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.

Clinical characteristics of central European and North American samples of pregnant women screened for opioid agonist treatment.

BACKGROUND: Little comparable information is available regarding clinical characteristics of opioid-dependent women from different countries. In the present study, women from the USA, Canada and a Central European country, Austria, screened for participation in the Maternal Opioid Treatment Human Experimental Research study, were compared with respect to their demographic and addiction histories. METHODS: Pregnant women (n = 1,074) were screened for study participation using uniformed clinical criteria and instruments. The screening results were compared with regard to exclusion, demographics, drug use, and psychosocial and treatment histories. RESULTS: Compared to the screened US and Canadian women, Austrian women were more likely to be younger (p < 0.001), white (p < 0.001), had significantly lower levels of educational attainment (p < 0.001), were less likely to use opioids daily (p < 0.001) and more likely to have been prescribed buprenorphine (p < 0.001). Compared to both rural and urban US groups, the Austrian group was less likely to have legal issues (p < 0.001) and was younger when first prescribed agonist medication (p < 0.001). CONCLUSION: The differences between North American and European groups may offer unique insights concerning treatment and pregnancy outcomes for opioid-dependent pregnant women.

Smoking in pregnant women screened for an opioid agonist medication study compared to related pregnant and non-pregnant patient samples.

BACKGROUND: Little is known about the prevalence and severity of smoking in pregnant opioid dependent patients. OBJECTIVES: To first characterize the prevalence and severity of smoking in pregnant patients screened for a randomized controlled trial, Maternal Opioid Treatment: Human Experimental Research (MOTHER), comparing two agonist medications; and second, to compare the MOTHER screening sample to published samples of other pregnant and/or patients with substances use disorders. METHODS: Pregnant women (N = 108) screened for entry into an agonist medication comparison study were retrospectively compared on smoking variables to samples of pregnant methadone-maintained patients (N = 50), pregnant opioid or cocaine dependent patients (N = 240), non-pregnant methadone-maintained women (N = 75), and pregnant non-drug-addicted patients (N = 1,516). RESULTS: Of screened patients, 88% (n = 95) smoked for a mean of 140 months (SD = 79.0) starting at a mean age of 14 (SD = 3.5). This rate was similar to substance use disordered patients and significantly higher compared to general pregnant patients (88% vs. 22%, p < .001). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Aggressive efforts are needed to reduce/eliminate smoking in substance-abusing pregnant women.

Comparison of the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate in light drug users.

This study compared the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate with placebo in healthy volunteers. Sixteen non-dependent light drug users participated in six experimental sessions, receiving placebo, atomoxetine (20, 45 and 90 mg) and methylphenidate (20 and 40 mg) using a double-blind, Latin square design. Subjective drug effects were assessed using Visual Analog Scales (VAS), the Addiction Research Center Inventory (ARCI) and Adjective Rating Scales (ARS). Psychomotor performance was evaluated using the Digit Symbol Substitution Test (DSST). Physiological measures were also collected throughout the sessions. Assessments were conducted before drug administration and 30, 60, 90, 120, 150, 180 and 240 min following dosing. Forty milligrams methylphenidate produced significant increases on the stimulant portions of the VAS and ARS and the benzedrine, amphetamine, morphine-benzedrine and lysergic acid diethylamine (LSD) subscales of the ARCI relative to placebo. Ninety mg atomoxetine was reported to be unpleasurable relative to placebo as indicated by significant increases on the 'bad' and 'sick' portions of the VAS, and on the LSD subscale of the ARCI. Compared with placebo, both methylphenidate doses significantly increased systolic blood pressure (BP) and heart rate (HR). For atomoxetine, 90 mg increased diastolic BP, 45 and 90 mg increased systolic BP, and all three doses increased HR relative to placebo. Neither compound produced significant differences from placebo on DSST performance. These results suggest that atomoxetine does not induce subjective effects similar to methylphenidate and suggest that it is unlikely that atomoxetine will have abuse liability.

Alcohol dependence among cocaine-dependent outpatients: demographics, drug use, treatment outcome and other characteristics.

OBJECTIVE: Concurrent dependence on alcohol is common among those seeking treatment for cocaine dependence. More information is needed about differences between those with and without concurrent alcohol dependence, including possible special treatment needs or outcome differences. METHOD: Data were obtained from 302 adults (70% men) enrolled in outpatient treatment for cocaine dependence. Individuals who did and those who did not meet criteria for alcohol dependence were compared on demographics, drug use, treatment outcome and other variables. RESULTS: With regard to cocaine use, alcoholics were more likely than nonalcoholics to report an intranasal route of administration, use of cocaine in social settings, more simultaneous use of cocaine and alcohol, and more adverse consequences of their cocaine use. With regard to alcohol use, alcoholics reported consuming alcohol more frequently and in larger amounts, had longer drinking histories and were more likely than nonalcoholics to report increases in alcohol consumption when using cocaine. Alcoholics were heavier cigarette smokers than nonalcoholics and reported more severe employment, legal, family and psychiatric problems. There were overall improvements in both groups from intake through 12 months after treatment. With regard to treatment retention and cocaine abstinence, alcoholics had better outcomes than nonalcoholics when treated with intensive behavioral counseling plus incentives, but the reverse was true when treated with control treatments. CONCLUSIONS: Compared with nonalcoholic cocaine-dependent subjects, codependent patients exhibit a wider array of problems, many of which merit professional attention. Both alcoholics and nonalcoholics exhibit substantial improvements during treatment, with alcoholics perhaps requiring extra treatment efforts for successful outcomes.

Chronic alcohol exposure and lactation: extended observations.

Previous results from our laboratory have indicated that chronic (8 days) alcohol administration inhibits suckling-induced prolactin (PRL) release in response to 30 min of suckling. In addition, chronic alcohol administration to dams resulted in growth retardation of their litters. The present study was done to examine how an extended period of suckling (120 min) affected suckling-induced PRL release after chronic alcohol exposure. In addition, it was also examined whether the growth retardation observed during alcohol exposure persisted after alcohol infusions were discontinued. Dams were implanted with an atrial catheter on day 3 of lactation and saline or alcohol (1.0- or 2.0-g/kg BW) was administered daily for 8 days (lactation days 5 through 12). Following administration of the initial alcohol dose, the infusion was continued at rates required to maintain blood alcohol levels (BALs) for 4 h each day. Testing took place on day 12. As previously reported, suckling-induced PRL release was inhibited in dams receiving 2.0-g/kg alcohol after 30 min of suckling. However, after 120 min of suckling, PRL release in these dams was much higher than in either control or 1.0-g/kg alcohol dams. In addition, while the body weights of litters of dams administered 2.0-g/kg alcohol were reduced compared to litters of dams in the other two groups on days 8-16, their body weights rebounded and were not different from the other litters on days 18 or 20.

Ethanol and lactation: effects of milk lipids and serum constituents.

To determine how chronic alcohol administration during lactation affects milk composition and the nutritional status of the dam, EtOH (3 g/kg) as a 20% solution was administered by intubation to Sprague-Dawley rats from days 2 through 15 of lactation. Control dams were pair fed to account for the reduction in food intake observed in the alcohol group, while another control group maintained ad lib food intake. Dams and their litters were weighed daily throughout the study. On day 16, dams were sacrificed and samples taken for further analysis. Blood alcohol levels as well as serum levels of calcium, cholesterol, glucose, iron, lipids, phosphorous, and triglycerides were measured. Liver lipid levels and the total composition and fatty acid profile of the phospholipids in milk were also measured. Results indicate that EtOH administration and pair feeding reduced dam body weight, but not litter growth. Serum iron levels was increased in both EtOH-exposed and pair-fed controls, whereas serum cholesterol was elevated only in EtOH-exposed dams. Finally, of the phospholipids in milk, only one, phosphatidylserine, was slightly but significantly increased by EtOH. If and how these changes impact the development of the offspring remain to be studied.

Activational and organizational actions of gonadal hormones and the sex-specific effects of prolactin on food intake by rats.

Results of previous studies indicate that there is a sex-specific feeding response to prolactin (PRL) by rats: Only female rats significantly increase their food intake. The possible roles of the activational and/or organizational actions of the gonadal hormones in this sex difference were explored. In the first experiment, activational hormone exposure was manipulated in adult male and female rats. The results suggest that the activational actions of estrogen are not necessary for, and that testosterone does not block, PRL-induced increases in food intake by female rats. In a second experiment, organizational hormone exposure was manipulated in male and female rats during the early postnatal period. Genetic male rats organized as females by postnatal Day-1 castration significantly increased their food intake, while genetic female rats organized as males by postnatal androgen treatment maintained baseline levels of food intake. Overall, these experiments suggest that organizational, but not activational, gonadal hormone exposure plays a critical role in the development of this sex-specific response to PRL.

Sex-specific effects of prolactin on food intake by rats.

While prolactin (PRL) has been reported to increase food intake by virgin female rats, its effects on food intake by male rats are relatively unexplored. The present studies examined the possibility that PRL has sex-specific effects on food intake by rats. In the first study, intact female and male rats were given subcutaneous injections of saline vehicle or ovine (o) PRL (1.0 mg/kg) twice daily at 08:00 and 20:00 h for 10 days. Food intake, body weight, and water intake were measured daily. Results indicate that oPRL administration increased food intake by an average of 4.5 g per day in female subjects, but did not significantly alter body weight or water intake. Male rats treated with oPRL did not significantly alter their food intake, even after an additional five days of treatment. In the second study, a wide range of oPRL doses (vehicle, 0.02, 0.2, 2.0, and 20.0 mg/kg/day) were tested in gonadectomized female and male rats. The results indicate that female rats responded to increasingly larger doses of oPRL with greater increases in food intake, with a maximum increase of approximately 6. 1 g per day at a dose of 20.0 mg/kg. In contrast, male rats maintained baseline levels of intake across all oPRL doses tested. These data suggest that PRL has sex-specific effects on food intake.

Alcohol and the hormonal control of lactation.

All mammals produce milk to nourish their young. Milk production (i.e., lactation), which occurs in the mammary glands, is regulated by several hormones, most prominently prolactin and oxytocin. Studies in both humans and laboratory animals have demonstrated that maternal alcohol consumption before and during lactation can interfere with the functions of both of those hormones. Moreover, animal studies found that maternal alcohol consumption during pregnancy and even earlier in the mother's life can impair mammary gland development. Maternal alcohol consumption during pregnancy and lactation also can alter the milk's nutrient composition and result in suckling deficits of the offspring. Alcohol (and possibly its breakdown products) can pass from the maternal circulation into the breast milk. The effects of these substances on the infant, however, are still unknown.