Menstrual cycle phase effects in the gender dimorphic stress cue reactivity of smokers.

INTRODUCTION: We previously reported that female smokers evidence greater subjective craving and stress/emotional reactivity to personalized stress cues than males. The present study employed the same dataset to assess whether females in the follicular versus luteal phase of the menstrual cycle accounted for the gender differences. METHODS: Two objective criteria, onset of menses and luteinizing hormone surge (evaluated via home testing kits), were used to determine whether female smokers were in either the follicular (n = 22) or the luteal (n = 15) phase of their menstrual cycle, respectively. The females and a sample of male smokers (n = 53) were then administered a laboratory-based cue reactivity paradigm that involved assessment of craving, stress, and emotional reactivity in response to counterbalanced presentations of both a personalized stress script and neutral/relaxed script. RESULTS: While there were no significant differences between females in the follicular versus luteal phase on any outcome measure, females in the luteal menstrual phase reported greater craving than males whereas females in the follicular phase reported greater stress and arousal than males and perceived the stress cues as more emotionally aversive than males. CONCLUSIONS: This preliminary investigation suggests that gender differences in craving versus affective responding to stress cues may, in part, be explained variation by menstrual cycle phase. Study limitations and implications of the findings for future research and treatment are briefly discussed.

Executive function in adults with attention-deficit/hyperactivity disorder during treatment with atomoxetine in a randomized, placebo-controlled, withdrawal study.

We assessed the executive function in adults with attention-deficit/hyperactivity disorder (ADHD) during atomoxetine treatment in a randomized withdrawal trial. Responders (Conners' ADHD Rating Scale-Investigator Rated: Screening Version [adult prompts] ≥30% reduction from baseline and Clinical Global Impression Scale-ADHD Severity score ≤3) to open-label atomoxetine (40-100 mg/d, 12 weeks) entered a 37-week double-blind maintenance period. Patients who maintained response (double-blind atomoxetine for 12 weeks) were randomized 1:1 to atomoxetine (80-100 mg/d, n = 266) or placebo (n = 258) for 25 weeks (total duration, 1 year). Patients and investigators were blinded to response criteria and randomization timing. Change in executive function was assessed with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report and Informant T scores from the randomization to the last-observation-carried-forward postrandomization week 25 (after week 17). Of the enrolled patients (n = 2017; mean age, 33.2 years; male, 58.7%), 524 responders were randomized. During open-label atomoxetine, subscales and individual items on both BRIEF-A questionnaires showed significant improvement (P < 0.001). After randomization, the following T scores improved significantly (P ≤ 0.05) with patients in the atomoxetine group versus those in the placebo group: global executive composite, behavioral regulation, and metacognition indices; plan/organize, working memory, inhibit, task monitor and shift (both BRIEF-A questionnaires), emotional control and organization of materials (BRIEF-A Informant), and initiate (BRIEF-A Self-Report). Atomoxetine significantly improved the executive function compared with placebo, which was maintained for 25 weeks or more; the executive function of patients in the placebo group worsened but did not return to baseline levels after randomization.

Craving, cue reactivity, and stimulus control among early-stage young smokers: effects of smoking intensity and gender.

INTRODUCTION: Smoking initiation usually begins in adolescence, but how and for whom nicotine dependence emerges during this period is unclear. The cue-reactivity paradigm is well suited to examine one marker of dependence: craving-related stimulus control, i.e., the ability of environmental cues to elicit craving to smoke. This study examined the effects of both level of smoking involvement (daily vs. occasional smoking) and gender on reactivity to both smoking and alcohol cues. METHODS: Young (age range 16-20; 42% female) daily (n = 55) and occasional (n = 52) smokers were exposed to each of three counterbalanced cues: (a) in vivo smoking (e.g., sight, smell, lighting of cigarette), (b) alcohol (e.g., opening, pouring, and smell of preferred beverage), and (c) neutral cue. RESULTS: Daily smokers exhibited higher levels of tonic (i.e., noncue-elicited) craving than did occasional smokers. Both groups showed significant increases in craving in response to cues (i.e., cue-elicited craving), with little evidence that cue-elicited craving differed between groups. Females were more cue reactive to both the alcohol and smoking cues than males, particularly for the positively reinforced aspects of smoking (i.e., hedonic craving). There were no gender × group interaction effects in response to either the alcohol or the smoking cue. CONCLUSIONS: Findings show the presence of cue-elicited craving even among occasional smokers and are consistent with literature demonstrating heightened sensitivity to environmental cues among females. Cue-elicited craving may be one mechanism that contributes to the maintenance of smoking behavior and perhaps to the development of nicotine dependence within early stage smokers.

Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial.

INTRODUCTION: Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. METHODS: In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (n = 14) and BAM + ETE (n = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (N = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. RESULTS: The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. CONCLUSION: WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19. TRIAL REGISTRATION NUMBER: NCT04427501.

Varenicline versus bupropion XL for smoking cessation in older adolescents: a randomized, double-blind pilot trial.

INTRODUCTION: Despite tremendous potential public health impact, little work has focused on development of evidence-based smoking cessation treatments for adolescents, including pharmacotherapies. No prior studies have explored the feasibility and safety of varenicline and bupropion XL, 2 potentially promising pharmacotherapies, as smoking cessation treatments in adolescents. METHODS: Treatment-seeking older adolescent smokers (ages 15-20) were randomized (double-blind) to varenicline (n = 15) or bupropion XL (n = 14), with 1-week titration and active treatment for 7 weeks. Structured safety, tolerability, and efficacy assessments (cotinine-confirmed 7-day point prevalence abstinence) were conducted weekly. RESULTS: There were no serious adverse events. Two participants discontinued bupropion XL due to adverse effects, and none discontinued varenicline. Over the course of treatment, participants receiving varenicline reduced from 14.1 ± 6.3 (mean ± SD) to 0.9 ± 2.1 cigarettes/day (CPD, 4 achieved abstinence), while those receiving bupropion XL reduced from 15.8 ± 4.4 to 3.1 ± 4.0 CPD (2 achieved abstinence). CONCLUSIONS: These preliminary results support the feasibility and safety of conducting adequately powered, placebo-controlled efficacy studies of varenicline and bupropion XL for adolescent smoking cessation.

Gender differences in craving and cue reactivity to smoking and negative affect/stress cues.

There is evidence that women may be less successful when attempting to quit smoking than men. One potential contributory cause of this gender difference is differential craving and stress reactivity to smoking- and negative affect/stress-related cues. The present human laboratory study investigated the effects of gender on reactivity to smoking and negative affect/stress cues by exposing nicotine dependent women (n = 37) and men (n = 53) smokers to two active cue types, each with an associated control cue: (1) in vivo smoking cues and in vivo neutral control cues, and (2) imagery-based negative affect/stress script and a neutral/relaxing control script. Both before and after each cue/script, participants provided subjective reports of smoking-related craving and affective reactions. Heart rate (HR) and skin conductance (SC) responses were also measured. Results indicated that participants reported greater craving and SC in response to smoking versus neutral cues and greater subjective stress in response to the negative affect/stress versus neutral/relaxing script. With respect to gender differences, women evidenced greater craving, stress and arousal ratings and lower valence ratings (greater negative emotion) in response to the negative affect/stressful script. While there were no gender differences in responses to smoking cues, women trended towards higher arousal ratings. Implications of the findings for treatment and tobacco-related morbidity and mortality are discussed.

Menstrual cycle and cue reactivity in women smokers.

INTRODUCTION: Emerging research suggests potential effects of the menstrual cycle on various aspects of smoking behavior in women, but results to date have been mixed. The present study sought to explore the influence of menstrual cycle phase on reactivity to smoking in vivo and stressful imagery cues in a sample of non-treatment-seeking women smokers. METHODS: Via a within-subjects design, nicotine-dependent women (N = 37) participated in a series of four cue reactivity sessions, each during a distinct biologically verified phase of the menstrual cycle (early follicular [EF], mid-follicular [MF], mid-luteal [ML], and late luteal [LL]). Subjective (Questionnaire of Smoking Urges-Brief; QSU-B) and physiological (skin conductance and heart rate) measures of craving and reactivity were collected and compared across phases. RESULTS: Subjective reactive craving (QSU-B) to smoking in vivo cues varied significantly across the menstrual cycle (p = .02) and was higher in both EF and MF phases versus ML and LL phases, but this finding was not sustained when controlling for reactivity to neutral cues. Heart rate reactivity to stressful imagery cues (p = .01) and skin conductance reactivity to smoking in vivo cues (p = .05) varied significantly across the menstrual cycle upon controlling for reactivity to neutral cues, with highest reactivity during the MF phase. DISCUSSION: Menstrual cycle phase may have an effect on reactivity to smoking-related and stressful cues among women smokers. These findings contribute to an expanding literature, suggesting menstrual cycle effects on smoking behaviors in women.

Attention-deficit/hyperactivity disorder confounds nicotine withdrawal self-report in adolescent smokers.

Individuals with attention-deficit/hyperactivity disorder (ADHD) are more likely than those without ADHD to initiate smoking and develop nicotine dependence. Recent research indicates that adults with ADHD experience more severe nicotine withdrawal symptoms than those without ADHD. However, little is known about nicotine withdrawal in adolescent smokers with history of ADHD. Among a sample of 134 nicotine-dependent adolescents entering a smoking cessation research study, participants completed the Minnesota Nicotine Withdrawal Scale (MNWS) and lifetime diagnostic assessment for ADHD during the baseline visit. Responses on individual items and MNWS total score were compared between participants with and without history of ADHD. In addition, correlations between MNWS responses and current ADHD symptoms were investigated among participants with history of ADHD. Forty-eight participants (36%) met lifetime ADHD criteria. Adolescent smokers with history of ADHD scored significantly higher on MNWS than those without history of ADHD. Among participants with history of ADHD, responses on the MNWS difficulty concentrating, restlessness/impatience, and anxiety/nervousness items each correlated positively with several current ADHD symptoms. Treatment-seeking adolescent smokers with history of ADHD are more likely to endorse nicotine withdrawal symptoms than those without history of ADHD. However, it does not appear that the symptoms reported in this sample represent a valid "withdrawal syndrome," particularly because these smokers had not yet formally attempted to quit. Rather, the data likely reflect common features between ADHD and nicotine withdrawal. Smoking research, particularly among adolescents in whom ADHD is so common, should carefully consider the complex issue of comorbid ADHD and nicotine dependence.

Stimulant formulation and motivation for nonmedical use of prescription attention-deficit/hyperactivity disorder medications in a college-aged population.

There is relatively little research examining motives for nonmedical use (NMU) of attention-deficit/hyperactivity disorder (ADHD) medications and predictors of motivation. We present results of a secondary analysis of an Internet-based epidemiological survey to explore the relationship between stimulant formulation and motivation for NMU of ADHD stimulant medications in a college-aged population. Demographic predictors of motivation to engage in NMU were also explored to investigate the potential correlates of recreational versus performance-enhancement motivations. Respondents scoring higher on the Adult ADHD Self-Report Scale were significantly more likely to engage in NMU of ADHD stimulant medications. Those using extended release (ER) stimulant formulations were less likely to endorse "staying awake" as a reason for NMU compared to those using immediate release (IR) stimulant formulations.

Maternal and fetal outcomes following exposure to duloxetine in pregnancy: cohort study.

OBJECTIVE: To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine. DESIGN: Cohort study nested in the Medicaid Analytic eXtract for 2004-13. SETTING: Publicly insured pregnancies in the United States. PARTICIPANTS: Pregnant women 18 to 55 years of age and their liveborn infants. INTERVENTIONS: Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy. MAIN OUTCOME MEASURES: Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage. RESULTS: Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses. CONCLUSIONS: On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient. TRIAL REGISTRATION: EUPAS 15946.

Efficacy and safety of duloxetine versus placebo in adolescents with juvenile fibromyalgia: results from a randomized controlled trial.

BACKGROUND: Currently, there are no medications approved for the treatment of juvenile fibromyalgia (JFM). We evaluated the safety and efficacy of duloxetine 30/60 mg once daily (QD) versus placebo in adolescents with JFM. METHODS: In this Phase 3b, multisite (US, Argentina, Puerto Rico, and India) trial, patients aged 13-17 years with JFM and a score of ≥4 on the Brief Pain Inventory-Modified Short Form: Adolescent Version (BPI) 24-h average pain severity score were randomized to duloxetine or placebo for the 13-week double-blind period. The starting duloxetine dose was 30 mg, with a target dose of 60 mg QD, as tolerated. The primary endpoint was the mean change in 24-h average pain severity of the Brief Pain Inventory (BPI) from baseline to Week 13, analyzed using mixed-model repeated measures (MMRM) technique. Secondary measures were BPI severity and interference scores; treatment response (≥30%, ≥50% reductions on BPI average pain severity); Pediatric Pain Questionnaire; Clinical Global Impression of Severity: Overall and Mental Illness scales; Functional Disability Inventory: child and parent versions; Children's Depression Inventory; Multidimensional Anxiety Scale for Children; and safety and tolerability. Continuous secondary efficacy measures were analyzed using analysis of covariance or MMRM, and categorical data using Cochran-Mantel-Haenszel test and Fisher's exact test, where appropriate. RESULTS: A total of 184 patients with JFM received duloxetine (N = 91) or placebo (N = 93), of which 149 patients (81.0%) completed the 13-week double-blind treatment period. Baseline characteristics were comparable between groups; majority of the patients were Caucasian (77.17%) and females (75.0%), with a mean age of 15.53 years. For the primary measure, BPI average pain severity, the mean change was not statistically different between duloxetine and placebo (- 1.62 vs. -0.97, respectively; p = .052). For secondary efficacy outcomes, statistically significantly more duloxetine- versus placebo-treated patients had a treatment response (≥30% and ≥50% reductions on BPI average pain severity) and improvement of the general activity and relationships items on the BPI interference subscale. The percentage of patients reporting at least 1 treatment-emergent adverse event was higher in the duloxetine versus placebo groups (82.42% vs. 62.37%, respectively; p = .003). The overall safety profile of duloxetine in this study was similar to that reported previously in duloxetine pediatric trials of other indications. CONCLUSIONS: The primary study outcome, mean change in 24-h BPI average pain severity rating from baseline to Week 13, did not significantly improve with duloxetine compared to placebo in patients with JFM. However, significantly more patients on duloxetine compared to placebo had a ≥30% and ≥50% reduction in pain severity. There were no new safety concerns related to duloxetine in the study population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01237587 . Registered 08 November, /2010.

Effects of gender and cigarette smoking on reactivity to psychological and pharmacological stress provocation.

We examined the influence of gender and smoking status on reactivity in two human laboratory stress paradigms. Participants were 46 (21 men, 25 women) healthy individuals who completed the Trier Social Stress Task (i.e., performed speech and math calculations in front of an audience) and a pharmacological stress provocation (i.e., administration of corticotrophin releasing hormone (CRH)) after an overnight hospital stay. Approximately half (53%) of the participants were smokers. Cortisol, adrenocorticotrophin hormone (ACTH), physiologic measures (heart rate, blood pressure), and subjective stress were assessed at baseline and at several time points post-task. Men demonstrated higher baseline ACTH and blood pressure as compared to women; however, ACTH and blood pressure responses were more pronounced in women. Women smokers evidenced a more blunted cortisol response as compared to non-smoking women, whereas smoking status did not affect the cortisol response in men. Finally, there was a more robust cardiovascular and subjective response to the Trier as compared to the CRH. Although preliminary, the findings suggest that women may be more sensitive than men to the impact of cigarette smoking on cortisol response. In addition, there is some evidence for a more robust neuroendocrine and physiologic response to acute laboratory stress in women as compared to men.

Menstrual phase effects on smoking cessation: a pilot feasibility study.

BACKGROUND AND OBJECTIVES: A growing body of research suggests that nicotine withdrawal and cigarette craving may vary across the menstrual cycle and that the luteal phase of the cycle may be associated with increases in each. This potential relationship suggests that careful timing of quit attempts during the menstrual cycle may improve initial success at abstinence, although there are no direct tests of this approach yet published. Our objectives were to preliminarily test the effect of timing of quit attempts for smoking cessation relative to menstrual cycle and to identify methodological procedures that could guide subsequent, larger clinical trials. METHODS: In this pilot study, we randomized female smokers aged 18-40 who were not currently using hormonal contraception to quit smoking during either the follicular (n = 25) or luteal phase (n = 19) of their menstrual cycle. Participants were provided with two sessions of smoking cessation counseling (90 minutes total). All participants were provided with a transdermal nicotine patch contingent on maintenance of abstinence throughout the course of the 6-week study. RESULTS: Among participants who initiated treatment, received the patch, and made a quit attempt (n = 35), carbon monoxide-verified repeated point prevalence abstinence 2 weeks after the target quit date was higher in the follicular than the luteal group (32% vs. 19%, respectively; OR = 2.0, 95% CI = 0.4-9.8). Within the overall study population, this difference was slightly lower (24% vs. 16%; OR = 1.7, 95% CI = 0.4-7.8). CONCLUSIONS: Timing quit attempts based on menstrual phase is feasible. Insights gained from this study and the recommendations made herein may inform future research on this important clinical question.

Tolerability and effects of oral Delta9-tetrahydrocannabinol in older adolescents with marijuana use disorders.

OBJECTIVE: The tolerability and effects of oral Delta9-tetrahydrocannabinol (THC) have been previously investigated in adult marijuana abusers. However, no studies have included adolescent participants. This double-blind laboratory study investigated the tolerability and effects of oral THC in a group of older adolescents with marijuana use disorders. METHODS: Eight participants (ages 16-21 years), smoking an average of 5.2 days/week and 2.5 "joints"/day, completed this four-session study, during which they received one of four oral THC doses (0, 2.5, 5, 10 mg) each session. Administration of oral THC doses was counterbalanced across participants. During each session, participants completed the Digit-Symbol Substitution Task (DSST) and subjective-effect ratings at baseline and 1, 2, and 3 h after oral THC administration. RESULTS: Oral THC (5 mg and 10 mg) increased several "positive" subjective-effect ratings (e.g., "Good Drug Effect"), while producing no significant effects on cardiovascular measures, DSST performance, or "negative" subjective-effect ratings. CONCLUSIONS: These results indicate that oral THC was well tolerated and suggest further study of this medication in adolescent marijuana abusers.

Substance use disorders in children and adolescents with attention-deficit/hyperactivity disorder: implications for treatment and the role of the primary care physician.

OBJECTIVES: Review the association between attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) in children and adolescents. Discuss treatment implications and the role of the primary care physician in the management of this comorbidity. DATA SOURCES: Articles published from 1991 to 2007 were identified through a MEDLINE search using the search terms attention-deficit/hyperactivity disorder and substance use disorder. STUDY SELECTION: Publications cited include reviews of substance use disorders in children and adolescents with ADHD, manuals of diagnostic tests, and 69 studies of substance use disorders in children and adolescents with ADHD. No non-English-language publications were identified. DATA SYNTHESIS: Recent reports identify SUD in a high proportion of respondents with ADHD and ADHD in a high proportion of respondents with many types of SUD. Factors that appear to increase the risk for SUD include comorbid psychiatric disorders, particularly conduct disorder. Pharmacotherapy for ADHD appears not to increase the risk for subsequent SUD. Guidelines for the evaluation and treatment of patients with comorbid ADHD and SUD are outlined. Psycho-stimulants carry the risk for misuse by both patients and family members through diversion. Although nonstimulants such as atomoxetine have low abuse potential, they appear to be less efficacious than stimulants. Formulations that have the potential to lower the abuse liability of stimulants are being developed. These include a transdermal form of methylphenidate that has been shown to be efficacious in the treatment of ADHD and a prodrug stimulant, lisdexamfetamine, recently approved for the treatment of ADHD. Clinical data indicate that lisdexamfetamine is efficacious, and significantly lower likability scores were seen with lisdexamfetamine than with equivalent oral doses of d-amphetamine sulfate. CONCLUSIONS: Pharmacotherapy may reduce the risk for SUD in patients with ADHD. Psycho-stimulants remain the first-line therapy for the core symptoms of ADHD. New formulations of pharmacologic agents with a reduced potential for abuse are being developed.

Is attention deficit hyperactivity disorder (ADHD) symptom severity associated with tobacco use?

Several studies report a strong link between ADHD and tobacco use; however, the nature of this relationship is not entirely clear. We examined the relationship between attention deficit hyperactivity disorder (ADHD) symptoms and tobacco use within a sample of college students. Although tobacco use was the main focus, we also examined alcohol and marijuana use. We examined the association between the number of ADHD symptoms endorsed (severity), and tobacco, alcohol, and marijuana use in a convenience sample of 334 college students in the southeastern United States. Survey data were based on the annual Core Alcohol and Drug Survey for substance use, and the Current Symptom Scale (CSS) for ADHD, conduct disorder (CD), and antisocial personality disorder (ASPD) symptoms. Among ever users of a substance, the number (severity) of current ADHD symptoms, including inattentive and hyperactive symptoms, were significantly associated with the frequency of tobacco and marijuana use in the past month and past year, as well as to the frequency of alcohol use in the past month. The results suggest that the number of ADHD symptoms is proportionally associated with tobacco, alcohol, and marijuana use.

Cue reactivity in young marijuana smokers: a preliminary investigation.

To develop and evaluate the feasibility of a cue reactivity paradigm for young marijuana smokers, the authors set up a laboratory procedure involving neutral and marijuana-related imagery, video, and in vivo cues. Fifteen adolescents and young adults with cannabis use disorders completed the procedure, which included continuous measurement of skin conductance and heart rate. Participants also completed questionnaires regarding marijuana craving before, during, and after cue presentations. Higher levels of craving and skin conductance were observed during marijuana cue presentations. The procedure appears to elicit cue reactivity among adolescents and young adults with cannabis use disorders and should be further evaluated and refined with a larger sample. Implications for future studies are discussed.

Evaluation of dystonia in children and adolescents treated with atomoxetine within the Truven MarketScan database: a retrospective cohort study.

OBJECTIVE: Atomoxetine is a non-stimulant drug indicated for the treatment of attention-deficit/hyperactivity disorder in children aged ≥6 years, adolescents, and adults. In this retrospective cohort study, the incidence and risk of dystonia in children and adolescents treated with atomoxetine was compared to a propensity score-matched cohort of stimulant users. METHODS: Data between 1 January 2006 and 31 December 2014 from patients aged 6-17 years in the Truven Health Analytics MarketScan database were used to generate two cohorts of patients: (1) atomoxetine users and (2) stimulant (methylphenidates or amphetamines) users. A Cox proportional hazards regression model was used to compare incidence of dystonia across propensity score-matched cohorts. RESULTS: Of the 70,657 atomoxetine users, 70,655 users were propensity score-matched to a stimulant user. In the atomoxetine- and stimulant-treated cohorts, the crude incidence rates of dystonia were 54.9 (95% CI: 27.1-82.7) and 77.9 (95% CI: 49.1-106.8) per 100,000 person-years, respectively. The hazard ratio for occurrence of dystonia with atomoxetine use relative to stimulant use was 0.68 (95% CI: 0.36 - 1.28; P = 0.23). CONCLUSION: In this large retrospective cohort study, there was no significant difference in incidence or risk of dystonia among patients treated with atomoxetine compared to stimulants.

Reactivity to nicotine cues over repeated cue reactivity sessions.

The present study investigated whether reactivity to nicotine-related cues would attenuate across four experimental sessions held 1 week apart. Participants were nineteen non-treatment seeking, nicotine-dependent males. Cue reactivity sessions were performed in an outpatient research center using in vivo cues consisting of standardized smoking-related paraphernalia (e.g., cigarettes) and neutral comparison paraphernalia (e.g., pencils). Craving ratings were collected before and after both cue presentations while physiological measures (heart rate, skin conductance) were collected before and during the cue presentations. Although craving levels decreased across sessions, smoking-related cues consistently evoked significantly greater increases in craving relative to neutral cues over all four experimental sessions. Skin conductance was higher in response to smoking cues, though this effect was not as robust as that observed for craving. Results suggest that, under the described experimental parameters, craving can be reliably elicited over repeated cue reactivity sessions.

Daily stressor sensitivity, abuse effects, and cocaine use in cocaine dependence.

This study highlights respondent sensitivity to daily hassles as it relates to situational cocaine use and perceived long-term effects of adverse events in childhood. Data were drawn from a larger study on stress reactivity in cocaine dependent individuals. Participants (n=104) were cocaine dependent men and women without comorbid posttraumatic stress disorder (PTSD). They completed the Early Trauma Inventory (ETI), the Daily Hassles Scale (DHS), the Inventory of Drug-Taking Situations (IDTS), and the Time-Line Follow-Back (TLFB; for 90 days prior to interview). There were no gender differences in the amount or frequency of cocaine use, although the patterns of use differed between male and female users. Overall, there were some associations in the patterns of cocaine use and sensitivity to daily hassles, particularly the use in response to conflict with others. Early negative life events were positively related to response to daily hassles, but current triggers were more relevant. Reactivity to cocaine cues was related to daily hassle sensitivity among women only. Limitations and implications of the findings are discussed.