A meta-analysis of electrophysiological biomarkers of reward and error monitoring in substance misuse.

Substance use disorders are characterized by marked changes in reward and error processing. The primary objective of this meta-analysis was to estimate effect sizes for the reward positivity (RewP) and error-related negativity (ERN), two event-related potential indicators of outcome monitoring, in substance users compared to controls. The secondary objective was to test for moderation by demographic, substance type, and EEG experiment parameters. Final PubMed searches were performed in August 2023. Inclusion criteria were substance use disorder/dependence or validated self-report of substance misuse, RewP/ERN means available, healthy control comparison group, non-acute drug study, peer-reviewed journal, English language, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. The RewP results (19 studies, 1641 participants) did not support an overall effect (Hedges' g = 0.07, 95% CI [-0.44, 0.58], p = .777) and nor effect of any moderators. The ERN results (20 studies, 1022 participants) indicated no significant overall effect (g = 0.41, 95%CI [-0.05, 0.88]). Subgroup analyses indicated that cocaine users had a blunted ERN compared to controls (g = 1.12, 95%CI [0.77, 1.47]). There was limited evidence for publication/small study bias. Although the results indicate a potential dissociation between substance types, this meta-analysis revealed the need for additional research on the RewP/ERN in substance using populations and for better designed experiments that adequately address research questions.

Mental Health Clinician Practices and Perspectives on Treating Adults with Co-Occurring Posttraumatic Stress and Substance Use Disorders.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) commonly co-occur and represent a complex, challenging clinical comorbidity. Meta-analytic studies and systematic reviews suggest that trauma-focused treatments are more efficacious than non-trauma focused interventions for co-occurring PTSD/SUD. However, relatively little is known about mental health clinicians' practices or preferences for treating co-occurring PTSD/SUD. The present study aimed to describe the current clinical practices of mental health clinicians who treat PTSD and/or SUD-related conditions and to assess interest in novel integrative treatments for PTSD/SUD. METHODS: Licensed mental health clinicians (N = 76; Mage = 39.59, SD = 8.14) who treat PTSD and/or SUD completed an anonymous online survey from April 2021 to July 2021. RESULTS: The majority (61.8%) of clinicians reported using integrative treatments for PTSD/SUD. The most commonly used trauma-focused treatments were 1) Cognitive Processing Therapy (CPT: 71.1%) and 2) Prolonged Exposure Therapy (PE: 68.4%) for PTSD. Approximately half (51.3%) of clinicians endorsed using Relapse Prevention (RP) for SUD. The vast majority (97.4%) of clinicians were somewhat or very interested in a new integrative CPT-RP intervention, and 94.7% of clinicians believed patients would be interested in a CPT-RP intervention. In the absence of an available evidence-based integrative treatment using CPT, 84.0% of clinicians reported modifying extant treatment protocols on their own to address PTSD and SUD concurrently. CONCLUSIONS: The findings demonstrate mental health clinician support of integrative treatments for PTSD/SUD. The most commonly used trauma-focused intervention was CPT and clinicians expressed strong interest in an integrative intervention that combines CPT and RP. Implications for future treatment development are discussed.

Distress tolerance: prospective associations with cognitive-behavioral therapy outcomes in adults with posttraumatic stress and substance use disorders.

74Distress tolerance (DT; perceived or actual ability to tolerate aversive physical or emotional states) is related to both posttraumatic stress disorder (PTSD) symptoms and substance use disorders (SUD). This investigation evaluates self-report and behavioral measures of DT as potential predictors of PTSD and SUD cognitive-behavioral therapy outcomes. Participants included 41 treatment-seeking adults (53.7% women; 73.2% African American; Mage = 44.90, SD = 9.68) who met at least four symptoms of DSM-5 PTSD and DSM-IV substance dependence, assessed via structured interviews. At baseline (pre-treatment), participants completed the Distress Tolerance Scale (DTS), Mirror-Tracing Persistence Task (MTPT), Breath Holding task, and Paced Auditory Serial Addition Task. The Clinician-Administered PTSD Scale for DSM-5 severity scores and percent days of primary substance use, measured via Timeline Follow-back, were used as indicators of PTSD symptoms and substance use, respectively. Covariates included treatment condition, baseline PTSD symptom severity, and baseline substance use. Lower perceived DT at baseline (DTS total score) was associated with higher PTSD symptom severity at end-of-treatment. Lower behavioral DT at baseline (MTPT duration) was associated with higher substance use at the conclusion of treatment (i.e. proportion of number of use days to total number of days between two final treatment sessions).

Initial development of a brief assessment of cocaine demand.

Cocaine demand is a behavioral economic measure assessing drug reward value and motivation to use drug. The purpose of the current study was to develop a brief assessment of cocaine demand (BACD). Results from the BACD were compared with self-report measures of cocaine use. Participants consisted of treatment-seeking individuals with cocaine use disorder (N = 22). Results revealed that indices of brief demand were significantly associated with various self-report measures of cocaine use. Overall, these results support the utility of a BACD for assessing cocaine demand.

Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: A Pilot Randomized Controlled Trial.

INTRODUCTION: Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving, and withdrawal symptoms, with post-cessation body weight as a secondary outcome. METHODS: Eighty-four prediabetic and/or overweight smokers were randomized (1 : 1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal, and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes. RESULTS: Exenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (risk ratio [RR] = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP = 97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively. CONCLUSIONS: Exenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies. IMPLICATIONS: Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.

A meta-analysis of tract-based spatial statistics studies examining white matter integrity in cocaine use disorder.

Tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) studies have consistently shown diminished white matter (WM) integrity for individuals with cocaine use disorder (CUD). The present study used seed-based d mapping (SDM) to determine the extent to which a systematic difference in the WM integrity of cocaine users may exist (as compared with that of healthy controls). Articles from 2006 (when TBSS was first developed) to present were reviewed, with eight selected for inclusion. Meta-analysis found lower fractional anisotropy (FA) in the genu of the corpus callosum for cocaine users, with a small-to-moderate peak effect size (Hedge's g = -0.331). Sensitivity analyses mostly supported the robustness of the obtained difference. Differences detected at exploratory thresholds for significance suggested insult to WM integrity extending beyond the corpus callosum. The present results compliment a previous region-of-interest (ROI)-based meta-analysis of DTI studies in individuals with CUD. These findings have significant implications for the potential role of neuroprotective agents in the treatment of CUD and merit additional iteration as more studies accrue in the literature.

Plasma pro- and anti-inflammatory cytokines may relate to cocaine use, cognitive functioning, and depressive symptoms in cocaine use disorder.

BACKGROUND: Inflammation is implicated in cocaine use and associated problems, including depression and cognitive impairment. OBJECTIVE: We assessed 18 cytokines, cocaine use, cognition, and depression in individuals with Cocaine Use Disorder. Our general hypothesis was that higher pro-inflammatory cytokines would relate to more cocaine use, poorer cognition, and more depression, while higher anti-inflammatory cytokines would relate to less cocaine use, better cognition, and less depression. METHODS: Data were collected from 85 individuals (76.5% male, 80% African American) aged 18-65. The ASI, Shipley-2, and BDI-II assessed frequency and duration of cocaine use, cognition, and depression. Cytokines were tested using Bio-Plex Pro™ assays. Elastic net regression identified which cytokines related to each measure, controlling for confounds. RESULTS: Lower IL-29 (B = -0.08, bootstrapped 95%CI = [-0.24,0.07]), scD163 (B = -0.11, bootstrapped 95%CI = [-0.27,0.04]), Eotaxin-1 CCL11 (B = -0.11, bootstrapped 95%CI = [-0.30,0.08]), and higher APRIL/TNFSF13 (B = 0.11, bootstrapped 95%CI = [-0.08,0.30]) related to more frequent cocaine use. Lower IL-29 (B = -0.24, bootstrapped 95% CI = [-2.26,1.79]) and IL-20 (B = -1.62, bootstrapped 95%CI = [-3.53,0.29]) related to longer duration of cocaine use. Higher Eotaxin-2 CCL24 (B = 2.79, bootstrapped 95%CI = [-0.59,6.17]) and TWEAK (B = 2.83, bootstrapped 95%CI = [-0.80,6.45]) related to better cognition. Finally, higher IL-20 (B = -1.83, bootstrapped 95%CI = [-3.70,0.04]) and Osteocalcin (B = -1.56, bootstrapped 95%CI = [-3.81,0.70]) related to lower depressive symptoms. However, none of these relationships survived bootstrapped analyses. CONCLUSION: Pro- and anti-inflammatory cytokines may relate to cocaine use, cognition, and depression, but inconsistent with our hypotheses, higher pro-inflammatory cytokines related to better functioning in several domains. Additionally, cytokines were selected at low frequencies and demonstrated weak relationships with outcomes. These preliminary findings suggest complex relationships between inflammation and cocaine use.

Prevalence and Correlates of Sex Selling and Sex Purchasing among Adults Seeking Treatment for Cocaine Use Disorder.

Exchange sex places individuals with cocaine use disorder (CUD) at particularly high risk for deleterious safety and health outcomes. A substance use treatment provider who is aware of a patient's exchange sex behavior is better able to provide appropriate screening, care, and/or referral to risk reduction services. However, little is known about exchange sex, especially purchasing, among treatment-seeking adults with CUD.The current study examined the prevalence and correlates of sex selling and sex purchasing among treatment-seeking men and women with CUD (n = 109; ClinicalTrials.gov #NCT02896712). Separate binary logistic regressions via backward elimination were used to identify best fitting models for sex selling and sex purchasing.Over 41% of participants endorsed exchange sex within the last 30 days; 20.2% reported selling sex and 30.3% reported purchasing sex. Sex selling and sex purchasing rates differed by gender and race. Number of sexual partners (OR = 5.83, 95% CI = 2.07-16.43), concern about contracting HIV/AIDS (OR = 2.01, 95% CI = 1.31-3.44), cumulative interpersonal trauma exposure (OR = 1.82, 95% CI = 1.20-2.77), years using cocaine (OR = 1.11, 95% CI = 1.03-1.20), drug-related problem days (OR = 1.07, 95% CI = 1.00-1.14), and sexual preference (OR = 9.50, 95% CI = .69-130.35) were retained in the final model estimating sex selling (Nagelkerke R2 = .56). In the final sex purchasing model (Nagelkerke R2 = .46), gender (OR = 36.17, 95% CI = 2.96-441.75), number of sexual partners (OR = 6.28, 95% CI = 2.69-14.66), number of convictions (OR = 1.13, 95% CI = 1.02-1.25), and drug-related problem days (OR = 0.96, 95% CI = .92-1.01) were retained.Predictive models in this study identified distinct sets of variables related to sex selling and purchasing. Findings may be used to improve identification of exchange sex in the substance use treatment setting and referral to targeted interventions to reduce associated risk.

Objective analysis of language use in cognitive-behavioral therapy: associations with symptom change in adults with co-occurring substance use disorders and posttraumatic stress.

Substance use disorders (SUD) commonly co-occur with posttraumatic stress disorder (PTSD) symptoms, and the comorbidity is prevalent and difficult-to-treat. Few studies have objectively analyzed language use in psychotherapy as a predictor of treatment outcomes. We conducted a secondary analysis of patient language use during cognitive-behavioral therapy (CBT) in a randomized clinical trial, comparing a novel, integrated CBT for PTSD/SUD with standard CBT for SUD. Participants included 37 treatment-seeking, predominantly African-American adults with SUD and at least four symptoms of PTSD. We analyzed transcripts of a single, matched session across both treatment conditions, using the Linguistic Inquiry and Word Count (LIWC) program. The program measures language use across multiple categories. Compared to standard CBT for SUD, patients in the novel, integrated CBT for PTSD/SUD used more negative emotion words, partially consistent with our hypothesis, but less positive emotion words. Further, exploratory analyses indicated an association between usage of cognitive processing words and clinician-observed reduction in PTSD symptoms, regardless of treatment condition. Our results suggest that language use during therapy may provide a window into mechanisms active in therapy.

Reducing Tobacco Smoke Exposure in High-Risk Infants: A Randomized, Controlled Trial.

OBJECTIVE: To evaluate a hospital-initiated intervention to reduce tobacco smoke exposure in infants in the neonatal intensive care unit. STUDY DESIGN: A randomized, controlled trial compared motivational interviewing plus financial incentives with conventional care on infant urine cotinine at 1 and 4 months' follow-up. Mothers of infants in the neonatal intensive care unit (N = 360) who reported a smoker living in the home were enrolled. Motivational interviewing sessions were delivered in both the hospital and the home. Financial incentives followed session attendance and negative infant cotinine tests postdischarge. RESULTS: The intervention effect on infant cotinine was not significant, except among mothers who reported high baseline readiness/ability to protect their infant (P ≤ .01) and mothers who completed the study within 6 months postdischarge (per protocol; P ≤ .05). Fewer mothers in the motivational interviewing plus financial incentives condition were smoking postdischarge (P ≤ .01). More mothers in the motivational interviewing plus financial incentives group reported a total home and car smoking ban at follow-up (P ≤ .05). CONCLUSIONS: Motivational interviewing combined with financial incentives reduced infant tobacco smoke exposure in a subset of women who were ready/able to protect their infant. The intervention also resulted in less maternal smoking postpartum. More robust interventions that include maternal and partner/household smoking cessation are likely needed to reduce the costly effects of tobacco smoke exposure on children and their families. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01726062.

Resting Heart Rate Variability: Exploring Associations With Symptom Severity in Adults With Substance Use Disorders and Posttraumatic Stress.

Objective: Substance use disorders and posttraumatic stress symptoms are commonly comorbid. Previous studies have established that those with substance use disorders or posttraumatic stress disorder (PTSD) have lower high frequency-heart rate variability (HF-HRV) compared to controls, suggesting that low HF-HRV may be a biomarker of a common physiological mechanism underlying both disorders. We evaluated HF-HRV as a potential biomarker of a common underlying process by testing whether lower HF-HRV related to greater severity of substance use and PTSD symptoms in individuals with both substance use disorders and at least four symptoms of PTSD. Methods: HF-HRV was measured in 49 adults with substance use disorders and at least four symptoms of PTSD. We performed a series of regressions controlling for age to test whether low HF-HRV was associated with greater substance use disorder and PTSD symptom severity. Substance use disorder symptoms were measured by the Addiction Severity Index and PTSD symptoms were measured by the Clinician-Administered PTSD Scale and the PTSD Checklist. Results: After controlling for age, low resting HF-HRV was significantly associated with drug and alcohol symptom severity but not PTSD symptom severity. Conclusions: HF-HRV may be more sensitive to the severity of drug and alcohol use rather than PTSD. Findings may suggest that in PTSD populations, HF-HRV may primarily index comorbid substance use disorder symptoms. HF-HRV could serve as an objective measure of substance use severity and should be further investigated as a predictor of outcomes in treatment for substance use disorders.

A Novel, Integrated Cognitive-Behavioral Therapy for Co-Occurring Posttraumatic Stress and Substance Use Disorders: A Case Study.

Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are complex psychiatric conditions that commonly co-occur. No preferred, evidence-based treatments for PTSD/SUD comorbidity are presently available. Promising integrated treatments have combined prolonged exposure therapy with cognitive-behavioral relapse prevention therapy for SUD. We describe a case study that showcases a novel, integrated cognitive-behavioral treatment approach for PTSD/SUD, entitled Treatment of Integrated Posttraumatic Stress and Substance Use (TIPSS). The TIPSS program integrates cognitive processing therapy with cognitive-behavioral therapy for SUD for the treatment of co-occurring PTSD/SUD. The present case report, based upon a woman with PTSD comorbid with both cocaine and alcohol dependence, demonstrates that TIPSS has the potential to effectively reduce PTSD symptoms as well as substance use.

Cognitive-behavioral therapies for depression and substance use disorders: An overview of traditional, third-wave, and transdiagnostic approaches.

BACKGROUND: The co-occurrence of depression and substance use disorders (SUD) is highly prevalent and associated with poor treatment outcomes for both disorders. As compared to individuals suffering from either disorder alone, individuals with both conditions are likely to endure a more severe and chronic clinical course with worse treatment outcomes. Thus, current practice guidelines recommend treating these co-occurring disorders simultaneously. OBJECTIVES: The overarching aims of this narrative are two-fold: (1) to provide an updated review of the current empirical status of integrated psychotherapy approaches for SUD and depression comorbidity, based on models of traditional cognitive-behavioral therapy (CBT) and newer third-wave CBT approaches, including acceptance- and mindfulness-based interventions and behavioral activation (BA); and (2) to propose a novel theoretical framework for transdiagnostic CBT for SUD-depression, based upon empirically grounded psychological mechanisms underlying this highly prevalent comorbidity. RESULTS: Traditional CBT approaches for the treatment of SUD-depression are well-studied. Despite advances in the development and evaluation of various third-wave psychotherapies, more work needs to be done to evaluate the efficacy of such approaches for SUD-depression. CONCLUSION: Informed by this summary of the evidence, we propose a transdiagnostic therapy approach that aims to integrate treatment elements found in empirically supported CBT-based interventions for SUD and depression. By targeting shared cognitive-affective processes underlying SUD-depression, transdiagnostic treatment models have the potential to offer a novel clinical approach to treating this difficult-to-treat comorbidity and relevant, co-occurring psychiatric disturbances, such as posttraumatic stress.

Bradycardia as a Marker of Chronic Cocaine Use: A Novel Cardiovascular Finding.

Few studies have examined the effects of chronic cocaine use on the resting surface electrocardiogram (ECG) between exposures to cocaine. Researchers compared 12-lead ECGs from 97 treatment-seeking cocaine-dependent patients, with ECG parameters from 8,513 non-cocaine-using control patients from the Atherosclerosis Risk in Communities study. After matching and adjusting for relevant covariates, cocaine use demonstrated large and statistically reliable effects on early repolarization, bradycardia, severe bradycardia, and heart rate. Current cocaine dependence corresponds to an increased odds of demonstrating early repolarization by a factor of 4.92 and increased odds of bradycardia and severe bradycardia by factors 3.02 and 5.11, respectively. This study demonstrates the novel finding that long-lasting effects of cocaine use on both the cardiac conduction and the autonomic nervous system pose a risk of adverse cardiovascular events between episodes of cocaine use, and that bradycardia is a marker of chronic cocaine use.

Prevalence of traumatic brain injury in cocaine-dependent research volunteers.

BACKGROUND: There is a high prevalence of traumatic brain injury (TBI) among those with substance dependence. However, TBI often remains undiagnosed in these individuals, due to lack of routine screening in substance use treatment settings or due to overlap in some of the cognitive sequelae (eg impulsivity, disinhibition) of TBI and cocaine dependence. METHODS: The prevalence of self-reported mild to moderate TBI in a group of cocaine-dependent (n = 95) and a group of healthy volunteers (n = 75) enrolled at the same facility was assessed. Additionally, the relationship between TBI and clinically relevant correlates, including impulsivity, cocaine use history, and treatment outcome in the cocaine-dependent group was also examined. RESULTS: A higher proportion of individuals with cocaine dependence (29.5%) reported having suffered a TBI in their lifetime compared to controls (8%) on a Closed Head Injury scale. Among cocaine users, the average age of sustaining TBI was significantly lower than the age of initiating cocaine use. Presence of TBI was not associated with higher impulsivity on the Barratt Impulsiveness Scale-11 or self-reported years of cocaine use. No differences were noted on treatment outcome for cocaine dependence as measured by treatment effectiveness scores (TES) between cocaine users with TBI and their non-TBI counterparts. CONCLUSIONS: These results are the first to highlight the high prevalence of TBI among individuals with cocaine dependence. This study underscores the possible role of TBI history as a risk factor for onset of cocaine use, however, more research is needed to determine the impact of co-morbid TBI as a complicating factor in the substance abuse treatment setting.

Hospital length of stay in individuals with schizophrenia with and without cocaine-positive urine drug screens at hospital admission.

Despite the high prevalence of cocaine use disorder (CUD) in individuals with schizophrenia, current understanding of the effect of cocaine on psychiatric hospital length of stay (LOS) in individuals with schizophrenia is limited. We therefore retrospectively examined the medical records of 5106 hospital admissions due to exacerbation of schizophrenia. Linear regression and t-test were used to compare LOS between individuals with schizophrenia with cocaine-positive urine drug test results and those with negative test results. Individuals with schizophrenia who were also positive for cocaine had shorter LOS from both unadjusted (geometric mean LOS, 8.07 ± 1.92 vs. 11.83 ± 1.83 days; p < 0.001) and adjusted (ß = 0.69; confidence interval, 0.63-0.76; p < 0.001) analyses. Our results suggest that individuals with schizophrenia who also have comorbid CUD may require shorter inpatient treatment during periods of exacerbation of symptoms. Replication of this finding has relevance in treatment planning and resource allocation for the subpopulation of individuals with schizophrenia who also have stimulant use disorders.

Demographic and psychological factors associated with lifetime cocaine use: An exploratory factor analysis of baseline questionnaires.

OBJECTIVES: Underlying heterogeneity among individuals with cocaine dependence is widely postulated in the literature, however, identification of a group of factors that explain risk of cocaine use severity has yet to be confirmed. METHODS: Latent mixture modeling evaluated 338 cocaine-dependent individuals recruited from the community to assess the evidence for the presence of distinct subgroups. Variables included 5 baseline questionnaires measuring cognitive function (Shipley), impulsivity (BIS), mood (BDI), affective lability (ALS), and addiction severity (ASI). Results failed to suggest multiple subgroups. Given a lack of evidence for discrete latent classes, an exploratory factor analysis (EFA) followed by exploratory structural equation modeling (ESEM) was implemented to identify functional dimensions to enhance interpretation of these variables. RESULTS: Findings from the EFA indicated a 3-factor model as the best fit, and the subsequent ESEM solution resulted in associations with lifetime cocaine use. Factor 1, best characterized by demographic factors (gender, age), is associated with less lifetime cocaine use. Psychological problems best characterize factor 2, which is associated with higher lifetime cocaine use. Finally, factor 3 is characterized by other substance use (alcohol and marijuana). Although this factor did not demonstrate a statistically reliable relation with self-reported, lifetime cocaine use, it did indicate a potentially meaningful positive association. CONCLUSIONS: These 3 factors delineate dimensions of functioning that likewise help characterize the variability found in previously established associations with self-reported cocaine use.

The influence of dopamine ß-hydroxylase gene polymorphism rs1611115 on levodopa/carbidopa treatment for cocaine dependence: a preliminary study.

Recent studies have suggested that heterogeneity in the level of dopamine activity and function might be useful for identifying a subgroup of cocaine-dependent patients responding better to dopamine-enhancement pharmacotherapy. Here we hypothesized that response to levodopa/carbidopa treatment would be greater in patients with genetically determined low levels of the dopamine metabolizing enzyme dopamine ß-hydroxylase (DßH). Seventy-one cocaine-dependent patients who participated in a 12-week randomized double-blind placebo-controlled trial of levodopa/carbidopa were genotyped for the DßH gene (DBH) polymorphism rs1611115. Our results showed that for patients with the low DßH activity genotypes (CT/TT) who received levodopa, the odds of having cocaine-positive urine decreased significantly over treatment compared with placebo-treated patients with the CT/TT genotypes (P=0.004). Individuals with the normal DßH activity genotype (CC) showed no differential response to levodopa. These preliminary results need to be confirmed in a larger sample focusing on the DBH polymorphism.

Behavioral therapies targeting reward mechanisms in substance use disorders.

Behavioral therapies are considered best practices in the treatment of substance use disorders (SUD) and used as first-line approaches for SUDs without FDA-approved pharmacotherapies. Decades of research on the neuroscience of drug reward and addiction have informed the development of current leading behavioral therapies that, while differing in focus and technique, have in common the overarching goal of shifting reward responding away from drug and toward natural non-drug rewards. This review begins by describing key neurobiological processes of reward in addiction, followed by a description of how various behavioral therapies address specific reward processes. Based on this review, a conceptual 'map' is crafted to pinpoint gaps and areas of overlap, serving as a guide for selecting and integrating behavioral therapies.

Contingency management plus acceptance and commitment therapy for initial cocaine abstinence: Results of a sequential multiple assignment randomized trial (SMART).

BACKGROUND: This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1. METHOD: For Phase 1 of treatment, participants (N=118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists. RESULTS: Phase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed. DISCUSSION: Adding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy.