Randomized trial of mindfulness- and reappraisal-based regulation of craving training among daily cigarette smokers.

OBJECTIVE: Craving predicts smoking, yet existing interventions may not adequately target regulation of craving. We evaluated two versions of regulation of craving-training (ROC-T), a computerized intervention with intensive practice of strategies when exposed to smoking-related images. METHOD: Ninety-two nicotine-dependent daily smokers were randomized to mindfulness-based therapy (MBT) ROC-T focusing on mindful acceptance, and cognitive behavioral therapy (CBT) ROC-T focusing on reappraisal or no intervention control. The ROC task was administered pre- and postintervention to assess changes in cue-induced craving and mindfulness- and reappraisal-based regulation of craving. RESULTS: MBT and CBT-versus control-showed significantly greater reductions in smoking during the intervention phase (baseline to Week 4), corresponding to large (d = -1.08, 95% CI [-1.64, -0.52]) and medium-to-large effect sizes (d = -0.69, 95% CI [-1.22, -0.15]), respectively. During follow-up (Week 4-16), CBT showed significant increases in smoking, whereas MBT and control did not. For the entire study (baseline to Week 16), MBT showed significantly greater reductions in smoking compared to control (d = -1.6, 95% CI [-2.56, -0.66]) but CBT was not significantly different than control (d = -0.82, 95% CI [-1.77, 0.13]). There were no effects on smoking when directly comparing MBT and CBT. Quit rates were low across the sample, with no difference among conditions. MBT and CBT-versus control-significantly reduced cue-induced craving. CBT (but not MBT)-versus control-significantly improved reappraisal-based regulation of craving. Both MBT and CBT-versus control-significantly improved mindfulness-based regulation of craving. CONCLUSIONS: MBT- and CBT-ROC-T may reduce cue-induced craving and smoking, and MBT may be more durable than CBT. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

An integrated behavioural intervention combined with varenicline for heavy-drinking smokers: a randomized pilot study.

OBJECTIVES: Combined smoking and heavy drinking is a significant health burden. Varenicline, an efficacious tobacco pharmacotherapy that also shows promise for drinking, has yielded mixed results among heavy-drinking smokers. This pilot study investigated integrated tobacco and alcohol counselling plus varenicline for this vulnerable group. DESIGN: Twelve-week parallel, randomized controlled pilot trial of two behavioural interventions in combination with open-label varenicline. Participants were randomized using computer-generated tables, stratified by sex. SETTING: Outpatient academic medical centre research clinic. PARTICIPANTS: Volunteers who reported smoking and heavy drinking and sought tobacco or alcohol treatment (N = 26). Intervention. (1) Integrated tobacco + alcohol counselling (INT; n = 13) or (2) counselling focused on their presenting concern (i.e., tobacco or alcohol) (SINGLE; n = 13), plus varenicline (2 mg) for 12 weeks. MAIN OUTCOMES: Feasibility/acceptability, smoking quit rates and heavy drinking. RESULTS: INT feasibility/acceptability was high among men but not women. More participants quit smoking in INT than SINGLE. This outcome was only in men, not significant, but had a medium effect size. Both conditions yielded significant drinking reductions. CONCLUSION: Integrated tobacco and alcohol behavioural counselling plus varenicline may be feasible and promote smoking cessation among men who smoke and drink heavily, but a larger sample is needed to replicate this finding.

Computerized Cognitive Behavioral Therapy for Substance Use Disorders in a Specialized Primary Care Practice: A Randomized Feasibility Trial to Address the RT Component of SBIRT.

OBJECTIVES: Screening, Brief Intervention, and Referral to Treatment (SBIRT) has demonstrated efficacy for addressing unhealthy alcohol use in primary care, yet recent research indicates weaker efficacy for drug use as well as very limited success in referral to specialty care for patients with substance use disorder (SUD). Technology-based interventions for SUD delivered in primary care settings are a potential strategy of efficiently delivering treatment to those who need it. METHODS: We conducted a randomized clinical trial evaluating feasibility, satisfaction, and substance use outcomes for 58 individuals with SUD. Participants being treated in a primary care practice which provides integrated addiction treatment were randomized to standard care or standard care plus access to a web-based SUD intervention (computer-based training in cognitive behavioral therapy, or CBT4CBT). Self-reported substance use and urine toxicology screens were assessed at 8 weeks after randomization. RESULTS: Uptake of CBT4CBT in this setting was high; 77% of those assigned to this condition accessed the program at least once; of those, 77% completed all 7 modules. Satisfaction with the program was very high. Participants reported >90% days abstinent for all classes of drugs; with no significant differences between conditions. CONCLUSIONS: This study demonstrates feasibility of implementing technology-based treatments in primary care settings to address weak follow-through with the referral component of SBIRT. The overall positive outcomes in this specialized, integrated treatment setting may have undercut the ability to demonstrate differential effects on substance use; results suggest evaluation in less specialized primary care settings is warranted. TRIAL REGISTRATION: clinicaltrials.gov NCT03013478.

The Cholinergic System as a Treatment Target for Opioid Use Disorder.

Opioid overdoses recently became the leading cause of accidental death in the US, marking an increase in the severity of the opioid use disorder (OUD) epidemic that is impacting global health. Current treatment protocols for OUD are limited to opioid medications, including methadone, buprenorphine, and naltrexone. While these medications are effective in many cases, new treatments are required to more effectively address the rising societal and interpersonal costs associated with OUD. In this article, we review the opioid and cholinergic systems, and examine the potential of acetylcholine (ACh) as a treatment target for OUD. The cholinergic system includes enzymes that synthesize and degrade ACh and receptors that mediate the effects of ACh. ACh is involved in many central nervous system functions that are critical to the development and maintenance of OUD, such as reward and cognition. Medications that target the cholinergic system have been approved for the treatment of Alzheimer's disease, tobacco use disorder, and nausea. Clinical and preclinical studies suggest that medications such as cholinesterase inhibitors and scopolamine, which target components of the cholinergic system, show promise for the treatment of OUD and further investigations are warranted.

Reward-related frontostriatal activity and smoking behavior among adolescents in treatment for smoking cessation.

BACKGROUND: Tobacco use is often initiated during adolescence and continued into adulthood despite desires to quit. A better understanding of the neural correlates of abstinence from smoking in adolescents may inform more effective smoking cessation interventions. Neural reward systems are implicated in tobacco use disorder, and adolescent smokers have shown reduced reward-related ventral striatal activation related to increased smoking. METHODS: The current study evaluated nondrug reward anticipation in adolescent smokers using a monetary incentive delay task in fMRI pre- and post- smoking cessation treatment (n=14). This study tested how changes in neural responses to reward anticipation pre- to post-treatment were related to reduced smoking. An exploratory analysis in a larger sample of adolescents with only pre-treatment fMRI (n=28) evaluated how neural responses to reward anticipation were related to behavioral inhibition and behavioral activation scales. RESULTS: Adolescent smokers showed pre- to post-treatment increases in reward anticipation-related activity in the bilateral nucleus accumbens and insula, and medial prefrontal cortex, and greater increases in reward anticipation-related activity were correlated with larger percent days of smoking abstinence during treatment. CONCLUSIONS: These findings suggest that reduced smoking during smoking cessation treatment is associated with a "recovery of function" in frontostriatal responses to nondrug reward anticipation in adolescent smokers, although comparison with a developmental control group of adolescent nonsmokers is warranted.

A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults.

BACKGROUND: Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. METHODS: In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18-50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. RESULTS: There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio=1.00, 95% confidence interval 0.63-1.59, p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. CONCLUSIONS: In contrast with prior findings in adolescents, there is no evidence that NAC 1200mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors.

Momentary Associations Between Reported Craving and Valuing Health in Daily Smokers.

INTRODUCTION: Research suggests that a blunted response to nondrug rewards, especially under conditions associated with strong cigarette cravings, is associated with reduced abstinence motivation in daily smokers. One limitation of previous studies is that they have largely focused on monetary rewards as broad representative of nondrug rewards. It remains unclear whether craving dampens responses to more abstract nondrug rewards, such as personal values. Personal values often have a positive valence and are frequently assumed to remain stable across time and situations. However, there may be time-varying and contextual influences on smokers' appraisal of values in daily life. Characterizing fluctuations in value importance in relation to relapse precipitants (eg, craving) may inform interventions that leverage personal values as motivation for cessation. METHODS: Daily smokers (n = 18) completed ecological momentary assessment surveys measuring the importance of specific personal values and smoking-related variables during 8 days of monetarily reinforced cigarette abstinence. We hypothesized that value ratings would demonstrate adequate within-person heterogeneity for multilevel modeling and that within-person fluctuations in craving would be negatively related to valuing personal health. RESULTS: All values demonstrated adequate within-person variability for multilevel modeling. Within-person craving was negatively related to health valuation (p = .012) and a cross-level interaction (p > .0001) suggested this effect is stronger for individuals who report greater overall craving. CONCLUSIONS: Greater craving is associated with decreased importance of personal health in the moment, particularly for those with high average levels of craving. Timely interventions that bolster importance of health during moments of elevated craving can potentially improve cessation outcomes. IMPLICATIONS: This study builds on research highlighting the positive influence of personal values in motivating behavior change. Values are an often used, but poorly studied, construct that has considerable utility in smoking cessation. Valuing personal health is frequently reported as a primary motivator for a quit attempt. Inasmuch as personal health is a distal nondrug reward used to motivate smoking abstinence, naturalistic evaluation of health importance, and motivators for continued smoking (ie, craving) could inform the timing and content of smoking treatment. This study is among the first to evaluate momentary assessment of personal values and craving within daily life.

The Role of Behavioral Interventions in Buprenorphine Maintenance Treatment: A Review.

OBJECTIVE: Although counseling is a required part of office-based buprenorphine treatment of opioid use disorders, the nature of what constitutes appropriate counseling is unclear and controversial. The authors review the literature on the role, nature, and intensity of behavioral interventions in office-based buprenorphine treatment. METHOD: The authors conducted a review of randomized controlled studies testing the efficacy of adding a behavioral intervention to buprenorphine maintenance treatment. RESULTS: Four key studies showed no benefit from adding a behavioral intervention to buprenorphine plus medical management, and four studies indicated some benefit for specific behavioral interventions, primarily contingency management. The authors examined the findings from the negative trials in the context of six questions: 1) Is buprenorphine that effective? 2) Is medical management that effective? 3) Are behavioral interventions that ineffective in this population? 4) How has research design affected the results of studies of buprenorphine plus behavioral treatment? 5) What do we know about subgroups of patients who do and those who do not seem to benefit from behavioral interventions? 6) What should clinicians aim for in terms of treatment outcome in buprenorphine maintenance? CONCLUSIONS: High-quality medical management may suffice for some patients, but there are few data regarding the types of individuals for whom medical management is sufficient. Physicians should consider a stepped-care model in which patients may begin with relatively nonintensive treatment, with increased intensity for patients who struggle early in treatment. Finally, with 6-month retention rates seldom exceeding 50% and poor outcomes following dropout, we must explore innovative strategies for enhancing retention in buprenorphine treatment.

Intra-individual changes in Stroop-related activations linked to cigarette abstinence in adolescent tobacco smokers: Preliminary findings.

BACKGROUND: Adolescence is a crucial time for initiation of tobacco-smoking. Developing more effective treatment interventions for tobacco-smoking in youth is therefore critical to reduce smoking rates in both adolescent and adult populations. Elucidation of the neural mechanisms of successful behavioral change (abstinence) will allow for improvement of therapies based on known brain mechanisms. METHODS: Twenty-one adolescent tobacco-smokers (14-19 years) participated in functional magnetic resonance imaging (fMRI) during performance of a cognitive control (Stroop) task prior to randomization to smoking cessation treatment (trial of combined nicotine replacement therapy/placebo and contingency management for attendance/abstinence; NCT01145001). Fourteen adolescents also participated in fMRI scanning following completion of the six-week trial. fMRI data were analyzed using random-effects models in SPM12. Paired t-tests were used to identify group-level changes (main effect of treatment exposure) in neural functional responses. Regression models were used to identify individual-level changes associated with treatment-outcomes (percent days abstinent, maximum days of consecutive abstinence). RESULTS: Main effects of Stroop task performance (contrast of incongruent versus congruent trials) were seen across a priori ROIs at both pre- and post-treatment (pFWE<0.05). At the group-level, no changes in neural responses were found following treatment. However, intra-individual reductions in Stroop-related activity (within the insula and anterior cingulate) were positively associated with measures of smoking abstinence during treatment (pFWE<0.05). CONCLUSIONS: Abstinence from tobacco during smoking cessation treatment among adolescents is associated with cognitive-control related reductions in neural activity within specific regions (anterior cingulate, insula), suggesting that increases in cognitive efficiency may underlie optimal treatment responses in this population.

Contingency management improves smoking cessation treatment outcomes among highly impulsive adolescent smokers relative to cognitive behavioral therapy.

BACKGROUND: Impulsive adolescents have difficulty quitting smoking. We examined if treatments that provide behavioral incentives for abstinence improve treatment outcomes among impulsive adolescent smokers, who have been shown to be highly sensitive to reward. METHODS: We ran secondary data analyses on 64 teen smokers (mean age=16.36 [1.44]; cigarettes/day=13.97 [6.61]; 53.1% female; 90.6% Caucasian) who completed a four-week smoking cessation trial to determine whether impulsive adolescents differentially benefit from receiving cognitive behavioral therapy (CBT), contingency management (CM), or the combination of the two (CM/CBT). Indices of treatment efficacy included self-report percent days abstinent and end of treatment biochemically-confirmed 7-day point prevalence abstinence (EOT abstinence). We assessed self-reported impulsivity using the Brief Barratt Impulsiveness Scale. We used univariate Generalized Linear Modeling to examine main effects and interactions of impulsivity and treatment condition as predictors of self-reported abstinence, and exact logistic regression to examine EOT abstinence. RESULTS: CM/CBT and CM were comparably effective in promoting abstinence, so analyses were conducted comparing the efficacy of CBT to treatments with a CM component (i.e., CM and CM/CBT). CBT and deficient self-regulation predicted lower self-reported abstinence rates within the total analytic sample. Treatments containing CM were more effective than CBT in predicting 1) self-reported abstinence among behaviorally impulsive adolescents (% days abstinent: CM 77%; CM/CBT 81%; CBT 30%) and 2) EOT point prevalence abstinence among behaviorally impulsive adolescents and adolescents with significant deficits in self-regulation. CONCLUSION: CM-based interventions may improve the low smoking cessation rates previously observed among impulsive adolescent smokers.

Achieving cannabis cessation -- evaluating N-acetylcysteine treatment (ACCENT): design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network.

Despite recent advances in behavioral interventions for cannabis use disorders, effect sizes remain modest, and few individuals achieve long-term abstinence. One strategy to enhance outcomes is the addition of pharmacotherapy to complement behavioral treatment, but to date no efficacious medications targeting cannabis use disorders in adults through large, randomized controlled trials have been identified. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) is currently conducting a study to test the efficacy of N-acetylcysteine (NAC) versus placebo (PBO), added to contingency management, for cannabis cessation in adults (ages 18-50). This study was designed to replicate positive findings from a study in cannabis-dependent adolescents that found greater odds of abstinence with NAC compared to PBO. This paper describes the design and implementation of an ongoing 12-week, intent-to-treat, double-blind, randomized, placebo-controlled study with one follow-up visit four weeks post-treatment. Approximately 300 treatment-seeking cannabis-dependent adults will be randomized to NAC or PBO across six study sites in the United States. The primary objective of this 12-week study is to evaluate the efficacy of twice-daily orally-administered NAC (1200 mg) versus matched PBO, added to contingency management, on cannabis abstinence. NAC is among the first medications to demonstrate increased odds of abstinence in a randomized controlled study among cannabis users in any age group. The current study will assess the cannabis cessation efficacy of NAC combined with a behavioral intervention in adults, providing a novel and timely contribution to the evidence base for the treatment of cannabis use disorders.

Integrating a Behavioural Sleep Intervention into Smoking Cessation Treatment for Smokers with Insomnia: A Randomised Pilot Study.

INTRODUCTION: Sleep disturbance is common among cigarette smokers and predicts smoking cessation failure. AIMS: The purpose of this study was to conduct a pilot test of whether provision of a sleep intervention might bolster smoking cessation outcomes among this vulnerable group. METHODS: Smokers with insomnia (N = 19) seeking smoking cessation treatment were randomly assigned to receive 8 sessions over 10 weeks of either: (1) cognitive-behavioural therapy for insomnia + smoking cessation counselling (CBT-I+SC; n = 9) or (2) smoking cessation counselling alone (SC; n = 10). Counselling commenced 4 weeks prior to a scheduled quit date, and nicotine patch therapy was also provided for 6 weeks starting on the quit date. RESULTS: There was no significant effect of counselling condition on smoking cessation outcomes. Most participants had difficulty initiating and maintaining smoking abstinence in that 7-day point prevalence abstinence rates at end of treatment (CBT-I+SC: 1/7, 14%; SC: 2/10, 20%) and follow-up (CBT-I+SC: 1/7, 14%; SC: 0/10, 0%) were low for both conditions. CBT-I+SC participants reported improvements in sleep efficiency, quality, duration and insomnia symptoms. Sleep changes were not associated with the likelihood of achieving smoking abstinence. CONCLUSIONS: This randomised pilot study suggests that behavioural interventions may improve sleep among smokers with insomnia, but a larger sample is needed to replicate this finding and evaluate whether these changes facilitate smoking cessation.

Smokers versus snorters: do treatment outcomes differ according to route of cocaine administration?

Smoking cocaine achieves maximal concentration and effect far more rapidly than through the intranasal ("snorting") route, and it is associated with greater propensity for dependence and more severe consequences. However, very little is known about differences in treatment outcome according to route of administration. This study compared treatment outcomes, such as frequency of cocaine use and Addiction Severity Index (ASI) composite scores, by primary route of cocaine administration (smoking vs. intranasal) among a pooled sample of 412 cocaine-dependent individuals participating in 1 of 5 randomized clinical trials. The majority (80%) reported smoking as their primary route of cocaine administration. Overall, results indicated better cocaine use outcomes both during the treatment phase and through a 12-month follow-up period for intranasal users compared to smokers, although not all differences reached statistical significance. Intranasal users remained in treatment longer, F(1, 408) = 3.55, p < .05, and showed a trend toward achieving longer periods of sustained abstinence within treatment, F(1, 378) = 2.68, p = .08, as well as less use over time during the follow-up period than smokers (Time × Route: t = 1.87, p = .06). Also, intranasal users' ASI cocaine composite score decreased more than smokers, but there were overall decreases in the other ASI domains for all participants over the course of the study period. These results suggest that intranasal users may achieve better cocaine use outcomes than smokers, yet this doesn't appear to translate to differential changes in the severity of problems experienced in other life areas.

Marijuana use is associated with risky sexual behaviors in treatment-seeking polysubstance abusers.

BACKGROUND: Multiple types of substance use are associated with HIV risk behaviors, but relatively little research has examined the association between marijuana use and risky sexual activities in treatment-seeking polysubstance abusing patients. OBJECTIVES: This study evaluated the relationship between marijuana use and sexual behaviors in 239 patients with cocaine, opioid or alcohol use disorders who were initiating outpatient substance use treatment. METHODS: Participants completed the HIV Risk Behavior Scale and were classified into one of three groups based on their marijuana use histories: never (n = 66), past but not current use (n = 124) or current use (n = 49). RESULTS: Compared to never marijuana users, current and former marijuana users had a greater likelihood of having more than 50 lifetime sexual partners (odds ratio [OR] and 95% confidence interval [CI] = 3.9 [1.0-15.7] and 5.2 [1.6-17.3], respectively). Former marijuana users had increased risk of low frequency condom use with casual partners relative to never users (OR [95% CI] = 2.9 [1.1-7.6]). Moreover, current marijuana users were more likely than never users to have had more than two recent sexual partners (OR [95% CI] = 8.1 [1.94-33.44]). CONCLUSION: Treatment-seeking polysubstance abusers with current or past marijuana use histories may be at greater risk of HIV infection than their counterparts who do not use marijuana. These data underscore the importance of increasing awareness about the potential association between marijuana use and increased high-risk sexual behavior among polysubstance abusing patients.

An exploratory randomized controlled trial of a novel high-school-based smoking cessation intervention for adolescent smokers using abstinence-contingent incentives and cognitive behavioral therapy.

BACKGROUND: There are few effective smoking cessation interventions for adolescent smokers. We developed a novel intervention to motivate tobacco use behavior change by (1) enhancing desire to quit through the use of abstinence-contingent incentives (CM), (2) increasing cessation skills through the use of cognitive behavioral therapy (CBT), and (3) removing cessation barriers through delivery within high schools. METHODS: An exploratory four-week, randomized controlled trial was conducted in Connecticut high schools to dismantle the independent and combined effects of CM and CBT; smokers received CM alone, CBT alone, or CM+CBT. Participants included 82 adolescent smokers seeking smoking cessation treatment. The primary outcome was seven-day end-of-treatment (EOT) point prevalence (PP) abstinence, determined using self-reports confirmed using urine cotinine levels. Secondary outcomes included one-day EOT PP abstinence and cigarette use during treatment and follow up. RESULTS: Among participants who initiated treatment (n=72), group differences in seven-day EOT-PP abstinence were observed (χ(2)=10.48, p<0.01) with higher abstinence in the CM+CBT (36.7%) and CM (36.3%) conditions when compared with CBT (0%). One-day EOT-PP abstinence evidenced similar effects (χ(2)=10.39, p<0.01; CM+CBT: 43%, CM: 43%, CBT: 4.3%). Survival analyses indicated differences in time to first cigarette during treatment (χ(2)=8.73, p=0.003; CBT: Day 3, CM: Day 9, CM+CBT: Day 20). At one- and three-month follow ups, while no differences were observed, the CM alone group had the slowest increase in cigarette use. CONCLUSIONS: High-school, incentive-based smoking cessation interventions produce high rates of short-term abstinence among adolescent smokers; adding cognitive behavioral therapy does not appear to further enhance outcomes.

Delay discounting in adults receiving treatment for marijuana dependence.

Delay discounting is an index of impulsive decision-making and reflects an individual's preference for smaller immediate rewards relative to larger delayed rewards. Multiple studies have indicated comparatively high rates of discounting among tobacco, alcohol, cocaine, and other types of drug users, but few studies have examined discounting among marijuana users. This report is a secondary analysis of data from a clinical trial that randomized adults with marijuana dependence to receive one of four treatments that involved contingency management (CM) and cognitive-behavioral therapy interventions. Delay discounting was assessed with the Experiential Discounting Task (Reynolds & Schiffbauer, 2004) at pretreatment in 93 participants and at 12 weeks posttreatment in 61 participants. Results indicated that higher pretreatment delay discounting (i.e., more impulsive decision-making) significantly correlated with lower readiness to change marijuana use (r = -0.22, p = .03) and greater number of days of cigarette use (r = .21, p = .04). Pretreatment discounting was not associated with any marijuana treatment outcomes. CM treatment significantly interacted with time to predict change in delay discounting from pre- to posttreatment; participants who received CM did not change their discounting over time, whereas those who did not receive CM significantly increased their discounting from pre- to posttreatment. In this sample of court-referred young adults receiving treatment for marijuana dependence, delay discounting was not strongly related to treatment outcomes, but there was some evidence that CM may protect against time-related increases in discounting.

Clinical correlates of co-occurring cannabis and tobacco use: a systematic review.

AIMS: A growing literature has documented the substantial prevalence of and putative mechanisms underlying co-occurring (i.e. concurrent or simultaneous) cannabis and tobacco use. Greater understanding of the clinical correlates of co-occurring cannabis and tobacco use may suggest how intervention strategies may be refined to improve cessation outcomes and decrease the public health burden associated with cannabis and tobacco use. METHODS: A systematic review of the literature on clinical diagnoses, psychosocial problems and outcomes associated with co-occurring cannabis and tobacco use. Twenty-eight studies compared clinical correlates in co-occurring cannabis and tobacco users versus cannabis- or tobacco-only users. These included studies of treatment-seekers in clinical trials and non-treatment-seekers in cross-sectional or longitudinal epidemiological or non-population-based surveys. RESULTS: Sixteen studies examined clinical diagnoses, four studies examined psychosocial problems and 11 studies examined cessation outcomes in co-occurring cannabis and tobacco users (several studies examined multiple clinical correlates). Relative to cannabis use only, co-occurring cannabis and tobacco use was associated with a greater likelihood of cannabis use disorders, more psychosocial problems and poorer cannabis cessation outcomes. Relative to tobacco use only, co-occurring use did not appear to be associated consistently with a greater likelihood of tobacco use disorders, more psychosocial problems or poorer tobacco cessation outcomes. CONCLUSIONS: Cannabis users who also smoke tobacco are more dependent on cannabis, have more psychosocial problems and have poorer cessation outcomes than those who use cannabis but not tobacco. The converse does not appear to be the case.

Primary outcome indices in illicit drug dependence treatment research: systematic approach to selection and measurement of drug use end-points in clinical trials.

AIMS: Clinical trials test the safety and efficacy of behavioral and pharmacological interventions in drug-dependent individuals. However, there is no consensus about the most appropriate outcome(s) to consider in determining treatment efficacy or on the most appropriate methods for assessing selected outcome(s). We summarize the discussion and recommendations of treatment and research experts, convened by the US National Institute on Drug Abuse, to select appropriate primary outcomes for drug dependence treatment clinical trials, and in particular the feasibility of selecting a common outcome to be included in all or most trials. METHODS: A brief history of outcomes employed in prior drug dependence treatment research, incorporating perspectives from tobacco and alcohol research, is included. The relative merits and limitations of focusing on drug-taking behavior, as measured by self-report and qualitative or quantitative biological markers, are evaluated. RESULTS: Drug-taking behavior, measured ideally by a combination of self-report and biological indicators, is seen as the most appropriate proximal primary outcome in drug dependence treatment clinical trials. CONCLUSIONS: We conclude that the most appropriate outcome will vary as a function of salient variables inherent in the clinical trial, such as the type of intervention, its target, treatment goals (e.g. abstinence or reduction of use) and the perspective being taken (e.g. researcher, clinical program, patient, society). It is recommended that a decision process, based on such trial variables, be developed to guide the selection of primary and secondary outcomes as well as the methods to assess them.

Quantification of proteins and their modifications using QconCAT technology.

Building a mathematical model of a biological system requires input of experimental data for each networked component, ultimately generating a model that can be used to test scientific hypotheses. A fundamental requirement in the computation of these systems is that the total amount of each component can be specified precisely. An added level of complexity occurs because a vast number of protein posttranslational modifications modulate protein function. Each of these modified forms therefore needs to be considered as a separate system component, and must therefore be quantified individually. In this chapter, we describe how designer QconCAT proteins can be used to determine the absolute amounts of both the polypeptide components and their covalently modified derivatives in both yeast and mammalian extracts derived from living cell populations.