Race-based differences in drug use prior to onset of opioid use disorder.

Rates of opioid use disorder (OUD) have increased dramatically over the past two decades, a rise that has been accompanied by changing demographics of those affected. Early exposure to drugs is a known risk factor for later development of opioid use disorder; but how and whether this risk factor may differ between racial groups is unknown. Our study seeks to identify race differences in self-report of current and past substance use in OUD-diagnosed treatment-seeking individuals. Patients (n = 157) presenting for methadone maintenance treatment at a racially diverse urban opioid treatment program were approached and consented for study involvement. Participants were administered substance use history questionnaires and urine drug screening at intake. Chi-square, t-tests, and rank-sum were used to assess race differences in demographic variables. Logistic and linear regressions assessed the relationship between race and substance use for binary and continuous variables, respectively. 61% of the population identified as Black and 39% as White. Black participants were significantly older; age was thus included as a covariate. Logistic regressions demonstrated that despite similar urine toxicology at intake, White participants were significantly more likely to report having used prescription opioids and psychedelic, stimulant, and sedative substance classes prior to their first use of non-pharmaceutical opioids. Compared to Black participants, White treatment-seeking OUD-diagnosed individuals reported using a wider range of substances ever and prior to first use of non-pharmaceutical opioids. There were no differences, however, in presentation for OUD treatment, suggesting different pathways to OUD, which may carry important clinical implications.

Toward a National System of Expanded Testing of Existing Urine Specimens: The Drug Outbreak Testing Service (DOTS).

BACKGROUND: NIDA's National Drug Early Warning System (NDEWS) was established in 2014 with the mission of identifying and monitoring emerging drugs in the United States. Identification of emerging drugs has been complicated, however, by the rapid development of novel psychoactive substances such that users often cannot identify and report the drugs they have ingested. Biologic testing of urine, hair or blood is the only way to reliably identify the substances recently used. Unfortunately, the large number of up-to-date tests required is beyond the resources available to most organizations. METHODS: The DOTS study tested the feasibility of recruiting organizations to submit up to 25 de-identified urine specimens for testing for approximately 240 drugs, at no cost to them. The results were for epidemiologic purposes only and not for clinical use. Eleven sites who had questions about their patients or the results of their organization's more limited urinalysis screens participated. These sites included drug treatment programs, medical examiners, hospitals and a criminal justice testing program. RESULTS: Extensive polydrug use and geographic differences in the drugs detected were found. All sites found the DOTS collaborating laboratory's test results to be very useful for understanding the types of drugs being used recently and to assess the adequacy of their testing protocols. CONCLUSIONS: The U.S. should consider establishing a program of expanded testing of already collected de-identified urine specimens in order to identify emerging drugs and track local patterns of use and availability.

Patient experiences of COVID-19-induced changes to methadone treatment in a large community-based opioid treatment program in Baltimore.

INTRODUCTION: Following the March 2020 federal declaration of a COVID-19 public health emergency, in line with recommendations for social distancing and decreased congregation, federal agencies issued sweeping regulation changes to facilitate access to medications for opioid use disorder (MOUD) treatment. These changes allowed patients new to treatment to receive multiple days of take-home medications (THM) and to use remote technology for treatment encounters-allowances that previously had been reserved exclusively for "stable" patients who met minimum adherence and time-in-treatment criteria. The impact of these changes on low-income, minoritized patients (frequently the largest recipients of opioid treatment program [OTP]-based addiction care), however, is not well characterized. We aimed to explore the experiences of patients who were enrolled in treatment prior to COVID-19 OTP regulation changes, with the goal of understanding patients' perceptions of the impact of these changes on treatment. METHODS: This study included semistructured, qualitative interviews with 28 patients. We used a purposeful sampling method to recruit individuals who were active in treatment just before COVID-19-related policy changes went into effect, and who were still in treatment several months later. To ensure a diverse array of perspectives, we interviewed individuals who either had or had not experienced challenges with methadone medication adherence from 3/24/21 to 6/8/21, approximately 12-15 months following the onset of COVID-19. Interviews were transcribed and coded using thematic analysis. RESULTS: Participants were majority male (57 %), Black/African American (57 %), with a mean age of 50.1 (SD = 9.3). Fifty percent received THM prior to COVID-19, which increased to 93 % during the pandemic. COVID-19 program changes had mixed effects on treatment and recovery experiences. Themes identified convenience, safety, and employment as reasons for preferring THM. Challenges included difficulty with managing/storing medications, experiencing isolation, and concern about relapse. Furthermore, some participants reported that telebehavioral health encounters felt less personal. CONCLUSIONS: Policymakers should consider patients' perspectives to foster a more patient-centered approach to methadone dosing that is safe, flexible, and accommodating to a diverse array of patients' needs. Additionally, technical support should be provided to OTPs to ensure interpersonal connections are maintained in the patient-provider relationship beyond the pandemic.

Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial.

Importance: Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects. Objective: To determine the effect of a pharmacologically conditioned open-label placebo (C-OLP) on 90-day methadone dose, retention, drug use, withdrawal, craving, quality of life, and sleep. Design, Setting, and Participants: This 2-arm, open-label, single-blind randomized clinical trial was conducted between December 5, 2017, and August 2, 2019, in an academically affiliated community opioid treatment program. Analyses were conducted between October 1, 2019, and April 30, 2020. A total of 320 newly enrolled adults seeking treatment for moderate to severe OUD were assessed for study eligibility; 131 met eligibility criteria, provided informed consent, and were randomized to either C-OLP or treatment as usual (TAU) in an unequal-block (3:2) manner. Exclusion criteria were pregnancy, hospital/program transfers, and court-ordered treatment. Interventions: Participants randomized to C-OLP received pharmacologic conditioning and a placebo pill and methadone, and participants randomized to TAU were given methadone only. Participants met with the study team 5 times: at baseline (treatment intake) and 2, 4, 8, and 12 weeks postbaseline. Interactions were balanced between the 2 groups. Main Outcomes and Measures: Outcomes included 90-day methadone dose (primary) and treatment retention, drug use, withdrawal, craving, quality of life, and sleep quality (secondary). Analyses were conducted as intention-to-treat. Results: Of the 131 people enrolled in the study, 54 were randomized to TAU and 77 to C-OLP. Mean (SD) age was 45.9 (11.2) years; most of the participants were Black or African American (83 [63.4%]) and male (84 [64.1%]). No significant group differences were observed in the mean (SD) 90-day methadone dose (83.1 [25.1] mg for group TAU, 79.4 [19.6] mg for group C-OLP; t = 0.621991; P = .43), but the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP (χ21 = 4.356; P = .04; number needed to treat for the beneficial outcome of 3-month treatment retention, 6; 95% CI, 4-119). C-OLP participants also reported significantly better sleep quality. Conclusions and Relevance: In this randomized clinical trial, C-OLP had no effect on the primary outcome of 90-day methadone dose. However, C-OLP participants were significantly more likely to remain in treatment. These findings support the use of C-OLP as a methadone treatment adjunct, but larger trials are needed to further examine the use of C-OLP. Trial Registration: ClinicalTrials.gov Identifier: NCT02941809.

"In their mind, they always felt less than": The role of peers in shifting stigma as a barrier to opioid use disorder treatment retention.

INTRODUCTION: A substantial, national need exists for culturally acceptable, accessible opioid use disorder (OUD) treatment. Medication for opioid use disorder (MOUD) is regarded as effective in treating OUD; however, retention in MOUD programs remains low nationally. One known barrier to MOUD retention is stigma, particularly within ethno-racial minority communities. Peer recovery specialists (PRSs), individuals with shared experience in substance use and recovery, may be particularly well suited to support patients in MOUD treatment, and may have capacity to play a key role in decreasing stigma-related barriers to MOUD retention. METHODS: This study used qualitative methods to solicit feedback on how patients receiving methadone treatment (MT) experience stigma (i.e., toward substance use [SU] and MT). Study staff also gathered information regarding how a PRS role may reduce stigma and improve retention in care, including barriers and facilitators to the PRS role shifting stigma. Study staff conducted semi-structured qualitative interviews and focus groups (N = 32) with staff and patients receiving MT at an opioid treatment program as well as PRSs in Baltimore. RESULTS: Participants identified experiences of internalized, as well as enacted and anticipated, MT and SU stigma, and described these as barriers to treatment. Participants also identified opportunities for PRSs to shift stigma-related barriers for patients receiving MT through unique aspects of the PRS role, such as their shared lived experience. CONCLUSIONS: Reducing stigma surrounding SUD and MT is critical for improving MOUD outcomes, and future research may consider how the PRS role can support this effort.

Emergency Department Drug Surveillance (EDDS) hospital's urinalysis results compared with expanded re-testing by an independent laboratory, a pilot study.

INTRODUCTION: Most hospital urine toxicology screens detect a fixed, limited set of common substances. These tests are fast and accurate but may miss emerging trends in substance use in the community and clinical acumen alone is insufficient for identifying new substances. METHODS: This prospective cohort study examined de-identified urine specimens obtained from patients visiting the Emergency Department (ED) at Prince George's Hospital Center (PGHC), between October 15, 2019 to November 6, 2019 and tested positive for one or more substances. The Emergency Department Drug Surveillance System (EDDS) collects quarterly exports from de-identified electronic health records (EHRs) containing urinalysis results for drug related ED visits. We performed a feasibility study of a new urine specimen submission by collecting a stratified sample of 151 urine specimens from PGHC ED patients. The specimens were tested for 240 drugs using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This paper presents a comparison between the PGHC and expanded testing results. RESULTS: The expanded urinalysis panel found more cocaine (37% vs. 20%; p < 0.01) and benzodiazepine positives (21% vs. 11%; p < 0.05) than would have been detected by the hospital screen. Additionally, the expanded toxicology panel identified fentanyl in 4-14% of the samples. CONCLUSION: The EHR data submitted to EDDS from the hospital urine toxicology screen correctly identified hospital substance use patterns over the approximate 1 month study period. The expanded testing also uncovered drugs that the hospital might consider adding to their routine screen. EDDS is a feasible system for monitoring and confirming recent substance use trends among ED patients.

Using socially-sensed data to infer ZIP level characteristics for the spatiotemporal analysis of drug-related health problems in Maryland.

This research investigated how socially sensed data can be used to detect ZIP level characteristics that are associated with spatial and temporal patterns of Emergency Department patients with a chief complaint and/or diagnosis of overdose or drug-related health problems for four hospitals in Baltimore and Anne Arundel County, MD during 2016-2018. Dynamic characteristics were identified using socially-sensed data (i.e., geo-tagged Twitter data) at ZIP code level over varying temporal resolutions. Data about three place-based variables including comments and concerns about crime, drug use, and negative or depressed sentiments, were extracted from tweets, along with data from four socio-environmental variables from the American Community Survey were collected to explore socio-environmental characteristics during the same period. Our study showed a statistically significant increase in adjusted rates of Emergency Department (ED) visits occurred between June and November 2017 for patients residing in ZIP codes in western Baltimore and northeastern Anne Arundel County. During this period, the three topics extracted from Twitter data were highly correlated with the ZIP codes where the patients were residing. Exploring the dynamic spatial associations between socio-environmental variables and ED visits for acute overdose assists local health officials in optimizing interventions for vulnerable locations.

Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment.

INTRODUCTION: More than 2 million individuals in the USA have an opioid use disorder (OUD). Methadone maintenance treatment is the gold standard of medication-based treatment for OUD, but high-dose methadone is associated with cardiotoxicity and respiratory complications, among other side effects. These adverse effects make enhancing the effectiveness of lower doses of methadone an attractive therapeutic goal. Long recognised for its capacity to enhance treatment outcomes for a wide range of neuropsychiatric disorders including pain, the placebo effect offers an as-yet untested avenue to such an enhancement. This approach is particularly compelling given that individuals with substance use disorder tend to have higher salience attribution and may thereby be more sensitive to placebo effects. Our study combines two promising clinical methodologies-conditioning/dose-extension and open-label placebo-to investigate whether placebo effects can increase the effective potency of methadone in treatment-seeking OUD patients. METHODS AND ANALYSIS: A total of 120 newly enrolled treatment-seeking OUD patients will be randomly assigned to one of two different groups: either methadone plus daily placebo dose-extension (PDE; treatment group) or methadone/treatment as usual (control). Participants will meet with study team members five times over the course of 3 months of treatment with methadone (baseline, 2 weeks, and 1, 2 and 3 months postbaseline). Throughout this study time period, methadone dosages will be adjusted by an addiction clinician blind to patient assignment, per standard clinical methods. The primary outcome is methadone dose at 3 months. Secondary outcomes include self-report of drug use; 3-month urine toxicology screen results; and treatment retention. Exploratory outcomes include several environmental as well as personality factors associated with OUD and with propensity to demonstrate a placebo effect. ETHICS AND DISSEMINATION: Human subjects oversight for this study is provided by the University of Maryland, Baltimore and University of Maryland, College Park Institutional Review Boards. Additionally, the study protocol is reviewed annually by an independent Data and Safety Monitoring Board. Study results will be disseminated via research conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02941809.

Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids.

Identifying non-addictive opioid medications is a high priority in medical sciences, but µ-opioid receptors mediate both the analgesic and addictive effects of opioids. We found a significant pharmacodynamic difference between morphine and methadone that is determined entirely by heteromerization of µ-opioid receptors with galanin Gal1 receptors, rendering a profound decrease in the potency of methadone. This was explained by methadone's weaker proficiency to activate the dopaminergic system as compared to morphine and predicted a dissociation of therapeutic versus euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-report of "high" in methadone-maintained patients. These results suggest that µ-opioid-Gal1 receptor heteromers mediate the dopaminergic effects of opioids that may lead to a lower addictive liability of opioids with selective low potency for the µ-opioid-Gal1 receptor heteromer, exemplified by methadone.