Avatar-assisted therapy: a proof-of-concept pilot study of a novel technology-based intervention to treat substance use disorders.

BACKGROUND: Avatar-assisted therapy (AAT) is a novel and emerging technology that uses the Internet to enable clinicians and clients in substance abuse treatment to participate in group counseling sessions from separate and remote locations in real time through the use of avatars and virtual environments. OBJECTIVES: The current study is a pilot proof-of-concept feasibility study involving individuals in outpatient substance abuse treatment. This report addresses two questions: (1) are individuals who present for substance abuse treatment interested in receiving AAT and (2) what factors are associated with better treatment success. METHODS: Individuals who presented at the treatment clinic who met study eligibility criteria, and provided their written informed consent to participate, were included in the current study (N = 59; 78% male). RESULTS: Twenty-eight (47.5%) participants completed 16 weeks of treatment and attended more sessions compared to non-completers (M = 14.3 vs. 7.5 p < .05). Those individuals who completed treatment were less likely to have a positive urine drug screen at baseline (21.5 vs. 78.6%; p < .05). Furthermore, those individuals who successfully completed treatment were less likely to have positive urine drug screens during treatment compared to those who did not complete (29.7% vs. 70.3%, p < .05). There were no arrests during treatment for completers and non-completers. CONCLUSION: Poor retention in substance use disorder treatment has long been a major problem for public health. AAT is a feasible approach that has the potential to expand treatment to individuals who might have difficulty accessing treatment. Moreover, AAT may be appealing to clients who are concerned about anonymity and confidentiality.

Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial.

IMPORTANCE: The effectiveness of buprenorphine treatment of opioid dependence is limited by suboptimal medication adherence, abuse, and diversion. OBJECTIVE: To determine whether 6-month buprenorphine implants are noninferior to daily sublingual buprenorphine as maintenance treatment for opioid-dependent patients with stable abstinence. DESIGN, SETTING, AND PARTICIPANTS: Outpatient, randomized, active-controlled, 24-week, double-blind, double-dummy study conducted at 21 US sites from June 26, 2014, through May 18, 2015. Outpatients were prescribed daily sublingual buprenorphine for 6 months or more, were abstinent while taking 8 mg/d or less of sublingual buprenorphine for 90 days or longer, and were determined to be clinically stable by their physician. INTERVENTIONS: Participants were randomized to receive sublingual buprenorphine plus 4 placebo implants or sublingual placebo plus four 80-mg buprenorphine hydrochloride implants (expected efficacy, 24 weeks). MAIN OUTCOME MEASURE: The primary end point was between-group difference in proportion of responders (≥4 of 6 months without opioid-positive urine test result [monthly and 4 times randomly] and self-report). The noninferiority established for the lower bound of the 95% confidence interval was greater than -0.20 (P < .025). Secondary end points included cumulative percentage of negative opioid urine results, abstinence, and time to first illicit opioid use. Safety was assessed by adverse event reporting. RESULTS: Of 177 participants (mean age, 39 years; 40.9% female), 90 were randomized to sublingual buprenorphine with placebo implants and 87 to buprenorphine implants with sublingual placebo; 165 of 177 (93.2%) completed the trial. Eighty-one of 84 (96.4%) receiving buprenorphine implants and 78 of 89 (87.6%) receiving sublingual buprenorphine were responders, an 8.8% difference (1-sided 97.5% CI, 0.009 to ∞; P < .001 for noninferiority). Over 6 months, 72 of 84 (85.7%) receiving buprenorphine implants and 64 of 89 (71.9%) receiving sublingual buprenorphine maintained opioid abstinence (hazard ratio, 13.8; 95% CI, 0.018-0.258; P = .03). Non-implant-related and implant-related adverse events occurred in 48.3% and 23% of the buprenorphine implant group and in 52.8% and 13.5% of participants in the sublingual buprenorphine group, respectively. CONCLUSIONS AND RELEVANCE: Among adults with opioid dependence maintaining abstinence with a stable dose of sublingual buprenorphine, the use of buprenorphine implants compared with continued sublingual buprenorphine did not result in an inferior likelihood of remaining a responder. However, the study population had an exceptionally high response rate in the control group, and further studies are needed in broader populations to assess the efficacy in other settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02180659.

Electronic cigarettes in adults in outpatient substance use treatment: Awareness, perceptions, use, and reasons for use.

BACKGROUND AND OBJECTIVES: Most studies on e-cigarettes have come from population-based surveys. The current research aimed to provide initial data on e-cigarette awareness, perceptions, use, and reasons for use among adults seeking substance use treatment. METHODS: A survey was conducted among 198 participants ≥18 years old in a community-based outpatient substance use treatment program. RESULTS: Of the 198 participants, 69% currently smoked cigarettes, 92% were aware of e-cigarettes, and 58% had ever used e-cigarettes. The proportion of the number of participants who had ever used e-cigarettes to the number who currently smoked (89.7%) appeared higher than the corresponding proportion in the 2012-13 National Adult Tobacco Survey (78.3%). Almost half of the sample who reported ever using e-cigarettes endorsed quitting or reducing smoking as a reason for use, and 32% endorsed reasons for use relating to curiosity/experimentation. A greater likelihood of e-cigarette ever-use was significantly associated with younger age (adjusted odds ratio [AOR] = 0.94, 95%confidence interval [CI] = 0.90, 0.98) and perceptions related to using e-cigarettes in public places where smoking cigarettes is not allowed (AOR = 2.96, 95%CI = 1.18, 7.42) but was not associated with primary drug of choice. DISCUSSION AND CONCLUSIONS: E-cigarette use in adults seeking substance use treatment appears higher than it is in the US general population of smokers. The high frequency of use may be due to curiosity/experimentation or attempts to quit or reduce smoking. SCIENTIFIC SIGNIFICANCE: Future research may consider how e-cigarettes interact with other substance use and affect high rates of nicotine and tobacco use in this population.

Buprenorphine Treatment for Probationers and Parolees.

BACKGROUND: Pharmacotherapy studies involving buprenorphine have rarely been conducted with U.S. community corrections populations. This is one of the first reports of buprenorphine treatment outcomes of adult opioid-dependent probationers and parolees. METHODS: This longitudinal study examined the 3-month treatment outcomes for a sample of probation and parole clients (N = 64) who received community-based buprenorphine treatment. RESULTS: Approximately two thirds of the sample (67%) were still in treatment at 3 months post baseline. Furthermore, there was a significant decline in the number of self-reported heroin use days and crime days from baseline to 3 months post baseline. Although there was not a significant reduction in reincarcerations, there was no evidence that they had increased. CONCLUSIONS: Given that buprenorphine is approved by the Food and Drug Administration (FDA) as a safe, effective treatment for opioid use disorders, individuals on parole or probation should have the opportunity to benefit from it through community-based programs.

Dopamine D3 receptors as a therapeutic target for methamphetamine dependence.

BACKGROUND: Methamphetamine (MA) use disorders are major public health problems nationally and worldwide and treatment remains an unmet need. OBJECTIVES: (1) To review preclinical and clinical studies identifying the dopamine D3 receptor as a therapeutic target for substance use disorders (SUDs), including MA dependence, (2) to consider buspirone (Buspar®) as a potential medication based on its dopamine D3 receptor antagonist properties, and (3) to evaluate the safety and initial efficacy of buspirone in a pilot study of MA-dependent individuals. METHODS: Literature on the dopamine D3 receptor as a therapeutic target and on the potential of buspirone as a novel therapy for MA dependence was reviewed. The cardiovascular and subjective effects of intravenous MA challenge were assessed in five non-treatment seeking individuals. Participants met DSM-IV criteria for MA dependence and were treated subacutely (9 days) with buspirone (60 mg daily). RESULTS: The literature identified the dopamine D3 receptor as a therapeutic target for MA dependence, a safe and approved medication, and a valuable opportunity to re-purpose buspirone for treating MA dependence and perhaps other SUDs. Pilot data (n = 5) indicated that buspirone is safe in MA-using individuals and comparison against historical placebo data from this laboratory suggested that at least some aspects of the subjective properties of MA may be diminished during buspirone treatment. CONCLUSION: Future studies should include a small-scale, placebo-controlled Phase IIa trial of buspirone in MA dependence.

Revisiting Preaddiction.

ABSTRACT: The directors of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism have proposed new efforts to enable earlier identification and intervention for harmful substance use and its consequences. As editors of The ASAM Principles of Addiction Medicine, we fully support this goal. The word "preaddiction" has been suggested as a diagnostic label to describe individuals who would be targeted for early intervention. In this commentary, we offer that "unhealthy substance use" would be a better descriptor than "preaddiction" and review several potential barriers to be addressed in order to maximize the impact of introducing this new paradigm.

Experience Starting an Addiction Medicine Practice-Based Research Network.

OBJECTIVES: This paper outlines the experience developing Addiction Medicine Practice-Based Research Network (AMNet), which promotes the adoption of patient-reported outcome measures (PROMs) and measurement-based care in outpatient addiction treatment practices and creates a platform for quality improvement and research. METHODS: From August 2019 to July 2023, the AMNet team selected patient-reported outcome measures for implementation in the American Psychiatric Association's clinical data registry (PsychPRO), recruited addiction medicine providers, and collected PROMs data. RESULTS: AMNet selected 12 PROMs for implementation in PsychPRO. Through July 2023, 1565 providers expressed interest, of whom 216 of the 929 eligible providers (23%) attended an onboarding call/webinar. Two hundred six providers (95%) from 54 practices returned Participation Agreements. Subsequently, 65 providers (32%) from 39 practices withdrew, resulting in 141 (68%) providers from 15 practices. From November 2020 to July 2023, 38 providers submitted PROMs data using 1 of 3 PsychPRO patient portals. Sixteen of the 53 providers (30%) who signed up for the initial portal collected data from 468 patients. As of July 2023, 83 of the 141 providers (59%) opted to submit PROMs data from their own portal or electronic health record. CONCLUSIONS: Next steps will include continued recruitment of providers, addressing barriers to data transfer and integrating data from providers' portals into the registry to create a platform for future research.

Patient Engagement in and Adaptations to Delivery of Outpatient Care for Opioid Use Disorder During the COVID-19 Pandemic.

OBJECTIVE: The authors investigated adaptations to outpatient care delivery and changes in treatment demand and engagement among patients receiving medications for opioid use disorder (MOUD) in the months after the declaration of the COVID-19 public health emergency in 2020. METHODS: Data were collected through an online survey (June-November 2020) of outpatient MOUD prescribers. The survey obtained information on outpatient practices' adaptations to MOUD treatment and urine drug screening (UDS) and elicited provider views on the effects of the COVID-19 pandemic on patient demand for, and engagement in, treatment. Multivariable regression analyses were used to examine associations among practice characteristics, patient engagement, and service adaptations. RESULTS: Of 516 respondents, 74% reported adaptations to MOUD delivery during the pandemic. Most respondents implemented virtual visits for initial (67%) and follow-up (77%) contacts. Prescribers of buprenorphine were more likely than those who did not prescribe the medication to report MOUD adaptations. Among respondents reporting any MOUD adaptation, 77% made adaptations to their UDS practices. Among 513 respondents who answered COVID-19-related questions, 89% reported that the pandemic had affected the treatment and engagement of their patients. Of these respondents, 30% reported increased difficulty with patient engagement, and 45% reported that their patients preferred virtual visits during this period, whereas 18% endorsed patient preference for in-person visits. CONCLUSIONS: Telehealth and federal regulatory easements in response to the COVID-19 pandemic enabled providers to continue treating patients for opioid use disorder in 2020. The results suggest that care adaptations and changes in patient demand and engagement were common in the practices surveyed.

Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial.

Objective: To test esmethadone (REL-1017) as adjunctive treatment in patients with major depressive disorder (MDD) and inadequate response to standard antidepressants.Methods: In this phase 3, double-blind, placebo-controlled trial, outpatients with MDD (DSM-5) were randomized to daily oral esmethadone (75 mg on day 1, followed by 25 mg daily on days 2 through 28) or placebo between December 2020 and December 2022. The primary efficacy measure was change from baseline (CFB) to day 28 in the Montgomery-Asberg Depression Rating Scale (MADRS) score. The intent-to-treat (ITT) population included all randomized participants. The per-protocol (PP) population included completers without major protocol deviations impacting assessment. Post hoc analyses included participants with severe depression (baseline MADRS score ≥35).Results: For the ITT analysis (n = 227), mean CFB was 15.1 (SD 11.3) for esmethadone (n = 113) and 12.9 (SD 10.4) for placebo (n = 114), with a mean difference (MD) of 2.3, which was not statistically significant (P = .154; Cohen effect size [ES] = 0.21). Remission rates were 22.1% and 13.2% (P = .076), and response rates were 39.8% and 27.2% (P = .044) with esmethadone and placebo, respectively. For the PP analysis (n = 198), mean CFB was 15.6 (SD 11.2) for esmethadone (n = 101) and 12.5 (SD 9.9) for placebo (n = 97), with an MD of 3.1 (P = .051; ES =0.29). In post hoc analyses of patients with baseline MADRS ≥35 in the ITT population (n = 112), MD was 6.9; P = .0059; ES = 0.57, and for the PP population (n = 98), MD was 7.9; P = .0015; ES = 0.69. Adverse events (AEs) were predominantly mild or moderate and transient, with no significant differences between groups.Conclusions: The primary end point was not met. Esmethadone showed stronger efficacy in PP than in ITT analyses, with the discrepancy not attributable to AEs impacting treatment adherence. Significant efficacy occurred in post hoc analyses of patients with severe depression. Esmethadone was well tolerated, consistent with prior studies.Trial Registration: ClinicalTrials.gov identifier: NCT04688164.

The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users.

Esmethadone (REL-1017) is the opioid-inactive dextro-isomer of methadone and a low-affinity, low-potency uncompetitive NMDA receptor antagonist. In a Phase 2, randomized, double-blind, placebo-controlled trial, esmethadone showed rapid, robust, and sustained antidepressant effects. Two studies were conducted to evaluate the abuse potential of esmethadone. Each study utilized a randomized, double-blind, active-, and placebo-controlled crossover design to assess esmethadone compared with oxycodone (Oxycodone Study) or ketamine (Ketamine Study) in healthy recreational drug users. Esmethadone 25 mg (proposed therapeutic daily dose), 75 mg (loading dose), and 150 mg (Maximum Tolerated Dose) were evaluated in each study. Positive controls were oral oxycodone 40 mg and intravenous ketamine 0.5 mg/kg infused over 40 min. The Ketamine study included oral dextromethorphan 300 mg as an exploratory comparator. The primary endpoint was maximum effect (Emax) for Drug Liking, assessed using a bipolar 100-point visual analog scale (VAS). A total of 47 and 51 participants completed the Oxycodone Study and the Ketamine Study, respectively (Completer Population). In both studies, esmethadone doses ranging from therapeutic (25 mg) to 6 times therapeutic (150 mg) had a meaningful and statistically significantly (p < 0.001) lower Drug Liking VAS Emax compared with the positive control. Results were consistent for all secondary endpoints in both studies. In both studies, all doses of esmethadone were statistically equivalent to placebo on Drug Liking VAS Emax (p < 0.05). In the Ketamine Study, Drug Liking VAS Emax scores for esmethadone at all tested doses were significantly lower vs. dextromethorphan (p < 0.05) (exploratory endpoint). These studies indicate no meaningful abuse potential for esmethadone at all tested doses.

Novel rapid-acting sublingual nicotine tablet as a cigarette substitution strategy.

RATIONALE: Current nicotine replacement products provide a much slower onset of nicotine delivery than cigarettes, and hence are only marginally effective at supplanting cigarette smoking. Therefore, more effective forms of nicotine replacement are needed. OBJECTIVES: This initial investigation characterized the pharmacokinetic (PK) and subjective effects of a novel sublingual (SL) nicotine tablet designed to deliver nicotine more rapidly to the bloodstream of smokers. METHODS: Study 1 (N = 6) characterized the pharmacokinetics of a 2 mg nicotine SL tablet in comparison to an FDA-approved, marketed 2 mg nicotine lozenge. Study 2 (N = 24) assessed subjective responses of smokers to a single use of a 1 mg and 2 mg SL tablet. RESULTS: Study 1 found that the time to maximum blood nicotine concentrations was significantly shorter for the SL tablet (14 min) than for the lozenge (82 min), and the initial rate of nicotine absorption was higher (0.4 ng/mL*min vs. 0.0 ng/mL*min), supporting the hypothesis that the SL tablet delivered nicotine more rapidly. Study 2 found that participants reported immediate relief of nicotine withdrawal symptoms after tablet administration, and craving reduction after the 2 mg tablet approached the degree reported for their usual brands of cigarettes (4.2 vs. 4.6 on a 7-point scale). Other subjective responses showed the tablet to be an appealing alternative to smoking. CONCLUSIONS: The novel SL tablet studied shows promise as a nicotine substitution strategy for tobacco harm reduction and smoking cessation treatment. Additional studies are warranted to further investigate the potential of this new approach.

Psychedelic drug abuse potential assessment research for new drug applications and Controlled Substances Act scheduling.

New medicines containing classic hallucinogenic and entactogenic psychedelic substance are under development for various psychiatric and neurological disorders. Many of these, including psilocybin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are Schedule I controlled substances of the United States Controlled Substances Act (US CSA), and similarly controlled globally. The implications of the CSA for research and medicines development, the path to approval of medicines, and their subsequent removal from Schedule I in the US are discussed. This entire process occurs within the framework of the CSA in the US and its counterparts internationally in accordance with international drug control treaties. Abuse potential related research in the US informs the eight factors of the CSA which provide the basis for rescheduling actions that must occur upon approval of a drug that contains a Schedule I substance. Abuse-related research also informs drug product labeling and the risk evaluation and mitigation strategies (REMS) will likely be required for approved medicines. Human abuse potential studies typically employed in CNS drug development may be problematic for substances with strong hallucinogenic effects such as psilocybin, and alternative strategies are discussed. Implications for research, medicinal development, and controlled substance scheduling are presented in the context of the US CSA and FDA requirements with implications for global regulation. We also discuss how abuse-related research can contribute to understanding mechanisms of action and therapeutic effects as well as the totality of the effects of the drugs on the brain, behavior, mood, and the constructs of spirituality and consciousness.

Addiction Medicine Practice-Based Research Network (AMNet): Building Partnerships.

This column describes the collaboration among the American Psychiatric Association (APA), American Society of Addiction Medicine, Friends Research Institute, and the National Institute on Drug Abuse to create the Addiction Medicine Practice-Based Research Network (AMNet). The collaboration, which aims to address the opioid overdose epidemic in the United States, leverages the APA's clinical data registry (PsychPRO) and is recruiting office-based addiction medicine and addiction psychiatry practices for AMNet. AMNet aims to address knowledge gaps regarding patient care in such practices, facilitate performance improvement efforts, and serve as a research platform.

Addiction Medicine Practice-Based Research Network (AMNet): Assessment Tools and Quality Measures.

INTRODUCTION: The need for innovative approaches to address the opioid epidemic in the United States is widely recognized. Many challenges exist to addressing this epidemic, including the obstacles outpatient substance use treatment practices face in implementing measurement-based care (MBC), quality measurement systems, and evidence-based treatments. Also, there are insufficient opportunities for clinicians in these settings to participate in research, resulting in diminished translation of research findings into community-based practice. To address these challenges, the Addiction Medicine Practice-Based Research Network (AMNet) was developed to facilitate the uptake of MBC in outpatient practices via implementation of patient-reported assessments and quality of care performance measures to improve patient outcomes. This network will offer clinicians in outpatient settings (not incuding opioid treatment programs [OTPs]) the opportunity to participate in future substance use disorder treatment research studies. METHODS: A key step in the development of AMNet was the selection of substance use-specific assessment tools and quality of care performance measures for incorporation into the American Psychiatric Association's mental health patient registry, PsychPRO. A scoping review and multi-step consensus-based process were used to identify, review and select candidate assessment tools and quality of care performance measures for opioid use disorders (OUD) and substance use disorders (SUD). RESULTS: Following a consensus-based methodology, 12 standardized assessment tools and 3 quality of care performance measures for OUD and SUD were selected to help facilitate the implementation of MBC and quality improvement for AMNet participants. These tools were further categorized as core and optional. CONCLUSION: By offering a collection of carefully vetted assessment tools and quality measures through PsychPRO, AMNet will help participating clinicians with the systematic uptake of MBC and delivery of evidence-based treatment for patients with SUD. Also, AMNet will act as a centralized repository of data collected from patients and clinicians in non-OTP outpatient addiction medicine practices and serve as a platform for opioid treatment research.

A clinical protocol of a comparative effectiveness trial of extended-release naltrexone versus extended-release buprenorphine with individuals leaving jail.

This study is a randomized, open label, controlled trial of extended-release buprenorphine (XR-B; BRIXADI™ formulation) versus extended-release naltrexone (XR-NTX) in Maryland jails. A 7-site, open-label, equivalence design will randomly assign 240 adults with a history of opioid use disorder (OUD), stratified by gender and jail, who are nearing release to one of two treatment arms: 1) XR-B in jail or 2) XR-NTX in jail, both followed by 6 monthly injections postrelease at a community treatment program. The primary aim is to determine the rate of pharmacotherapy adherence (number of monthly injections received) of XR-B compared to XR-NTX. The proposed study is innovative because it will be the first randomized clinical trial in the U.S. assessing the effectiveness of receiving XR-B vs. XR-NTX in county jails. The public health impact of the study will be highly significant and far-reaching because most individuals with OUD do not receive treatment while incarcerated, thereby substantially raising their likelihood of relapse to drug use, overdose death, and re-incarceration. Understanding how to expand acceptance of medications for OUD in jails, particularly extended-release medications, and supporting treatment engagement and medication adherence in transition to the community, has far-reaching implications for improving treatment access and success in this population.

Health and economic outcomes of treatment with extended-release naltrexone among pre-release prisoners with opioid use disorder (HOPPER): protocol for an evaluation of two randomized effectiveness trials.

BACKGROUND: Persons with an opioid use disorder (OUD) who were incarcerated face many challenges to remaining abstinent; concomitantly, opioid-overdose is the leading cause of death among this population, with the initial weeks following release proving especially fatal. Extended-release naltrexone (XR-NTX) is the most widely-accepted, evidence-based OUD pharmacotherapy in criminal justice settings, and ensures approximately 30 days of protection from opioid overdose. The high cost of XR-NTX serves as a barrier to uptake by many prison/jail systems; however, the cost of the medication should not be viewed in isolation. Prison/jail healthcare budgets are ultimately determined by policymakers, and the benefits/cost-offsets associated with effective OUD treatment will directly and indirectly affect their overall budgets, and society as a whole. METHODS: This protocol describes a study funded by the National Institute of Drug Abuse (NIDA) to: evaluate changes in healthcare utilization, health-related quality-of-life, and other resources associated with different strategies of XR-NTX delivery to persons with OUD being released from incarceration; and estimate the relative "value" of each strategy. Data from two ongoing, publicly-funded, randomized-controlled trials will be used to evaluate these questions. In Study A, (XR-NTX Before vs. After Reentry), participants are randomized to receive their first XR-NTX dose before release, or at a nearby program post-release. In Study B, (enhanced XR-NTX vs. XR-NTX), both arms receive XR-NTX prior to release; the enhanced arm receives mobile medical (place of residence) XR-NTX treatment post-release, and the XR-NTX arm receives referral to a community treatment program post-release. The economic data collection instruments required to evaluate outcomes of interest were incorporated into both studies from baseline. Moreover, because the same instruments are being used in both trials on comparable populations, we have the opportunity to not only assess differences in outcomes between study arms within each trial, but also to merge the data sets and test for differences across trials. DISCUSSION: Initiating XR-NTX for OUD prior to release from incarceration may improve patient health and well-being, while also producing downstream cost-offsets. This study offers the unique opportunity to assess the effectiveness and cost-effectiveness of multiple strategies, according to different stakeholder perspectives.

A randomized controlled trial of buprenorphine for probationers and parolees: Bridging the gap into treatment.

BACKGROUND: Buprenorphine can be effective in a variety of community substance use treatment settings outside of methadone programs, including outpatient programs and medical practices. In these settings, it has been found to be effective in reducing opioid use and retaining patients in treatment. Despite its effectiveness and safety, it is rarely provided to individuals with opioid use disorders in probation and parole settings. METHODS: Male and female individuals under probation or parole supervision (N = 320) with histories of opioid use disorder will be enrolled in this randomized controlled trial. Participants will be randomized to one of two study arms: Buprenorphine Bridge Treatment (BBT): Participants will begin buprenorphine using the MedicaSafe dispensing device immediately after an on-site intake at a community supervision office and continue such treatment until they are transitioned to a community program; or Treatment as Usual (TAU): Participants will receive a referral to buprenorphine pharmacotherapy treatment in the community. Treatment outcomes will be: (a) illicit opioid oral saliva drug test results; and (b) treatment adherence (i. entered community based treatment; ii. number of days receiving opioid treatment). RESULTS: We describe the background and rationale for the study, its aims, hypotheses, and study design. CONCLUSIONS: If shown to increase compliance rates with conditions of probation and parole, buprenorphine treatment co-located at community supervision field offices could have a major impact on delivery of buprenorphine treatment to the criminal justice population. The public health impact of the proposed study would be widespread because this intervention could be implemented throughout areas of the US.

Longitudinal analysis of HIV-risk behaviors of participants in a randomized trial of prison-initiated buprenorphine.

BACKGROUND: It has been estimated that approximately 15% of people who are incarcerated in the US have histories of opioid use disorder. Relapse to opioid use after release from prison poses a serious risk of HIV infection. Prison-initiated buprenorphine may help to reduce HIV infection given the association between opioid use and HIV-risk behaviors. METHODS: The present study is a secondary analysis of longitudinal data gathered from a randomized controlled trial of buprenorphine-naloxone for people who were incarcerated (N = 211) between 2008 and 2012. It compares the impact of assignment to initiate buprenorphine in prison (N = 106 randomized, N = 104 analyzed) versus in the community (N = 107 randomized, N = 107 analyzed) and whether or not participants entered community treatment on the frequency of HIV-risk behaviors in the 12 months following release from prison. Data were analyzed hierarchically and for each outcome variable, a multilevel, over-dispersed Poisson model was fit to the data. Outcome variables were the number of times the following behaviors occurred in the last 30 days: (1) having sex without a condom (2) injecting drugs (3) using unsterilized needles, and (4) sharing injection paraphernalia. RESULTS: Participants assigned to begin buprenorphine in the community experienced a greater decrease in injection drug use over time compared to participants assigned to begin buprenorphine in prison. There were no significant associations between treatment assignment or community treatment entry and instances of having sex without a condom, sharing injection paraphernalia, or using unsterilized needles. CONCLUSIONS: Overall, the present study did not find support for the initiation of buprenorphine in prison (as opposed to the community) as a means to reduce incidences of HIV-risk behaviors. Avenues for future research in the nexus of HIV-risk reduction, criminal justice, and pharmacotherapy are discussed. Trial registration This study was supported by the National Institute on Drug Abuse (NIDA), Buprenorphine for Prisoners (PI: Kinlock; R01DA021579). ClinicalTrials.gov identifier: NCT00574067.

A cholecystokinin B receptor antagonist and cocaine interaction, phase I study.

AIMS: RPR 102681, a cholecystokinin-B antagonist, increased dopamine (DA) release and reduced cocaine self-administration in animals. This pilot study sought to assess the safety and pharmacokinetics (PK) of co-administration of RPR 102681 and cocaine, and to confirm the DA release mechanism of RPR 102681. METHODS: Sixteen cocaine-dependent participants were randomized to either placebo or RPR102681 at 3 ascending doses; cocaine was co-administered at steady state of RPR 102681. [11 C]raclopride positron emission tomography scans were conducted at baseline and at each RPR102681 dose. RESULTS: RPR 102681 was well tolerated, and safe to co-administer with cocaine. RPR 102681 did not alter the PK of either cocaine or its metabolite benzoylecgonine and showed no intrinsic abuse liability. There was a trend toward reduction of cocaine craving scores. In contrast to animal studies, RPR 102681 significantly increased the binding potential of [11 C]raclopride in the ventral striatum (t test, P < .001) and caudate nucleus (t test, P < .0001) in a small subset of patients, suggesting that it may reduce intrasynaptic striatal DA. CONCLUSION: Overall, this pilot study suggests that RPR 102681 would be unlikely candidate, as an agonist medication for the treatment for cocaine addiction but worth investigating further for possible role in reducing craving.