Regulatory strategies to reduce tobacco addiction in youth.

Preventing tobacco addiction and achieving cessation in established users are the cornerstones of efforts to reduce tobacco use and disease. It has been increasingly recognised that reducing tobacco toxin exposure has theoretical potential to reduce disease in continuing tobacco users. This has been controversial because such approaches also carry the potential to undermine prevention and cessation. As complicated as harm reduction issues are for adults, they are still more complicated for youth. Harm reduction is not a singular approach, but rather a concept that encompasses an extremely diverse array of potential approaches. These carry equally diverse potential risks and benefits. The regulatory framework (for example, whether or not the Food and Drug Administration regulates the approach) is also predicted to be a major factor in determining the consequences of harm reduction approaches. This paper examines the various issues and potential approaches concerning the application of harm reduction to youth. We conclude that although some carry great risk, others may actually support broader tobacco control efforts to prevent tobacco use and foster cessation in youth and adults.

Correlates of expired air carbon monoxide: effect of ethnicity and relationship with saliva cotinine and nicotine.

AIMS: To assess the accuracy of expired air carbon monoxide (CO) measurement vs. saliva cotinine and nicotine and to estimate the degree of misclassifications of smoking status as a function of ethnicity. DESIGN AND MEASUREMENTS: Comparison for accuracy of expired air CO, saliva nicotine and cotinine in simultaneously collected specimens. SETTING: Outpatient clinic of a clinical research ward. PARTICIPANTS: 228 current African-American and Caucasian cigarette smokers. RESULTS: Expired-air CO concentration was significantly associated with saliva cotinine, but not with saliva nicotine. Saliva cotinine but not expired CO or saliva nicotine showed a significant between-ethnic difference when adjusted for number of cigarettes smoked and for time since last cigarette. Agreement between expired air CO and saliva cotinine was substantial at expired CO < or = 8 ppm but only moderate at < or = 10 ppm. False negative rates were twice as high at < or = 10 ppm than at < or = 8 ppm at each saliva cotinine cut-off tested. At saliva cotinine of < or = 15 ng/ml, more African-Americans were classified as false negative. CONCLUSIONS: Expired CO is strongly associated with saliva cotinine but not with saliva nicotine. Despite this association, misclassifications for no smoking are frequent if true classification is based on saliva cotinine. False negative results occur more frequently in African-Americans.

A comparison of Roche Kinetic Interaction of Microparticles in Solution (KIMS) assay for cannabinoids and GC-MS analysis for 11-nor-9-carboxy-delta9-tetrahydrocannabinol.

In this study, we investigated the effectiveness of the Roche Kinetic Interaction of Microparticles in Solution (KIMS) screening assay for cannabinoid metabolites. Urine specimens (N = 1689) were collected during elimination of cannabinoids from 25 subjects with a history of marijuana use. Specimens were analyzed concurrently for cannabinoid metabolites by a customized Department of Defense (DOD) cannabinoid KIMS kit (50-ng/mL cutoff) and for 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THC-COOH) by GC-MS (15-ng/mL cutoff). As compared to GC-MS results, the sensitivity, specificity, and efficiency of the KIMS assay were 69.7%, 99.8%, and 88.6%, respectively. Many of the false-negative results had GC-MS concentrations between 15 and 26 ng/mL (N = 151). The cannabinoid screening results for the DOD samples tested by the laboratory during the same 8-month period were also evaluated. The linear regression analyses of GC-MS results in the 15-50 ng/mL range and KIMS data resulted in regression coefficients of 0.689 for the research specimens and 0.546 for DOD specimens. The results suggest that the KIMS cannabinoid screening assay is deficient in detecting positives around the cutoff (15-25 ng/mL THC-COOH). This limitation of the KIMS cannabinoid screening method compromises the identification of true positive specimens, therefore reducing the effectiveness of the assay. The success of the DOD program is dependent on sensitive and specific screening assays; the high prevalence of false-negative cannabinoid results compromises the program's primary objective of drug deterrence.

Behavioral and neural consequences of prenatal exposure to nicotine.

OBJECTIVE: To review evidence for the neurodevelopmental effects of in utero exposure to nicotine. Concerns about long-term cognitive and behavioral effects of prenatal exposure to nicotine arise from reports of increased rates of disruptive behavioral disorders in children whose mothers smoked during pregnancy. The relatively high rate of tobacco smoking among pregnant women (25% of all pregnancies in the U.S.) underlines the seriousness of these concerns. METHOD: This review examines the largest and most recent epidemiological and clinical studies that investigated the association of prenatal nicotine exposure with health, behavioral, and cognitive problems. Because of the numerous potential confounding variables in human research, findings from animal studies, in which environmental factors are strictly controlled, are also discussed. Finally, neural and molecular mechanisms that are likely to underlie neurodevelopmental disruptions produced by prenatal nicotine exposure are outlined. RESULTS: A dose-response relationship between maternal smoking rates and low birth weight (potentially associated with lower cognitive ability) and spontaneous abortion is consistently found, whereas long-term developmental and behavioral effects in the offspring are still controversial, perhaps because of the difficulty of separating them from other genetic and environmental factors. Despite the wide variability of experimental paradigms used in animal studies, common physical and behavioral effects of prenatal exposure to nicotine have been observed, including low birth weight, enhanced locomotor activity, and cognitive impairment. Finally, disturbances in neuronal pathfinding, abnormalities in cell proliferation and differentiation, and disruptions in the development of the cholinergic and catecholaminergic systems all have been reported in molecular animal studies of in utero exposure to nicotine. CONCLUSIONS: Prenatal exposure to nicotine may lead to dysregulation in neurodevelopment and can indicate higher risk for psychiatric problems, including substance abuse. Knowledge of prenatal exposure to nicotine should prompt child psychiatrists to closely monitor at-risk patients.

Therapeutic drug monitoring in methadone maintenance: choosing a matrix.

Methadone maintenance is the premier pharmacological treatment for opioid addiction, but it is rarely informed by evidence-based practice guidelines for dosage monitoring and adjustment. Such guidelines are crucial because the pharmacokinetics of methadone vary greatly among patients, and this variation may account for differences in treatment outcome. We review the pharmacokinetics of methadone and factors that may alter it (including drug interactions, disease states, and idiosyncratic differences among patients). Also reviewed are prospects for therapeutic drug monitoring (TDM) of methadone in plasma, urine, sweat, and saliva. Due to its ease of collection and its presumed representation of the bioavailable free-fraction of methadone, saliva may be a promising matrix. However, saliva methadone concentrations are influenced by salivary pH, and future studies are needed to determine how to control for that. Administrative, medical, and social implications of methadone TDM are briefly discussed.

A factor analysis of the fagerstrom tolerance questionnaire.

A factor analysis of 1309 Fagerstrom Tolerance Questionnaires (FTQ) was performed with LISCOMP software, which utilizes tetrachoric correlations to account for the dichotomous responses of the FTQ. Three factors with eigenvalues greater than 1.0 were obtained, accounting for 56.6% of the variance. Factor 1 was loaded by questions "How soon on waking do you smoke your first cigarette?," "Do you find it difficult to refrain from smoking in places it is forbidden?," "How many cigarettes a day do you smoke?," and "Do you smoke if you are so ill that you are in bed most of the day?" Factor 2 was loaded by questions "Which cigarette would you hate to give up?" and "Do you smoke more during the morning than during the rest of the day?" Factor 3 was loaded exclusively by question "What brand do you smoke?" The question "Do you inhale always, sometimes, or never?" loaded exclusively on a fourth factor, however its eigenvalue did not reach significance. Support is provided for the modification of the eight-item FTQ to the six-item Fagerstrom Test for Nicotine Dependence (FTND). Based on the wording of the questions that loaded on each factor, we propose that Factor 2 assesses the degree of urgency to initiate smoking after overnight abstinence and that Factor 1 reflects the persistence of smoking during waking hours.

Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716.

BACKGROUND: SR141716, a recently developed CB1 cannabinoid receptor antagonist, blocks acute effects of Delta-9-tetrahydrocannabinol (THC) and other CB1 cannabinoid agonists in vitro and in animals. These findings suggest that CB1 receptors mediate many of the effects of marijuana, but this has not been evaluated in humans. METHODS: Sixty-three healthy men with a history of marijuana use were randomly assigned to receive oral SR141716 or a placebo in an escalating dose (1, 3, 10, 30, and 90 mg) design. Each subject smoked an active (2.64% THC) or placebo marijuana cigarette 2 hours later. Psychological effects associated with marijuana intoxication and heart rate were measured before and after antagonist and marijuana administration. RESULTS: Single oral doses of SR141716 produced a significant dose-dependent blockade of marijuana-induced subjective intoxication and tachycardia. The 90-mg dose produced 38% to 43% reductions in visual analog scale ratings of "How high do you feel now?" "How stoned on marijuana are you now?" and "How strong is the drug effect you feel now?" and produced a 59% reduction in heart rate. SR141716 alone produced no significant physiological or psychological effects and did not affect peak THC plasma concentration or the area under the time x concentration curve. SR141716 was well tolerated by all subjects. CONCLUSIONS: SR141716 blocked acute psychological and physiological effects of smoked marijuana without altering THC pharmacokinetics. These findings confirm, for the first time in humans, the central role of CB1 receptors in mediating the effects of marijuana.

Cocaine and metabolite elimination patterns in chronic cocaine users during cessation: plasma and saliva analysis.

Several reports suggest a prolonged elimination of cocaine and metabolites after chronic use compared with single or occasional use. This study was designed to measure the half-lives of cocaine in plasma and saliva of individuals who consumed cocaine on a frequent basis. The disposition and elimination patterns of cocaine and metabolites in the body fluids of chronic high-dose cocaine users during acute cessation of use were investigated. Plasma and saliva specimens were collected over a 12-h period during cessation and analyzed by gas chromatography-mass spectrometry. Pharmacokinetic parameters were derived by noncompartmental analysis of plasma and saliva data. Results indicated a cocaine terminal T(1/2) of 3.8 h in plasma and 7.9 h in saliva. The terminal T(1/2) of benzoylecgonine was 6.6 h in plasma and 9.2 h in saliva. Compared with prior studies of acute low-dose cocaine administration, these findings suggest that cocaine's half-life is longer in active street users than in occasional users though the half-life of its main metabolite benzoylecgonine remains similar (as do cocaine saliva-to-plasma ratios). Thus, regular use of cocaine appears to alter the disposition and elimination of cocaine when compared to single or occasional use.

Placebo cigarettes in smoking research.

This review outlines the development and use of placebo cigarettes in smoking research. Research on effects of smoking has been disadvantaged by the lack of an adequate placebo condition. Recently, tobacco-based denicotinized cigarettes have been used in smoking research to distinguish effects of smoking due to the delivery of nicotine, other components of tobacco smoke, and the sensory process of smoking. Placebo cigarettes do not increase heart rate and blood pressure or produce electroencephalogram changes ordinarily associated with nicotine. However, placebo cigarettes reduce subjective measures of tobacco craving, desire to smoke, and tobacco withdrawal. These findings indicate that the effects of cigarette smoking are dependent on the delivery of nicotine, tar, other compounds of tobacco smoke, and the sensory stimuli. The next generation of research may begin to investigate the mechanisms that modulate these placebo effects.

A review of tobacco smoking in adolescents: treatment implications.

OBJECTIVE: To review current data on the tobacco epidemic in adolescents that impact treatment decisions. METHOD: Epidemiological and pharmacological data, risk factors, characteristics of nicotine use in adolescents, and treatment intervention reports from the literature are discussed. RESULTS: Of students in grades 9 to 12, 42.7% have used tobacco; 75% of teenage smokers will smoke as adults. Environmental and biological factors influence adolescent smoking, including sociodevelopmental aspects of adolescence, psychiatric history, genetic background, ethnic and gender characteristics, drug effects, and regulatory factors. Criteria for nicotine dependence are currently based on the experience with adult smokers. Overall, smoking cessation treatment for adolescents has been disappointing because of low participation, high attrition, and low quit rates. CONCLUSION: Characterization of nicotine dependence and further assessment of the safety and efficacy of pharmacological treatment interventions in adolescents are needed given the formidable challenge of the tobacco epidemic in adolescents.

Tobacco craving: intensity-related effects of imagery scripts in drug abusers.

Two experiments were conducted to determine whether active imagery would elicit tobacco craving in smokers with histories of drug abuse who were not interested in quitting smoking. In Experiment 1, the authors used scripts that contained positive, negative, or neutral affective content with and without descriptions of smoking urge. Scripts with urge content and negative affect scripts increased subjective reports of tobacco craving. An interaction between affective manipulation and urge content was observed on self-reported mood. In Experiment 2, positive affect scripts that varied in amount of urge content produced an orderly increase in tobacco craving as a function of urge intensity, suggesting that changes were specific to the imagery manipulation. In both experiments, increases in tobacco craving were positively correlated with craving for drug of choice, suggesting that stimuli that engender smoking urges may occasion craving for other drugs of abuse.

African-American teen smokers: issues to consider for cessation treatment.

Previous reports have indicated ethnic differences in both tobacco-related morbidity and treatment outcome for smoking cessation among adults. We assessed smoking-related characteristics in African-American and non-African American teenagers applying to a cessation trial. 115 teens (15.9 +/- 1.8 years, 68% females, 27% African-American) responded via telephone to media ads. Self-reported sociodemographic, medical and smoking-related data were obtained to determine pre-eligibility for a full intake screen prior to trial participation. Compared to non-African American, African American teen applicants were older (16.4 +/- 1.7 years versus 15.6 +/- 1.6; p = 0.015), had lower Fagerström Test for Nicotine Dependence (FTND) scores (5.3 +/- 2.3 versus 6.1 +/- 1.8; p = 0.018, ANOVA controlling for age) and smoked fewer cigarettes on the weekend (27 +/- 16 versus 38 +/- 17; p = 0.001). African American teens reported similar duration of smoking (3.3 +/- 1.4 versus 3.1 +/- 1.5 years) and time elapsed between first cigarette ever smoked and daily smoking (0.7 +/- 0.9 versus 0.6 +/- 0.7 years). African American and non-African American teens had similar motivation to quit scores and frequency of reported health problems (e.g., asthma, psychiatric conditions). These data suggest that cessation treatment programs designed for African American youth should include lower Fagerstrom-defined levels, and possibly other criteria for tobacco dependence. These observations also highlight the importance of ethnocultural issues in treatment research programs.

Relative rates of AIDS among racial/ethnic groups by exposure categories.

The relative rates of acquired immunodeficiency syndrome (AIDS) were calculated among racial/ethnic populations using Centers for Disease Control and Prevention HIV (human immunodeficiency virus)/Surveillance reports assuming that racial/ethnic distributions reflect that of the US Census Data from 1990. For comparison, a rate of 1 was assigned to whites in each calculation. The overall relative rates were whites--1, African Americans--4.7, Hispanics--3, Asian/Pacific Islanders--0.4, and Native Americans--0.5. Acquired immunodeficiency syndrome surveillance data show higher rates of AIDS for African Americans and Hispanics compared with whites, Asians/Pacific Islanders, and Native Americans. The relative rates for African Americans and Hispanics compared with whites were highest for injecting drug users, heterosexual contact, and pediatric patients. These results led us to explore possible explanations for increased AIDS reporting in African Americans and Hispanics. We then explored available national datasets regarding those variables. The analyses indicate that variables such as access and receptivity to HIV prevention and treatment efforts, race/ethnicity, sexual behaviors, sexually transmitted diseases, socioeconomic status, and substance abuse interact in a complex fashion to influence HIV transmission and progression to AIDS in affected communities.

The phases-of-treatment model for methadone maintenance: implementation and evaluation.

The phases-of-treatment model for methadone maintenance provides a clinical framework for the use of methadone to effectively meet the needs of individual patients. The therapeutic process is highly structured and is divided into several phases of treatment for opioid addiction. The first three phases--Intensive Stabilization, Commitment, and Rehabilitation--provide intensive services and are designed to stabilize patients and allow them to attain an optimal level of productive functioning. Then, in consultation with the treatment team, patients select one of two tracks, the Medical Maintenance phase or the Tapering phase, followed by the Reinforcement phase. This article provides an overview of the phases-of-treatment model and discusses procedures for its implementation. Also discussed are staffing patterns and staff training issues, as well as the use of performance-based standards for program evaluation and quality improvement within the context of the phases model.

Phases of treatment: a practical approach to methadone maintenance treatment.

There has been an on-going controversy in the United States as to whether methadone should be used in the treatment of opiate addiction as a long-term pharmacological treatment or as a short-term medical intervention to help addicts attain an opiate-free state. This article describes a practical treatment approach which resolves this dichotomy and presents a clinical framework for the variable use of methadone to effectively meet the needs of each individual patient. The therapeutic process is highly structured and is divided into several phases of treatment for opiate addiction. The article describes each of these phases and illustrates how they can be translated into clinical/medical practice. Some of the issues regarding medical maintenance, as well as methadone tapering and maintaining subsequent abstinence, are also addressed.