Recent progress in the neurotoxicology of natural drugs associated with dependence or addiction, their endogenous agonists and receptors. (1/1791)

Nicotine in tobacco, tetrahydrocannabinol (delta 9-THC) in marijuana and morphine in opium are well known as drugs associated with dependence or addiction. Endogenous active substances that mimic the effects of the natural drugs and their respective receptors have been found in the mammalian central nervous system (CNS). Such active substances and receptors include acetylcholine (ACh) and the nicotinic ACh receptor (nAChR) for nicotine, anandamide and CB1 for delta 9-THC, and endomorphins (1 and 2) and the mu (OP3) opioid receptor for morphine, respectively. Considerable progress has been made in studies on neurotoxicity, in terms of the habituation, dependence and withdrawal phenomena associated with these drugs and with respect to correlations with endogenous active substances and their receptors. In this article we shall review recent findings related to the neurotoxicity of tobacco, marijuana and opium, and their toxic ingredients, nicotine, delta 9-THC and morphine in relation to their respective endogenous agents and receptors in the CNS.  (+info)

Durability of tobacco control activities in 11 north American communities: life after the Community Intervention Trial for Smoking Cessation (COMMIT). (2/1791)

Durability of tobacco control activities in the 11 intervention sites of the Community Intervention Trial for Heavy Smokers (COMMIT) was examined. Although continuation of COMMIT activities was not a major goal, all communities made plans to continue some tobacco control activity. Information was gathered at focus groups of former COMMIT volunteers and staff who were assembled in each community and asked to describe tobacco control activities in their communities during the past 12-16 months-the period after the termination of COMMIT funding. It was found that a tobacco coalition, board or other structure was still operating in nine of the 11 communities and 10 had some level of paid staff dedicated to smoking control. There was also substantial activity in three of the four channels that COMMIT used as an intervention framework: worksites, public education and cessation resources. Many communities were currently engaged in considerable smoking control activity aimed at youth, an area that was intentionally de-emphasized by COMMIT. Implications for the durability of health promotion programs by communities are discussed.  (+info)

Minor tobacco alkaloids as biomarkers for tobacco use: comparison of users of cigarettes, smokeless tobacco, cigars, and pipes. (3/1791)

OBJECTIVES: This study (1) determined levels of various tobacco alkaloids in commercial tobacco products. (2) determined urinary concentrations, urinary excretion, and half-lives of the alkaloids in humans; and (3) examined the possibility that urine concentrations of nicotine-related alkaloids can be used as biomarkers of tobacco use. METHODS: Nicotine intake from various tobacco products was determined through pharmacokinetic techniques. Correlations of nicotine intake with urinary excretion and concentrations of anabasine, anatabine, nornicotine, nicotine, and cotinine were examined. By using urinary excretion data, elimination half-lives of the alkaloids were calculated. RESULTS: Alkaloid levels in commercial tobacco products, in milligrams per gram, were as follows: nicotine, 6.5 to 17.5; nornicotine, 0.14 to 0.66; anabasine, 0.008 to 0.030; and anatabine, 0.065 to 0.27. Measurable concentrations of all alkaloids were excreted in the urine of most subjects smoking cigarettes, cigars, and pipes and using smokeless tobacco. Correlations between nicotine intake and alkaloid concentrations were good to excellent. CONCLUSIONS: Anabasine and anatabine, which are present in tobacco but not in nicotine medications, can be used to assess tobacco use in persons undergoing nicotine replacement therapy.  (+info)

Upregulation of surface alpha4beta2 nicotinic receptors is initiated by receptor desensitization after chronic exposure to nicotine. (4/1791)

It is hypothesized that desensitization of neuronal nicotinic acetylcholine receptors (nAChRs) induced by chronic exposure to nicotine initiates upregulation of nAChR number. To test this hypothesis directly, oocytes expressing alpha4beta2 receptors were chronically incubated (24-48 hr) in nicotine, and the resulting changes in specific [3H]nicotine binding to surface receptors on intact oocytes were compared with functional receptor desensitization. Four lines of evidence strongly support the hypothesis. (1) The half-maximal nicotine concentration necessary to produce desensitization (9.7 nM) was the same as that needed to induce upregulation (9.9 nM). (2) The concentration of [3H]nicotine for half-maximal binding to surface nAChRs on intact oocytes was also similar (11.1 nM), as predicted from cyclical desensitization models. (3) Functional desensitization of alpha3beta4 receptors required 10-fold higher nicotine concentrations, and this was mirrored by a 10-fold shift in concentrations necessary for upregulation. (4) Mutant alpha4beta2 receptors that do not recover fully from desensitization, but not wild-type channels, were upregulated after acute (1 hr) applications of nicotine. Interestingly, the nicotine concentration required for half-maximal binding of alpha4beta2 receptors in total cell membrane homogenates was 20-fold lower than that measured for surface nAChRs in intact oocytes. These data suggest that cell homogenate binding assays may not accurately reflect the in vivo desensitization affinity of surface nAChRs and may account for some of the previously reported differences in the efficacy of nicotine for inducing nAChR desensitization and upregulation.  (+info)

Analyzing health surveys for cancer-related objectives. (5/1791)

Large-scale health surveys conducted by government agencies record information on a large number of health-related variables. We review the use of these data for performing analyses that address cancer-related objectives. After describing the conduct of a large-scale health survey (the third National Health and Nutrition Examination Survey [NHANES III]), we discuss some of the issues involved in analyzing data collected in such a survey. In particular, the use of sample weights in the analysis and the importance of accounting for the complex survey design when estimating standard errors are discussed. Six applications are then presented that involve the following: 1) estimating demographic factors associated with snuff use, 2) estimating the association of type of health insurance with the probability of receiving a digital rectal examination, 3) estimating the association of body iron stores with the probability of later developing cancer, 4) estimating the changing rates of mammography screening in the United States between 1987 and 1992, 5) evaluating smoking and alcohol consumption as risk factors for digestive cancer by use of a population-based, case-control study, and 6) evaluating a randomized community-intervention experiment to encourage smoking cessation. These applications use data from the National Health Interview Survey, the NHANES I Epidemiologic Followup Study, the 1986 National Mortality Followback Survey, and the Community Intervention Trial for Smoking Cessation. The availability of public-use data files is discussed for surveys sponsored by the U.S. government that collect health-related information. We demonstrate that statistical methods and computer software are available for analyzing public-use data files of surveys to address different types of cancer-related objectives.  (+info)

Nicotine withdrawal and psychiatric symptoms in cigarette smokers with schizophrenia. (6/1791)

The prevalence of smoking is markedly elevated in schizophrenia. Low smoking cessation rates and reports that some smokers with schizophrenia experience an acute increase in symptoms during attempts to quit smoking, suggest a self-medication model. Alternatively, smoking may modulate medication side effects. The effects of treated and untreated smoking abstinence on psychotic symptoms and medication side effects were examined in this study. Nineteen outpatients with schizophrenia or schizoaffective disorder participated in a randomized, double-blind, balanced crossover study: 1 day of ad libitum smoking followed by 3 days of acute smoking abstinence while wearing 22 mg/day active or placebo transdermal nicotine patches, with a return to 3 days of smoking between patch conditions. Daily symptom and side-effect ratings, nicotine and cotinine blood levels were collected. Twelve subjects completed the study. Neither positive symptoms nor mood symptoms changed. An increase in negative symptoms during the first abstinent day occurred in both placebo and active patch conditions, but was not sustained over subsequent abstinent days. Despite physiological signs of withdrawal, completers did not endorse increased nicotine withdrawal symptoms. Dropouts reported higher withdrawal symptoms, but also had no increase in psychiatric symptoms in either phase of the study. Of note, dyskinesias decreased during abstinence and placebo patch treatment, but increased during abstinence and the active patch conditions. Acute exacerbation of psychiatric symptoms is an unlikely explanation for any difficulty smokers with schizophrenia have in early abstinence.  (+info)

Smoking status by proxy and self report: rate of agreement in different ethnic groups. (7/1791)

OBJECTIVE: To examine the rate of agreement between proxy and self report of smoking status in Hispanics compared with other ethnic groups. DESIGN: Data source is the 1990 California Tobacco Survey (CTS) which includes proxy and self reported smoking status. The CTS is a random digit dialed survey conducted in 57,244 households. A sample of 10,011 adults was included in the analyses. MAIN OUTCOME MEASURE: Percentages of agreement and disagreement between self report and report by other member of the household on smoking status. RESULTS: Cohen's kappa coefficients of agreement on smoking status between self report and proxy report was highest in non-Hispanic whites and African Americans (kappa = 0.91), followed by Asian Americans (kappa = 0.82) and Hispanics (kappa = 0.76). Among adults identified as current smokers by proxy, a lower percentage of Hispanics compared with non-Hispanics indicated that they were current smokers (odds ratio (OR) = 3.74, 95% confidence intervals (CI) = 3.28 to 4.20). Furthermore, agreement between proxy and self report was also lower in Hispanics of low acculturation compared with Hispanics with a high level of acculturation (OR = 0.40, 95% CI = 0 to 0.94). CONCLUSIONS: The agreement between self reported and proxy reported smoking status is higher among non-Hispanics compared with Hispanics. Smoking rates in different ethnic groups that are estimated by telephone surveys including proxy and self report might not be comparable.  (+info)

Determinants of smoking behaviour among adolescents in Semarang, Indonesia. (8/1791)

OBJECTIVES: To determine the smoking prevalence and to examine the determinants of smoking behaviour among male adolescents in Semarang, Indonesia. DESIGN: A random sample of schools in Semarang (population 1.5 million) was obtained using a stratified sampling procedure (strata based on type of school and district). A total of 149 schools were selected (response rate 72%). Within the schools 186 classes were selected, targeting the 11, 13, 15, and 17 year olds. An anonymous, self administered questionnaire was filled in by all students present at the day of the survey (total sample size 6276). OUTCOME MEASURES: Smoking prevalence, exposure to family and peer smoking, and other variables that may be related to smoking. Logistic regression was used to examine the determinants of smoking behaviour. Only male students were included in the analysis. RESULTS: Smoking increased dramatically between the ages of 11 and 17, from 8.2% to 38.7%. The variance explained by the regression model increased from 19.8% for 11 year olds to 53% for 17 year olds. The smoking behaviour of best friends was the most powerful determinant of smoking, and this was consistent across the age groups. Best friends' attitudes towards smoking and older brothers' smoking behaviour were also important determinants of smoking. CONCLUSIONS: Smoking prevalence among male adolescents in Semarang, Indonesia is high. Effective smoking prevention programmes should take into account the dominant influence of peers in the onset and maintenance of smoking behaviour. In general, school related items had a less important role in predicting smoking behaviour than expected.  (+info)