Cocaine (2.0 milligrams per kilogram) given by the oral route is at least as effective as the same dose given intranasally. Cocaine is not detected in the plasma until 30 minutes after oral administration, but peak plasma concentrations are similar after both routes. The subjective "highs" in man are greater after oral than after intranasal administration.
We evaluated the effects of acute pretreatment with lamotrigine, a putative glutamate release inhibitor, on the physiological and behavioral responses to intranasal cocaine in cocaine-dependent volunteers (N = 8). The study employed a double-blind, placebo-controlled, within-subject design. Subjects participated in six experimental sessions. On each study day, placebo, lamotrigine 125 mg, or lamotrigine 250 mg was administered orally in the morning, followed 2 hours later by intranasal cocaine 120 mg/70 kg or placebo. Measurements of heart rate and blood pressure were acquired, and subjects responded to mood state questionnaires at predetermined time intervals. Cocaine alone produced increases in heart rate, blood pressure, and several measures of pleasurable mood and drug effects. Lamotrigine alone produced a mild relaxing effect. Lamotrigine pretreatment altered neither the physiological responses nor the subjective ratings of cocaine's pleasurable or aversive mood effects.
Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting.Smokers (N=172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post-quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date.The difference in weight at 26 weeks post-quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs ± 8.94 vs placebo: 9.7 lbs ± 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43).For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence.
Compared to the general U.S. population, smokers with comorbid psychiatric and/or substance use disorders have lower quit rates after evidence-based treatments and disproportionately high smoking-related deaths. Improved modalities for reducing tobacco-related harm in this subpopulation are needed. Because electronic cigarettes (e-cigarettes) can now deliver physiologically relevant levels of nicotine to consumers, they represent an additional nicotine delivery system that could be used in cessation interventions. While current data suggest that the use of e-cigarettes by smokers promotes a reduction in combustible cigarette use, smoking quit rates through use of e-cigarettes appears to be low. The goal of this study was to examine impact of e-cigarette use on combustible tobacco use as well as on the readiness to quit smoking and changes in nicotine dependence in a multimorbid population.We conducted a 4-week, open-label study in 43 military veteran smokers who had no immediate intention to stop smoking and were currently receiving psychiatric services from the Department of Veterans Affairs health care system. Participants were provided with a study e-cigarette they could use ad libitum along with other tobacco products and were encouraged to attend weekly laboratory visits and a one-month follow-up visit. Main outcome measures were number of cigarettes smoked per day (CPD), the frequency of e-cigarette use, the amount of money spent on combustible cigarettes (U.S. dollars/week), alveolar carbon monoxide (CO) levels, and urine cotinine levels.Mean e-cigarette use was 5.7 days per week and only 9% of participants used the e-cigarette for fewer than 4 days per week. Significant reductions in breath CO (9.3 ppm to 7.3 ppm, p < .02) and CPD (from 16.6 to 5.7, p < .001) were observed across study weeks, and no serious adverse events were reported. Three participants (10% of completers) reported smoking cessation that was corroborated biochemically. At one-month follow-up, motivation to quit smoking remained significantly higher and the level of nicotine dependence was significantly lower than at baseline.E-cigarettes are acceptable to smokers with psychiatric comorbidities, as indicated by sustained and frequent e-cigarette use by 90% of participants, and may promote reduction and/or cessation of combustible cigarette use. E-cigarettes appear to be a viable harm reduction modality in smokers with psychiatric comorbidities.
