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Introduction: Some evidence suggests that female smokers may show more context-dependent smoking and that males may show more stereotyped smoking (regardless of stress or cue exposure). The goal of this study was to characterize sex differences in response to stressful and smoking cues ecologically presented in daily life and variability in day-to-day smoking behavior., Methods: Adult smokers (N = 177) provided ratings of mood and cigarette craving before and after stress and smoking cues were presented four times daily for 14 days via a mobile device. Linear mixed models tested whether (1) female smokers exhibited greater reactivity to stressful cues than male smokers; (2) pre-cue negative affect increased reactivity to smoking cues more in female smokers than male smokers; (3) across both sexes, greater reactivity to stressful and smoking cues correlated with greater quantity of smoking within a day; and (4) female smokers exhibited greater variability in cigarettes per day (CPD) relative to males., Results: Relative to male smokers, female smokers reported greater negative affect, stress, and craving in response to stressful cues, but not smoking cues, after accounting for time since last cigarette and pre-cue responding. No sex differences in CPD or variability in CPD were detected. Days with higher subjective reactivity to cues were not associated with increased smoking, in either males or females., Conclusions: Sex differences were observed in response to stress but not smoking cues in the natural environment of regular cigarette smokers. Further research is necessary to evaluate whether stress reactivity in female smokers is associated with reduced latency to smoke following stress exposure in daily life., Implications: This study provides naturalistic evidence that female smokers may not be more reactive to smoking cues than males, but experience heightened stress and craving following stress exposure. There was no evidence to support the hypothesis that amount smoked per day varied more for females, relative to males, as a result of more context-driven smoking for females., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Recent research on addiction-related memory processes suggests that protracted extinction training following brief cue-elicited memory retrieval (ie, retrieval-extinction [R-E] training) can attenuate/eradicate the ability of cues to elicit learned behaviors. One study reported that cue-elicited craving among detoxified heroin addicts was substantially attenuated following R-E training and through 6-month follow-up., Objective: To build on these impressive findings by examining whether R-E training could attenuate smoking-related craving and behavior., Design, Setting, and Participants: This prospective, mixed-design, human laboratory randomized clinical trial took place between December 2013 and September 2015. Participants were recruited in Charleston, South Carolina. Study sessions took place at the Medical University of South Carolina. The participants were 168 screened volunteer smokers, of whom 88 were randomized; 72 of these 88 participants (81.8%) attended all the follow-up sessions through 1 month. The primary eligibility criteria were current nicotine dependence (DSM criteria), smoking 10 or more cigarettes per day, and a willingness to attempt smoking cessation., Interventions: Participants were randomly assigned to receive either smoking-related memory retrieval followed by extinction training (the R-E group) or nonsmoking-related retrieval followed by extinction training (the NR-E group)., Main Outcomes and Measures: Primary outcomes were cue-elicited craving and physiological responding to familiar and novel cues in the R-E group vs the NR-E group over a 1-month follow-up period. Secondary outcomes were smoking-related behaviors., Results: A total of 44 participants were randomly assigned to the R-E group (mean age, 48.3 years; 72.7% male); a total of 44 participants were randomly assigned to the NR-E group, with 43 attending at least 1 training session (mean age, 46.7 years; 55.8% male). The mean craving response to both familiar and novel smoking cues was significantly lower for participants in the R-E group than for participants in the NR-E group at 1-month follow-up (for both cue types: t1225 = 2.1, P = .04, d = 0.44, and Δ = 0.47 [95% CI, 0.04-0.90]). The mean numbers of cigarettes smoked per day at 2 weeks and 1-month were significantly lower for the R-E group than for the NR-E group (treatment main effect: F1,68 = 5.4, P = .02, d = 0.50, and Δ = 2.4 [95% CI, 0.4-4.5]). Significant differences in physiological responses, urine cotinine level, number of days abstinent, lapse, and relapse were not observed between groups (all between P = .06 and .75)., Conclusions and Relevance: Retrieval-extinction training substantially attenuated craving to both familiar and novel smoking cues and reduced the number of cigarettes smoked per day by participants 1 month after treatment relative to extinction training alone. Between-group differences were not observed for physiological responses, cotinine level, number of days abstinent, relapse, or lapse. In summary, R-E training is a brief behavioral treatment that targets smoking-related memories and has the potential to enhance relapse prevention., Trial Registration: clinicaltrials.gov Identifier: NCT02154685.

Background and Rationale: The high prevalence of co-occurring alcohol and tobacco use underscores the importance of understanding the influence of alcohol consumption on risk factors for smoking and relapse. Alcohol has been shown to impact reactivity to smoking and stress-related cues, both of which are common antecedents to smoking and smoking relapse., Objective: The objective of the current study is to examine associations between alcohol use, cigarette craving, and stress reactivity following exposure to smoking and stress cues delivered in participants' daily lives., Methods: Using cue-reactivity ecological momentary assessment (CREMA), adult smokers (n = 138) reported cigarette craving, stress, and past hour alcohol use on a mobile device four times per day for 2 weeks, resulting in a range of 4493-5983 data points per analysis. Questions were followed by exposure to pictorial neutral, stressful, or smoking cues delivered via the mobile device. Craving and affect were re-assessed following cue exposure., Results: Results showed that recent (past hour) alcohol use was significantly associated with increases in the following: (a) tonic (non-cue-elicited) cigarette craving, (b) stress cue-elicited cigarette craving, and (c) stress cue-elicited stress reactivity, in the context of high-baseline stress. There was no significant association between alcohol use and smoking cue-elicited craving., Conclusions: Alcohol use may increase risk for smoking and relapse to smoking by increasing cigarette craving and, in certain contexts, stress following stress cue exposure. Though alcohol is known for its anxiolytic properties, under some conditions, it may increase reactivity to stress cues., Competing Interests: The authors declare that they have no conflict of interest.

Background: Varenicline (VAR) has demonstrated superior efficacy over other smoking cessation pharmacotherapies, though 50-60% of those treated do maintain abstinence. Some preclinical findings suggest that new nicotine dependence pharmacotherapies should target the glutamatergic system, given its demonstrated role in addiction. Attention has been given to N-acetylcysteine (NAC), which appears to restore normal glutamate signaling in animal models. It is possible that NAC and VAR may work in concert to promote abstinence at higher rates than with either medication alone., Objective: To demonstrate the feasibility and safety of co-administering NAC and VAR in nicotine-dependent participants., Methods: Participants (n = 19) were daily cigarette smokers, and did not need to be seeking treatment. They received 4 weeks of open-label treatment with NAC (1200 mg twice daily) and VAR (1 mg twice daily, following titration) and were assessed weekly for adverse events (AEs), smoking, craving and withdrawal., Results: Sixteen participants reported a total of 40 AEs, and most were mild (88%). The most commonly reported AE was nausea (15%). Medication adherence, assessed via self-reports and pill counts, was excellent (98%). Exploratory analyses showed reductions in cigarettes per day, though point prevalence abstinence at the end of the study was low., Conclusions: These preliminary data provide the first demonstration of safety and feasibility of the co-administration of NAC and VAR in cigarette smokers. AEs were consistent with those typically reported for VAR and NAC. These data support future efficacy research on NAC and VAR for smoking cessation.

Background and Objectives: Tobacco and cannabis use are both highly prevalent worldwide. Their co-use is also common in adults and adolescents. Despite this frequent co-occurrence, cessation from both substances is rarely addressed in randomized clinical trials. Given evidence that tobacco use may increase during cannabis cessation attempts, and additionally that tobacco users have poorer cannabis cessation outcomes, we explored tobacco outcomes, specifically cigarette smoking, from an adolescent cannabis cessation trial that tested the efficacy of N-acetylesteine (NAC)., Methods: Cannabis-dependent adolescents (ages 15-21; n = 116) interested in cannabis treatment were randomized to NAC (1200 mg bid) or matched placebo for 8 weeks. Participants did not need to be cigarette smokers or be interested in smoking cessation to qualify for inclusion., Results: Approximately 59% of enrolled participants were daily and non-daily cigarette smokers, and only differed from non-smoking participants on the compulsion sub-scale of the Marijuana Craving Questionnaire. Among cigarette smokers who were retained in the study, there was no change in cigarettes per day for either NAC or placebo groups during the eight-week treatment phase. Being a cigarette smoker did not appear to influence the effects of NAC on cannabis abstinence, though there was a trend in the placebo group of poorer cannabis outcomes for cigarette smokers vs. non-smokers., Conclusions: No evidence was found of compensatory cigarette smoking during this cannabis cessation trial in adolescents. Further work assessing interventions to reduce both cannabis and tobacco use in this population is greatly needed.

Preliminary evidence, within both adults and adolescents, suggests that the intensity with which cigarettes are smoked (i.e., smoking topography) is predictive of success during a cessation attempt. These reports have also shown topography to be superior compared to other variables, such as cigarettes per day, in the prediction of abstinence. The possibility that gender may influence this predictive relationship has not been evaluated but may be clinically useful in tailoring gender-specific interventions. Within the context of a clinical trial for smoking cessation among women, adult daily smokers completed a laboratory session that included a 1-hour ad libitum smoking period in which measures of topography were collected (N=135). Participants were then randomized to active medication (nicotine patch vs. varenicline) and abstinence was monitored for 4weeks. Among all smoking topography measures and all abstinence outcomes, a moderate association was found between longer puff duration and greater puff volume and continued smoking during the active 4-week treatment phase, but only within the nicotine patch group. Based on the weak topography-abstinence relationship among female smokers found in the current study, future studies should focus on explicit gender comparisons to examine if these associations are specific to or more robust in male smokers., (© 2013 Elsevier Ltd. All rights reserved.)

Introduction Females, versus males, have shown a slower decline in smoking prevalence, greater smoking-related mortality and morbidity, and tend to have more difficulty achieving and maintaining abstinence. Identifying sex-specific risk factors is needed to improve outcomes. Though ovarian hormones have been evaluated for their role in smoking and relapse, measures tend to be static and infrequent, failing to capture the influence of increasing or decreasing levels. Aims and Methods The present study evaluated the effect of static and fluctuating levels of ovarian hormones (ie, progesterone, estradiol, and estrogen to progesterone [E/P] ratio) on stress reactivity, cigarette craving, and smoking during a laboratory relapse paradigm. Female participants (assigned female at birth) reporting daily cigarette smoking (N  = 91, ages 18–45) were recruited from the community. Participants provided daily salivary ovarian hormone levels leading up to a laboratory session, in which stress was induced and stress reactivity, cigarette craving, latency to smoke, and ad-libitum smoking were measured. Results Static levels of estradiol were associated with stress reactivity (β  = 0.28, SE = 0.13) and static E/P ratio was associated with smoking in the laboratory (HR = 1.4). Preceding 3-day changes in estradiol and E/P ratio, but neither static levels nor preceding 3-day changes in progesterone were associated with stress reactivity, cigarette craving, or smoking in a relapse paradigm. Conclusions Ovarian hormones are among several sex-specific factors involved in the complex neuroendocrine response to stress, and their interaction with other biological, social, and psychological factors in the real-world environment is not yet fully understood. Implications Findings of the present study provide novel information regarding the role of ovarian hormones among female participants who smoke daily in stress reactivity and smoking in the context of a laboratory relapse paradigm and highlight several avenues for future research. We found that same-day estradiol levels were associated with increased subjective stress reactivity and same-day estrogen to progesterone ratio was associated with increased likelihood of smoking in a relapse paradigm. Ovarian hormones are among several sex-specific factors contributing to the complex neuroendocrine response to stress, and their interaction with other biological, social, and psychological factors in the real-world environment is not yet fully understood. [ABSTRACT FROM AUTHOR]

Background: Understanding the relationship between tobacco use and symptom burden may inform tobacco treatment interventions tailored to the needs of individuals with cancer. Methods: The study included 1409 adult cancer survivors from Wave 5 of the US Food and Drug Administration Population Assessment of Tobacco and Health (PATH) Study. A multivariate analysis of variance controlling for age, sex, and race/ethnicity assessed the association of cigarette smoking and vaping on cancer‐related symptom burden (fatigue, pain, emotional problems) and quality of life (QoL). Generalized linear mixed models controlling for the same factors were used to assess associations among symptom burden, QoL, and quit‐smoking intentions, quit‐smoking likelihood, and past 12‐month smoking quit attempts. Results: Weighted rates of current cigarette smoking and vaping were 14.21% and 2.88%, respectively. Current smoking was associated with greater fatigue (p <.0001; partial η2 =.02), pain (p <.0001; partial η2 =.08), emotional problems (p <.0001; partial η2 =.02), and worse QoL (p <.0001; partial η2 =.08). Current vaping was associated with greater fatigue (p =.001; partial η2 =.008), pain (p =.009; partial η2 =.005), and emotional problems (p =.04; partial η2 =.003), but not worse QoL (p =.17). Higher cancer symptom burden was not associated with reduced interest in quitting, likelihood of quitting, or odds of past year quit attempts (p >.05 for each). Conclusions: Among adults with cancer, current smoking and vaping were associated with greater symptom burden. Survivors' interest in and intentions to quit smoking were not related to symptom burden. Future research should examine the role of tobacco cessation in improving symptom burden and QoL. Among adults with cancer, current smoking and current vaping were associated with greater symptom burden, but interest in and intentions to quit smoking were not related to symptom burden or quality of life. Future research should examine the role of tobacco cessation in improving symptom burden and quality of life. [ABSTRACT FROM AUTHOR]

Despite advances in prevention and treatment, cigarette smoking remains a leading cause of preventable death in the United States. Although men and women are equally likely to attempt to quit smoking cigarettes, women are far less likely to achieve abstinence both during and following cessation treatment. Recent evidence suggests that ovarian hormone levels may play a role in successful abstinence attempts in women smokers. The primary goal of this exploratory prospective observational study was to estimate the association between within-participant levels of progesterone and estradiol with associated cigarettes smoked per day in adult women smokers (n = 104). The primary study outcome was self-reported cigarettes smoked per day (CPD) during a 2-week observational period collected using a daily smoking diary. Additionally, participants collected saliva daily, from which hormone levels (progesterone and estradiol) were derived. Higher within-participant progesterone levels were associated with a significant decrease in CPD (p = .008) whereas within-participant estradiol levels were unrelated to CPD (p = .25). Regression models indicated a single change in the trajectory of smoking behavior for both within-participant progesterone and estradiol. When progesterone values were below the change point, there was a significant inverse relationship between within-participant progesterone levels and smoking behavior (p = .025) whereas the relationship was attenuated for higher within-participant progesterone levels (p = .59). The effect of estradiol on smoking behavior was not significant when it was either below (p = .92) or above (p = .16) the change point. Higher within-participant levels of progesterone but not estradiol are associated with reduced CPD in nontreatment seeking women smokers. [ABSTRACT FROM AUTHOR]

Introduction: The co-use of cannabis and alcohol among tobacco-using youth is common. Alcohol co-use is associated with worse tobacco cessation outcomes, but results are mixed regarding the impact of cannabis on tobacco outcomes and if co-use leads to increased use of non-treated substances. This secondary analysis from a youth smoking cessation trial aimed to (1) evaluate the impact of cannabis or alcohol co-use on smoking cessation, (2) examine changes in co-use during the trial, and (3) explore secondary effects of varenicline on co-use.Methods: The parent study was a 12-week, randomized clinical trial of varenicline for smoking cessation among youth (ages 14-21, N = 157; Mage = 19, 40% female; 76% White). Daily cigarette, cannabis, and alcohol use data were collected via daily diaries during treatment and Timeline Follow-back for 14 weeks post-treatment.Results: Baseline cannabis co-users (68%) had double the odds of continued cigarette smoking throughout the trial compared with noncannabis users, which was pronounced in males and frequent cannabis users. Continued smoking during treatment was associated with higher probability of concurrent cannabis use. Baseline alcohol co-users (80%) did not have worse smoking outcomes compared with nonalcohol users, but continued smoking was associated with higher probability of concurrent drinking. Varenicline did not affect co-use.Conclusions: Inconsistent with prior literature, results showed that alcohol co-users did not differ in smoking cessation, whereas cannabis co-users had poorer cessation outcomes. Youth tobacco treatment would benefit from added focus on substance co-use, particularly cannabis, but may need to be tailored appropriately to promote cessation.Implications: Among youth cigarette smokers enrolled in a pharmacotherapy evaluation clinical trial, alcohol and/or cannabis co-use was prevalent. The co-use of cannabis affected smoking cessation outcomes, but more so for males and frequent cannabis users, whereas alcohol co-use did not affect smoking cessation. Reductions in smoking were accompanied by concurrent reductions in alcohol or cannabis use. Substance co-use does not appear to affect all youth smokers in the same manner and treatment strategies may need to be tailored appropriately for those with lower odds of smoking cessation. [ABSTRACT FROM AUTHOR]

Introduction: The Intolerance for Smoking Abstinence Discomfort Questionnaire (IDQ-S) assesses distress tolerance specific to nicotine withdrawal. Though developed to assess withdrawal-related distress, the IDQ-S has not been validated among nicotine-deprived, treatment-seeking smokers. The present study extended previous research by examining the predictive utility of the IDQ-S among abstinent, motivated-to-quit smokers.Methods: Abstinent, treatment-seeking smokers completed the IDQ-S Withdrawal Intolerance and Lack of Cognitive Coping scales, assessments of nicotine dependence and reinforcement, and smoking history at baseline. At baseline and at 24-h, 2-week, and 1-month follow-up, participants completed a smoking cue-reactivity task (collection of cue-elicited craving and negative affect), and assessments of cigarettes per day (CPD; daily diaries at follow-up), carbon monoxide (CO), and cotinine.Results: Greater IDQ-S Withdrawal Intolerance was associated with younger age, higher nicotine dependence and reinforcement, and less smoking years (ps < .03). Greater IDQ-S Lack of Cognitive Coping was associated with less education, lower nicotine dependence and reinforcement, higher baseline CPD, and no prior quit attempts (ps < .04). IDQ-S scales did not significantly predict cue-elicited craving or negative affect, CPD, CO, or cotinine levels at follow-up (ps > .10).Conclusions: Withdrawal intolerance and lack of cognitive coping did not predict smoking outcomes among nicotine-deprived, treatment-seeking smokers, but were associated with smoking characteristics, including nicotine dependence and reinforcement. Withdrawal intolerance and lack of cognitive coping may not be especially useful in predicting craving and smoking behavior, but future studies should replicate the present study's findings and assess the stability of the IDQ-S before forming firm conclusions about its predictive utility. [ABSTRACT FROM AUTHOR]

Introduction: Despite the public health relevance of smoking in adolescents and emerging adults, this group remains understudied and underserved. High technology utilisation among this group may be harnessed as a tool for better understanding of smoking, yet little is known regarding the acceptability of mobile health (mHealth) integration.Methods: Participants (ages 14–21 years) enrolled in a smoking cessation clinical trial provided feedback on their technology utilisation, perceptions, and attitudes; and interest in remote monitoring for smoking. Characteristics that predicted greater technology acceptability for smoking treatment were also explored.Results: Participants (N = 87) averaged 19 years old and were mostly male (67%). Technology utilisation was high for smart phone ownership (93%), Internet use (98%), and social media use (94%). Despite this, only one-third of participants had ever searched the Internet for cessation tips or counselling (33%). Participants showed interest in mHealth-enabled treatment (48%) and felt that it could be somewhat helpful (83%). Heavier smokers had more favourable attitudes toward technology-based treatment, as did those with smartphones and unlimited data.Conclusions: Our results demonstrate high technology utilisation, favourable attitudes towards technology, and minimal concerns. Technology integration among this population should be pursued, though in a tailored fashion, to accomplish the goal of providing maximally effective, just-in-time interventions. [ABSTRACT FROM PUBLISHER]

Abstract: Introduction: Tobacco use often starts in adolescence, yet assessment of dependence among adolescent smokers remains a challenge, particularly given the potential discord between self-reports of smoking behavior and actual use. We could find no prior study, among adolescents, that directly compares the association between objective biomarkers of tobacco exposure (e.g., cotinine) and multiple measures of dependence. This study examined the concurrent validity of two common dependence measures: the Fagerström Test for Nicotine Dependence (FTND) and the Hooked on Nicotine Checklist (HONC). We further examined the FTND by removing the one item on cigarettes smoked per day. Methods: Based within a parent clinical trial for adolescent smoking cessation, eligible participants were 12–21years old, smoking ≥5cigarettes per day on average, and with urine cotinine >100ng/ml at baseline. Results are based on participants who completed each measure and who provided a urine cotinine sample at baseline (N=73). Results: Results showed that the FTND was associated with cotinine (p<0.001; R2 =0.25), and that this relationship held true for the revised FTND as well (p<0.001; R2 =0.18). However, the HONC was only marginally associated with cotinine (p=0.06; R2 =0.09). Discussion: Our results suggest that the FTND may be better associated with actual smoking behavior in adolescents as compared to the HONC. Pending replication, our data provide caution with regard to assessment of nicotine dependence at least among established adolescent smokers who have more entrenched smoking behavior. [ABSTRACT FROM AUTHOR]

Abstract: There is a significant need for evidence-based treatments for adolescent smoking cessation. Prior research, although limited, has suggested potential roles for bupropion sustained-release (SR) and contingency management (CM), but no previous studies have assessed their combined effect. In a double-blind, placebo-controlled design, 134 adolescent smokers were randomized to receive a 6-week course of bupropion SR + CM, bupropion SR + non-CM, placebo + CM, or placebo + non-CM, with final follow-up at 12 weeks. The primary outcome was 7-day cotinine-verified point prevalence abstinence, allowing for a 2-week grace period. Combined bupropion SR + CM treatment yielded significantly superior abstinence rates during active treatment when compared with placebo + non-CM treatment. In addition, combined treatment showed greater efficacy at multiple time points than did either bupropion SR + non-CM or placebo + CM treatment. Combined bupropion SR and CM appears efficacious, at least in the short-term, for adolescent smoking cessation and may be superior to either intervention alone. [ABSTRACT FROM AUTHOR]

• We examined the effect of sex, childhood adversity, and oxytocin on stress responses in smokers. • The relation between childhood adversity and stress reactivity was differentially affected by sex. • Stress-reducing oxytocin effects were more pronounced in male smokers with childhood adversity. Adverse childhood experiences (ACE) are associated with greater neuroendocrine responses to social stress in substance users. The neuropeptide oxytocin might attenuate this relationship. Given sex differences in ACE exposure and neuroendocrine stress reactivity, it is unknown whether this association is similar for males and females. Therefore, this secondary analysis evaluated the interactive effect of sex, ACE, and acute oxytocin administration on neuroendocrine stress responses in adult cigarette smokers (N = 144). Participants completed the Adverse Childhood Experiences Questionnaire at screening and were randomized to receive intranasal oxytocin or placebo before undergoing the Trier Social Stress Task (TSST). Cortisol levels were assessed at pre- and post-medication administration and at 20 and 40 min following the TSST. Generalized linear mixed models were developed to predict post-TSST cortisol levels. Predictors included treatment assignment (placebo vs. oxytocin), sex (male vs. female), ACE (0–10 total score), pre-medication cortisol levels, and minutes since medication administration. The hypothesized three-way interaction between sex, oxytocin, and ACE scores was significant. Linear associations between ACE scores and cortisol reactivity indicated higher ACE scores were associated with attenuated cortisol response in females, regardless of treatment condition. For males, higher ACE scores were associated with heightened cortisol response, an effect that was attenuated by oxytocin. Results indicate that the association between ACE and neuroendocrine reactivity to social stress, as well as the attenuating effect of oxytocin, is differentially impacted by sex. Males with greater childhood adversity may be more likely to benefit from oxytocin's anxiolytic properties. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]