Outpatient Parenteral Antimicrobial Therapy Plus Buprenorphine for Opioid Use Disorder and Severe Injection-related Infections.

In a pilot randomized trial in persons with opioid use disorder hospitalized with injection-related infections, an innovative care model combining outpatient parenteral antimicrobial therapy with buprenorphine treatment had similar clinical and drug use outcomes to usual care (inpatient intravenous antibiotic completion) and shortened hospital length of stay by 23.5 days. CLINICAL TRIALS REGISTRATION: NCT03048643.

A Pharmacokinetic Study Examining Acetazolamide as a Novel Adherence Marker for Clinical Trials.

RATIONALE: Accurate assessment of medication adherence is critical for determination of medication efficacy in clinical trials, but most current methods have significant limitations. This study tests a subtherapeutic (microdose) of acetazolamide as a medication ingestion marker because acetazolamide is rapidly absorbed and excreted without metabolism in urine and can be noninvasively sampled. METHODS: In a double-blind, placebo-controlled, residential study, 10 volunteers received 15 mg oral acetazolamide for 4 consecutive days. Acetazolamide pharmacokinetics were assessed on day 3, and its pharmacokinetic and pharmacodynamic interactions with a model medication (30 mg oxycodone) were examined on day 4. The rate of acetazolamide elimination into urine was followed for several days after dosing cessation. RESULTS: Erythrocyte sequestration (half-life = 50.2 ± 18.5 h, mean ± SD, n = 6), resulted in the acetazolamide microdose exhibiting a substantially longer plasma half-life (24.5 ± 5.6 hours, n = 10) than previously reported for therapeutic doses (3-6 hours). After cessation of dosing, the rate of urinary elimination decreased significantly (F3,23 = 247: P < 0.05, n = 6) in a predictable manner with low intersubject variability and a half-life of 16.1 ± 3.8 h (n = 10). For each of 4 consecutive mornings after dosing cessation, the rates of urinary acetazolamide elimination remained quantifiable.There was no overall effect of acetazolamide on the pharmacodynamics, Cmax, Tmax, or elimination half-life of the model medication tested. Acetazolamide may have modestly increased overall oxycodone exposure (20%, P < 0.05) compared with one of the 2 days when oxycodone was given alone, but there were no observed effects of acetazolamide on oxycodone pharmacodynamic responses. CONCLUSIONS: Coformulation of a once-daily trial medication with an acetazolamide microdose may allow estimation of the last time of medication consumption for up to 96 hours postdose. Inclusion of acetazolamide may therefore provide an inexpensive new method to improve estimates of medication adherence in clinical trials.

Pharmacodynamic effects of oral oxymorphone: abuse liability, analgesic profile and direct physiologic effects in humans.

Oxymorphone is a semisynthetic µ-opioid agonist, marketed as a prescription analgesic purported to be twice as potent as oxycodone for pain relief. Oral formulations of oxymorphone were reintroduced in the United States in 2006 and reports of abuse ensued; however, there are limited data available on its pharmacodynamic effects. The current study aimed to examine the direct physiologic effects, relative abuse liability, analgesic profile and overall pharmacodynamic potency of oxymorphone in comparison with identical doses of oxycodone. Healthy, non-dependent opioid abusers (n = 9) were enrolled in this within-subject, double-blind, placebo-controlled, 3-week inpatient study. Seven experimental sessions (6.5 hours) were conducted, during which an oral dose of immediate-release formulations of oxymorphone (10, 20 and 40 mg), oxycodone (10, 20 and 40 mg) or placebo was administered. An array of physiologic, abuse liability and experimental pain measures was collected. At identical doses, oxymorphone produced approximately twofold less potent effects on miosis, compared with oxycodone. Oxymorphone also produced lesser magnitude effects on measures of respiratory depression, two experimental pain models and observer-rated agonist effects. However, 40 mg of oxymorphone was similar to 40 mg of oxycodone on several abuse-related subjective ratings. Formal relative potency analyses were largely invalid because of the substantially greater effects of oxycodone. Overall, oxymorphone is less potent on most pharmacodynamic measures, although at higher doses, its abuse liability is similar to oxycodone. These data suggest that the published clinical equianalgesic estimates may not be consistent with the observed direct physiologic effects of opioids, results of experimental pain models or abuse liability measures, as assessed in the human laboratory.

Minor Cannabinoid Profile of Unregulated Cannabidiol Products.

Background: Although the majority of cannabinoid research has focused on delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), there is increasing interest in the therapeutic effects of other phytocannabinoid compounds (i.e., minor cannabinoids), as there is little known about their effects or interaction with CBD. The current study objective was to determine the concentrations of 15 minor cannabinoids in unregulated, over-the-counter CBD products. Methods: A cross-section sample of 80 local and national brands of hemp-derived oil products was purchased both online and in local retail outlets in central Kentucky. Epidiolex® was included as a regulated control. Samples from each product were extracted by solvent extraction and quantified by liquid-chromatography tandem mass-spectrometry. The targeted cannabinoids were: cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabidivarinic acid, Δ9-tetrahydrocannabivarin, Δ9-tetrahydrocannabivarinic acid, Δ9-tetrahydrocannabinolic acid-A, Δ8-tetrahydrocannabinol (Δ8-THC), cannabigerol (CBG), cannabigerolic acid, cannabinol (CBN), cannabinolic acid, cannabicyclol (CBL), cannabicyclolic acid, cannabichromene (CBC) and cannabichromenic acid. Results: Among the unregulated products included in this analysis, the most frequently detected minor cannabinoids were CBDV (100% of samples tested), CBG (77%), CBC (72%), CBN (67%), CBL (67%), and CBDA (51%). Δ8-THC was not detected in any of the products tested. Concentrations of these cannabinoids varied widely from trace concentrations to several mg/mL (e.g., CBDA: 0.006-12.258 mg/mL). Conclusions: These data indicate CBD products often contain minor cannabinoids, although the array and concentrations of these cannabinoids vary widely across products. The concentrations of these minor cannabinoids are largely absent from product labels, leaving consumers uninformed about product contents.

Effects of the NK1 antagonist, aprepitant, on response to oral and intranasal oxycodone in prescription opioid abusers.

Pre-clinical studies suggest that the neurokinin-1 (NK1) receptor may modulate the response to opioids, with NK(1) inactivation leading to decreased opioid reinforcement, tolerance and withdrawal. Aprepitant is a selective NK1 antagonist currently marketed for clinical use as an anti-emetic. This 6-week in-patient study used a randomized, double-blind, double-dummy, within-subject, crossover design. Subjects (n = 8; 6 male/2 female) were healthy, adult volunteers who provided subjective and objective evidence of current prescription opioid abuse (without physical dependence) and underwent careful medical and psychiatric screening. Fifteen experimental conditions, consisting of one aprepitant dose (0, 40 and 200 mg, p.o. given as a 2-hour pre-treatment) in combination with one oxycodone dose [placebo, oral (20 and 40 mg/70 kg) and intranasal (15 and 30 mg/70 kg)], were examined. Sessions were conducted at least 48-hour apart and multi-dimensional measures were collected repeatedly throughout the 6-hour session duration. Oxycodone, by both routes of administration, produced significant dose-related effects on the predicted measures (e.g. subjective measures of abuse liability, respiratory depression and miosis). Pre-treatment with aprepitant (200 mg) significantly enhanced ratings of oxycodone subjective effects related to euphoria and liking and doubled the street value estimates for the highest test doses of oxycodone by both routes. Some objective measures (respiratory function, observer-rated opioid agonist effects) were similarly enhanced by pre-treatment with the highest dose of aprepitant. All dose combinations were safely tolerated. These findings are discussed in the context of the potential utility of NK1 antagonists in the treatment of opioid use disorders.

Design and protocol of the Buprenorphine plus Outpatient Parenteral Antimicrobial Therapy (B-OPAT) study: a randomized clinical trial of integrated outpatient treatment of opioid use disorder and severe, injection-related infections.

Introduction: A marked increase in hospitalizations for severe, injection-related infections (SIRI) has been associated with the opioid epidemic. Outpatient parenteral antibiotic therapy (OPAT) is typically not offered to persons with opioid use disorder (OUD) and SIRI, though increasing evidence suggests it may be feasible and safe. This study evaluates the efficacy and cost-effectiveness of an integrated care model combining Buprenorphine treatment of OUD with OPAT for SIRI (B-OPAT) compared with treatment as usual on key OUD, infectious disease, and health economic outcomes. B-OPAT expands and incorporates key elements of established clinical models, including inpatient initiation of buprenorphine for OUD, inpatient infectious disease consultation for SIRI, office-based treatment of OUD, and OPAT, and includes more frequent clinical outpatient visits than standard OPAT. A qualitative evaluation is included to contextualize effectiveness outcomes and identify barriers and facilitators to intervention adoption and implementation. Methods: B-OPAT is a single-site, randomized, parallel-group, superiority trial recruiting 90 adult inpatients hospitalized with OUD and SIRI who require at least 2 weeks of intravenous (IV) antibiotic therapy. After screening, eligible participants are randomized 1:1 to either discharge once medically stable to an integrated outpatient treatment care model combining Buprenorphine and OPAT (B-OPAT) or to Treatment As Usual (TAU). The primary outcome measure is the proportion of urine samples negative for illicit opioids in the 12 weeks after discharge from the hospital. Key secondary OUD outcomes include self-reported number of days of illicit opioid abstinence and 12-week retention in buprenorphine treatment. The infection outcomes are completion of recommended IV antibiotic therapy, peripherally inserted central catheter (PICC) complications, and readmission related to primary SIRI. Conclusions: The B-OPAT study will help address the important question of whether it is clinically effective and cost-effective to discharge persons with OUD and SIRI to an integrated outpatient care model combining OUD treatment with OPAT relative to TAU (Clinicaltrials.gov Identifier: NCT04677114).

Buprenorphine Induction in Persons With Opioid Use Disorder Hospitalized with Acute Hepatitis A.

BACKGROUND: It is not known whether buprenorphine/naloxone (bup/nx) can be safely initiated in hospitalized patients with acute hepatitis A infection. We assessed liver function and tolerability of bup/nx induction in patients with acute Hepatitis A Virus (HAV). METHODS: Retrospective review of patients (N = 31) admitted to a tertiary care facility for acute HAV who were evaluated by an addiction medicine consultant. RESULTS: No significant difference was seen in aspartate aminotransferase, alanine aminotransferase, total bilirubin, or INR trends in patients receiving bup/nx during hospitalization versus those not receiving bup/nx. Nausea was the most common reported symptom in patients receiving bup/nx. DISCUSSION AND CONCLUSIONS: With careful monitoring and induction dose adjustment, bup/nx can be administered to patients with acute HAV without hepatic encephalopathy. Similarly, patients on bup/nx before hospitalization should not have this medication held in the setting of acute HAV. SCIENTIFIC SIGNIFICANCE: This strategy may engage patients with acute HAV in treatment of OUD earlier and minimize disruptions in treatment.

Evaluation of tradipitant, a selective NK1 antagonist, on response to oxycodone in humans.

RATIONALE: Preclinical studies demonstrate that the NK1 receptor is involved in opioid reinforcement and withdrawal expression. Few studies have examined the impact of treatment with NK1 antagonists on opioid response in humans. OBJECTIVE: To explore the potential for a selective NK1 antagonist, tradipitant, to attenuate the abuse liability and reinforcing and analgesic effects of oxycodone in opioid-experienced individuals. METHODS: Participants with recreational opioid use, but without opioid physical dependence, were enrolled as inpatients for ~6 weeks (n = 8). A within-subject, double-blind, randomized, placebo-controlled, crossover design was employed. The pharmacodynamic response to intranasal oxycodone across a range of doses (0 to 30 mg) was examined during two counterbalanced maintenance periods (tradipitant 0 or 85 mg/bid). Oxycodone self-administration was assessed with a modified progressive ratio procedure, and analgesia was assessed with the cold pressor test. RESULTS: Oxycodone produced significant and dose-related increases on a broad array of prototypic opioid measures, including subjective ratings related to abuse liability (e.g., liking) and physiological outcomes (i.e., expired CO2). Oxycodone self-administration increased with increasing dose, as did analgesia. Tradipitant largely did not alter any of these effects of oxycodone, with the exception of producing a reduction in ratings of desire for opioids. CONCLUSIONS: Given that the vast majority of oxycodone effects were unchanged by tradipitant, these data do not provide support for the utility of NK1 antagonists as a potential treatment for opioid use disorder.

Smartphone-based incentives for promoting adherence to antiretroviral therapy: A randomized controlled trial.

Antiretroviral therapy can improve the lives of people living with HIV and reduce the rate of transmission. However, high levels of adherence are required. Some people living with HIV, including people who use drugs, are at elevated risk for non-adherence. Contingency management is a promising intervention for promoting adherence to antiretroviral therapy. Barriers to adoption of contingency management include lack of provider expertise and implementation effort. To address these barriers, a smartphone-based adherence intervention was developed. HIV + people with a substance use disorder were required to submit video selfies of medication consumption that met validity criteria. Monetary incentives were delivered to participants via reloadable debit cards, contingent upon a valid video. The intervention was evaluated in a small (n = 50) randomized controlled trial. Intervention participants submitted 75% of possible videos, and 81% of videos met validity criteria, indicating a high level of usability. Participants also rated the intervention as highly acceptable. Adherence was measured as the percent of participants who achieved a 95% adherence threshold, and also as the overall percent of days in which participants were adherent to their antiretroviral therapy. The former showed a significant effect for group, (p = .034) but this was not maintained when adjusting for stratification variables as covariates (p = .094). The latter measure showed a significant group × time interaction. Smartphone-based contingency management is a promising method for promoting adherence to antiretroviral therapy. Assessing the cost-benefit of the intervention and development of strategies for long-term adherence are priorities for future research.

Acute administration of oxycodone, alcohol, and their combination on simulated driving-preliminary outcomes in healthy adults.

RATIONALE: Epidemiological data indicate that drivers testing positive for an opioid drug are twice as likely to cause a fatal car crash; however, there are limited controlled data available. OBJECTIVES: The primary aim of this study was to assess the effects of a therapeutic dose range of oxycodone alone and in combination with alcohol on simulated driving performance. METHODS: Healthy participants (n = 10) completed this within-subject, double-blind, placebo-controlled, randomized outpatient study. Six 7-h sessions were completed during which oxycodone (0, 5, 10 mg, p.o.) was administered 30 min before alcohol (0, 0.8 g/kg (15% less for women), p.o.) for a total of 6 test conditions. Driving assessments and participant-, observer-rated, psychomotor and physiological measures were collected in regular intervals before and after drug administration. RESULTS: Oxycodone alone (5, 10 mg) did not produce any changes in driving outcomes or psychomotor task performance, relative to placebo (p > 0.05); however, 10 mg oxycodone produced increases in an array of subjective ratings, including sedation and impairment (p < 0.05). Alcohol alone produced driving impairment (e.g., decreased lateral control) (p < 0.05); however, oxycodone did not potentiate alcohol-related driving or subjective effects. CONCLUSIONS: These preliminary data suggest that acute doses of oxycodone (5, 10 mg) do not significantly impair acuity on laboratory-based simulated driving models; however, 10 mg oxycodone produced increases in self-reported outcomes that are not compatible with safe driving behavior (e.g., sedation, impairment). Additional controlled research is needed to determine how opioid misuse (higher doses; parenteral routes of administration) impacts driving risk.

Relative potency of intravenous oxymorphone compared to other µ opioid agonists in humans - pilot study outcomes.

AIMS: Intravenous (IV) misuse of the µ opioid analgesic oxymorphone has caused significant public health harms; however, no controlled data on its IV abuse potential are available. The primary aims of this pilot study were to directly compare IV oxymorphone to IV oxycodone, morphine, and hydromorphone on a subjective measure of drug liking and to assess relative potency. METHODS: Participants (n = 6) with opioid use disorder, physical dependence, and current IV use completed this two-site, within-subject, double-blind, placebo-controlled, inpatient pilot study. During each session, one IV dose (mg/70 kg) was administered: oxymorphone (1.8, 3.2, 5.6, 10, 18, 32), hydromorphone (1.8, 3.2, 5.6, 10, 18), oxycodone (18, 32, 56), morphine (18, 32), and placebo. Data were collected before and for 6 h after dosing. Primary outcomes included safety/physiological effects, subjective reports of drug liking, and relative potency estimates. RESULTS: All active test drugs produced prototypical, dose-related µ opioid agonist effects (e.g., miosis). Oxymorphone was more potent than the comparator opioids on several measures, including drug liking and respiratory depression (p < 0.05). Across abuse-related subjective outcomes, oxymorphone was 2.3-2.8-fold more potent than hydromorphone and 12.5-14-fold more potent than oxycodone (p < 0.05). CONCLUSIONS: Despite the relatively small sample size, this pilot study detected robust oxymorphone effects. Oxymorphone was far more potent than the comparator opioids, particularly on abuse potential outcomes. Overall, these findings may help explain surveillance reports that demonstrate, after adjusting for prescription availability, oxymorphone is injected at the highest frequency, relative to other prescription opioids.

Behavioral and Enhanced Perinatal Intervention (B-EPIC): A randomized trial targeting tobacco use among opioid dependent pregnant women.

BACKGROUND: Opioid use during pregnancy is a significant public health issue. The standard of care for treating opioid use disorder during pregnancy includes medications for opioid disorder (MOUD). However, tobacco use often goes unaddressed among pregnant women on MOUD. In 2018, our team received a National Institute on Drug Abuse (NIDA) funded R34 to conduct a three year-randomized trial to test the feasibility of a novel tobacco intervention for pregnant women receiving MOUD. AIMS: The aims of this study are: (1) to determine the impact of the B-EPIC intervention on maternal tobacco use and stage of change; (2) to determine the impact of B-EPIC on tobacco-related maternal and infant health outcomes including gestational age at birth, birthweight, NAS diagnosis and severity, and number of ear and respiratory infections during the first six months; (3) to compare healthcare utilization and costs incurred by pregnant patients that receive the B-EPIC intervention versus TAU. METHODS: We plan to enroll 100 pregnant women on MOUD for this randomized controlled trial (B-EPIC intervention n = 50 and treatment as usual n = 50). A major strength of this study is its wide range of health and economic outcomes assessed on mother, neonate and the infant. CONCLUSIONS: Despite the very high rates of smoking among pregnant women with OUD, there are few tobacco treatment interventions that have been tailored for this high - risk population. The overall goal of this study is to move towards a tobacco treatment standard for pregnant women receiving treatment for OUD.

Cannabinoid modulation of opioid analgesia and subjective drug effects in healthy humans.

RATIONALE: Dozens of preclinical studies have reported cannabinoid agonist potentiation of the analgesic effects of µ-opioid agonists. OBJECTIVES: The aim of this study was to determine if a cannabinoid agonist could potentiate opioid analgesia in humans using several laboratory pain models. METHODS: Healthy participants (n = 10) with/out current drug use/pain conditions completed this within-subject, double-blind, placebo-controlled, randomized outpatient study. Nine 8-h sessions were completed during which dronabinol (0, 2.5, 5 mg, p.o.) was administered 1 h before oxycodone (0, 5, 10 mg, p.o.) for a total of 9 test conditions. Outcomes included sensory threshold and tolerance from four experimental pain models (cold pressor, pressure algometer, hot thermode, cold hyperalgesia), along with participant- and observer-rated, performance and physiological effects. RESULTS: Oxycodone produced miosis (p < 0.05) and analgesic responses (e.g., pressure algometer [p < 0.05]), while dronabinol did not (p > 0.05). Depending on the dose combination, dronabinol attenuated or did not alter oxycodone analgesia; for example, dronabinol (2.5 mg) decreased the analgesic effects of oxycodone (10 mg) on pressure tolerance. Conversely, dronabinol increased oxycodone subjective effects (e.g., drug liking) (p < 0.05); oxycodone (5 mg) ratings of "high" were potentiated by 5 mg dronabinol (p < 0.05; placebo = 1.1 [± 0.7]; 5 mg oxycodone = 4.7 [± 2.2]; 5 mg dronabinol = 9.9 [± 8.4]; 5 mg oxycodone + 5 mg dronabinol = 37.4 [± 11.3]). CONCLUSIONS: This study indicates that dronabinol did not enhance the analgesic effects of oxycodone and increased abuse- and impairment-related subjective effects. These data suggest that dronabinol may not be an effective or appropriate opioid adjuvant; it could potentially increase opioid dose requirements, while increasing psychoactive opioid effects.

The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription opioid abusers.

Abuse of prescription opioids has risen precipitously in the United States. Few controlled comparisons of the abuse liability of the most commonly abused opioids have been conducted. This outpatient study employed a double-blind, randomized, within-subject, placebo-controlled design to examine the relative abuse potential and potency of oral oxycodone (10, 20 and 40 mg), hydrocodone (15, 30 and 45 mg), hydromorphone (10, 17.5 and 25mg) and placebo. Healthy adult volunteers (n=9) with sporadic prescription opioid abuse participated in 11 experimental sessions (6.5h in duration) conducted in a hospital setting. All three opioids produced a typical mu opioid agonist profile of subjective (increased ratings of liking, good effects, high and opiate symptoms), observer-rated, and physiological effects (miosis, modest respiratory depression, exophoria and decrements in visual threshold discrimination) that were generally dose-related. Valid relative potency assays revealed that oxycodone was roughly equipotent to or slightly more potent than hydrocodone. Hydromorphone was only modestly more potent (less than two-fold) than either hydrocodone or oxycodone, which is inconsistent with prior estimates arising from analgesic studies. These data suggest that the abuse liability profile and relative potency of these three commonly used opioids do not differ substantially from one another and suggest that analgesic potencies may not accurately reflect relative differences in abuse liability of prescription opioids.

QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial.

BACKGROUND: Levomethadyl acetate, methadone hydrochloride, and buprenorphine hydrochloride are equally effective treatments for opioid dependence. Each blocks the human ether-a-go-go-related gene (hERG)-associated channel in vitro and represents a risk for QT prolongation. To compare the effects of 3 known hERG-associated channel blockers on the corrected QT (QTc), we conducted a randomized, controlled trial of opioid-addicted subjects. METHODS: We analyzed 12-lead electrocardiograms collected at baseline and every 4 weeks from 165 opioid-addicted participants in a 17-week randomized double-blind clinical trial of equally effective doses of levomethadyl, methadone, and buprenorphine at a major referral center. Analyses were limited to the 154 patients with a normal baseline QTc = (QT/ radical R-R) who had at least 1 subsequent in-treatment electrocardiogram. Patients were randomized to receive treatment with levomethadyl, methadone, or buprenorphine (hereinafter, levomethadyl, methadone, and buprenorphine groups, respectively). The prespecified end points were a QTc greater than 470 milliseconds in men (or >490 milliseconds in women), or an increase from baseline in QTc greater than 60 milliseconds. RESULTS: Baseline QTc was similar in the 3 groups. The levomethadyl and methadone groups were significantly more likely to manifest a QTc greater than 470 or 490 milliseconds (28% for the levomethadyl group vs 23% for the methadone group vs 0% for the buprenorphine group; P < .001) or an increase from baseline in QTc greater than 60 milliseconds (21% of the levomethadyl group [odds ratio, 15.8; 95% confidence interval, 3.7-67.1] and 12% of the methadone group [odds ratio, 8.4; 95% confidence interval, 1.9-36.4]) compared with the buprenorphine group (2% of subjects; P < .001). In subjects whose dosage of levomethadyl or methadone remained fixed over at least 8 weeks, the QTc continued to increase progressively over time (P = .08 for the levomethadyl group, P = .01 for the methadone group). CONCLUSION: Buprenorphine is associated with less QTc prolongation than levomethadyl or methadone and may be a safe alternative.

In-hospital illicit drug use, substance use disorders, and acceptance of residential treatment in a prospective pilot needs assessment of hospitalized adults with severe infections from injecting drugs.

OBJECTIVE: To conduct a pilot needs assessment of underlying substance use disorders (SUD), motivation for SUD treatment, and willingness to enter residential SUD treatment in hospitalized adults who inject drugs with complex infections requiring intravenous (IV) antibiotics, and to assess the presence of in-hospital illicit substance use. PATIENTS AND METHODS: From March 8, 2016 through August 25, 2016 hospitalized, English-speaking, adult patients not currently in SUD treatment with a history of injection drug use and a current infection requiring treatment with IV antibiotics, were prospectively enrolled. Participants were followed weekly during the hospitalization and for 60 days after discharge via interview and medical record review. RESULTS: Of the 42 participants, 8 (19.0%) accepted discharge to residential SUD treatment, 16 (38.0%) completed at least one follow-up research visit after hospital discharge, and 3 (7.1%) died during the 5-month study period. The majority (33; 78%) were hospitalized with endocarditis, and 37 (88.0%) had an opioid use disorder (DSM-5). Mean days of self-reported IV opioid use in the 30 days before hospitalization compared to 30 days after discharge decreased significantly (16.5 to 1.5, P = .001) despite not receiving SUD treatment. Illicit in-hospital drug use was identified in 17 (40.5%) participants, with opioids most commonly detected. CONCLUSION: Hospitalization is a 'reachable moment' and critical opportunity to initiate evidence-based treatment for opioid use disorder. The ongoing in-hospital illicit drug use and high short-term mortality observed in this study contribute to the mandate to expand access to effective pharmacotherapy for opioid use disorder and integrate it into health care settings.

Lobeline Effects on Cognitive Performance in Adult ADHD.

OBJECTIVE: In preclinical studies, lobeline inhibited hyperactivity induced by nicotine and amphetamine, and improved performance and learning in studies utilizing radial-arm maze and spatial-discrimination water maze. This laboratory proof-of-concept study investigated lobeline as a treatment for ADHD symptoms in adults (31.11 ± 7.08 years). METHOD: Using cognitive tasks and self-report measures, the effects of lobeline (0, 7.5, 15, or 30 mg, s.l.) and methylphenidate (0, 15, or 30 mg, p.o.) were assessed in nine volunteers with ADHD. RESULTS: Evidence suggested that lobeline could modestly improve working memory in adults with ADHD, but no significant improvement in attention was observed. Lobeline administration was associated with mild adverse side effects (nausea). CONCLUSION: Further investigation of lobeline on working memory may be warranted.

A randomized trial of employment-based reinforcement of cocaine abstinence in injection drug users.

High-magnitude and long-duration abstinence reinforcement can promote drug abstinence but can be difficult to finance. Employment may be a vehicle for arranging high-magnitude and long-duration abstinence reinforcement. This study determined if employment-based abstinence reinforcement could increase cocaine abstinence in adults who inject drugs and use cocaine during methadone treatment. Participants could work 4 hr every weekday in a workplace where they could earn about $10.00 per hour in vouchers; they were required to provide routine urine samples. Participants who attended the workplace and provided cocaine-positive urine samples during the initial 4 weeks were invited to work 26 weeks and were randomly assigned to an abstinence-and-work (n = 28) or work-only (n = 28) group. Abstinence-and-work participants had to provide urine samples showing cocaine abstinence to work and maintain maximum pay. Work-only participants could work independent of their urinalysis results. Abstinence-and-work participants provided more (p = .004; OR = 5.80, 95% CI = 2.03-16.56) cocaine-negative urine samples (29%) than did work-only participants (10%). Employment-based abstinence reinforcement can increase cocaine abstinence.

Effects of Short-Term Oxycodone Maintenance on Experimental Pain Responses in Physically Dependent Opioid Abusers.

A common clinical problem with opioid analgesics is the loss of analgesic efficacy after repeated dosing; when this occurs, it is not clear what principles should guide providing effective analgesia among opioid-dependent individuals. This within-subject inpatient study aimed to determine if physically dependent opioid abusers (n = 11) experience changes in oxycodone-induced analgesia during 2 oxycodone maintenance (30 mg orally 4 times per day) phases: initial stabilization (days 1-3) and after 6 weeks of chronic dosing. Six sessions (3 each phase), measured threshold, tolerance, and pain ratings for a Pressure Pain Test and Cold Pressor Test after a single double-blind dose of oxycodone 30 mg (initial stabilization) and 0, 30, and 60 mg (chronic dosing) given in place of a scheduled maintenance dose. Physiologic and opioid agonist effects were assessed during chronic dosing sessions. There was no analgesic response to oxycodone 30 mg. Oxycodone (60 mg) produced a 25% increase in peak Cold Pressor Test threshold compared with placebo, and significantly increased expired breath CO2, miosis, and ratings of abuse liability measures. These data suggest that more than twice the acute oxycodone maintenance dose is needed to produce robust acute analgesia, although adverse effects (eg, respiratory depression and abuse signals) may occur with lower doses. PERSPECTIVE: To understand sensitivity to opioid analgesia in opioid-dependent individuals, this article describes experimental pain, subjective and physiological responses during stabilization and after 6 weeks of oxycodone maintenance. Oxycodone produced euphoric effects and miosis with limited evidence of analgesia.

Randomized controlled trial of a computerized opioid overdose education intervention.

BACKGROUND: Opioid overdose (OD) has become a significant public health problem in need of effective interventions. The majority of existing educational interventions target provision of naloxone and are conducted in-person; these elements present logistical barriers that may limit wide-spread implementation. This study developed and evaluated an easily disseminated opioid OD educational intervention and compared computerized versus pamphlet delivery METHODS: Participants (N=76) undergoing opioid detoxification were randomly assigned to receive OD education via a Pamphlet (N=25), Computer (N=24), or Computer+Mastery (N=27) with identical content for all delivery modalities. Primary outcomes were changes from pre- to post-intervention in knowledge of opioid effects, opioid OD symptoms, and recommended opioid OD responses, as well as intervention acceptability. Also assessed at 1 and 3-month follow-ups were retention of knowledge and change in reported OD risk behaviors. RESULTS: Knowledge increased following all three intervention-delivery modalities with few between-group differences observed in knowledge gain or acceptability ratings. Largest gains were in the domain of opioid OD response (from 41.8% to 73.8% mean correct responses; p<0.001). Knowledge was well sustained at the 1 and 3-month follow-ups among completers, where a significant reduction was seen in the critical behavioral risk factor of using opioids while alone. CONCLUSION: Opioid overdose education delivered by computer or written pamphlet produced sustained increases in knowledge and reduction in a key behavioral risk factor. RESULTS: Results support further evaluation of this educational intervention that can be used alone or to complement naloxone-training programs.