Predictors of Adherence Among Vulnerable Populations of Adults Assigned to Smoke Very Low Nicotine Content Cigarettes.

INTRODUCTION: Regulators are considering reducing the nicotine content in cigarettes to a minimally addictive level. This could particularly benefit smokers from populations vulnerable to heavy smoking and difficulties quitting. We assessed predictors of adherence among adults from vulnerable populations assigned to use very low nicotine content cigarettes (VLNCs) in randomized clinical trials, to identify characteristics of those who require additional assistance if a nicotine reduction policy were implemented. AIMS AND METHODS: Data came from three populations of vulnerable adult smokers assigned to use VLNC cigarettes (0.4 mg/g nicotine) during 12-week randomized controlled trials (n = 286): Socioeconomically disadvantaged women of reproductive age, opioid-maintained adults, and adults with affective disorders. Logistic and linear regressions modeled predictors of adherence based on changes in cotinine at week-6 and week-12 assessments relative to baseline, and as a 90% reduction in cotinine relative to baseline (full adherence: yes/no). Predictors included satisfaction with study cigarettes, craving, nicotine dependence severity, withdrawal, population membership, baseline affective-disorder symptoms, and sociodemographic characteristics. RESULTS: Dependence severity was negatively associated with both adherence measures at week 6 (p < .01), whereas increased satisfaction with study cigarettes and age were positively associated with both measures at weeks 6 and 12 (p < .01). Opioid-maintained adults exhibited reduced adherence and were less likely to reach full adherence at week 12 compared to disadvantaged women (p = .02). CONCLUSIONS: Factors associated with VLNC adherence in vulnerable populations are similar to those in the general population of smokers. Furthermore, studies are indicated investigating nicotine supplements (e.g., e-cigarettes, NRT) to support highly dependent adults faced with using VLNCs. IMPLICATIONS: This study identified factors predicting difficulty maintaining adherence to a regimen of very low nicotine content cigarettes (VLNC) among adults from vulnerable populations. Findings suggested that factors predicting difficulty maintaining adherence (greater nicotine dependence and low satisfaction with study-provided VLNC) were common across vulnerable smokers and the general population of adults who smoke. Furthermore, research should investigate alternatives to support highly dependent adults, such as pairing VLNC with supplemental, noncombusted nicotine. Some vulnerable populations (e.g., opioid-maintained adults) may be especially in need of supplemental, noncombusted nicotine.

Trend differences in men and women in rural and urban U.S. settings.

BACKGROUND: Smoking prevalence is declining at a slower rate in rural than urban settings in the United States (U.S.), and known predictors of smoking do not readily account for this trend difference. Given that socioeconomic and psychosocial determinants of health disparities accumulate in rural settings and that life-course disadvantages are often greater in women than men, we examined whether smoking trends are different for rural and urban men and women. METHOD: We used yearly cross-sectional data (n = 303,311) from the U.S. National Survey on Drug Use and Health (NSDUH) from 2007 through 2014 to compare cigarette smoking trends in men and women across rural and urban areas. Current smoking status was modelled using logistic regression controlling for confounding risk factors. RESULTS: Regression derived graphs predicting unadjusted prevalence estimates and 95% confidence bands revealed that whereas the smoking trends of rural men, urban men, and urban women significantly declined from 2007 to 2014, the trend for rural women was flat. Controlling for demographic, socioeconomic and psychosocial predictors of smoking did not explain rural women's significantly different trend from those of the other three groups. CONCLUSION: Rural women lag behind rural men, urban men and urban women in decreasing smoking, a health disparity finding that supports the need for tobacco control and regulatory policies and interventions that are more effective in reducing smoking among rural women.

A growing geographic disparity: Rural and urban cigarette smoking trends in the United States.

Rural areas of the United States have a higher smoking prevalence than urban areas. However, no recent studies have rigorously examined potential changes in this disparity over time or whether the disparity can be explained by demographic or psychosocial characteristics associated with smoking. The present study used yearly cross sectional data from the National Survey on Drug Use and Health from 2007 through 2014 to examine cigarette smoking trends in rural versus urban areas of the United States. The analytic sample included 303,311 respondents. Two regression models were built to examine (a) unadjusted rural and urban trends in prevalence of current smoking and (b) whether differences remained after adjusting for demographic and psychosocial characteristics. Results of the unadjusted model showed disparate and diverging cigarette use trends during the 8-year time period. The adjusted model also showed diverging trends, initially with no or small differences that became more pronounced across the 8-year period. We conclude that differences reported in earlier studies may be explained by differences in rural versus urban demographic and psychosocial risk factors, while more recent and growing disparities appear to be related to other factors. These emergent differences may be attributable to policy-level tobacco control and regulatory factors that disproportionately benefit urban areas such as enforcement of regulations around the sale and marketing of tobacco products and treatment availability. Strong federal policies and targeted or tailored interventions may be important to expanding tobacco control and regulatory benefits to vulnerable populations including rural Americans.

Incentives improve outcome in outpatient behavioral treatment of cocaine dependence.

OBJECTIVE: To assess whether incentives improved treatment outcome in ambulatory cocaine-dependent patients. METHOD: Forty cocaine-dependent adults were randomly assigned to behavioral treatment with or without an added incentive program. The behavioral treatment was based on the Community Reinforcement Approach and was provided to both groups. Subjects in the group with incentives received vouchers exchangeable for retail items contingent on submitting cocaine-free urine specimens during weeks 1 through 12 of treatment, while the group without incentives received no vouchers during that period. The two groups were treated the same during weeks 13 through 24. RESULTS: Seventy-five percent of patients in the group with vouchers completed 24 weeks of treatment vs 40% in the group without vouchers (P = .03). Average durations of continuous cocaine abstinence documented via urinalysis during weeks 1 through 24 of treatment were 11.7 +/- 2.0 weeks in the group with vouchers vs 6.0 +/- 1.5 weeks in the group without vouchers (P = .03). At 24 weeks after treatment entry, the voucher group evidenced significantly greater improvement than the no-voucher group on the Drug scale of the Addiction Severity Index (ASI), and only the voucher group showed significant improvement on the ASI Psychiatric scale. CONCLUSIONS: Incentives delivered contingent on submitting cocaine-free urine specimens significantly improve treatment outcome in ambulatory cocaine-dependent patients.

Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers.

Twenty-two coffee drinkers (three to seven cups per day) underwent repeated double-blind trials to test for caffeine self-administration, withdrawal, and adverse effects. Each trial consisted first of a randomized crossover period of 1 day of decaffeinated coffee and 1 day of caffeinated coffee (100 mg) to assess withdrawal and adverse effects of caffeine. Next, subjects were given 2 days of concurrent access to the two coffees. The relative use of the two coffees was used to assess caffeine self-administration. Reliable caffeine self-administration occurred in three of 10 subjects in study 1 and seven of 12 subjects in study 2. Withdrawal symptoms were headaches, drowsiness, and fatigue. The major adverse effect from self-administration was tremulousness. The occurrence of headaches on substitution of decaffeinated coffee prospectively predicted subsequent self-administration of caffeine. These results indicate that some coffee drinkers exhibit signs of a caffeine dependence, ie, they self-administer coffee for the effects of caffeine, have withdrawal symptoms on cessation, and experience adverse effects.

Sustained cocaine abstinence in methadone maintenance patients through voucher-based reinforcement therapy.

BACKGROUND: Chronic cocaine abuse remains a serious and costly public health problem. This study assessed the effectiveness of a voucher-based reinforcement contingency in producing sustained cocaine abstinence. METHODS: A randomized controlled trial compared voucher-based reinforcement of cocaine abstinence to noncontingent voucher presentation. Patients were selected from 52 consecutively admitted injecting heroin abusers in a methadone maintenance treatment program. Patients with heavy cocaine use during baseline period (N = 37) participated. Except where otherwise indicated, the term cocaine abuse is used in this article in a generic sense and not according to the DSM-III-R definition. Patients exposed to abstinence reinforcement received a voucher for each cocaine-free urine sample (ie, negative for benzoylecgonine) provided three times per week throughout a 12-week period; the vouchers had monetary values that increased as the number of consecutive cocaine-free urine samples increased. Control patients received noncontingent vouchers that were matched in pattern and amount to the vouchers received by patients in the abstinence reinforcement group. RESULTS: Patients receiving vouchers for cocaine-free urine samples achieved significantly more weeks of cocaine abstinence (P = .007) and significantly longer durations of sustained cocaine abstinence (P = .001) than controls. Nine patients (47%) receiving vouchers for cocaine-free urine samples achieved between 7 and 12 weeks of sustained cocaine abstinence; only one control patient (6%) achieved more than 2 weeks of sustained abstinence. Among patients receiving vouchers for cocaine-free urine samples, those who achieved sustained abstinence ( > or = 5 weeks) had significantly lower concentrations of benzoylecgonine in baseline urine samples than those who did not achieve sustained abstinence (P < or = .01). Patients receiving voucher reinforcement rated the overall treatment quality significantly higher than controls (P = .002). CONCLUSION: Voucher-based reinforcement contingencies can produce sustained cocaine abstinence in injecting polydrug abusers.

Long-term use of nicotine vs placebo gum.

Medical patients (n = 315) who wished to quit smoking were randomly assigned in a double-blind manner to receive either nicotine or placebo gum. Subjects were advised to stop gum use by 4 months. Among abstinent smokers, 46% of those receiving nicotine gum and 17% of those receiving placebo gum used the gum beyond the recommended 4-month period. By 10 months after cessation 17% of quitters receiving nicotine gum and 6% receiving placebo gum were still using gum. Gradual reduction of nicotine gum did not result in withdrawal and cessation of nicotine gum did not increase the probability of relapse to smoking or weight gain. We conclude that use of nicotine gum is due, in part, to the effects of nicotine; however, long-term use is uncommon.

Abuse liability of alprazolam relative to other commonly used benzodiazepines: a review.

Nonhuman and human studies comparing the abuse liability of alprazolam to other commonly used benzodiazepines are reviewed. These studies are reviewed to determine to what extent prospective, controlled, experimental studies support opinions that alprazolam's abuse liability is greater than that of other commonly used benzodiazepines. Studies comparing the self-administration of alprazolam, the discriminative stimulus effects of alprazolam, self-reported effects of alprazolam, physiological dependence on alprazolam, and adverse effects of alprazolam relative to other benzodiazepines are reviewed. Overall, the experimental literature does not support the widely held belief that alprazolam's abuse liability is greater than that of other benzodiazepines, but much more research is needed. Such research should focus explicitly on alprazolam's reinforcing effects, and the nature and severity of the discontinuation syndrome associated with its long-term use. Important issues such as selection of an appropriate comparison drug, selection of an appropriate population, dosing regimen and test doses need to be considered in future studies.

Pupillary response to methadone challenge in heroin users.

The relationship between self-reported illicit heroin use and pupillary response to a low-dose methadone challenge was examined in 28 men beginning methadone therapy for opiate dependence. Pupil diameter was assessed before and 60, 90, and 120 minutes after a 20 mg methadone dose on day 1 of treatment. Self-reports of opiate drug effects were also taken at these times. There was a significant negative correlation (r = -0.53) between pupillary constriction 120 minutes after drug dosing and the average dollar value of subjects' reported heroin use per week. In other words, those who showed the least pupillary constriction generally reported the highest amount of illicit heroin use. Total years since first opiate use was also a significant predictor of pupillary response (r = -0.46). Self-reported amount of heroin use and years since first opiate use together accounted for 60% of the total variance in pupillary response to the challenge (Mult r = 0.77). Pupillary response to a low-dose methadone challenge appears to be a clinically practical and objective method for determining opiate tolerance levels in applicants for methadone therapy.

Effects of caffeine on tobacco withdrawal.

Smoking cessation increases caffeine blood levels, and this has been hypothesized to cause some of the symptoms of tobacco withdrawal (e.g., anxiety and insomnia). To test this hypothesis, 10 coffee drinkers who smoked cigarettes were entered into a completely within-subjects experimental design in which the effects of caffeine dose (0, 50, and 100 mg/coffee serving) and smoking status (smoking versus abstinence) were examined over a 4-day period. Self-reported and observed measures of tobacco withdrawal, caffeine withdrawal, and intoxication, as well as psychomotor tasks and vital signs, were completed daily; blood was drawn at the end of each period. Temporary abstinence produced typical withdrawal symptoms but did not significantly increase caffeine blood levels. Caffeine did not increase the severity of symptoms but did decrease the severity of withdrawal-induced hunger. These findings suggest that, in the absence of increased blood levels, caffeine does not increase the severity of tobacco withdrawal.

Should caffeine abuse, dependence, or withdrawal be added to DSM-IV and ICD-10?

OBJECTIVE: The authors reviewed basic science and clinical data on caffeine abuse, dependence, and withdrawal in order to make a conclusion about whether these disorders exist and should be included in DSM-IV and ICD-10. METHOD: Studies were located through computerized searches, reference sections of published articles, and written requests. RESULTS: The studies show that abstinence from caffeine induces a withdrawal syndrome of headache, fatigue, and drowsiness which begins within 12-24 hours and lasts about 1 week. The syndrome can be severe and appears to be one reason for continued use of coffee. The prevalence of this caffeine withdrawal syndrome is unknown. Use of caffeine may aggravate some common behavioral and medical disorders. In double-blind tests, a subset of coffee and soda drinkers reliably self-administered caffeinated beverages in preference to uncaffeinated beverages. Clinical indicators of dependence, such as difficulty stopping use of caffeine and use despite harm, have not been documented. CONCLUSIONS: Caffeine withdrawal but not caffeine abuse or dependence should be included as a diagnosis in DSM-IV and ICD-10. Future research should focus on whether some caffeine users exhibit clinical indicators of drug dependence.

Achieving cocaine abstinence with a behavioral approach.

OBJECTIVE: The authors compared the efficacy of a multicomponent behavioral treatment and drug abuse counseling for cocaine-dependent individuals. METHOD: The 38 patients were enrolled in outpatient treatment and were randomly assigned to the two treatments. Counseling in the behavioral treatment was based on the community reinforcement approach, while the drug abuse counseling was based on the disease model of dependence and recovery. Patients in the behavioral, but not the drug counseling, treatment also received incentives contingent on submitting cocaine-free urine specimens. RESULTS: Of the 19 patients who received behavioral treatment, 58% completed 24 weeks of treatment, versus 11% of the patients who received counseling. In the behavioral treatment group 68% and 42% of the patients achieved at least 8 and 16 weeks of documented continuous cocaine abstinence, respectively, versus 11% and 5% in the drug abuse counseling group. CONCLUSIONS: This multicomponent behavioral treatment appears to be an effective intervention for retaining outpatients in treatment and establishing cocaine abstinence.

A behavioral approach to achieving initial cocaine abstinence.

OBJECTIVE: The aim of this study was to assess the efficacy of a behavioral treatment program for achieving initial cocaine abstinence in individuals enrolled in outpatient treatment for cocaine dependence. METHOD: Thirteen consecutively admitted outpatients were offered behavioral treatment consisting of contingency management procedures and the community reinforcement approach. Fifteen consecutively admitted outpatients were offered treatment with 12-step counseling. All 13 of the patients who were offered the behavioral treatment accepted it; 12 of the patients offered 12-step counseling accepted it. RESULTS: Eleven of the 13 patients in the behavioral treatment were retained for 12 weeks of treatment, compared with five of the 12 patients given 12-step counseling. Ten of the patients given behavioral therapy achieved 4 weeks of continuous cocaine abstinence, compared with only three of those given 12-step counseling. Six of the patients in the behavioral treatment group achieved 8 weeks, and three achieved 12 weeks; none of the patients in the 12-step counseling program achieved 8 weeks. CONCLUSIONS: The behavioral treatment described in this paper offers promise as an effective intervention for achieving initial cocaine abstinence. A randomized trial is underway to assess the generality of these findings.

Acute marijuana effects on social conversation.

The present study assessed the acute effects of smoked marijuana on social conversation. Speech quantity was recorded continuously in seven moderate marijuana users during separate 1 h experimental sessions following the paced smoking of 0, 1.01, 1.84, and 2.84% THC marijuana cigarettes. Subjects engaged in conversation with undrugged partners who smoked placebo marijuana cigarettes. The active marijuana produced significant decreases in speech quantity, increases in heart rate, and increases in self-reports of "high" and sedation. Partners showed no effects in speech quantity or self-reports of drug effects that were systematically related to the doses administered to the subject pair members. The effects on speech quantity observed in the present study after acute dosing are similar to the effects on social conversation reported previously during chronic marijuana dosing. Marijuana appears to be an exception to the general rule that drugs of abuse increase verbal interaction.

Effects of alcohol on speaking in isolated humans.

Drugs of abuse often increase human social interaction, as is suggested in our cultural drug use practices and has been demonstrated in controlled laboratory studies. The environmental and pharmacological mechanisms controlling these effects remain unclear. The present study examined the importance of a social context for obtaining drug-produced increases in human speech by examining the acute effects of alcohol (0, 22, 45, 67 g) on the amount of speech emitted by six normal volunteers who were producing speech monologues in an isolated context. A within-subject repeated-measures experimental design was used. Alcohol produced a significant dose-dependent increase in total speech. Conversely, response rates on a nonverbal behavioral task (circular-lights device) decreased as an orderly function of alcohol dose. These results suggest that a social context is not a necessary condition for alcohol to increase rates of human speech. Moreover, the decreases in response rates observed in the nonverbal task rule out the possibility that alcohol affected total speech via a generalized increase in overall activity levels.

d-amphetamine increases choice of cigarette smoking over monetary reinforcement.

RATIONALE: Psychomotor stimulants previously have been found to increase the frequency of cigarette smoking, but it is unclear whether this is due to a non-specific increase in general activity or a specific increase in the reinforcing effects of smoking. OBJECTIVES: To investigate whether d-amphetamine increases the relative reinforcing effects of cigarette smoking. METHODS: Ninety minutes after d-amphetamine (7.5, 15 mg/70 kg) or placebo administration, 13 male and female subjects participated in 3-h sessions during which they could make a maximum of 20 choices between cigarette smoking (two puffs per choice), earning money ($0.25 per choice), or neither. In separate sessions, using the same subjects, the effects of d-amphetamine on the frequency of ad libitum smoking was assessed. RESULTS: During choice sessions, d-amphetamine dose-dependently increased smoking choices from 4.2 +/- 0.6 to 5.7 +/- 0.6. During sessions in which subjects smoked ad libitum, d-amphetamine increased number of cigarettes smoked from 2.8 +/- 0.4 to 3.8 +/- 0.6. Breath carbon monoxide (CO) levels, a measure of smoke exposure, showed corresponding dose-related increases. CONCLUSIONS: These results are consistent with previous findings that d-amphetamine increases smoking and provide evidence that this effect is due to a drug-produced increase in the relative reinforcing effects of cigarette smoking.

The behavioral economics of concurrent drug reinforcers: a review and reanalysis of drug self-administration research.

In economics, goods can function as substitutes, complements, or be independent of one another. These concepts refer to increases, decreases, or no change in the consumption of one item as the price of a second item increases. This review examined whether these economic terms can be used to describe relationships between concurrently available reinforcers in drug self-administration research. Sixteen drug self-administration studies that examined the effects of concurrent reinforcers were identified through a MEDLINE search. Across these studies, the following substances were employed: caffeinated coffee, cocaine, etonitazene, ethanol, heroin, food, methadone, morphine, nicotine cigarettes, pentobarbital, phencyclidine, sucrose and water. These studies were reanalyzed and the results were shown to be consistent with these economic notions. These analyses also showed that relationships among the concurrently available reinforcers were reliable within and across studies, that concurrently available reinforcers can affect each other asymmetrically, and that the relative price may determine the magnitude of effect for substitutes. These findings suggest that these economic concepts may be useful in characterizing the type and magnitude of interactions between concurrently available reinforcers and may suggest potential mechanisms that determine these relationships.

Alcohol pretreatment increases preference for cocaine over monetary reinforcement.

Non-dependent cocaine users participated in a two-phase experiment conducted under controlled laboratory conditions. During phase 1, subjects sampled intranasal cocaine (100 mg) and placebo (96 mg lactose + 4 mg cocaine) in separate sessions and under double-blind conditions. Sampling sessions were followed by a single choice session in which subjects made a maximum of ten choices between 10 mg unit doses of cocaine or placebo. Only subjects who reliably (> or = 70%) chose cocaine over placebo in phase 1 participated in phase 2. During phase 2, subjects participated in a series of nine experimental sessions conducted on different days in which they were pretreated with varying doses of alcohol (placebo, 0.5, and 1.0 g/kg) and made a maximum of ten choices between 10 mg unit doses of cocaine and an alternative reinforcer (i.e., varying amounts of money). Visual-analog ratings of drug effects and cardiac function were monitored across all experimental sessions. Cocaine was reliably chosen over placebo by the majority (9 of 11) of subjects during phase 1, demonstrating that the drug functioned as a reinforcer. During phase 2, alcohol pretreatment significantly increased choice of cocaine over the alternative reinforcer, while increasing monetary value decreased cocaine choice. Ratings on some visual-analog scales (e.g., good effects) paralleled cocaine choice, with alcohol pretreatment increasing ratings and greater monetary value decreasing them. Cardiac output increased above baseline levels across all alcohol and monetary conditions, but maximal effects were observed during sessions involving pretreatment with the active alcohol doses. Overall, these results demonstrate (a) that alcohol can increase preference for cocaine over alternative reinforcers and thereby may thwart efforts to reduce or abstain from cocaine use, (b) that availability of an alternative, non-drug reinforcer can effectively decrease preference for cocaine, and (c) that combined use of alcohol and cocaine increases cardiac risk compared to use of cocaine alone.

Effects of response requirement and the availability of an alternative reinforcer on cigarette smoking by schizophrenics.

Cigarette smoking and other forms of drug abuse are more prevalent among schizophrenics than the general population. Despite the clinical importance of this problem, there has been relatively little experimental study of schizophrenic drug use. We examined under controlled laboratory conditions the effects of response requirement and the availability of an alternative (monetary) reinforcer on cigarette smoking by schizophrenics. Subjects were six heavy smokers with diagnoses of schizophrenia or schizoaffective disorder. Before each session, subjects provided carbon monoxide samples indicating recent smoking abstinence. During 3-h sessions, subjects obtained opportunities to smoke (2 puffs/opportunity) under a fixed ratio (FR) schedule of reinforcement, which varied across sessions from FR50 to FR6400. In half of the sessions, subjects also were able to earn a small amount of money ($0.25/ratio completed) under an FR400 schedule. Increasing the response requirement for smoking decreased smoking and increased smoking-maintained responding. The availability of the monetary reinforcer decreased smoking and smoking-maintained responding by approximately half. These results are consistent with those seen previously in community volunteers without major mental illness studied under the same experimental conditions, suggesting that smoking by these two populations is controlled, at least in part, by a common set of determinants.

Behavioral economics of drug self-administration. III. A reanalysis of the nicotine regulation hypothesis.

The maintenance of a characteristic level of nicotine in a smoker's body is referred to as nicotine regulation. Considerable research has examined this question of whether smokers regulate nicotine intake. This is because nicotine regulation raises the question of whether smokers who, to decrease their intake of tar, switch to low tar/low nicotine cigarettes will increase the number and/or intensity of cigarettes smoked. Although the results of studies examining nicotine regulation are reported as generally consistent, considerable variability exists across these analyses such that the health hazards of smoking low tar/nicotine cigarettes remains uncertain. In the present analysis, these studies were analyzed to ascertain whether a behavioral-economic interpretation could better quantify the effects of changing nicotine yield on individuals' nicotine and smoke consumption. Specifically, 17 nicotine-regulation studies were reanalyzed using a unit-price analysis (i.e., cost-benefit analysis). The reanalysis showed less variability across regulation studies than previously reported; a positively-decelerating demand curve was found across most studies, consistent with previous unit-price analyses of food- and drug-maintained behavior. The benefits of this reanalysis versus the traditional regulation interpretation are that the behavioral economics approach: 1) brings unity to a variable set of data, 2) shows a nonlinear relationship, previously considered to be linear, between nicotine consumption and nicotine yield, 3) shows that nicotine yields higher, and not lower, than the smoker's usual brand decrease smoke consumption and thus decreases consumption of the harmful agents in tobacco, 4) better quantifies the data and provides a more parsimonious interpretation that generalizes to other drugs and food-maintained behavior in humans and nonhumans and, 5) integrates behavioral and pharmacological factors that control the consumption of reinforcers. These results suggest the value of behavioral economics in the study of consumptive behaviors and clinically suggest, in agreement with the studies contained herein, that decreasing the smoker's usual nicotine yield can have potential health risks for smokers who are unable to stop smoking.