Faculty Bibliography

OBJECTIVES/OBJECTIVE:HIV/STD sexual risk behavior is common among women who use drugs. To effectively implement interventions in busy drug treatment programs, it is important to have a rapid and accurate measure of sexual risk. This study compared 2 dichotomous ratings of unprotected sex among women in substance abuse treatment who participated in a HIV sexual risk reduction clinical trial: (1) any unprotected vaginal/anal sex occasions in the last 3 months, versus (2) unprotected vaginal/anal sex at last sexual occasion (LSO). METHODS:Sexually active women from 12 methadone maintenance or psychosocial outpatient programs who had a main (n = 363) or other male partner(s) (n = 117) were assessed at baseline for unprotected sex in the last 3 months and at LSO. These 2 measures were compared for congruence. RESULTS:Participants who reported unprotected sex at LSO consistently reported at least 1 unprotected sex occasion in the last 3 months: 99.1% for main male partner sex and 93.8% for other male partner sex. Participants who reported using a condom at LSO were less consistent of those reporting condom use at LSO; only 30.3% reported protected sex at all sex occasions in the last 3 months with main male partner and only 67.6% for other male partner(s). CONCLUSIONS:Use of one question about condom protected sex at LSO appears to be a partially useful tool. It can be useful for detecting sexual risk in clinical or research settings wherein the central focus is not on sexual behavior or when time is limited.

INTRODUCTION/BACKGROUND:A preponderance of relevant research has indicated reduction in anxiety and depressive symptoms following smoking abstinence. This secondary analysis investigated whether the phenomenon extends to smokers with attention deficit hyperactivity disorder (ADHD). METHODS:The study setting was an 11-Week double-blind placebo-controlled randomized trial of osmotic release oral system methylphenidate (OROS-MPH) as a cessation aid when added to nicotine patch and counseling. Participants were 255 adult smokers with ADHD. The study outcomes are: anxiety (Beck Anxiety Inventory (BAI)) and depressed mood (Beck Depression Inventory II (BDI)) measured one Week and six Weeks after a target quit day (TQD). The main predictor is point-prevalence abstinence measured at Weeks 1 and 6 after TQD. Covariates are treatment (OROS-MPH vs placebo), past major depression, past anxiety disorder, number of cigarettes smoked daily, demographics (age, gender, education, marital status) and baseline scores on the BAI, BDI, and the DSM-IV ADHD Rating Scale. RESULTS:Abstinence was significantly associated with lower anxiety ratings throughout the post-quit period (p<0.001). Depressed mood was lower for abstainers than non-abstainers at Week 1 (p<0.05), but no longer at Week 6 (p=0.83). Treatment with OROS-MPH relative to placebo showed significant reductions at Week 6 after TQD for both anxiety (p<0.05) and depressed mood (p<0.001), but not at Week 1. Differential abstinence effects of gender were observed. Anxiety and depression ratings at baseline predicted increased ratings of corresponding measures during the post-quit period. CONCLUSION/CONCLUSIONS:Stopping smoking yielded reductions in anxiety and depressed mood in smokers with ADHD treated with nicotine patch and counseling. Treatment with OROS-MPH yielded mood reductions in delayed manner.

BACKGROUND:Evidence suggests that the cannabinoid system is involved in the maintenance of opioid dependence. We examined whether dronabinol, a cannabinoid receptor type 1 partial agonist, reduces opioid withdrawal and increases retention in treatment with extended release naltrexone (XR-naltrexone). METHODS:Opioid dependent participants were randomized to receive dronabinol 30mg/d (n=40) or placebo (n=20), under double-blind conditions, while they underwent inpatient detoxification and naltrexone induction. Before discharge all participants received an injection of XR-naltrexone, with an additional dose given four weeks later. Dronabinol or placebo was given while inpatient and for 5 weeks afterwards. The primary outcomes were the severity of opioid withdrawal, measured with the Subjective Opioid Withdrawal Scale, and retention in treatment at the end of the inpatient phase and at the end of the 8-week trial. RESULTS:The severity of opioid withdrawal during inpatient phase was lower in the dronabinol group relative to placebo group (p=0.006). Rates of successful induction onto XR-naltrexone (dronabinol 66%, placebo 55%) and completion of treatment (dronabinol 35%, placebo 35%) were not significantly different. Post hoc analysis showed that the 32% of participants who smoked marijuana regularly during the outpatient phase had significantly lower ratings of insomnia and anxiety and were more likely to complete the 8-week trial. CONCLUSION/CONCLUSIONS:Dronabinol reduced the severity of opiate withdrawal during acute detoxification but had no effect on rates of XR-naltrexone treatment induction and retention. Participants who elected to smoke marijuana during the trial were more likely to complete treatment regardless of treatment group assignment.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Extended-release (XR) injection naltrexone has proved promising in the treatment of opioid dependence. Induction onto naltrexone is often accomplished with a procedure known as rapid naltrexone induction. The purpose of this study was to evaluate pre-treatment patient characteristics as predictors of successful completion of a rapid naltrexone induction procedure prior to XR naltrexone treatment. METHODS:A chart review of 150 consecutive research participants (N = 84 completers and N = 66 non-completers) undergoing a rapid naltrexone induction with the buprenorphone-clonidine procedure were compared on a number of baseline demographic, clinical and psychosocial factors. Logistic regression was used to identify client characteristics that may predict successful initiation of naltrexone after a rapid induction-detoxification. RESULTS:Patients who failed to successfully initiate naltrexone were younger (AOR: 1.040, CI: 1.006, 1.075), and using 10 or more bags of heroin (or equivalent) per day (AOR: 0.881, CI: 0.820, 0.946). Drug use other than opioids was also predictive of failure to initiate naltrexone in simple bivariate analyses, but was no longer significant when controlling for age and opioid use level. CONCLUSIONS:Younger age, and indicators of greater substance dependence severity (more current opioid use, other substance use) predict difficulty completing a rapid naltrexone induction procedure. Such patients might require a longer period of stabilization and/or more gradual detoxification prior to initiating naltrexone. SCIENTIFIC SIGNIFICANCE/CONCLUSIONS:Our study findings identify specific characteristics of patients who responded positively to rapid naltrexone induction.

BACKGROUND: Extended-release naltrexone (XR-NTX, Vivitrol(R); Alkermes Inc.) is an injectable monthly sustained-release mu opioid receptor antagonist. XR-NTX is a potentially effective intervention for opioid use disorders and as relapse prevention among criminal justice system (CJS) populations. METHODS: This 5-site open-label randomized controlled effectiveness trial examines whether XR-NTX reduces opioid relapse compared with treatment as usual (TAU) among community dwelling, non-incarcerated volunteers with current or recent CJS involvement. The XR-NTX arm receives 6 monthly XR-NTX injections at Medical Management visits; the TAU group receives referrals to available community treatment options. Assessments occur every 2weeks during a 24-week treatment phase and at 12- and 18-month follow-ups. The primary outcome is a relapse event, defined as either self-report or urine toxicology evidence of >/=10days of opioid use in a 28-day (4week) period, with a positive or missing urine test counted as 5days of opioid use. RESULTS: We describe the rationale, specific aims, and design of the study. Alternative design considerations and extensive secondary aims and outcomes are discussed. CONCLUSIONS: XR-NTX is a potentially important treatment and relapse prevention option among persons with opioid dependence and CJS involvement. ClinicalTrials.gov: NCT00781898.

OBJECTIVE:To evaluate efficacy and safety of injectable extended-release naltrexone (XR-NTX, Vivitrol), an opioid receptor antagonist, in the treatment of opioid dependence, we carried out a 1-year open-label extension study. MATERIAL AND METHODS/METHODS:The study followed the initial 6-month randomized, double-blind, PBO-controlled investigation of XR-NTX, used in dose 380 mg, as a treatment for opioid dependence. The study was conducted at 13 clinical sites in Russia. The main measurements were monthly urine samples (efficacy) and adverse events (safety). RESULTS AND CONCLUSION/CONCLUSIONS:The open-label extension included 114 patients (67 continued on XR-NTX and 47 switched from placebo). Overall, 62.3% (95% CI: 52.7%, 71.2%) of patients completed the extension. Urine testing revealed that 50.9% (41.5%, 60.4%) were abstinent from opioids at all assessments during the 1-year open-label phase. Adverse events were reported by 21.1% of patients. Elevations in liver function tests occurred in 16.7% of patients. No severe adverse events were reported. The data obtained demonstrate the long-term safety and efficacy of XR-NTX in opioid dependent patients.

BACKGROUND AND AIMS/OBJECTIVE:Cannabis-dependent participants with depressive disorder are less likely to achieve abstinence with venlafaxine-XR (VEN-XR) treatment. Individuals on VEN-XR reported more severe withdrawal, despite not reducing their smoking behavior. We hypothesized that withdrawal-like symptoms, likely medication side effects, led to continued marijuana smoking in this group. METHODS:We conducted a secondary analysis using Marijuana Withdrawal Checklist (MWC) scores and urine THC to test whether severity of withdrawal-like symptoms mediates the relationship between VEN-XR treatment and continued marijuana smoking. We included 103 participants (VEN-XR=51, Placebo=52). Marijuana use was dichotomized into smoking (THC>100 ng/ml) and non-smoking (THC ≤ 100 ng/ml) weeks. MWC scores were obtained weekly. We used three models in a regression based mediation analysis. RESULTS:The estimated risk of smoking marijuana was greater for individuals on VEN-XR in weeks 7-9, even when controlling for MWC scores (week 7 Risk Difference (RD)=0.11, p=0.034; week 8 RD=0.20, p=0.014), and higher scores mediated this effect. In weeks 10 and 11, the estimated effect was stronger (week 10 RD=0.03, p=0.380; week 11 RD=0.07, p=0.504), and worse withdrawal-like symptoms more fully accounted for continued marijuana smoking in the VEN-XR group, according to the models. CONCLUSIONS:Individuals treated with VEN-XR had more severe withdrawal-like symptoms, which mediated their continued marijuana smoking. Noradrenergic agents, such as VEN-XR, may negatively impact treatment outcomes in cannabis-dependent patients attempting to reduce or stop their use.

BACKGROUND:Developing personalized treatments for cocaine dependence remains a significant clinical challenge. Positron emission tomography (PET) has shown that the [(11)C]raclopride signal in the ventral striatum is associated with treatment success in a positively reinforced contingency management program. The present study investigates whether this signal can be used to predict treatment outcome at an individual level. METHODS:Predictive models were developed using PET signals from 5 regions of the striatum and follow-up data in 24 patients, and evaluated using cross-validation. RESULTS:The ventral striatal PET signal alone can predict individual treatment response with a substantial degree of accuracy (cross-validated correct rate=82%). Incorporating information from other regions-of-interest (ROIs) in the striatum does not improve predictive performance, except for a small improvement with adding the posterior caudate. The addition of baseline demographic variables, including baseline severity measures, does not improve predictive performance. On the other hand, early treatment response and motivation, reflected by cumulative clinic attendance, performs as well as the PET signal (83%) by week 3 in the 24-week study. The combined model with both PET signals and cumulative clinic attendance demonstrates a significant improvement of performance, peaking at 96% during week 3 of the trial. CONCLUSIONS:These results suggest that a multimodal model can predict treatment success in cocaine dependence at an individual level, and pose hypotheses for the underlying neural circuitry mechanisms responsible for individual variations in treatment outcome.

BACKGROUND:There are no efficacious pharmacotherapies for cannabis dependence. The effects of quetiapine are well matched to the symptoms of cannabis withdrawal and could be useful in the treatment of cannabis dependence. OBJECTIVES/OBJECTIVE:To evaluate quetiapine for the treatment of cannabis dependence and determine the optimal dosing. METHODS:In an eight-week open-label outpatient pilot trial, we evaluated the feasibility of quetiapine treatment for cannabis dependence in 15 outpatients. Quetiapine was gradually titrated to 600 mg or the maximum tolerated dose. RESULTS:The mean study retention was 6.5 weeks (±2.3), with 67% of participants completing all eight weeks of the trial. The mean maximum dose achieved was 197 mg/day (range: 25-600 mg/day). Only two of the 15 participants were able to achieve the target dose of 600 mg daily. There were no serious adverse events and no participants were discontinued from the trial due to adverse effects. The most common reported adverse effects were fatigue (80% of participants) and somnolence (47%). From baseline to week 8, the modeled overall decrease in daily dollar value of marijuana was 76.3% (CI: 63.4%, 84.7%). Over the eight weeks of the study, there was a 46.9% (CI: 11%, 68.3%) decrease in urine tetrahydrocannabinol-9-carboxylic acid (THCOOH) levels. CONCLUSIONS:These preliminary results are promising in that quetiapine treatment was tolerated by cannabis-dependent patients and associated with decreased cannabis use. The recommended maximum target dose for cannabis-dependent patients is 300 mg daily. These preliminary data support further evaluation of quetiapine as a treatment for cannabis dependence.

BACKGROUND:This study describes early treatment drug use status and associated clinical characteristics in a diverse sample of patients entering outpatient substance abuse psychosocial counseling treatment. The goal is to more fully characterize those entering treatment with and without active use of their primary drug in order to better understand associated treatment needs and resilience factors. METHODS:We examined baseline data from a NIDA Clinical Trials Network (CTN) study (Web-delivery of Treatment for Substance Use) with an all-comers sample of patients (N = 494) entering 10 outpatient treatment centers. Patients were categorized according to self-identified primary drug of abuse (alcohol, cocaine/stimulants, opioids, marijuana) and by baseline drug use status (positive/negative) based on urine testing or self-reports of recent use (alcohol). Characteristics were examined by primary drug and early use status. RESULTS:Classified as drug-negative were 84%, 76%, 62%, and 33% of primary opioid, stimulant, alcohol, and marijuana users; respectively. Drug-positive versus -negative patients did not differ on demographics or rates of substance abuse/dependence diagnoses. However, those negative for active use had better physical and mental health profiles, were less likely to be using a secondary drug, and were more likely to be attending 12-step self-help meetings. CONCLUSIONS:Early treatment drug abstinence is common among substance users entering outpatient psychosocial counseling programs, regardless of primary abused drug. Abstinence (by negative UA) is associated with better health and mental health profiles, less secondary drug use, and more days of 12-step attendance. These data highlight differential treatment needs and resiliencies associated with early treatment drug use status. TRIAL REGISTRATION/BACKGROUND:NCT01104805.