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Background: Adverse childhood experiences (ACEs) show a graded association with the development of substance use disorders (SUDs) and engagement in risky substance use behaviors. Women are overrepresented among individuals with more severe childhood adversity (≥4 types of ACEs) and may be at particular risk for aberrant substance use. Objectives: To assess the prevalence of ACEs among men and women with cannabis, opioid, cocaine, and tobacco use disorders. Methods: Non-treatment-seeking individuals participating in clinical addiction research at a single site completed the ACE questionnaire and provided a detailed substance use history. Data were analyzed using proportional odds models and logistic regression. Results: Most participants (424/565; 75%) reported at least one ACE, and more than one-quarter (156/565; 27%) reported severe childhood adversity. Relative to men (n = 283), women (n = 282) reported more ACEs (OR = 1.49; p =.01) and more experiences of emotional/physical abuse (OR = 1.52; p =.02), sexual abuse (OR = 4.08; p =.04), and neglect (OR = 2.30; p <.01). Participants in the cocaine (OR = 1.87; n =.01) and opioid (OR = 2.21; p =.01) use disorder, but not cannabis use disorder (OR = 1.46; p =.08), studies reported more severe adversity relative to the tobacco group. Relative to tobacco users, emotional/physical abuse (OR = 1.92; p =.02) and neglect (OR = 2.46; p =.01) scores were higher in cocaine users and household dysfunction scores were higher in opioid users (OR = 2.67; p =.01). Conclusion: The prevalence of ACEs differs with respect to both participant gender and primary substance used. Novel SUD treatment strategies that incorporate ACEs may be uniquely beneficial in specific subpopulations of people with SUDs. [ABSTRACT FROM AUTHOR]

Background: Cannabis use disorder (CUD) is a common condition with few treatments. Several studies in other substance use disorders have found that applying repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) decreases cue-elicited craving and possibly decreases use. To date, there have been no studies attempting to use rTMS in CUD.Objectives: This study was conducted to determine if rTMS could be feasibly delivered to a group of non-treatment seeking CUD participants. Secondarily, the study aimed to estimate the effect of rTMS on craving.Methods: In a double-blind, sham-controlled, crossover design, a single session of active or sham rTMS (Left DLPFC, 10 Hz, 110% rMT, 4000 pulses) was delivered during a validated cannabis cue paradigm. Participants crossed over to complete the other condition one week later. The feasibility and tolerability were measured by the rate of retention, and the percentage of participants able to tolerate full dose rTMS, respectively. Craving was measured using the Marijuana Craving Questionnaire (MCQ).Results: Eighteen non-treatment seeking CUD participants were recruited from the community; 16 (three women) completed the trial (89% retained for the three study visits). All of the treatment completers tolerated rTMS at full dose without adverse effects. There was not a significant reduction in the total MCQ when participants received active rTMS as compared to sham rTMS.Conclusion: rTMS can be safely and feasibly delivered to CUD participants, and treatment is well tolerated. A single session of rTMS applied to the DLPFC may not reduce cue-elicited craving in heavy cannabis users. [ABSTRACT FROM AUTHOR]

Background: Stress and drug-paired cues increase drug craving and noradrenergic activity in cocaine-dependent individuals. Thus, medications that attenuate noradrenergic activity may be effective therapeutic treatment options for cocaine-dependent individuals. Objectives: To examine the impact of acute administration of the α2 adrenergic receptor agonist guanfacine on responses to multiple risk factors for relapse in cocaine-dependent individuals. Methods: In a double-blind, placebo-controlled study, cocaine-dependent individuals ( n = 84), were randomized to receive either 2 mg guanfacine ( n = 50) or placebo ( n = 34). Within each treatment arm, subjects were randomized to either a stress (guanfacine n = 26; placebo n = 15) or a no-stress (guanfacine n = 24; placebo n = 19) group. Participants in the stress group performed the Trier Social Stress Test. Subjects in each group were exposed to a neutral cue and then to cocaine-related cues. Plasma cortisol and subjective responses were compared between the four groups. Results: The no-stress guanfacine group reported greater craving in response to cocaine cues as compared to the neutral cue ( p < 0.001). The guanfacine stress group reported greater subjective stress at the neutral cue than at baseline ( p = 0.032). The cocaine cue increased subjective stress in the guanfacine ( p < 0.001) no-stress group. There were no effects of guanfacine on cortisol levels in either the stress or no stress groups (all p > 0.70). Conclusion: This study found no effects of a single 2 mg dose of guanfacine on reactivity to stress and cues alone or on the interaction of stress and drug cues. In cocaine-dependent individuals an acute 2 mg dose of guanfacine may not be an effective therapeutic treatment strategy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Chronic methamphetamine abuse is associated with cognitive deficits that may impede treatment in methamphetamine-dependent patients. Exposure to methamphetamine-related cues can elicit intense craving in chronic users of the drug, but the effects of exposure to drug cues on cognitive performance in these individuals are unknown. Objectives: This study assessed whether exposure to methamphetamine-related visual cues can elicit craving and/or alter dual task cognitive performance in 30 methamphetamine-dependent subjects and 30 control subjects in the laboratory. Methods: Reaction time, response errors, and inhibition errors were assessed on an auditory Go-No Go task performed by adult participants (total N == 60) while watching neutral versus methamphetamine-related video cues. Craving was assessed with the Within-Session Rating Scale modified for methamphetamine-dependent subjects. Results: Exposure to methamphetamine-related cues elicited craving only in methamphetamine-dependent subjects. Even in the absence of methamphetamine cues, methamphetamine-dependent subjects exhibited slower reaction times and higher rates of both inhibition and response errors than control subjects did. Upon exposure to methamphetamine cues, rates of both response errors and inhibition errors increased significantly in methamphetamine-dependent subjects. Control subjects exhibited no increase in inhibition errors and only slightly increased rates of response errors upon exposure to methamphetamine cues. Response error rates, but not inhibition error rates or reaction times, during methamphetamine cue exposure were significantly associated with craving scores in methamphetamine-dependent subjects. Conclusions and Significance: Methamphetamine-dependent individuals exhibit cognitive performance deficits that are more pronounced during exposure to methamphetamine-related cues. Interventions that reduce cue reactivity may have utility in the treatment of methamphetamine dependence. [ABSTRACT FROM AUTHOR]

Objective: Craving for methamphetamine is commonly reported by heavy users of the drug and may increase the risk of relapse in newly abstinent individuals. Exposure to methamphetamine-associated cues in the laboratory can elicit measureable craving and autonomic reactivity in some individuals with methamphetamine dependence. In this study, clinical and demographic correlates of methamphetamine craving and the optimal conditions for its measurement in the laboratory are explored. Methods: Subjective (craving) and physiologic (heart rate and skin conductance) reactivity to presentation of methamphetamine-associated photo, video, and paraphernalia cues were evaluated in 43 subjects with methamphetamine dependence. Association of cue reactivity with demographic and clinical characteristics including duration, frequency, amount, and recency of methamphetamine use were assessed. Results: Craving was reported by fewer than half of subjects at baseline and by approximately 70% of subjects after methamphetamine cue exposure. Relative to baseline, subjective craving was increased by all three cue modalities to a similar extent. In general, physiological cue reactivity correlated poorly with cue-induced craving. Craving at baseline was strongly predictive of cue-induced craving. Differences in cue-induced craving were not associated with age, sex, education, employment, treatment status, or number of days using methamphetamine in the 60 days prior to study entry. In contrast, the degree of baseline craving was strongly associated with employment status and the number of days using methamphetamine in the past 60 days. Conclusions: Cue-induced craving for methamphetamine may be reliably measured in methamphetamine-dependent individuals in the laboratory. Further studies employing the cue reactivity paradigm in methamphetamine dependence are warranted. [ABSTRACT FROM AUTHOR]