Daniel Roche | University of Maryland School of Medicine (original) (raw)

Papers by Daniel Roche

Aims: Women often experience poorer smoking cessation outcomes in comparison to men. Menstrual cy... more Aims: Women often experience poorer smoking cessation outcomes in comparison to men. Menstrual cycle phase and sex hormones may influence smoking behavior and alter response to opioid antagonist medications. Less is known about the effects of sex hormones in response to pharmacotherapy for female heavy drinking smokers. Methods: This study is a secondary analysis of premenopausal female heavy drinking smokers who completed a 12-week randomized clinical trial comparing varenicline plus placebo versus varenicline plus naltrexone for smoking cessation and drinking reduction. Participants (n = 26; total observations = 66) provided saliva samples for assays of progesterone (P4) and estradiol (E2) post-randomization at Weeks 4, 8 and 12. We examined the effects of P4/E2 ratio and medication on smoking and drinking outcomes. Results: For drinking outcomes, there was a significant interaction for percent days abstinent (b = 0.017, P = 0.05), suggesting that greater P4/E2 ratio is associated with greater percent days abstinent for women assigned to the varenicline plus naltrexone condition. There were no interaction effects for the remaining drinking outcomes (P's ≥ 0.12). Results found no significant interaction effect of P4/E2 ratio and medication on smoking abstinence (P = 0.19). Conclusion: Our results imply that when women show a greater P4/E2 ratio, typically observed during the luteal phase of the menstrual cycle, they experience an added benefit of naltrexone, versus placebo, for drinking outcomes as shown by greater percent days abstinent. Additional studies in larger samples are warranted as sex hormones offer important information above and beyond comparing women versus men.

Alcohol & Alcoholism, 2022

Background: Polysubstance use is a common, problematic behavior that increases risk of harm to se... more Background: Polysubstance use is a common, problematic behavior that increases risk of harm to self and others. Research suggests that rates may vary based on gender, sex and sexuality. Understanding the current state of this literature may inform prevention and treatment of polysubstance use, leading to reduced public health burden. Objectives: This review aimed to synthesize research on gender, sex and sexuality differences in polysubstance use in adults and adolescents. Methods: A scoping review was conducted using all EBSCO databases, PubMed and Google Scholar to identify articles examining the effects of gender, sex and sexuality on polysubstance use. Polysubstance use was defined broadly as the use of any combination of substances over any time period and included licit (alcohol, tobacco) and illicit substances, concurrent and simultaneous use, from lifetime to daily use and use at any frequency. Studies were considered if they were published in peer-reviewed journals between January 1990 and October 2020 and were written in English. Publicly available data sources were also utilized to fully capture prevalence data that has not been published elsewhere. Results: Findings were mostly inconsistent and often conflicting. Only two findings were generally consistent: adult men were overall more likely to report polysubstance use than adult women, and sexual and gender minorities report more frequent polysubstance use than non-minorities. Conclusions: Research has been unable to clearly elucidate differences in polysubstance use prevalence and patterns according to gender, sex and sexuality. Several recommendations are offered to advance future research and address limitations of current research.

Journal of Dual Diagnosis, 2021

Experimental and Clinical Psychopharmacology, 2021

The Hamilton Anxiety Inventory (HAM-A) is one of the oldest and most commonly used anxiety rating... more The Hamilton Anxiety Inventory (HAM-A) is one of the oldest and most commonly used anxiety rating scales in clinical research. Despite its ubiquity, no studies have examined the scale's underlying factor structure and criterion validity among Black and African American adults with psychopathology (M age = 42.25, SD = 11.44). Therefore, we estimated a confirmatory factor analysis of the commercially available Structured Interview Guide for the Hamilton Anxiety scale (SIGH-A; Williams, 1996) among African American adults (n = 88; 43% female) with co-occurring heavy alcohol use and trauma-related symptoms. Next, we examined the criterion validity of its Psychic and Somatic factors and overall anxiety severity score from participants who completed a single screening session (i.e., cross-sectional analysis) for a larger study. Results indicated that a two-factor solution provided an adequate fit to the data. Regression analyses indicated that the total SIGH-A score, but not its subscales, significantly predicted posttraumatic stress disorder (PTSD) severity. Neither the SIGH-A subscales nor total scores were significant predictors of alcohol consumption. The current findings suggest that the SIGH-A factor structure among African American adults with alcohol and trauma-related conditions is similar to previous reports that have tested largely White samples but highlight potential shortcomings when its subscales are used independently. Public Health Significance This study examines the psychometric properties of the widely used Hamilton Anxiety Scale, which has limited research examining its psychometric properties with diverse samples. These findings support a two-factor solution among Black and African American adults with histories of trauma and heavy alcohol consumption. Findings also suggest that overall anxiety severity levels, but not the Hamilton's anxiety subscales, are associated cross sectionally with posttraumatic stress symptoms but not alcohol consumption.

Neuropsychopharmacology, 2021

Behavioral pharmacology paradigms have been used for early efficacy testing of novel compounds fo... more Behavioral pharmacology paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). However, the degree to which early efficacy in the human laboratory predicts clinical efficacy remains unclear. To address this gap in the literature we employed a novel meta-analytic approach. We searched the literature for medications tested for AUD using both behavioral pharmacology (i.e., alcohol administration) and randomized clinical trials (RCTs). For behavioral pharmacology, we computed medication effects on alcohol-induced stimulation, sedation, and craving during the alcohol administration (k = 51 studies, 24 medications). For RCTs, we computed medication effects on any drinking and heavy drinking (k = 118 studies, 17 medications). We used medication as the unit of analysis and applied the Williamson-York bivariate weighted least squares estimation to preserve the errors in both the independent and dependent variables. Results, with correction for publication bias, revealed a significant and positive relationship between medication effects on alcohol-induced stimulation (β = 1.18 p < 0.05), sedation (β = 2.38, p < 0.05), and craving (β = 3.28, p < 0.001) in the laboratory, and drinking outcomes in RCTs, such that medications that reduced stimulation, sedation, and craving during the alcohol administration were associated with better clinical outcomes. A leave-one-out Monte Carlo analysis examined the predictive utility of these laboratory endpoints for each medication. The observed clinical effect size was within one standard deviation of the mean predicted effect size for all but three pharmacotherapies. This proof-of-concept study demonstrates that behavioral pharmacology endpoints of alcohol-induced stimulation, sedation, and craving track medication effects from the human laboratory to clinical trial outcomes. These results apply to alcohol administration phenotypes and may be especially useful to medications for which the mechanisms of action involve alterations in subjective responses to alcohol (e.g., antagonist medication). These methods and results can be applied to a host of clinical questions and can streamline the process of screening novel compounds for AUD. For instance, this approach can be used to quantify the predictive utility of cue-reactivity screening models and even preclinical models of medication development.

Alcoholism: Clinical & Experimental Research, 2021

Background: Alcohol administration paradigms have been used for early efficacy testing of novel c... more Background: Alcohol administration paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). There has been an ongoing debate about sample characteristics and methodological features that affect the likelihood of detecting an early efficacy signal for AUD medications. We conducted a meta-regression to test whether the drinking level of the study sample and the peak breath alcohol concentration (BrAC) in the alcohol administration study predict the efficacy of AUD pharmacotherapies on the subjective responses to alcohol.
Methods: We computed the effects of 21 medications on alcohol-induced stimulation, sedation, negative mood, and craving during alcohol administration in 49 studies.
Results: Meta-regression analyses indicated a significant and positive effect of pre-study
drinks per month on alcohol-induced stimulation (β = 0.142, p < 0.0001), such that as drinking increases, the benefit of medication over placebo decreases. There was an effect of drinks per month on negative mood (β = −0.164, p = 0.0248), such that at higher levels of drinks per month, the effects of medications on negative mood are stronger. For sedation, there was an effect of peak BrAC (β = 0.119, p = 0.0002), such that at low levels of peak BrAC, the effects of medication on sedation were null. For craving, there was a peak BrAC drinks per month interaction such that at low levels of BrAC, a heavier drinking sample is required to detect the effects of medication on craving. Sensitivity analyses comparing naltrexone studies and non-naltrexone studies suggested that naltrexone was less sensitive to drinks per month across subjective response domains.
Conclusions: These analyses show that design features are critical in studies that test
the effects of medications on the subjective responses to alcohol. By specifying the significance and directionality of these effects, as well as the specific points in BrAC or drinks per month at which medication effects are detectable, the study offers recommendations for design features of alcohol administration studies that aim to inform AUD medication development.

Addiction Biology, 2019

Naltrexone (NTX) has been widely studied for the treatment of alcohol use disorder with overall s... more Naltrexone (NTX) has been widely studied for the treatment of alcohol use disorder with overall support for its efficacy. The mechanisms of action of naltrexone are thought to involve attenuation of the hedonic effects of alcohol and potentiation of its aversive effects. In order to provide a quantitative estimate of the effects of naltrexone on subjective response to alcohol, the aims of this meta-analytic review are to examine the effects of naltrexone across four domains of subjective response. Meta-analyses of naltrexone effects on alcohol craving (k = 16, N = 686), stimulation (k = 15, N = 675), sedation (k = 18, N = 777), and negative mood (k = 9, N = 281) suggested that under laboratory conditions and compared with placebo, naltrexone reduces craving (Hedges g = −0.252; SE = 0.054; 95% CI, −0.375 to −0.130; P < 0.01), reduces stimulation (g = −0.223; SE = 0.067; 95% CI, −0.372 to −0.074; P < 0.01), increases sedation (g = 0.251; SE = 0.064; 95% CI, 0.112-0.389; P < 0.01), and increases negative mood (g = 0.227; SE = 0.047; 95% CI, 0.100-0.354; P < 0.01). Results were robust when drinks per month and alcohol dose were added to the models as covariates. The effects of naltrexone varied by severity of alcohol use with medication effects on craving and stimulation being observed in sample of both heavy drinkers and AUD individuals. These results are consistent with the hypothesized mechanisms of action of NTX, although the effects are of small magnitude. This meta-analysis aggregates across multiple human laboratory studies of NTX's effects on subjective response to alcohol, providing a comprehensive summary of a key mechanism of NTX efficacy, namely, alteration of the subjective experience of alcohol.

Drug and Alcohol Dependence, 2019

Background: Little is known about event-level patterns of marijuana co-or tri-use with alcohol an... more Background: Little is known about event-level patterns of marijuana co-or tri-use with alcohol and tobacco. Thus, the study goal was to examine patterns of same-day alcohol, cigarette, and marijuana co-and tri-use at the individual level in non-treatment-seeking alcohol users. Methods: Participants (N = 551) completed an in-person interview for alcohol, cigarette, and marijuana use over the previous 30 days, and the event-level substance use patterns of n = 179 participants who reported using each of these substances at least once per month were analyzed. Results: The use of alcohol, marijuana, or cigarettes independently increased the probability of subsequent, simultaneous co-use of one of the two remaining substances. The co-use of alcohol with cigarettes and marijuana with cigarettes produced generally additive effects on the odds of same day tri-use of marijuana and alcohol, respectively. Conversely, the co-use of alcohol and marijuana produced sub-additive effects on likelihood of cigarette use. Sex moderated several of the observed patterns of co-and tri-use: the relationship between alcohol or cigarette use predicting marijuana co-use was stronger in men, whereas the observed additive relationships between drug co-use leading to tri-use was stronger in women. Conclusions: The presented results may aid in the understanding of how simultaneous co-use of marijuana with alcohol and/or tobacco relates to the etiology, maintenance, and treatment of comorbid and trimorbid substance use disorder. Replication and extension of the results in treatment seeking populations using more fine-grained analysis approaches, e.g. ecological momentary assessment, is needed.

Alcohol and Alcoholism, 2019

Aims: The present study examined how variation in mu-(OPRM1), kappa-(OPRK), and delta-(OPRD) opio... more Aims: The present study examined how variation in mu-(OPRM1), kappa-(OPRK), and delta-(OPRD) opioid receptor genes may influence the efficacy of naltrexone in the context of a smoking cessation trial. Methods: The study's primary objective was to examine the association of the Asn40Asp OPRM1 single nucleotide polymorphism (SNP) with naltrexone's effects on smoking quit rate, weight gain, and heavy drinking behavior during a double-blind, randomized clinical trial in 280 adult DSM-IV nicotine-dependent participants. The secondary goal of the study was to examine the relationship of 20 additional SNPs of OPRM1, OPRK, and OPRD with the aforementioned outcomes. Results: Results indicated a null association between any opioid-receptor gene SNP and naltrexone's effects on smoking quit rate, weight gain, and heavy drinking behavior in this sample of nicotine dependent participants. Conclusions: In sum, these results do not suggest that genetic variation in opioid-receptors is related to treatment responses to naltrexone in a smoking cessation trial.

Distress Tolerance and Craving for Cigarettes Among Heavy Drinking Smokers, 2018

Alcoholism, clinical and experimental research, Jan 3, 2018

As the development of novel pharmacotherapies for alcohol use disorder (AUD) has been slow, the d... more As the development of novel pharmacotherapies for alcohol use disorder (AUD) has been slow, the discovery and testing of more efficacious pharmacotherapies for AUD represent a high priority research area. In fact, the transition from preclinical to clinical testing of novel compounds has been termed the "valley of death" in medications development. One key obstacle consists of the lack of an articulated set of goals for each stage of medications development. Specifically, the knowledge outputs required to make the transition from safety testing, to early efficacy detection, to confirming clinical efficacy remain unclear, and this is despite a great deal of interest and substantial financial investment in developing novel therapeutics for AUD. This qualitative critical review seeks to draw parallels and lessons from the well-established stage model for behavioral therapies research with alcohol and other substance use disorders and to apply these insights into AUD pharmacot...

Current Addiction Reports, 2018

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018

The Allostatic Model proposes that Alcohol Use Disorder (AUD) is associated with a transition in ... more The Allostatic Model proposes that Alcohol Use Disorder (AUD) is associated with a transition in the motivational structure of alcohol drinking: from positive reinforcement in early-stage drinking to negative reinforcement in late-stage dependence. However, direct empirical support for this preclinical model from human experiments is limited. This study tests predictions derived from the Allostatic Model in humans. Specifically, this study tested whether alcohol use severity (1) independently predicts subjective responses to alcohol (SR; comprised of stimulation/hedonia, negative affect, sedation and craving domains), and alcohol self-administration and 2) moderates associations between domains of SR and alcohol self-administration. Heavy drinking participants ranging in severity of alcohol use and problems (N = 67) completed an intravenous alcohol administration paradigm combining an alcohol challenge (target BrAC = 60 mg%), with progressive ratio self-administration. Alcohol use s...