Matthew J. Worley

Mediating Influences of Negative Affect and Risk Perception on the Relationship Between Sensation Seeking and Adolescent Cigarette Smoking

INTRODUCTION A substantial number of adolescents are current and regular cigarette smokers, and there is a need to better understand factors that contribute to smoking behavior during these years. Sensation seeking (SS) is one factor that has consistently been associated with smoking, but less is known about mechanisms that may explain this relationship. METHODS The present study tested the hypothesis that high school students high in SS would report heavier cigarette smoking and that this relationship would be mediated by negative affect and by perceptions about the risks of smoking. Students (n = 1,688) participated in an annual survey of substance use and related attitudes and characteristics. RESULTS As expected, higher SS was associated with greater levels of past 30-day (odds ratio [OR] = 1.46, p = .004) and lifetime (OR = 1.37, p = .004) smoking, particularly for males. Multiple mediation models indicated that effect of SS on both 30-day (combined indirect effect z = 5.38, p < .001) and lifetime (z = 6.14, p < .001) smoking was mediated by both negative affect and risk perception. CONCLUSIONS These findings suggest a need for increasing the sensation value of anti-tobacco messages to increase their efficacy for high SS youth. High SS youth may also benefit from prevention efforts designed to teach healthy ways of coping with negative affect.

Pre-Adolescent Alcohol Expectancies: Critical Shifts and Associated Maturational Processes

Childrens alcohol expectancies shift in late childhood/early adolescence in ways thought to lead to increased risk for adolescent alcohol use. The precise nature of this shift and the maturational processes that may influence it remain to be clarified. To these ends, we compared expectancy endorsement by grade across four expectancy domains: positive, negative, arousal, and sedation, in a cross-sectional sample of 3rd-6th grade children attending afterschool programs (n = 299). Structural equation modeling (SEM) was then used to describe the relationships between expectancies and differences in (a) cognitive ability and concept formation, (b) risk-taking personality traits, and (c) social exposure or values regarding alcohol-related information. Results showed those children in higher grades endorsed significantly more positive, negative, and sedating expectancies for alcohol than their younger peers. Concept formation partially and fully mediated the relationships between grade and both positive and sedating expectancies, respectively, but not the relationship between grade and negative expectancies. Sensation seeking did not increase across grades in this sample, and the relationship between sensation seeking and positive expectancies was fully mediated by reported alcohol exposure and values. This study provides a basis for future exploration of developmental influences on alcohol expectancies, an understanding of which may be helpful in the design of prevention efforts targeting high-risk youth before adolescence.

Comorbid depression and substance use disorder: Longitudinal associations between symptoms in a controlled trial

This study examined the longitudinal association between substance use and depressive symptoms in veterans receiving outpatient treatment for comorbid substance use disorder and major depression. Veterans (N = 237, mean age = 48.2 years, 90% male, 70% Caucasian) received either 6 months of group integrated cognitive-behavioral therapy or twelve-step facilitation. Hamilton Depression Rating Scale scores and percent days using any substance were assessed every 3 months up to 1 year posttreatment. Greater substance use predicted time-varying elevations in depression above individual patterns of change in depression. Moreover, change in depressive symptoms was associated with change in both the likelihood of any substance use and the frequency of use during the treatment and follow-up periods. Changes in these symptoms appear to be linked, such that individuals with greater reductions in substance use have greater reductions in depressive symptoms (and vice versa).

Predictors of sustained abstinence during psychosocial treatments for cocaine dependence

Abstract Using data from the National Institute of Drug Abuse Collaborative Cocaine Treatment Study, the authors examined 24 patient pretreatment variables as predictors of outcome. The most clinically meaningful outcome in the treatment of substance dependence—degree of sustained abstinence—was used. Predictor variables included demographic features, aspects of the disorder and the recovery environment, expectations about treatment, and beliefs about addiction, relapse, and the 12-step philosophy. Four of the 24 examined variables—craving, acuity of biomedical problems, belief in the 12-step philosophy, and expectations for improvement—were significantly predictive of degree of sustained abstinence using a Bonferroni-corrected alpha level. No significant interactions with treatment condition were noted. The joint effect of the 4 predictor variables had a clinically meaningful impact on outcome.

Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study

BACKGROUND Despite numerous clinical trials no efficacious medications for methamphetamine (MA) have been identified. Neuroinflammation, which has a role in MA-related reward and neurodegeneration, is a novel MA pharmacotherapy target. Ibudilast inhibits activation of microglia and pro-inflammatory cytokines and has reduced MA self-administration in preclinical research. This study examined whether ibudilast would reduce subjective effects of MA in humans. METHODS Adult, non-treatment seeking, MA-dependent volunteers (N=11) received oral placebo, moderate ibudilast (40 mg), and high-dose ibudilast (100mg) via twice-daily dosing for 7 days each in an inpatient setting. Following infusions of saline, MA 15 mg, and MA 30 mg participants rated 12 subjective drug effects on a visual analog scale (VAS). RESULTS As demonstrated by statistically-significant ibudilast × MA condition interactions (p<.05), ibudilast reduced several MA-related subjective effects including High, Effect (i.e., any drug effect), Good, Stimulated and Like. The ibudilast-related reductions were most pronounced in the MA 30 mg infusions, with ibudilast 100mg significantly reducing Effect (97.5% CI [-12.54, -2.27]), High (97.5% CI [-12.01, -1.65]), and Good (97.5% CI [-11.20, -0.21]), compared to placebo. CONCLUSIONS Ibudilast appeared to reduce reward-related subjective effects of MA in this early-stage study, possibly due to altering the processes of neuroinflammation involved in MA reward. Given this novel mechanism of action and the absence of an efficacious medication for MA dependence, ibudilast warrants further study to evaluate its clinical efficacy.

Neural predictors of alcohol use and psychopathology symptoms in adolescents

Adolescence is a period marked by increases in risk taking, sensation seeking, and emotion dysregulation. Neurobiological models of adolescent development propose that lagging development in brain regions associated with affect and behavior control compared to regions associated with reward and emotion processing may underlie these behavioral manifestations. Cross-sectional studies have identified several functional brain networks that may contribute to risk for substance use and psychopathology in adolescents. Determining brain structure measures that prospectively predict substance use and psychopathology could refine our understanding of the mechanisms that contribute to these problems, and lead to improved prevention efforts. Participants (N = 265) were healthy substance-naïve adolescents (ages 12-14) who underwent magnetic resonance imaging and then were followed annually for up to 13 years. Cortical thickness and surface area measures for three prefrontal regions (dorsolateral prefrontal cortex, inferior frontal gyrus, and orbitofrontal cortex) and three cortical regions from identified functional networks (anterior cingulate cortex, insular cortex, and parietal cortex) were used to predict subsequent binge drinking, externalizing symptoms, and internalizing symptoms. Thinner dorsolateral prefrontal cortex and inferior frontal cortex in early adolescence predicted more binge drinking and externalizing symptoms, respectively, in late adolescence (ps < .05). Having a family history of alcohol use disorder predicted more subsequent binge drinking and externalizing symptoms. Thinner parietal cortex, but not family history, predicted more subsequent internalizing symptoms (p < .05). This study emphasizes the temporal association between maturation of the salience, inhibition, and executive control networks in early adolescence and late adolescent behavior outcomes. Our findings indicate that developmental variations in these brain regions predate behavioral outcomes of substance use and psychopathology, and may therefore serve as prospective biomarkers of vulnerability.

Service utilization during and after outpatient treatment for comorbid substance use disorder and depression

Patients with comorbid substance use disorder (SUD) and depression incur greater treatment costs than those with either disorder alone. Integrated treatment targeting both issues concurrently has been shown to reduce substance use and depression in this population, but little is known about the effects of such treatment on the utilization of costly health services. This study compared 18-month patterns of service utilization for 236 veterans with comorbid SUD depression randomly assigned to 6 months of either Integrated Cognitive Behavioral Therapy (ICBT) or Twelve-Step Facilitation Therapy. Treatment group differences were found for the utilization of psychotropic medication services and inpatient hospitalization. Higher rates of therapy attendance, lower baseline depression, and receiving ICBT all predicted shorter admissions for those hospitalized during treatment. Ethnicity and gender predicted medication service use both during and following treatment. The findings provide evidence supporting the long-term cost-effectiveness of integrated treatment for this high-risk population.

Mediational relations between 12‐Step attendance, depression and substance use in patients with comorbid substance dependence and major depression

AIMS Among patients with substance dependence and comorbid major depressive disorder (MDD) receiving treatment in a controlled trial, we examined if group differences in depression were mediated by 12-Step involvement, and if the effects of 12-Step involvement on future alcohol and drug use were mediated by reductions in depression. DESIGN Controlled trial of Twelve-Step facilitation (TSF) and integrated cognitive-behavioral therapy (ICBT), delivered in out-patient groups for 6 months with adjunct pharmacotherapy. SETTING Out-patient dual diagnosis clinic in Veterans Affairs Healthcare Center. PARTICIPANTS Veterans (n = 209) diagnosed with alcohol, stimulant or marijuana dependence and substance-independent MDD. MEASUREMENTS Twelve-Step attendance and affiliation, depression severity, percentage of days drinking and percentage of days using drugs assessed at baseline and months 3, 6 and 9. FINDINGS In multi-level analyses greater 12-Step meeting attendance predicted lower depression and mediated the superior depression outcomes of the TSF group, explaining 24.3% of the group difference in depression. Independent of treatment group, lower depression severity predicted lower future alcohol use and mediated the effects of 12-Step meetings, explaining 15.7% of their effects on future drinking. Controlled, lagged models indicated these effects were not confounded by current substance use, suggesting that depression had unique associations with 12-Step meeting attendance and future drinking. CONCLUSIONS For patients with substance dependence and major depressive disorder, attendance at 12-Step meetings is associated with mental health benefits that extend beyond substance use, and reduced depression could be a key mechanism whereby 12-Step meetings reduce future drinking in this population.

Supportive-Expressive Psychodynamic Therapy for Cocaine Dependence: A Closer Look

Using data from the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, this article focuses on the outcomes of patients who received supportive-expressive (SE) psychodynamically-oriented psychotherapy (plus group drug counseling; GDC). Short-term SE for cocaine dependent individuals, while not the most efficacious treatment examined in the study (individual drug counseling [IDC] plus GDC was), produced large improvements in cocaine use. In addition, there was evidence that SE was superior to IDC on change in family/social problems at the 12 month follow-up assessment, particularly for those patients with relatively more severe difficulties in this domain at baseline. For patients who achieved abstinence early in treatment, SE produced comparable drug use outcomes to IDC, with mean drug use scores numerically lower for SE at all of the follow-up assessments (9, 12, 15, and 18 months). SE patients who achieved initial abstinence decreased cocaine use from a mean 10.1 days per month at baseline to a mean of 1.3 days at 12 months.

Using behavioral economics to predict opioid use during prescription opioid dependence treatment

BACKGROUND Research grounded in behavioral economics has previously linked addictive behavior to disrupted decision-making and reward-processing, but these principles have not been examined in prescription opioid addiction, which is currently a major public health problem. This study examined whether pre-treatment drug reinforcement value predicted opioid use during outpatient treatment of prescription opioid addiction. METHODS Secondary analyses examined participants with prescription opioid dependence who received 12 weeks of buprenorphine-naloxone and counseling in a multi-site clinical trial (N=353). Baseline measures assessed opioid source and indices of drug reinforcement value, including the total amount and proportion of income spent on drugs. Weekly urine drug screens measured opioid use. RESULTS Obtaining opioids from doctors was associated with lower pre-treatment drug spending, while obtaining opioids from dealers/patients was associated with greater spending. Controlling for demographics, opioid use history, and opioid source frequency, patients who spent a greater total amount (OR=1.30, p<.001) and a greater proportion of their income on drugs (OR=1.31, p<.001) were more likely to use opioids during treatment. CONCLUSIONS Individual differences in drug reinforcement value, as indicated by pre-treatment allocation of economic resources to drugs, reflects propensity for continued opioid use during treatment among individuals with prescription opioid addiction. Future studies should examine disrupted decision-making and reward-processing in prescription opioid users more directly and test whether reinforcer pathology can be remediated in this population.