A tale of two stimulants: Mentholated cigarettes may play a role in cocaine,but not methamphetamine,dependence

Background

Research suggests that mentholated cigarettes may play a role in cocaine dependence. The purpose of the present study was to expand upon the research on mentholated cigarettes and cocaine dependence and to evaluate the role of mentholated cigarettes in methamphetamine dependence.

Methods

Secondary analysis of a multisite, randomized trial evaluating the impact of smoking-cessation treatment in stimulant-dependent outpatients (N = 538). Participants’ reasons for concurrent use of cigarettes and illicit stimulants were assessed via self-report. Stimulant-abstinence was measured by self-report and urine drug screens. Smoking cessation was assessed via self-report and carbon monoxide levels.

Results

Of the 301 cocaine-dependent participants, 201 (67%) were menthol and 100 (33%) were non-menthol cigarette smokers. Cocaine-dependent participants who smoked menthol, compared to non-menthol, cigarettes were significantly more likely to report that cigarettes prolong their cocaine high (X²(1) = 16.3, p < .0001, OR = 3.58 [95% CI: 1.88–6.79]) and were less likely to be stimulant abstinent during active treatment (W = 3.6, p < 0.001, d = .39 [95% CI: 0.16–0.62]), at 3-month follow-up (X²(1) = 14.4, p < 0.001, OR = .32 [95% CI: 0.17–0.58]), and at 6-month follow-up (X²(1) = 4.6, p = 0.03, OR = .53 [95% CI: 0.29–0.95]). No parallel differences were found between menthol and non-menthol methamphetamine-dependent smokers. The prevalence of Caucasian menthol smokers was significantly greater in the cocaine-dependent participants (37.2%) than in the methamphetamine-dependent participants (17.61%), (X²(1) = 14.4, p < .001, OR = 2.77 [95% CI:1.62–4.73]). Smoking cessation was not significantly associated with cigarette type for either cocaine- or methamphetamine-dependent participants.

Conclusions

The present results suggest that mentholated cigarettes play a role in cocaine, but not methamphetamine, dependence.     

Criminal justice referral and incentives in outpatient substance abuse treatment

A substantial number of substance abusers entering outpatient psychosocial counseling treatment are referred from the criminal justice (CJ) system. This secondary analysis of previously published findings from a large (N = 415) multi-site trial of a prize-based abstinence incentive intervention ( Petry et al., 2005) examined the influence of CJ referral on usual care outcomes and response to the incentive procedure. CJ referrals (n = 138) were more likely than those not CJ referred (n = 277) to provide stimulant negative urine samples whether missing samples were counted as positive (50 versus 41%, p = .016) or as missing (96 versus 91%, p < .001). A significant interaction term was found only for percentage of treatment completers (p = .027). However, on that retention variable, and three additional drug use measures, significant incentive effects were confined to participants who entered treatment without referral from the criminal justice system. The study suggests that abstinence incentives should be offered as a first priority to stimulant users entering treatment without criminal justice referral. However, incentives can be considered for use with CJ-referred stimulant users based on the observation that best outcomes were obtained in CJ referrals who also received the abstinence incentive program.     

Efficacy of an emergency department-based multicomponent intervention for smokers with substance use disorders

The efficacy of brief emergency department (ED)-based interventions for smokers with concurrent alcohol or substance use is unknown. We performed a subgroup analysis of a trial enrolling adult smokers in an urban ED, focusing on subjects who screened positive for alcohol abuse or illicit drug use. Subjects receiving usual care (UC) were given a smoking cessation brochure; those receiving enhanced care (EC) got the brochure, a brief negotiated interview, 6 weeks of nicotine patches, and a telephone call. Follow-up occurred at 3 months. Of 340 subjects in the parent study, 88 (25.9%) reported a substance use disorder. At 3 months, substance users receiving EC were more likely to be tobacco-abstinent than those receiving UC (14.6% versus 0%, p = .015), and to self-identify as nonsmokers (12.5% v. 0%, p = .03). This finding suggests that concurrent alcohol or substance use should not prevent initiation of tobacco dependence treatment in the ED.     

Rate of progression from first use to dependence on cocaine or opioids: A cross-substance examination of associated demographic,psychiatric, and childhood risk factors

Background

A number of demographic factors, psychiatric disorders, and childhood risk factors have been associated with cocaine dependence (CD) and opioid dependence (OD), but little is known about their relevance to the rate at which dependence develops. Identification of the subpopulations at elevated risk for rapid development of dependence and the risk factors that accelerate the course of dependence is an important public health goal.

Methods

Data were derived from cocaine dependent (n = 6333) and opioid dependent (n = 3513) participants in a multi-site study of substance dependence. Mean age was approximately 40 and 40% of participants were women; 51.9% of cocaine dependent participants and 29.5% of opioid dependent participants self-identified as Black/African–American. The time from first use to dependence was calculated for each substance and a range of demographic, psychiatric, and childhood risk factors were entered into ordinal logistic regression models to predict the (categorical) transition time to CD and OD.

Results

In both the cocaine and opioid models, conduct disorder and childhood physical abuse predicted rapid development of dependence and alcohol and nicotine dependence diagnoses were associated with slower progression to CD or OD. Blacks/African Americans were at greater risk than European Americans to progress rapidly to OD.

Conclusions

Only a subset of factors known to be associated with CD and OD predicted the rate at which dependence developed. Nearly all were common to cocaine and opioids, suggesting that sources of influence on the timing of transitions to dependence are shared across the two substances.     

Training workshops positively impact beliefs about contingency management in a nationwide dissemination effort

In 2011, the Veterans Administration called for nationwide implementation of contingency management (CM) in its intensive outpatient substance use disorders treatment programs, and this study evaluated the impact of the initial 1 and ½ day training workshops on knowledge and perceptions about CM among 159 clinical leaders from 113 clinics. Workshop attendance significantly increased CM-related knowledge (d = 1.88) and changed attendees' perceptions of CM (ds = 0.26–0.74). Endorsement of barriers to CM adoption decreased and positive impressions of CM increased. These perceptions about CM emerged as key correlates of post-training preparedness to implement CM. Results suggest that training workshops can be an effective avenue for increasing CM-related knowledge, as well as addressing persistent misperceptions about CM that may impede adoption efforts. Continued efforts to introduce educational materials and offer training and consultation opportunities may increase understanding about this evidence-based intervention among clinicians, thereby leading to improved patient outcomes.     

Clinical characteristics as a function of referral status among substance users in residential treatment

In the United States, substance users who voluntarily (VO) elect to receive treatment and substance users who are court-mandated (CM) to receive treatment typically obtain care within the same facilities. Little is known about the clinical characteristics that differentiate these individuals. The current study provides rates of specific DSM-IV Axis I and Axis II psychiatric and substance use disorders, comorbidities, childhood trauma, motivation, and other clinical and demographic characteristics as a function of referral status, among individuals in residential substance use treatment (463 participants, M age = 43.3; 69.7% male; 88.4% African American). Participants were interviewed and diagnosed using the Structure Clinical Interview for DSM-IV and the Diagnostic Interview for Personality Disorders. Within our sample, VO individuals, as compared to CM individuals had significantly higher rates of psychiatric disorders (68.7% versus 55.2%, respectively), including mood disorders, major depressive disorder, generalized anxiety disorder, and borderline personality disorder. Additionally, they were significantly more likely to have alcohol dependence (43.0% versus 20.8%) and cocaine dependence (66.5% versus 48.9%). Elevated rates of comorbidities and childhood abuse were also observed among VO individuals, while motivation did not differ as a function of referral status. Overall, VO individuals appeared to have more severe problems than their CM counterparts which may suggest that they require more intensive or different types of treatment.     

Preliminary evidence for normalization of risk taking by modafinil in chronic cocaine users

Modafinil, a wake-promoting agent used to treat sleep disorders, is thought to enhance cognition. Although modafinil has shown promise as a pharmacotherapy for the treatment of cocaine dependence, it is unknown to what extent cognitive effects may play a role in such treatment. We examined the effect of modafinil on the Balloon Analogue Risk Task (BART), a behavioral measure in which higher scores are purported to reflect a greater propensity for risk-taking. Thirty cocaine dependent individuals, enrolled in a randomized clinical trial of modafinil 400 mg (n = 12) versus placebo (n = 18), were administered the BART during the second week of inpatient treatment for cocaine dependence. A comparison cohort of healthy participants (n = 19) performed the BART under similar conditions. Modafinil treatment was associated with significantly higher BART scores (p = 0.01), which were comparable to scores in healthy persons. BART scores in placebo treated participants were much lower than previously reported in healthy participants, and lower than those observed in the comparison cohort. As propensity toward risk taking is typically associated with higher BART scores as well as increased risk for substance use, our findings may reflect a novel aspect of cognitive impairment related to chronic cocaine use. Notably, the low BART scores reflect highly suboptimal performance on the task, and the observed effect of modafinil may indicate a normalization of this impairment and have implications for treatment outcome.     

Patterns of alcohol dependence in Thai drinkers: a differential item functioning analysis of gender and age bias

In Caucasians, the patterns of alcohol use disorders in women and adolescents are likely to be different from those in men and adults, respectively. The authors examined these differences in a Southeast Asian sample of Thai people living in communities. A two-parameter logistic model of the IRT log-likelihood-ratio (IRTLR) test for differential item functioning (DIF) procedure was used. Participants were a subsample of 3718 current drinkers participating in the 2008 Thai National Mental Health Survey (n = 17,140). The 1-year prevalence rates of alcohol dependence were 1.4% in women and 13.7% in men. Based on the Mini International Neuropsychiatric Interview (MINI), alcohol dependence and abuse module, all current drinkers were interviewed for a yes/no response to each of seven alcohol dependence criteria. Confirmatory factor analysis suggested a single-factor model of alcohol dependence criteria (χ2 = 211.51, RMSEA = 0.06, SRMR = 0.03 and CFI = 0.96). Compared with 3174 men, 544 women had a significantly higher threshold estimate for quit/control problems and a lower threshold value for drinking despite physical/mental problems (b parameter difference of 0.25 and − 0.30, respectively). Thai adolescents (n = 272) and Thai adults (n = 3446) had no statistically significant DIF on any criterion. The criterion of time spent drinking had significantly high discrimination estimates in women, men, adolescent and adults (a parameters of 2.50, 2.08, 2.33 and 2.16, respectively). Gender bias on alcohol dependence criteria can be found in Thai drinkers. Time spent drinking may be the most useful criterion for discriminating the severity of alcohol dependence across age and gender groups of Thai drinkers.     

Small financial incentives increase smoking cessation in homeless smokers: A pilot study

Although over 70% of homeless individuals smoke, few studies have examined the effectiveness of smoking cessation interventions in this vulnerable population. The purpose of this pilot study was to compare the effectiveness of shelter-based smoking cessation clinic usual care (UC) to an adjunctive contingency management (CM) treatment that offered UC plus small financial incentives for smoking abstinence. Sixty-eight homeless individuals in Dallas, Texas (recruited in 2012) were assigned to UC (n = 58) or UC plus financial incentives (CM; n = 10) groups and were followed for 5 consecutive weeks (1 week pre-quit through 4 weeks post-quit). A generalized linear mixed model regression analysis was conducted to compare biochemically-verified abstinence rates between groups. An additional model examined the interaction between time and treatment group. The participants were primarily male (61.8%) and African American (58.8%), and were 49 years of age on average. There was a significant effect of treatment group on abstinence overall, and effects varied over time. Follow-up logistic regression analyses indicated that CM participants were significantly more likely than UC participants to be abstinent on the quit date (50% vs. 19% abstinent) and at 4 weeks post-quit (30% vs. 1.7% abstinent). Offering small financial incentives for smoking abstinence may be an effective way to facilitate smoking cessation in homeless individuals.     

Alcohol dependent inpatients who receive general hospital care vs. detoxification in psychiatric care and alcohol problem 1 year later

Aim

The aims were to investigate differences between alcohol dependent inpatients who seek alcohol treatment and those who do not seek alcohol specific but general hospital treatment, and to investigate problem drinking 12 months after hospitalization.

Methods

Two samples of alcohol dependent inpatients were recruited: N = 571 at general hospitals and N = 473 at psychiatric alcohol detoxification units, and were followed-up 12 months later.

Results

Multivariate logistic regression analyses revealed that higher age, living alone, being employed, previous help-seeking, increased severity of dependence, increased adverse consequences from drinking and increased motivation were significant predictors of receiving alcohol detoxification vs. general hospital treatment. A composite assessment of motivation to change and to seek help was the strongest predictor of positive outcome 12 months later.

Conclusions

Alcohol dependent individuals who receive detoxification in psychiatric care have a more severe alcohol problem and fewer social resources than those treated in general hospitals. Interventions targeting at enhancing motivation to change and to seek help should be part of routine general hospital care and of detoxification treatment in psychiatric care.     

Self-perceived problem with alcohol use among opioid substitution treatment clients

Background and aim

Excessive alcohol use increases mortality and morbidity among opioid substitution therapy (OST) clients. Regular attendance for OST dosing presents key opportunities for screening and treatment. However, individuals' perception of their alcohol consumption as problematic or otherwise may impact their willingness to change. This study examines patterns of alcohol consumption among OST clients, perceptions of their own use and correlates of excess consumption.

Methods

Confidential, structured interviews were conducted with 264 clients of two Sydney OST clinics. Alcohol consumption was assessed using the Alcohol Use Disorders Identification Test (AUDIT); and illicit drug dependence with the Severity of Dependence Scale.

Results

Forty-one percent of the participants scored ≥ 8 on the AUDIT (‘AUDIT-positive’), indicating excessive alcohol use. The higher a participant's AUDIT score, the more likely they were to demonstrate insight into the potential problems associated with their drinking (linear trend, p < 0.01). However, only half of AUDIT-positive participants believed they drank too much and/or had a problem with alcohol. One-third had discussed their drinking with OST staff, and a similar proportion reported a history of alcohol treatment. AUDIT-positive participants were more likely than others to be classified as dependent on an illicit drug in the last six months (AOR = 1.76, 95% CI:1.00–3.09), report a history of alcohol treatment (AOR = 5.70, 95% CI:2.83–11.48) and believe it is safe to drink 4 + standard drinks in one session (AOR = 5.30, 95% CI:2.79–10.06).

Conclusions

OST clients with AUDIT scores ≥ 8 appear to underestimate the risks associated with their alcohol consumption. Regular assessments of alcohol use and targeted brief alcohol interventions may improve health outcomes among OST clients.     

Combined effects of alcohol and hepatitis C: A secondary analysis of alcohol use biomarkers and high-risk behaviors from two medication trials for alcohol dependence

Objectives

The goal of this secondary analysis was to examine the combined effects of HCV infection and recent alcohol use on baseline biologic markers of alcohol consumption in two outpatient medication trials for alcohol dependence. In addition, the relationship between Hepatitis C virus (HCV) infection and behavioral risk factors for HCV infection in these clinical populations were examined.

Methods

Data (n = 345) from two randomized, placebo-controlled trials of naltrexone and psychosocial treatment for alcohol dependence (Study I, n = 212) and comorbid alcohol and cocaine dependence (Study II, n = 133) were used to examine baseline measures of HCV risk behaviors (injection drug use, needle sharing), and biomarkers of alcohol use (AST, ALT, GGT and CDT) were compared by HCV serostatus first within each study and then across studies.

Results

Although groups had differing sociodemographic profiles (as indicated by race, marital status, level of education) subjects in Study I exhibited no statistically significant differences from the Study II cohort in HCV prevalence (12.7 vs. 20.0%, p = 0.07), lifetime history of injection drug use (13.8 vs. 22.0%, p = 0.74), lifetime history of needle sharing (9.1 vs. 18.0%, p = 0.62). As such, the data from both studies were analyzed together. Regardless of drinking status, HCV infection was significantly associated with an upward shift in the baseline level of ALT, AST, and GGT (p < 0.006 for all measures) and a downward shift in baseline CDT (p = 0.002). When using standard laboratory cutoff values to determine clinically significant elevations, HCV seropositivity was significantly associated with elevations in ALT, AST, GGT (p < 0.001), and with decreases in CDT (p = .002).

Conclusions

These data emphasize the importance of evaluating HCV infection and HCV risk behaviors at intake in medication trials for alcohol dependence and also raise questions regarding the use of cutoff scores for ALT, AST, GGT and CDT levels as biologic markers of alcohol use in subjects when HCV status is unknown.     

Contingency management with community reinforcement approach or twelve-step facilitation drug counseling for cocaine dependent pregnant women or women with young children

Background

Cocaine abuse among women of child-bearing years is a significant public health problem. This study evaluated the efficacy of contingency management (CM), the community reinforcement approach (CRA), and twelve-step facilitation (TSF) for cocaine-dependent pregnant women or women with young children.

Methods

Using a 2 × 2 study design, 145 cocaine dependent women were randomized to 24 weeks of CRA or TSF and to monetary vouchers provided contingent on cocaine-negative urine tests (CM) or non-contingently but yoked in value (voucher control, VC). Primary outcome measures included the longest consecutive period of documented abstinence, proportion of cocaine-negative urine tests (obtained twice-weekly), and percent days using cocaine (PDC) during treatment. Documented cocaine abstinence at baseline and 3, 6, 9 and 12 months following randomization was a secondary outcome.

Findings

CM was associated with significantly greater duration of cocaine abstinence (p < .01), higher proportion of cocaine-negative urine tests (p < 0.01), and higher proportion of documented abstinence across the 3-, 6-, 9- and 12-month assessments (p < 0.05), compared to VC. The differences between CRA and TSF were not significant for any of these measures (all p values ≥0.75). PDC decreased significantly from baseline during treatment in all four groups (p < 0.001) but did not differ significantly between CM and VC (p = 0.10) or between TSF and CRA (p = 0.23).

Interpretation

The study findings support the efficacy of CM for cocaine dependent pregnant women and women with young children but do not support greater efficacy of CRA compared to TSF or differential efficacy of CM when paired with either CRA or TSF.     

Double-blind,randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence

Alcohol dependence is associated with severe nutritional and vitamin deficiency. Vitamin B1 (thiamine) deficiency erodes neurological pathways that may influence the ability to drink in moderation. The present study examines tolerability of supplementation using the high-potency thiamine analog, benfotiamine (BF), and BF's effects on alcohol consumption in severely affected, self-identified, alcohol dependent subjects. A randomized, double-blind, placebo-controlled trial was conducted on 120 non-treatment seeking, actively drinking, alcohol dependent men and women volunteers (mean age = 47 years) from the Kansas City area who met DSM-IV-TR criteria for current alcohol dependence. Subjects were randomized to receive 600 mg benfotiamine or placebo (PL) once daily by mouth for 24 weeks with 6 follow-up assessments scheduled at 4 week intervals. Side effects and daily alcohol consumption were recorded. Seventy (58%) subjects completed 24 weeks of study (N = 21 women; N = 49 men) with overall completion rates of 55% (N = 33) for PL and 63% (N = 37) for BF groups. No significant adverse events were noted and alcohol consumption decreased significantly for both treatment groups. Alcohol consumption decreased from baseline levels for 9 of 10 BF treated women after 1 month of treatment compared with 2 of 11 on PL. Reductions in total alcohol consumption over 6 months were significantly greater for BF treated women (BF: N = 10, −611 ± 380 standard drinks; PL: N = 11, −159 ± 562 standard drinks, p-value = 0.02). BF supplementation of actively drinking alcohol dependent men and women was well-tolerated and may discourage alcohol consumption among women. The results do support expanded studies of BF treatment in alcoholism.     

A placebo-controlled trial of memantine as an adjunct to injectable extended-release naltrexone for opioid dependence

There is preclinical support for using NMDA receptor glutamatergic antagonists to aid in naltrexone-based treatment of opioid dependence. We hypothesized that adding memantine will improve efficacy of extended-release (XR) naltrexone to prevent relapse. In this double blind study opioid-dependent participants (N = 82) underwent inpatient detoxification and naltrexone induction. During naltrexone initiation participants were randomized to receive memantine 40 mg or placebo and continued treatment for 12-weeks with XR naltrexone and relapse-prevention therapy. Sixty eight percent of participants completed detoxification and received the first dose of XR naltrexone. Rates of trial completion were significantly greater in participants receiving placebo than memantine (70% vs. 43%, p < 0.05). Severity of opioid withdrawal symptoms during the first 3 weeks of the trial appeared to be lower in the group receiving memantine (p = 0.07). Adding memantine does not appear to increase the effectiveness of injectable XR naltrexone as a relapse prevention strategy in opioid dependence and may lead to an increase in treatment drop-out.     

Antisocial personality disorder predicts methamphetamine treatment outcomes in homeless,substance-dependent men who have sex with men

One-hundred-thirty-one homeless, substance-dependent MSM were enrolled in a randomized controlled trial to assess the efficacy of a contingency management (CM) intervention for reducing substance use and increasing healthy behavior. Participants were randomized into conditions that either provided additional rewards for substance abstinence and/or health-promoting/prosocial behaviors (“CM-full”; n = 64) or for study compliance and attendance only (“CM-lite”; n = 67). The purpose of this secondary analysis was to determine the affect of ASPD status on two primary study outcomes: methamphetamine abstinence, and engagement in prosocial/health-promoting behavior. Analyses revealed that individuals with ASPD provided more methamphetamine-negative urine samples (37.5%) than participants without ASPD (30.6%). When controlling for participant sociodemographics and condition assignment, the magnitude of this predicted difference increases to 10% and reached statistical significance (p < .05). On average, participants with ASPD earned fewer vouchers for health-promoting/prosocial behaviors than participants without ASPD ($10.21 [SD = $7.02] versus $18.38 [SD = $13.60]; p < .01). Participants with ASPD displayed superior methamphetamine abstinence outcomes regardless of CM schedule; even with potentially unlimited positive reinforcement, individuals with ASPD displayed suboptimal outcomes in achieving health-promoting/prosocial behaviors.     

Drug users’ adherence to a 6-month vaccination protocol: Effects of motivational incentives

Vaccines represent a new and promising avenue of treatment for drug abuse but pose new medication adherence challenges due to prolonged and widely spaced administration schedules. This study examined effects of prize-based incentives on retention and medication adherence among 26 cocaine users involved in a 6-month hepatitis B vaccination series. Participants could meet with research staff weekly for 24 weeks and receive 7 injections containing either the Hepatitis B vaccine or a placebo. All participants received $10 at each weekly visit (maximum of $240). Those randomly assigned to the incentive program received additional monetary payments on an escalating schedule for attendance at weekly monitoring and vaccination visits with maximum possible earnings of $751. Group attendance diverged after study week 8 with attendance better sustained in the incentive than control group (group by time interaction, p = .035). Overall percent of weekly sessions attended was 82% for incentive versus 64% for control (p = .139). Receiving all scheduled injections were 77% of incentive versus 46% of control participants (p = .107). A significantly larger percentage (74% versus 51%; p = .016) of injections were received by incentive versus control participants on the originally scheduled day. Results suggest that monetary incentives can successfully motivate drug users to attend sessions regularly and to receive injected medications in a more reliable and timely manner than may be seen under usual care procedures. Thus, incentives may be useful for addressing adherence and allowing participants to reap the full benefits of newly developed medications.