit and about 46% have tried to quit,. The typical smoker who becomes a confirmed former smoker usually makes at least two or three attempts, or more, before quitting successfully (Robert Wood Johnson Foundation, 2001).

There are “now seven different efficacious agents in the smoking cessation pharmacopoeia”, according to Tobacco Use and Dependence Guideline Panel (Public Health Service, 2000). These agents include nicotine replacements in the form of gum, skin patches, nasal spray and inhalers. In addition, the panel reported that the antidepressant bupropion SR (Zyban) has been found to block nicotine’s pleasurable effects; clonidine (Catapres), a medication used to lower blood pressure has proved helpful in reducing withdrawal symptoms; and the tricyclic antidepressant nortriptyline (Elavil, Pamelor) has been found efficacious in promoting long-term smoking cessation. The panel also stated that combining the nicotine patch with a self-administered form of nicotine replacement therapy (e.g., nicotine gum or nasal spray) is more efficacious than a single form of nicotine replacement therapy.

With regard to psychotherapy, the panel said recent evidence “has identified new, efficacious counseling strategies. In particular, proactive telephone counseling is efficacious, as is counseling that helps smokers attain social support outside of the treatment context…the data are compelling that pharmacologic and counseling treatment each independently boost cessation success.”

Many factors, however, can affect the efficacy of tobacco dependence treatments, including gender, race/ethnicity and comorbidity (Public Health Service, 2000). Researchers at Brown University School of Medicine, for example, have found that smokers with a history of recurrent major depressive disorder who received standard treatment for smoking cessation combined with behavioral-coping therapy for depression were more likely to be successful in quitting than those receiving standard treatment alone (Brown et al., 20001, as cited in NIDA, 2001). Participants in the study had been smoking on average 27 cigarettes per day and had been smokers for more than 27 years. A year after the six-week treatment program, 24.7% of the standard therapy group compared to 32.5% of the combination therapy group had stopped smoking.

Other special populations being studied include veterans, women, racial and ethnic minorities, hospitalized smokers and older adults.

New Pharmacological Approaches

New pharmacologic approaches being studied for treating nicotine addiction include nicotine replacement therapy combined with bupropion; mecamylamine, a nicotinic antagonist; mecamylamine in combination with nicotine replacement therapy; methoxsalen (Oxsoralen-Ultra), a drug approved for the treatment of psoriasis that inhibits nicotine metabolism and decreases the urge to smoke; and NicVAX, a vaccine that may immunize smokers against nicotine’s effects.

The nicotine vaccine “is based on technology we have been developing for a unique way of treating staphylococcus aureus, a blood-borne bacterial infection, using a conjugate vaccine to put a unique antigen onto a known protein and injecting it into the individual to cause an antibody reaction,” said David Gury, chairman, president and chief executive officer of Nabi, a Florida-based biopharmaceutical company.

The company’s researchers are using a similar process to create nicotine-specific antibodies, something the body doesn’t normally do, Gury explained. Nicotine gets into the blood rapidly after smoking. It crosses the blood-brain barrier where it reaches the dopamine receptors, raises heart rate and blood pressure, and creates what is believed to be the sources of nicotine addiction.

NicVAX generates high levels of nicotine-specific antibodies in vaccinated animals. Preclinical studies by researchers at the Minneapolis Research Foundation and Hennepin County Research Center in Minneapolis and at the University of Houston at Clear Lake have demonstrated the ability of the vaccine to reduce the entrance of nicotine into the brain and to modify animal behavior in response to nicotine injections (Pentel et al., 1999, as cited in Shine, 2000).

The nicotine molecules attach to the antibodies and become too large to cross the blood-brain barrier. And with the normal immune response, those antibodies then are collected and eliminated from the system, Gury added.

Preclinical safety studies of the vaccine were completed in November, and the company plans to move forward on human clinical testing.

The absence of toxicological effects in animals in response to even extremely high doses of the vaccine “is considered to be a crucial precursor to the continued development of this vaccine in upcoming safety and immunogenicity trials in humans,” Robert Nasco, Ph.D., Nabi’s senior vice president of quality, regulatory and product development, said in a press statement.

Gury said the company is in the process of filing the IND [investigational new drug] application and plans to begin the first human trial early in 2002. NIDA will partially fund the study, and the research will be conducted at the University of Minnesota.

“This first trial will be Phase I (safety trial) and will involve a limited number of former smokers, who have quit within 30 days,” Gury said.

If everything goes well, Gury expects the product to be launched in about four years. The vaccine, he said, provides as a chance to really make a difference in the treatment of nicotine addiction.

References

Brown RA, Kahler CW, Niaura R et al. (2001), Cognitive-behavioral treatment for depression in smoking cessation. J Consult Clin Psychol 69(3):471-480.

Johnston LD, O’Malley PM, Bachman JG (2001), Cigarette smoking among American teens declines sharply in 2001. Based upon the Monitoring the Future Survey released jointly by the Department of Health and Human Services in Washington, D.C., which sponsors the study and University of Michigan Institute for Social Research, which conducts the study. Press release issued Dec. 19.

Public Health Service (2000), Clinical Practice Guideline – Treating Tobacco Use and Dependence. Available at www.surgeongeneral.gov/tobacco/default.htm. Accessed Dec. 6.

Robert Wood Johnson Foundation (2001), Substance Abuse. The Nation’s Number One Health Problem. Key Indicators for Policy Update. Princeton, NJ: Robert Wood Johnson Foundation.

Shine B (2000), Nicotine vaccine moves toward clinical trials. NIDA Notes 15(5). Available at www.drugabuse/gov/NIDA_Notes/NNVol15N5/Vaccine. Accessed Dec. 6, 2001.

Zickler P (2001), Adolescents, women, and whites more vulnerable than others to becoming nicotine dependent. NIDA Notes 16(2). Available at www.nida.nih.gov/NIDA-Notes/NNVol16N2/Adolescents. Accessed Dec. 21.

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