Effects of current smoking severity on brain gray matter volume in opioid use disorder - a voxel-based morphometry study.

Background: Cigarette smoking (CS) and opioid use disorder (OUD) significantly alter brain structure. Although OUD and cigarette smoking are highly comorbid, most prior neuroimaging research in OUD did not control for smoking severity. Specifically, the combined effect of smoking and OUD on the brain gray matter volume (GMV) remains unknown.Objectives: We used structural magnetic resonance imaging (sMRI) to examine: (1) the GMV differences between OUD and non-OUD individuals with comparable smoking severity; and (2) the differential effect of smoking severity on the brain GMV between individuals with and without OUD.Methods: We performed a secondary analysis of existing sMRI datasets of 116 individuals who smoked cigarettes daily, among whom 60 had OUD (CS-OUD; 37 male, 23 female) and 56 did not (CS; 31 male, 25 female). Brain GMV was estimated by voxel-based morphometry analysis.Results: Compared to the CS group, the CS-OUD group had a higher GMV in the occipital cortex and lower GMV in the prefrontal and temporal cortex, striatum, and pre/postcentral gyrus (whole-brain corrected-p < .05). There was a significant interaction between group and smoking severity on GMV in the medial orbitofrontal cortex (whole-brain corrected-p < .05), such that heavier smoking was associated with lower medial orbitofrontal GMV in the CS-OUD but not CS participants (r=-0.32 vs. 0.12).Conclusions: Our findings suggest a combination of independent and interactive effects of cigarette smoking and OUD on the brain gray matter. Elucidating the neuroanatomical correlates of comorbid opioid and tobacco use may shed the light on the development of novel interventions for affected individuals.

Multivariate pattern analysis links drug use severity to distributed cortical hypoactivity during emotional inhibitory control in opioid use disorder.

Opioid use disorder (OUD) is characterized by emotional and cognitive impairements that are associated with poor treatment outcomes. The present study investigated the neural mechanism underlying emotion evaluation and inhibitory control using an affective go/no-go (AGN) task and its association with drug use severity and craving in patients with OUD. Twenty-six recently detoxified patients with OUD underwent functional magnetic resonance imaging (fMRI) while performing the AGN task that required response to frequently presented appetitive stimuli ("go") and inhibition of response to infrequently presented aversive stimuli ("no-go"). The fMRI session was immediately followed by an injection of extended-release opioid antagonist naltrexone (XR-NTX). Participants' opioid craving was assessed immediately before fMRI and 10 ± 2 days after XR-NTX injection. Multivariate pattern analysis (MVPA) showed that drug use severity was associated with distributed brain hypoactivity in response to aversive no-go stimuli, with particularly large negative contributions from the cognitive control and dorsal attention brain networks. While drug use severity and its associated MVPA brain response pattern were both correlated with opioid craving at baseline, only the brain response pattern predicted craving during XR-NTX treatment. Our findings point to widespread functional hypoactivity in the brain networks underlying emotional inhibitory control in OUD. Such a distributed pattern is consistent with the multifaceted nature of OUD, which affects multiple brain networks. It also highlights the utility of the multivariate approach in uncovering large-scale cortical substrates associated with clinical severity in complex psychiatric disorders and in predicting treatment response.

The Persistent Challenge of Developing Addiction Pharmacotherapies.

There are currently effective Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid use disorders. This article will review the development of eight compounds used in the treatment of drug addiction with an emphasis on pharmacological mechanisms and the utility of preclinical animal models of addiction in therapeutic development. In contrast to these successes, animal research has identified a number of promising medications for the treatment of psychostimulant use disorder, none of which have proven to be clinically effective. A specific example of an apparently promising pharmacotherapeutic for cocaine that failed clinically will be examined to determine whether this truly represents a challenge to the predictive validity of current models of cocaine addiction. In addition, the development of promising cocaine use disorder therapeutics derived from animal research will be reviewed, with some discussion regarding how preclinical studies might be modified to better inform clinical outcomes.

The role of withdrawal in mesocorticolimbic drug cue reactivity in opioid use disorder.

Opioid use disorder (OUD) is characterized by heightened cognitive, physiological, and neural responses to opioid-related cues that are mediated by mesocorticolimbic brain pathways. Craving and withdrawal are key symptoms of addiction that persist during physiological abstinence. The present study evaluated the relationship between the brain response to drug cues in OUD and baseline levels of craving and withdrawal. We used functional magnetic resonance imaging (fMRI) to examine brain responses to opioid-related pictures and control pictures in 29 OUD patients. Baseline measures of drug use severity, opioid craving, and withdrawal symptoms were assessed prior to cue exposure and correlated with subsequent brain responses to drug cues. Mediation analysis was conducted to test the indirect effect of drug use severity on brain cue reactivity through craving and withdrawal symptoms. We found that baseline drug use severity and opioid withdrawal symptoms, but not craving, were positively associated with the neural response to drug cues in the nucleus accumbens, orbitofrontal cortex, and amygdala. Withdrawal, but not craving, mediated the effect of drug use severity on the nucleus accumbens' response to drug cues. We did not find similar effects for the neural responses to stimuli unrelated to drugs. Our findings emphasize the central role of withdrawal symptoms as the mediator between the clinical severity of OUD and the brain correlates of sensitization to opioid-related cues. They suggest that in OUD, baseline withdrawal symptoms signal a high vulnerability to drug cues.

Development of the Revised Opioid Risk Tool to Predict Opioid Use Disorder in Patients with Chronic Nonmalignant Pain.

The Opioid Risk Tool (ORT) is a commonly used measure of risk of aberrant drug-related behaviors in patients with chronic pain prescribed opioid therapy. In this study, the discriminant predictive validity of the ORT was evaluated in a unique cohort of patients with chronic nonmalignant pain (CNMP) on long-term opioid therapy who displayed no evidence of developing an opioid use disorder (OUD) and a sample of patients with CNMP who developed an OUD after commencing opioid therapy. Results revealed that the original ORT was able to discriminate between patients with and without OUDs (odds ratio = 1.624; 95% confidence interval [CI] = 1.539-1.715, P < .001). A weighted ORT eliminating the gender-specific history of preadolescent sexual abuse item revealed comparable results (odds ratio = 1.648, 95% CI = 1.539-1.742, P < .001). A revised unweighted ORT removing the history of preadolescent sexual abuse item was notably superior in predicting the development of OUD in patients with CNMP on long-term opioid therapy (odds ratio = 3.085; 95% CI = 2.725-3.493; P < .001) with high specificity (.851; 95% CI = .811-.885), sensitivity (.854; 95% CI = .799-.898), positive predictive value (.757; 95% CI = .709-.799), and negative predictive value (.914; 95% CI = .885-.937). Perspective: The revised ORT is the first tool developed on a unique cohort to predict the risk of developing an OUD in patients with CNMP receiving opioid therapy, as opposed to aberrant drug-related behaviors that can reflect a number of other issues. The revised ORT has clinical usefulness in providing clinicians a simple, validated method to rapidly screen for the risk of developing OUD in patients on or being considered for opioid therapy.

Incidence of future arrests in adults involved in the criminal justice system with opioid use disorder receiving extended release naltrexone compared to treatment as usual.

BACKGROUND: Criminal justice involved (CJS) populations with opioid use disorder (OUD) have high rates of relapse, future arrests, and death upon release. While medication for OUD (MOUD) reduces opioid relapse, concerns regarding diversion and stigma limit treatment in CJS populations. Extended release naltrexone (XR-NTX), as an opioid antagonist, may be more acceptable to CJS administrators. However, the impact of XR-NTX on criminal recidivism remains unknown. METHODS: Arrest data from a published randomized trial comparing XR-NTX to treatment as usual (TAU) was captured by self-report and official state arrest records. Comparisons of future arrests, time to first arrest and total number of arrests were performed using chi square tests and multivariable generalized regression models. Secondary outcomes explored differences in arrests by type and severity of crime, use of opioid and other drugs, and study phase. RESULTS: Of 308 participants randomized, 300 had arrest data. The incidence of arrests did not differ between XR-NTX (47.6%) and TAU (42.5%) participants. (ChiSq p = 0.37). Additionally, there was no significant difference in time to first arrest (adjusted HR 1.35, CI 0.96-1.89) and number of arrests per participant (adjusted IR 1.33, CI 0.78-2.27). Controlling for gender, age, previous criminal activity, and use of non-opioid drugs, logistic regression demonstrated no significant difference in incidence of arrests between groups (adjusted OR 1.38, 95% CI 0.85-2.22). CONCLUSIONS: We detected no significant difference in arrests between CJS participants with OUD randomized to XR-NTX or TAU. Despite its efficacy in reducing opioid use, XR-NTX alone may be insufficient to reduce criminal recidivism.

Molecular Genetics and New Medication Strategies for Opioid Addiction.

The opioid epidemic is at the epicenter of the drug crisis, resulting in an inconceivable number of overdose deaths and exorbitant associated medical costs that have crippled many communities across the socioeconomic spectrum in the United States. Classic medications for the treatment of opioid use disorder predominantly target the opioid system and thus have been underutilized, in part due to their own potential for abuse and heavy regulatory burden for patients and clinicians. Opioid antagonists are now evolving in their use, not only to prevent acute overdoses but as extended-use treatment options. Strategies that target specific genetic and epigenetic factors, along with novel nonopioid medications, hold promise as future therapeutic interventions for opioid abuse. Success in increasing the treatment options in the clinical toolbox will, hopefully, help to end the historical pattern of recurring opioid epidemics. [AJP at 175: Remembering Our Past As We Envision Our Future Drug Addiction in Relation to Problems of Adolescence Zimmering and colleagues wrote in the midst of an opiate epidemic among young people that "only the human being, or rather certain types of human beings, will return to the enslaving, self-destructive habit." (Am J Psychiatry 1952; 109:272-278 )].

Effects of extended-release naltrexone on the brain response to drug-related stimuli in patients with opioid use disorder.

BACKGROUND: Heightened response to drug-related cues is a hallmark of addiction. Extended-release naltrexone (XR-NTX) is a US Food and Drug Administration-approved pharmacotherapy for relapse prevention in patients with opioid use disorder (OUD). In these patients, XR-NTX has been shown to reduce brain responses to opioid-related visual stimuli. To assess the biomarker potential of this phenomenon, it is necessary to determine whether this effect is limited to opioid-related stimuli and whether it is associated with key OUD symptoms. METHODS: Using functional MRI (fMRI), we measured the brain responses to opioid-related and control (i.e., sexual and aversive) images in detoxified patients with OUD before, during and after XR-NTX treatment. Craving and withdrawal severity were evaluated using clinician- and self-administered instruments during each session. RESULTS: We included 24 patients with OUD in our analysis. During XR-NTX treatment, we found reduced responses to opioid-related stimuli in the nucleus accumbens (NAcc) and medial orbitofrontal cortex (mOFC). The reduction in mOFC response was specific to the opioid-related stimuli. The reduced NAcc and mOFC opioid cue reactivity was correlated with reduction in clinician-assessed and self-reported withdrawal symptoms, respectively. LIMITATIONS: The study was not placebo-controlled owing to ethical, safety and feasibility concerns. CONCLUSION: Extended-release naltrexone reduces the NAcc and mOFC cue reactivity in patients with OUD. This effect is specific to opioid-related stimuli in the mOFC only. The reduction in neural response to opioid-related stimuli is more robust in patients with greater decline in withdrawal severity. Our results support the clinical utility of mesocorticolimbic cue reactivity in monitoring the XR-NTX treatment outcomes and highlight the link between opioid withdrawal symptomatology and neural opioid cue reactivity.

Effects of extended-release naltrexone on the brain response to drug-related stimuli in patients with opioid use disorder.

BACKGROUND: Heightened response to drug-related cues is a hallmark of addiction. Extended-release naltrexone (XR-NTX) is a US Food and Drug Administration-approved pharmacotherapy for relapse prevention in patients with opioid use disorder (OUD). In these patients, XR-NTX has been shown to reduce brain responses to opioid-related visual stimuli. To assess the biomarker potential of this phenomenon, it is necessary to determine whether this effect is limited to opioid-related stimuli and whether it is associated with key OUD symptoms. METHODS: Using functional MRI (fMRI), we measured the brain responses to opioid-related and control (i.e., sexual and aversive) images in detoxified patients with OUD before, during and after XR-NTX treatment. Craving and withdrawal severity were evaluated using clinician- and self-administered instruments during each session. RESULTS: We included 24 patients with OUD in our analysis. During XR-NTX treatment, we found reduced responses to opioid-related stimuli in the nucleus accumbens (NAcc) and medial orbitofrontal cortex (mOFC). The reduction in mOFC response was specific to the opioid-related stimuli. The reduced NAcc and mOFC opioid cue reactivity was correlated with reduction in clinician-assessed and self-reported withdrawal symptoms, respectively. LIMITATIONS: The study was not placebo-controlled owing to ethical, safety and feasibility concerns. CONCLUSION: Extended-release naltrexone reduces the NAcc and mOFC cue reactivity in patients with OUD. This effect is specific to opioid-related stimuli in the mOFC only. The reduction in neural response to opioid-related stimuli is more robust in patients with greater decline in withdrawal severity. Our results support the clinical utility of mesocorticolimbic cue reactivity in monitoring the XR-NTX treatment outcomes and highlight the link between opioid withdrawal symptomatology and neural opioid cue reactivity.

Personal Control Over Decisions to Participate in Research by Persons With Histories of Both Substance Use Disorders and Criminal Justice Supervision.

Individuals must feel free to exert personal control over decisions regarding research participation. We present an examination of participants' perceived personal control over, as well as reported pressures and threats from others, influencing their decision to join a study assessing the effectiveness of extended-release naltrexone in preventing opioid dependence relapse. Most participants endorsed a strong sense of control over the decision; few reported pressures or threats. Although few in number, participants' brief narrative descriptions of the pressures and threats are illuminating and provide context for their perceptions of personal control. Based on this work, we propose a useful set of tools to help ascertain participants' sense of personal control in joining research.

Healthcare utilization in adults with opioid dependence receiving extended release naltrexone compared to treatment as usual.

BACKGROUND: Opioid use disorders have reached epidemic proportions, with overdose now the leading cause of accidental death in the United States. Extended release naltrexone (XR-NTX) has emerged as a medication treatment that reduces opioid use and craving. However, the effect of XR-NTX therapy on acute healthcare utilization, including emergency department visits and inpatient hospitalizations, remains uncertain. The objective of the current study is to evaluate hospital-based healthcare resource utilization in adults involved in the criminal justice system with a history of opioid use disorder randomized to XR-NTX therapy compared with treatment as usual (TAU) during a 6-month treatment phase and 12months post-treatment follow up. METHODS: This retrospective exploratory analysis uses data collected in a published randomized trial. Comparisons of the number of emergency department visits and hospital admissions (for drug detox, psychiatric care and other medical reasons) were performed using chi square tests for any admission and negative binomial models for number of admissions. RESULTS: Of the 308 participants randomized, 96% had utilization data (76% complete 6months, 67% complete follow up). No significant differences were seen in overall healthcare utilization (IRR=0.88, 95%CI 0.63-1.23, p=0.45), or substance use-related drug detox hospitalizations (IRR=0.83, 95%CI 0.32-2.16, p=0.71). Despite having more participants report chronic medical problems at baseline (43% vs. 32%, p=0.05), those receiving XR-NTX generally experienced equivalent or lower rates of healthcare utilization compared to TAU. The XR-NTX group had significantly lower medical/surgical related hospital admissions (IRR=0.55, 95%CI 0.30-1.00, p=0.05) during the course of the entire study. CONCLUSIONS: XR-NTX did not significantly increase rates of healthcare utilization compared to TAU. Provider concerns regarding healthcare utilization should not preclude the consideration of XR-NTX as therapy for opioid use disorders.

Relapse to opioid use disorder after inpatient treatment: Protective effect of injection naltrexone.

BACKGROUND: Opioid use disorder is often treated with short term hospitalization and medically supervised withdrawal from opioids followed by counseling alone without medication assisted treatment (MAT). More evidence is needed to confirm the expectation that the rate of relapse would be high after short term inpatient treatment and withdrawal from opioids without follow-up MAT. OBJECTIVE/METHODS: To examine relapse to opioid use disorder in a randomized, multi-site effectiveness trial of extended-release injection naltrexone (XR-NTX) vs community-based treatment as usual (TAU) without medication, as a function of the type of clinical service where treatment was initiated-short-term inpatient (N=59), long-term inpatient (N=48), or outpatient (N=201). Inpatients typically were admitted to treatment actively using opioids and had completed withdrawal from opioids before study entry. Outpatients typically presented already abstinent for varying periods of time. RESULTS: One month after randomization, relapse rates on TAU by setting were: short-term inpatient: 63%; long term inpatient: 14%; outpatient: 28%. On XR-NTX relapse rates after one month were low (<12%) across all three settings. At the end of the 6 month trial, relapse rates on TAU were high across all treatment-initiation settings (short term inpatient 77%; long term inpatient 59%; outpatient 61%), while XR-NTX exerted a modest protective effect against relapse across settings (short term inpatient: 59%; long term inpatient 46%; outpatient 38%). CONCLUSIONS: Short term inpatient treatment is associated with a high rate of relapse among patients with opioid use disorder. These findings support the recommendation that medically supervised withdrawal from opioids should be followed by medication assisted treatment.

Do patient characteristics moderate the effect of extended-release naltrexone (XR-NTX) for opioid use disorder?

BACKGROUND: Extended release naltrexone (XR-NTX) injected intramuscularly monthly has been shown to reduce relapse in persons with opioid use disorder. Baseline factors, including patients' demographics, comorbidities and lifestyle, may help identify patients who will benefit most or least from XR-NTX treatment. METHODS: Potential moderators of XR-NTX's effect were examined in the largest North American randomized open-label effectiveness trial of XR-NTX. Relapse status (Yes/No) at 6-month follow-up was regressed on treatment group (XR-NTX, N=153; or Treatment-as-Usual [TAU], N=155), baseline covariates, and their two-way interaction to identify moderator effects. Baseline covariates included age, gender, summary scores for depression, suicidal thoughts, drug abuse risk, substance use, medical, psychiatric and employment status, socialization, legal and family/social issues, history of abuse and quality of life measures. RESULTS: Alcohol use to intoxication in the 30days before randomization was a significant moderator: during the treatment phase, those who reported being recently intoxicated before randomization to XR-NTX relapsed to opioids at a rate (56%) similar to TAU (58%), while those without alcohol intoxication in the prior 30days had a lower rate of opioid relapse (41% vs. 65%, respectively, P<0.04). CONCLUSIONS: XR-NTX appeared to work equally well across subgroups with diverse demographic, addiction, mental health and environmental characteristics, with the possible exception of working better among those without recent alcohol intoxication. These findings should be reassuring to practitioners increasingly using XR-NTX as medical addiction therapy in diverse and often vulnerable populations.

Low Risk of Producing an Opioid Use Disorder in Primary Care by Prescribing Opioids to Prescreened Patients with Chronic Noncancer Pain.

Objective: To examine the risk of developing aberrant behaviors that might lead to a substance use disorder (addiction) when prescribing opioids for the relief of chronic noncancer pain in primary care settings. Design: Longitudinal, prospective, descriptive design with repeated measures. Setting: Private community-based internal medicine and family medicine clinics. Subjects: Patients with chronic musculoskeletal pain. Methods: Standardized measures of patient status (pain, functional impairment, psychiatric disorders, family history) and treatments provided, urine drug monitoring, and medical chart audits (presence of aberrant drug-related behaviors) were obtained in a cohort of 180 patients at the time of initiating opioids for chronic noncancer pain and at three, six, and 12 months thereafter. Results: Over the 12-month follow-up period, subjects demonstrated stable, mild to moderate levels of depression (PHQ-9 scores ranging from 9.43 to 10.92), mild anxiety (BAI scores ranging from 11.80 to 14.67), minimal aberrant drug-related behaviors as assessed by chart reviews, and a low percentage of illicit drug use as revealed by results of urine drug monitoring. Less than 5% of our study population revealed any evidence of substance use disorder. Conclusions: This prospective study suggests that patients without a recent or prior history of substance use disorder who were prescribed primarily short-acting opioids in low doses for chronic noncancer pain have a low risk for developing a substance use disorder. This finding supports the importance of prescreening patients being considered for opioid therapy and that prescription of opioids for noncancer pain may carry a lower risk of abuse in selected populations such as in private, community-based practices.

Assessing informed consent in an opioid relapse prevention study with adults under current or recent criminal justice supervision.

Concerns persist that individuals with substance use disorders who are under community criminal justice supervision experience circumstances that might compromise their provision of valid, informed consent for research participation. These concerns include the possibilities that desire to obtain access to treatment might lead individuals to ignore important information about research participation, including information about risks, or that cognitive impairment associated with substance use might interfere with attending to important information. We report results from a consent quiz (CQ) administered in a multisite randomized clinical trial of long-acting naltrexone to prevent relapse to opioid use disorder among adults under community criminal justice supervision-a treatment option difficult to access by this population of individuals. Participants were required to answer all 11 items correctly before randomization. On average, participants answered 9.8 items correctly (89%) at baseline first attempt (n=306). At week 21 (n=212), participants scored 87% (9.5 items correct) without review. Performance was equivalent to, or better than, published results from other populations on a basic consent quiz instrument across multiple content domains. The consent quiz is an efficient method to screen for adequate knowledge of consent information as part of the informed consent process. Clinical researchers who are concerned about these issues should consider using a consent quiz with corrected feedback to enhance the informed consent process. Overall, while primarily useful as an educational tool, employing a CQ as part of the gateway to participation in research may be particularly important as the field continues to advance and tests novel experimental treatments with significant risks and uncertain potential for benefit.

Cost-effectiveness of extended release naltrexone to prevent relapse among criminal justice-involved individuals with a history of opioid use disorder.

BACKGROUND AND AIMS: Criminal justice-involved individuals are highly susceptible to opioid relapse and overdose-related deaths. In a recent randomized trial, we demonstrated the effectiveness of extended-release naltrexone (XR-NTX; Vivitrol® ) in preventing opioid relapse among criminal justice-involved US adults with a history of opioid use disorder. The cost of XR-NTX may be a significant barrier to adoption. Thus, it is important to account for improved quality of life and downstream cost-offsets. Our aims were to (1) estimate the incremental cost per quality-adjusted life-year (QALY) gained for XR-NTX versus treatment as usual (TAU) and evaluate it relative to generally accepted value thresholds; and (2) estimate the incremental cost per additional year of opioid abstinence. DESIGN: Economic evaluation of the aforementioned trial from the taxpayer perspective. Participants were randomized to 25 weeks of XR-NTX injections or TAU; follow-up occurred at 52 and 78 weeks. SETTING: Five study sites in the US Northeast corridor. PARTICIPANTS: A total of 308 participants were randomized to XR-NTX (n = 153) or TAU (n = 155). MEASUREMENTS: Incremental costs relative to incremental economic and clinical effectiveness measures, QALYs and abstinent years, respectively. FINDINGS: The 25-week cost per QALY and abstinent-year figures were $162 150 and $46 329, respectively. The 78-week figures were $76 400/QALY and $16 371/abstinent year. At 25 weeks, we can be 10% certain that XR-NTX is cost-effective at a value threshold of $100 000/QALY and 62% certain at $200 000/QALY. At 78 weeks, the cost-effectiveness probabilities are 59% at $100 000/QALY and 76% at $200 000/QALY. We can be 95% confident that the intervention would be considered 'good value' at $90 000/abstinent year at 25 weeks and $500/abstinent year at 78 weeks. CONCLUSIONS: While extended-release naltrexone appears to be effective in increasing both quality-adjusted life-years (QALYs) and abstinence, it does not appear to be cost-effective using generally accepted value thresholds for QALYs, due to the high price of the injection.

Emotional, physical and sexual abuse are associated with a heightened limbic response to cocaine cues.

Drug-reward cues trigger motivational circuitry, a response linked to drug-seeking in animals and in humans. Adverse life events have been reported to increase sensitivity to drug rewards and to bolster drug reward signaling. Therefore, we hypothesized that cocaine-dependent individuals with prior emotional, physical and sexual abuse might have a heightened mesolimbic brain response to cues for drug reward in a new brief-cue probe. Cocaine-dependent human individuals (N = 68) were stabilized in an inpatient setting and then completed an event-related blood-oxygen-level dependent functional magnetic resonance imaging task featuring 500-ms evocative (cocaine, sexual, aversive) and comparator (neutral) cues. Responses to three questions about emotional, physical and sexual abuse from the Addiction Severity Index were used to divide the patients into subgroups (history of Abuse [n = 40] versus No Abuse [n = 28]). When subjects were grouped by the historical presence or absence of emotional, physical or sexual abuse, the Abuse group showed a heightened midbrain, thalamic, caudate, and caudal orbitofrontal cortex response to cocaine cues; a similar result was found in other evocative cues, as well. These findings are the first reported for a 500-ms cocaine-cue probe, and they highlight the ability of very brief evocative cues to activate the brain's motivational circuitry. Although all participants had severe cocaine use disorders, individuals reporting prior abuse had a heightened mesolimbic response to evocative cues. To our knowledge, this is the first study in humans linking a history of abuse to a brain vulnerability (heightened mesolimbic response to drug cues) previously shown to contribute to drug-seeking.

Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment.

BACKGROUND: Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases has been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. METHODS: Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. RESULTS: We describe the background and rationale for the study, its aims, hypotheses, and study design. CONCLUSIONS: The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. ClinicalTrials.gov: NCT02867124.