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1.  “I Use Weed for My ADHD”: A Qualitative Analysis of Online Forum Discussions on Cannabis Use and ADHD 
PLoS ONE  2016;11(5):e0156614.
Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for problematic cannabis use. However, clinical and anecdotal evidence suggest an increasingly popular perception that cannabis is therapeutic for ADHD, including via online resources. Given that the Internet is increasingly utilized as a source of healthcare information and may influence perceptions, we conducted a qualitative analysis of online forum discussions, also referred to as threads, on the effects of cannabis on ADHD to systematically characterize the content patients and caregivers may encounter about ADHD and cannabis.
A total of 268 separate forum threads were identified. Twenty percent (20%) were randomly selected, which yielded 55 separate forum threads (mean number of individual posts per forum thread = 17.53) scored by three raters (Cohen’s kappa = 0.74). A final sample of 401 posts in these forum threads received at least one endorsement on predetermined topics following qualitative coding procedures.
Twenty-five (25%) percent of individual posts indicated that cannabis is therapeutic for ADHD, as opposed to 8% that it is harmful, 5% that it is both therapeutic and harmful, and 2% that it has no effect on ADHD. This pattern was generally consistent when the year of each post was considered. The greater endorsement of therapeutic versus harmful effects of cannabis did not generalize to mood, other (non-ADHD) psychiatric conditions, or overall domains of daily life. Additional themes emerged (e.g., cannabis being considered sanctioned by healthcare providers).
Despite that there are no clinical recommendations or systematic research supporting the beneficial effects of cannabis use for ADHD, online discussions indicate that cannabis is considered therapeutic for ADHD—this is the first study to identify such a trend. This type of online information could shape ADHD patient and caregiver perceptions, and influence cannabis use and clinical care.
PMCID: PMC4882033  PMID: 27227537
2.  Pharmacotherapy of the Preschool ADHD Treatment Study (PATS) Children Growing Up 
To describe the long-term psychopharmacological treatment of children first diagnosed with attention-deficit/hyperactivity disorder (ADHD) as preschoolers.
In a systematic, prospective, naturalistic follow-up, 206 (68.0%) of the 303 children who participated in the Preschool ADHD Treatment Study (PATS) were reassessed 3 years (mean age 7.4 years), and 179 (59.1%), 6 years (mean age 10.4 years), after completion of the controlled study. Pharmacotherapy and clinical data were obtained from the parents. Pharmacotherapy was defined as use of a specific class of medication for at least 50% of the days in the previous 6 months.
At year 3, 34.0% were on no pharmacotherapy, 41.3% were on stimulant monotherapy, 9.2% on atomoxetine, alone or with a stimulant, 8.3% on an antipsychotic, usually together with a stimulant, and the remaining 7.2% on other pharmacotherapy; overall, 65.0% were on an indicated ADHD medication. At year 6, 26.8% were on no pharmacotherapy, 40.2% were on stimulant monotherapy, 4.5% on atomoxetine, alone or with a stimulant, 13.4% on an antipsychotic, and 15.1% on other pharmacotherapy; overall, 70.9% were on an indicated ADHD medication. Antipsychotic treatment was associated with more comorbidity, in particular disruptive behavior disorders and pervasive development disorders, and a lower level of functioning.
The long-term pharmacotherapy of preschoolers with ADHD was heterogeneous. While stimulant medication continued to be used by most children, about 1 child in 4 was off medication, and about 1 in 10 was on an antipsychotic.
PMCID: PMC4475273  PMID: 26088659
ADHD; preschoolers; medication; stimulant
3.  Monetary Incentives Promote Smoking Abstinence in Adults With Attention Deficit Hyperactivity Disorder (ADHD) 
Individuals with attention deficit hyperactivity disorder (ADHD) smoke at rates significantly higher than the general population and have more difficulty quitting than nondiagnosed individuals. Currently, there are no evidence-based approaches for reducing smoking specifically in individuals with ADHD. Adult regular smokers with or without ADHD participated in a study of extended smoking withdrawal where monetary incentives were used to promote abstinence. Participants were paid according to an escalating schedule for maintaining abstinence measured as self-report of no smoking and an expired air carbon monoxide (CO) level of ≤4 parts per million. Sixty-four percent (14/22) of smokers with ADHD and 50% (11/22) of smokers without ADHD maintained complete abstinence for the 2-week duration of the study. Twenty-two percent (5/22) and 9% (2/22) of smokers with ADHD and without ADHD, respectively, maintained continued abstinence for up to 10 days following the removal of the contingencies. Though abstinence rates were higher for the smokers with ADHD, the group differences were not statistically significant. Results suggest that monetary incentives may be a useful approach for promoting abstinence in adult smokers with ADHD, perhaps owing to altered reinforcement processes in these individuals.
PMCID: PMC3354633  PMID: 20545386
ADHD; smoking; nicotine dependence; contingency management
4.  An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults 
Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10 mg oral doses of delta-9-tetrahydocannibinol (THC); and 0 mg, 10 mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10 mg THC + 0 mg, 10 mg, and 40 mg MPH = 89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of “Feel Drug,” “Good Effects,” and “Take Drug Again.” THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures.
PMCID: PMC4250392  PMID: 25175495
Methylphenidate; Prescription stimulant; Cannabis; Delta-9-tetrahydrocannabinol (THC)
5.  A Randomized Placebo-Controlled Double-Blind Study Evaluating the Time Course of Response to Methylphenidate Hydrochloride Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder 
Objective: The purpose of this study was to assess the time of onset and time course of efficacy over 12.0 hours of extended-release multilayer bead formulation of methylphenidate (MPH-MLR) compared with placebo in children 6–12 years of age with attention-deficit/hyperactivity disorder (ADHD) in a laboratory school setting.
Methods: This randomized double-blind placebo-controlled study included children 6–12 years of age with ADHD. Enrolled children went through four study phases: 1) Screening period (≤4 weeks) and a 2 day medication washout period; 2) open-label period with dose initiation of MPH-MLR 15 mg daily and individual dose optimization treatment period (2–4 weeks); 3) double-blind crossover period in which participants were randomized to sequences (1 week each) of placebo and the optimized MPH-MLR dose given daily; and 4) follow-up safety call. Analog classroom time course evaluations were performed at the end of each double-blind week. The primary efficacy end-point was the mean of the on-treatment/postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)-Total scores over time points collected 1.0–12.0 hours after dosing. End-points were evaluated using a mixed-effects analysis of covariance.
Results: The evaluable population included 20 participants. The least-squares mean postdose SKAMP-Total score was higher for placebo than for MPH-MLR (2.18 vs. 1.32, respectively; p=0.0001), indicating fewer symptoms with MPH-MLR therapy than with placebo. No difference in SKAMP-Total score between participants who received sequence 1 or sequence 2 was noted. From each of hours 1.0–12.0, least-squares mean SKAMP-Total score was significantly lower for those receiving MPH-MLR than for those receiving placebo (p≤0.0261). Neither serious adverse events nor new or unexpected safety findings were noted during the study.
Conclusions: MPH-MLR showed a significant decrease in SKAMP scores compared with placebo in children with ADHD 6–12 years of age, indicating a decrease in ADHD symptoms. The estimated onset was observed within 1.0 hour, and duration was measured to 12.0 hours postdose.
Trial registration: Identifier: NCT01269463
PMCID: PMC4268556  PMID: 25470572
6.  Dasotraline for the Treatment of Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial in Adults 
Neuropsychopharmacology  2015;40(12):2745-2752.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity associated with clinically significant impairment in functioning. ADHD has an early onset, but frequently persists, with a prevalence estimate of 4% in adults. Dasotraline is a novel compound that is a potent inhibitor of dopamine and norepinephrine transporters that achieves stable plasma concentrations with once-daily dosing. In this study, adult outpatients meeting DSM-IV-TR criteria for ADHD were randomized to 4 weeks of double-blind, once-daily treatment with dasotraline 4 and 8 mg/day or placebo. The primary efficacy end point was change from baseline at week 4 in the ADHD Rating Scale, Version IV (ADHD RS-IV) total score. Secondary efficacy end points included the Clinical Global Impression, Severity (CGI-S) scale, modified for ADHD symptoms. Least squares (LS) mean improvements at week 4 in ADHD RS-IV total score were significantly greater for dasotraline 8 mg/day vs placebo (−13.9 vs −9.7; P=0.019), and nonsignificantly greater for 4 mg/day (−12.4; P=0.076). The LS mean improvements in modified CGI-S were significantly greater at week 4 for dasotraline 8 mg/day vs placebo (−1.1 vs −0.7; P=0.013), and for 4 mg/day vs placebo (−1.1 vs −0.7; P=0.021). The most frequent adverse events reported were insomnia, decreased appetite, nausea, and dry mouth. Discontinuations due to treatment-emergent adverse events were 10.3% and 27.8% of patients in 4 and 8 mg/day treatment groups, respectively. This study provides preliminary evidence that once-daily dosing with dasotraline, a long-acting, dual monoamine reuptake inhibitor, may be a safe and efficacious treatment for adult ADHD.
PMCID: PMC4864650  PMID: 25948101
7.  Methylphenidate does not influence smoking-reinforced responding or attentional performance in adult smokers with and without Attention Deficit Hyperactivity Disorder (ADHD) 
Individuals with Attention Deficit Hyperactivity Disorder (ADHD) smoke cigarettes at rates higher than the general population and questions have been raised about how stimulant drugs – the frontline pharmacological treatment for ADHD – influence smoking risk and behavior in those with ADHD. In the present study adult regular smokers with (n=16) and without (n=17) ADHD participated in 3 experimental sessions in which they completed a Progressive Ratio (PR) task to measure the relative reinforcing effects of cigarette smoking and money following oral administration of placebo and 2 active doses of methylphenidate (10 mg and 40 mg). We also measured attention and inhibitory control via a Continuous Performance Test (CPT). Methylphenidate had no effect on smoking-reinforced responding, attention, or inhibitory control in either group. Attention and inhibitory control were associated with smoking-reinforced responding, but unsystematically and only in the non-ADHD group. Several design features, such as the value of the monetary response option, the PR schedule, and the potential effects of smoking on attention and inhibitory control, could have contributed to the negative findings and are discussed as such. Although inconsistent with some previous human laboratory studies of stimulant drugs and smoking, results are consistent with recent trials of stimulant drugs as adjuncts for smoking cessation in adult smokers with ADHD. In general, methylphenidate at mild and moderate doses did not influence the relative reinforcing effects of cigarette smoking in adults with and without ADHD.
PMCID: PMC4145471  PMID: 24099358
9.  A Pilot Study of Lis-Dexamfetamine Dimesylate (LDX/SPD489) to Facilitate Smoking Cessation in Nicotine-Dependent Adults With ADHD 
Journal of attention disorders  2012;18(2):10.1177/1087054712440320.
The goal of this study was to assess the efficacy and tolerability of lis-dexamfetamine dimesylate (LDX) as an adjunct to nicotine replacement therapy in adult smokers with ADHD who were undergoing a quit attempt.
Thirty-two regular adult smokers with ADHD were randomized to receive LDX (n = 17) or placebo (n = 15) in addition to nicotine patch concurrent with a quit attempt.
There were no differences between smokers assigned to LDX versus placebo in any smoking outcomes. Participants treated with LDX demonstrated significant reductions in self-reported and clinician-rated ADHD symptoms. LDX was well tolerated in smokers attempting to quit.
In general, LDX does not facilitate smoking cessation in adults with ADHD more than does placebo, though both groups significantly reduced smoking. LDX demonstrated efficacy for reducing ADHD symptoms in adult smokers engaging in a quit attempt.
PMCID: PMC3421044  PMID: 22508760
adult ADHD; lis-dexamfetamine dimesylate; smoking
10.  A Pilot Trial of Mindfulness Meditation Training for Attention-Deficit/Hyperactivity Disorder in Adulthood: Impact on Core Symptoms, Executive Functioning, and Emotion Dysregulation 
Journal of attention disorders  2013;10.1177/1087054713513328.
Mindfulness meditation training is garnering increasing empirical interest as an intervention for attention-deficit/hyperactivity disorder (ADHD) in adulthood, although no studies of mindfulness as a standalone treatment have included a sample composed entirely of adults with ADHD or a comparison group. The aim of this study was to assess the feasibility, acceptability, and preliminary efficacy of mindfulness meditation for ADHD, executive functioning (EF), and emotion dysregulation symptoms in an adult ADHD sample.
Adults with ADHD were stratified by ADHD medication status and otherwise randomized into an eight-week group-based mindfulness treatment (n=11) or waitlist (n=9) group.
Treatment feasibility and acceptability were positive. In addition, self-reported ADHD and EF symptoms (assessed in the laboratory and ecological momentary assessment), clinician ratings of ADHD and EF symptoms, and self-reported emotion dysregulation improved for the treatment group relative to the waitlist group over time with large effect sizes. Improvement was not observed for EF tasks.
Findings support preliminary treatment efficacy, though require larger trials.
PMCID: PMC4045650  PMID: 24305060
attention-deficit/hyperactivity disorder; adults; mindfulness meditation training; executive functioning; emotion dysregulation; ecological momentary assessment
11.  Stimulant Treatment of ADHD and Cigarette Smoking: A Meta-Analysis 
Pediatrics  2014;133(6):1070-1080.
Individuals with attention-deficit/hyperactivity disorder (ADHD) have a significantly higher risk of cigarette smoking. The nature of the relationship between smoking and psychostimulant medications commonly used to treat ADHD is controversial. Our objective was to examine the relationship between stimulant treatment of ADHD and cigarette smoking by using meta-analysis, and to identify study and sample characteristics that moderate this relationship.
Literature searches on PubMed and PsycInfo databases identified published studies for inclusion. Included studies compared cigarette smoking outcomes for stimulant-treated and untreated ADHD individuals. Seventeen studies met inclusion criteria, and 14 (total n = 2360) contained sufficient statistical information for inclusion in the meta-analysis. Two authors extracted odds ratios or frequencies of smokers in the treatment or nontreatment groups, and coded study characteristics including sample source, percentage of male participants, follow-up length, treatment consistency, type of smoking measure, prospective study, and controlling for comorbidities.
Meta-analysis revealed a significant association between stimulant treatment and lower smoking rates. Meta-regression indicated that effect sizes were larger for studies that used clinical samples, included more women, measured smoking in adolescence rather than adulthood, conceptualized stimulant treatment as consistent over time, and accounted for comorbid conduct disorder.
Nearly all studies were naturalistic, precluding causal inferences. Available data were insufficient to examine additional influences of patient demographics, treatment effectiveness, or other comorbidities. Consistent stimulant treatment of ADHD may reduce smoking risk; the effect was larger in samples with more severe psychopathology. Implications for further research, treatment of ADHD, and smoking prevention are discussed.
PMCID: PMC4531271  PMID: 24819571
ADHD; psychostimulant medication; cigarette smoking; meta-analysis
12.  The Efficacy and Safety of Evekeo, Racemic Amphetamine Sulfate, for Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms: A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled Crossover Laboratory Classroom Study 
Objective: The study goal was to determine the efficacy and safety of an optimal dose of Evekeo, racemic amphetamine sulfate, 1:1 d-amphetamine and l-amphetamine (R-AMPH), compared to placebo in treating children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting.
Methods: A total of 107 children ages 6–12 years were enrolled in this multicenter, dose-optimized, randomized, double-blind, placebo-controlled crossover study. After 8 weeks of open-label dose optimization, 97 subjects were randomized to 2 weeks of double-blind treatment in the sequence of R-AMPH followed by placebo (n=47) or placebo followed by R-AMPH (n=50). Efficacy measures included the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP) administered predose and at 0.75, 2, 4, 6, 8, and 10 hours postdose on 2 laboratory classroom days. Safety assessments included physical examination, chemistry, hematology, vital signs, and treatment-emergent adverse events (TEAEs).
Results: Compared to placebo, a single daily dose of R-AMPH significantly improved SKAMP-Combined scores (p<0.0001) at each time point tested throughout the laboratory classroom days, with effect onset 45 minutes postdose and extending through 10 hours. R-AMPH significantly improved PERMP number of problems attempted and correct (p<0.0001) throughout the laboratory classroom days. During the twice-daily dose-optimization open-label phase, improvements were observed with R-AMPH in scores of the ADHD-Rating Scale IV and Clinical Global Impressions Severity and Improvement Scales. TEAEs and changes in vital signs associated with R-AMPH were generally mild and not unexpected. The most common TEAEs in the open-label phase were decreased appetite (27.6%), upper abdominal pain (14.3%), irritability (14.3%), and headache (13.3%).
Conclusions: Compared to placebo, R-AMPH was effective in treating children aged 6–12 years with ADHD, beginning at 45 minutes and continuing through 10 hours postdose, and was well tolerated.
Trial registration: identifier: NCT01986062.
PMCID: PMC4491157  PMID: 25692608
13.  Mindfulness Meditation Training for Attention-Deficit/Hyperactivity Disorder in Adulthood: Current Empirical Support, Treatment Overview, and Future Directions 
Cognitive and behavioral practice  2015;22(2):172-191.
Research examining nonpharmacological interventions for adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) has expanded in recent years and provides patients with more treatment options. Mindfulness-based training is an example of an intervention that is gaining promising preliminary empirical support and is increasingly administered in clinical settings. The aim of this review is to provide a rationale for the application of mindfulness to individuals diagnosed with ADHD, describe the current state of the empirical basis for mindfulness training in ADHD, and summarize a treatment approach specific to adults diagnosed with ADHD: the Mindful Awareness Practices (MAPs) for ADHD Program. Two case study examples are provided to demonstrate relevant clinical issues for practitioners interested in this approach. Directions for future research, including mindfulness meditation as a standalone treatment and as a complementary approach to cognitive-behavioral therapy, are provided.
PMCID: PMC4403871  PMID: 25908900
attention-deficit/hyperactivity disorder; ADHD; mindfulness meditation training
14.  Effects of Postnatal Parental Smoking on Parent and Teacher Ratings of ADHD and Oppositional Symptoms 
To assess the effects of postnatal parental smoking on subsequent parent and teacher ratings of DSM-IV attention deficit hyperactivity disorder (ADHD) symptoms and oppositional behaviors in children diagnosed with ADHD and their siblings. Children between 5 and 12 years of age with ADHD and their siblings were included. DSM-IV ADHD symptom subscales (Inattentive and hyperactive-impulsive), and oppositionality subscale scores from Conners’ Rating Scales were predicted on the basis of parental smoking status in the first 7 years after birth using Generalized Estimating Equations controlling for a range of relevant covariates. Postnatal parental smoking was associated with both parent and teacher ratings of ADHD symptoms and oppositional behavior. After controlling for a number of covariates, several of these relationships were still significant. The risk of maternal smoking for the development of ADHD symptoms does not end during pregnancy. Research on the mechanisms underlying the observed associations is needed.
PMCID: PMC3678953  PMID: 19525745
ADHD; smoking; disruptive behavior; nicotine dependence
15.  Alpha-2 Adrenergic Receptors and Attention—Deficit/Hyperactivity Disorder 
Current psychiatry reports  2010;12(5):366-373.
Pharmacological management of attention-deficit hyperactivity disorder (ADHD) has expanded beyond stimulant medications to include alpha 2 adrenergic agonists. These agents exert their actions through presynaptic stimulation and likely involve facilitation of both dopamine and noradrenaline neurotransmission, which are both thought to play critical roles in the pathophysiology of ADHD. Further, frontostratial dysfunction giving rise to neuropsychological weaknesses has been well-established in patients with ADHD and may explain how alpha 2 agents exert their beneficial effects. In the following review, we consider relevant neurobiological underpinnings of ADHD with respect to why alpha 2 agents may be effective in treating this condition. We also review new formulations of alpha 2 agonists, emerging data on their use in ADHD, and implications for clinical practice. Integrating knowledge of pathphysiological mechanisms and mechanisms of drug action may inform our medication choices and facilitate treatment of ADHD and related disorders.
PMCID: PMC3676929  PMID: 20652773
guanfacine; clonidine; prefrontal; noradrenaline; ADHD
16.  Combined Ecological Momentary Assessment and Global Positioning System Tracking to Assess Smoking Behavior: A Proof of Concept Study 
Journal of dual diagnosis  2014;10(1):19-29.
Ecological momentary assessment (EMA) methods have provided a rich assessment of the contextual factors associated with a wide range of behaviors including alcohol use, eating, physical activity, and smoking. Despite this rich database, this information has not been linked to specific locations in space. Such location information, which can now be easily acquired from global positioning system (GPS) tracking devices, could provide unique information regarding the space-time distribution of behaviors and new insights into their determinants. In a proof of concept study, we assessed the acceptability and feasibility of acquiring and combining EMA and GPS data from adult smokers with attention deficit hyperactivity disorder (ADHD).
Participants were adults with ADHD who were enrolled in a larger EMA study on smoking and psychiatric symptoms. Among those enrolled in the latter study who were approached to participate (N = 11), 10 consented, provided daily EMA entries, and carried a GPS device with them during a 7-day assessment period to assess aspects of their smoking behavior.
The majority of those eligible to participate were willing to carry a GPS device and signed the consent (10 out of 11, 91%). Of the 10 who consented, 7 participants provided EMA entries and carried the GPS device with them daily for at least 70% of the sampling period. Data are presented on the spatial distribution of smoking episodes and ADHD symptoms on a subset of the sample to demonstrate applications of GPS data.
We conclude by discussing how EMA and GPS might be used to study the ecology of smoking and make recommendations for future research and analysis.
PMCID: PMC4036229  PMID: 24883050
global positioning system; geographic information system; ecological momentary assessment; nicotine dependence; smoking; ADHD
17.  Smoking Motivation in Adults With Attention-Deficit/Hyperactivity Disorder Using the Wisconsin Inventory of Smoking Dependence Motives 
Nicotine & Tobacco Research  2013;16(1):120-125.
Smokers with attention-deficit/hyperactivity disorder (ADHD) differ from smokers without ADHD across a range of smoking outcomes (e.g., higher prevalence rates of smoking, faster progression to regular smoking, and greater difficulty quitting). Moreover, ADHD as a disorder has been characterized by deficits in fundamental motivational processes. To date, few studies have examined how motivation for smoking might differ between nicotine-dependent individuals with and without ADHD. The goal of this study was to assess whether specific smoking motivation factors differentiate smokers with and without ADHD as measured by an empirically derived self-report measure of smoking motivations.
Smokers with (n = 61) and without (n = 89) ADHD participated in a range of laboratory and clinical studies that included the Wisconsin Inventory of Smoking Dependence Motives (WISDM).
A series of one-way analysis of covariances statistically controlling for age and race indicated that smokers with ADHD scored higher on the following WISDM subscales than their non-ADHD peers: automaticity, loss of control, cognitive enhancement, cue exposure, and negative reinforcement. Smokers in the non-ADHD group yielded higher scores on the social– environmental goads WISDM subscale. No group by gender interactions emerged.
Cigarette smokers with ADHD report different motives for smoking than smokers without ADHD. Clarifying the role of these motivational factors has implications for smoking prevention and treatment.
PMCID: PMC3916731  PMID: 24078759
18.  Clonidine Extended-Release Tablets as Add-on Therapy to Psychostimulants in Children and Adolescents With ADHD 
Pediatrics  2011;127(6):e1406-e1413.
To assess the efficacy and safety of clonidine hydrochloride extended-release tablets (CLON-XR) combined with stimulants (ie, methylphenidate or amphetamine) for attention-deficit/hyperactivity disorder (ADHD).
In this phase 3, double-blind, placebo-controlled trial, children and adolescents with hyperactive- or combined-subtype ADHD who had an inadequate response to their stable stimulant regimen were randomized to receive CLON-XR or placebo in combination with their baseline stimulant medication. Predefined efficacy measures evaluated change from baseline to week 5. Safety was assessed by spontaneously reported adverse events, vital signs, electrocardiogram recordings, and clinical laboratory values. Improvement from baseline for all efficacy measures was evaluated using analysis of covariance.
Of 198 patients randomized, 102 received CLON-XR plus stimulant and 96 received placebo plus stimulant. At week 5, greater improvement from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score (95% confidence interval: −7.83 to −1.13; P = .009), ADHD-RS-IV hyperactivity and inattention subscale scores (P = .014 and P = .017, respectively), Conners' Parent Rating Scale scores (P < .062), Clinical Global Impression of Severity (P = .021), Clinical Global Impression of Improvement (P = .006), and Parent Global Assessment (P = .001) was observed in the CLON-XR plus stimulant group versus the placebo plus stimulant group. Adverse events and changes in vital signs in the CLON-XR group were generally mild.
The results of this study suggest that CLON-XR in combination with stimulants is useful in reducing ADHD in children and adolescents with partial response to stimulants.
PMCID: PMC3387872  PMID: 21555501
α2-adrenergic agonist; attention-deficit/hyperactivity disorder; clonidine–hydrochloride extended-release tablets; psychostimulant
19.  Childhood Economic Strains in Predicting Substance Use in Emerging Adulthood: Mediation Effects of Youth Self-Control and Parenting Practices 
Journal of Pediatric Psychology  2013;38(10):1130-1143.
Objective To examine the influence of childhood economic strains on substance use in young adulthood and to assess the mediating roles of self-control as well as positive parenting during adolescence in a nationally representative longitudinal cohort. Methods The study included data from participants (n = 1,285) in the Panel Study of Income Dynamics, Child Development Supplement, and Transition to Adult. Structural equation modeling was used to evaluate the associations among risk factors during childhood and adolescence that predicted substance use in early adulthood. Results Conditions of economic strains, especially poverty, during childhood were associated with an increased likelihood of regular smoking in adulthood, which was partially mediated by poorer self-control during adolescence. Conclusions Self-control is negatively affected by economic strains and serves as a mediator between poverty and risk of regular smoking. Additional research is needed to better understand how economic strains effect the development of self-control.
PMCID: PMC3809729  PMID: 23899658
adolescents; alcohol use; drug abuse and exposure; parent stress; parenting; tobacco use
20.  Nicotinic receptor gene variants interact with attention deficient hyperactive disorder symptoms to predict smoking trajectories from early adolescence to adulthood 
Addictive behaviors  2013;38(11):10.1016/j.addbeh.2013.06.013.
To examine the association of single nucleotide polymorphisms (SNPs) of the CHRNB3 (rs13280604) and CHRNA6 (rs892413) nicotinic acetylcholine receptor (nAChR) genes and symptoms of attention deficit hyperactivity disorder (ADHD) in predicting smoking patterns from early adolescence to adulthood.
A longitudinal cohort of 1137 unrelated youths from the National Longitudinal Study of Adolescent Health provided responses to four surveys from Waves I to IV, and a genetic sample in Wave III. Growth mixture modeling was used to identify smoking patterns and to assess the effects of the two SNPs and ADHD symptoms on cigarette use over time.
There were significant main effects of ADHD symptoms and CHRNA6 variants in predicting the number of cigarettes smoked and the pattern of use over time, respectively. There were no main effects of the CHRNB3 variants. However, a significant CHRNB3 variant × ADHD symptom interaction was observed, such that individuals with elevated ADHD symptoms and a particular CHRNB3 variant were at increased risk of cigarette use over time.
These findings demonstrate that a SNP in a nicotinic receptor gene may interact with ADHD symptoms to link with increased cigarette use across adolescence and young adulthood. Unique associations between specific variants and patterns of ADHD symptoms were identified which may be useful for targeting prevention efforts to individuals at greatest risk for cigarette smoking.
PMCID: PMC3875162  PMID: 23899432
nAChR SNPs; ADHD; Smoking development
21.  Individual- and community-level correlates of cigarette-smoking trajectories from age 13 to 32 in a U.S. population-based sample 
Drug and alcohol dependence  2013;132(0):301-308.
Characterizing smoking behavior is important for informing etiologic models and targeting prevention efforts. This study explored the effects of both individual- and community-level variables in predicting cigarette use vs. non-use and level of use among adolescents as they transition into adulthood.
Data on 14,779 youths (53% female) were drawn from the National Longitudinal Study of Adolescent Health (Add Health); a nationally representative longitudinal cohort. A cohort sequential design allowed for examining trajectories of smoking typologies from age 13 to 32 years. Smoking trajectories were evaluated by using a zero-inflated Poisson (ZIP) latent growth analysis and latent class growth analysis modeling approach.
Significant relationships emerged between both individual- and community-level variables and smoking outcomes. Maternal and peer smoking predicted increases in smoking over development and were associated with a greater likelihood of belonging to any of the four identified smoking groups versus Non-Users. Conduct problems and depressive symptoms during adolescence were related to cigarette use versus non-use. State-level prevalence of adolescent smoking was related to greater cigarette use during adolescence.
Individual- and community-level variables that distinguish smoking patterns within the population aid in understanding cigarette use versus non-use and the quantity of cigarette use into adulthood. Our findings suggest that efforts to prevent cigarette use would benefit from attention to both parental and peer smoking and individual well-being. Future work is needed to better understand the role of variables in the context of multiple levels (individual and community-level) on smoking trajectories.
PMCID: PMC3701734  PMID: 23499056
Smoking trajectories; zero-inflated Poisson; ZIP; LCGA; National Longitudinal Study of Adolescent Health; Add Health
22.  Ecological Momentary Assessment of Antecedents and Consequences of Smoking in Adults with Attention-Deficit/Hyperactivity Disorder 
Substance use & misuse  2014;49(11):1446-1456.
The current study assessed antecedents and consequences of ad lib cigarette smoking in smokers diagnosed with attention-deficit/hyperactivity disorder (ADHD) using ecological momentary assessment (EMA). Adult smokers with ADHD (n = 17) completed 870 smoking and 622 nonsmoking electronic diary entries over a seven-day observation period of their naturalistic smoking behavior. Data collection occurred from 2011 to 2012. Generalized estimating equations indicated that ADHD smokers were more likely to smoke when urge to smoke, negative affect, boredom, stress, worry, and restlessness were elevated. In addition, participants were more likely to smoke in situations that elicited higher levels of nervousness and frustration. ADHD symptoms, in general, did not differ between smoking and nonsmoking contexts, though hyperactive-impulsive ADHD symptoms were elevated prior to smoking in frustrating situations. Additional situational antecedent variables were associated with smoking, including being in the presence of others smoking, being in a bar or restaurant, while outside, and while consuming caffeinated or alcoholic beverages. Participants also reported a significant improvement in urge to smoke, negative affect, stress, hunger, and ADHD symptoms after smoking a cigarette. Findings suggest certain contextual factors that may maintain ad lib cigarette smoking in smokers with ADHD and identify potential treatment targets in smoking cessation interventions for this at-risk group. Clinical implications and future research directions are discussed. Funding for this study was provided by the National Institute on Drug Abuse.
PMCID: PMC4116432  PMID: 24827866
attention-deficit/hyperactivity disorder; nicotine dependence; cigarette smoking; affect; emotion dysregulation; ecological momentary assessment
23.  Effects of smoking abstinence on smoking-reinforced responding, withdrawal, and cognition in adults with and without attention deficit hyperactivity disorder 
Psychopharmacology  2012;227(1):19-30.
Individuals with attention deficit hyperactivity disorder (ADHD) have a more difficult time quitting smoking compared to their non-ADHD peers. Little is known about the underlying behavioral mechanisms associated with this increased risk.
This study aims to assess the effects of 24-h smoking abstinence in adult smokers with and without ADHD on the following outcomes: smoking-reinforced responding, withdrawal, and cognitive function.
Thirty-three (n=16 with ADHD, 17 without ADHD) adult smokers (more than or equal to ten cigarettes/day) were enrolled. Each participant completed two experimental sessions: one following smoking as usual and one following biochemically verified 24-h smoking abstinence. Smoking-reinforced responding measured via a progressive ratio task, smoking withdrawal measured via questionnaire, and cognition measured via a continuous performance test (CPT) were assessed at each session.
Smoking abstinence robustly increased responding for cigarette puffs in both groups, and ADHD smokers responded more for puffs regardless of condition. Males in both groups worked more for cigarette puffs and made more commission errors on the CPT than females, regardless of condition. Smoking abstinence also increased ratings of withdrawal symptoms in both groups and smokers with ADHD, regardless of condition, reported greater symptoms of arousal, habit withdrawal, and somatic complaints. Across groups, smoking abstinence decreased inhibitory control and increased reaction time variability on the CPT. Abstinence-induced changes in inhibitory control and negative affect significantly predicted smoking-reinforced responding across groups.
Smokers with ADHD reported higher levels of withdrawal symptoms and worked more for cigarette puffs, regardless of condition, which could help explain higher levels of nicotine dependence and poorer cessation outcomes in this population. Abstinence-induced changes in smoking-reinforced responding are associated with changes in inhibitory control and negative affect regardless of ADHD status, a finding that may lead to novel prevention and treatment programs.
PMCID: PMC3624067  PMID: 23247366
ADHD; Nicotine; Reinforcement; Self-administration
24.  Association between smoking and retrospectively reported attention-deficit/hyperactivity disorder symptoms in a large sample of new mothers 
Nicotine & Tobacco Research  2009;11(3):313-322.
This study investigated the association between retrospectively reported attention-deficit/hyperactivity disorder (ADHD) symptoms experienced during childhood and five cigarette smoking–related outcomes in adulthood.
A large sample (N = 1,117) of new mothers participating in an ongoing longitudinal study completed retrospective reports of their childhood ADHD symptomatology, as well as concurrent and retrospective reports of their smoking behavior. Linear regression models tested the association between ADHD symptomatology and smoking outcomes.
Childhood ADHD symptomatology was predictive of the number of cigarettes smoked per day currently and during pregnancy, as well as the age at onset of smoking. We found nonlinear associations between hyperactive–impulsive symptoms and the number of cigarettes smoked per day in pregnancy, as well as between inattentive symptoms and the number of cigarettes smoked per day currently. Women who retrospectively reported intermediate levels of ADHD symptoms during their childhood reported smoking more cigarettes per day than women who reported low or high levels of ADHD symptoms during childhood. We also found multiplicative relationship between inattentive and hyperactive–impulsive symptoms, such that inattentive symptoms were predictive of an earlier age at smoking onset only when hyperactive–impulsive symptoms were low; moreover, the magnitude of this association was stronger for Black relative to White women.
These findings demonstrate the importance of considering differential effects of ADHD symptoms and smoking outcomes as a function of sex and race. They also represent a potentially indirect means through which women who have even a moderate childhood history of ADHD symptomatology may create a set of circumstances that compromise the health and well-being of their own children.
PMCID: PMC2666380  PMID: 19307443
25.  The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-Year Follow-up 
To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3–5 to 9–12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS).
207 participants (75% male) from the original PATS, assessed at Baseline (mean age 4.4 years, when all met criteria for ADHD) and 3-months later (prior to medication treatment), were re-evaluated in three follow-up assessment visits (Year 3, mean age 7.4 years; Year 4, 8.3 years and Year 6, 10.4 years). Parents and teachers rated symptom severity and clinicians established psychiatric diagnoses. Analyses examined longitudinal changes in symptom severity and ADHD diagnosis.
Parent- and teacher-rated symptom severity decreased from Baseline to Year 3 but remained relatively stable and in the moderate-to-severe clinical range through Year 6. Girls showed generally steeper decreases in symptom T-scores. At Year 6, 89% (160/180) of remaining participants met ADHD symptom and impairment diagnostic criteria. Comorbidity of oppositional defiant disorder and/or conduct disorder was associated with a 30% higher risk of having an ADHD diagnosis at Year 6 in the multiple logistic model. Medication status during follow-up, on vs. off, did not predict symptom severity change from Year 3 to Year 6 after adjustment for other variables.
ADHD in preschoolers is a relatively stable diagnosis over a 6-year period. The course is generally chronic, with high symptom severity and impairment, in very young children with moderate-to-severe ADHD, despite treatment with medication. Development of more effective ADHD intervention strategies is needed for this age group.
PMCID: PMC3660093  PMID: 23452683
attention-deficit/hyperactivity disorder (ADHD); follow-up; pre-schoolers; development

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