Illicit Opioid Use Research Articles

Disclosing Recovery: A pilot randomized controlled trial of a patient decision aid to improve disclosure processes for people in treatment for opioid use disorder

IntroductionPeople engaged in treatment for opioid use disorder (OUD) report struggling with whether and how to disclose, or share information about their OUD history and/or treatment with others. Yet, disclosure can act as a gateway to re-establishing social connection and support during recovery. The current study describes a pilot randomized controlled trial of Disclosing Recovery: A Decision Aid and Toolkit, a patient decision aid designed to facilitate disclosure decisions and build disclosure skills. MethodsParticipants (n = 50) were recruited from a community-based behavioral health organization in 2021–2022 and randomized to receive the Disclosing Recovery intervention versus an attention-control comparator. They responded to surveys immediately after receiving the intervention as well as one month following the intervention at a follow-up appointment. Primary outcome analyses examined indicators of implementation of the intervention to inform a future efficacy trial. Secondary outcome analyses explored impacts of the intervention on the decision-making process, disclosure rates, and relationships. ResultsParticipants were successfully recruited, randomized, and retained, increasing confidence in the feasibility of future efficacy trials to test the Disclosing Recovery intervention. Moreover, participants in the Disclosing Recovery intervention agreed that the intervention is acceptable, feasible, and appropriate. They additionally reported a higher quality of their decision-making process and decisions than participants in the comparator condition. At their follow-up appointment, participants with illicit opioid use who received the Disclosing Recovery intervention were less likely to disclose than those who received the comparator condition. Moreover, significant interactions between illicit opioid use and the intervention condition indicated that participants without illicit opioid use who received the Disclosing Recovery intervention reported greater closeness to and social support from their planned disclosure recipient than those who received the comparator condition. ConclusionsThe Disclosing Recovery intervention appears to be an acceptable, feasible, and appropriate patient decision aid for addressing disclosure processes among people in treatment for OUD. Moreover, preliminary results suggest that it shows promise in improving relationship closeness and social support in patients without illicit opioid use. More testing is merited to determine the intervention's efficacy and effectiveness in improving relationship and treatment outcomes for people in treatment for OUD.

Rise in child suicide linked to reduced quality of life, parental addiction

After generally declining for decades, suicide rates among children aged 10–17 rose dramatically from 2011 to 2018, according to an article released in December 2023. The author, from RAND, writes that the illicit opioid crisis is responsible. This began with the August 2010 introduction of an abuse‐resistant form of the painkiller OxyContin. No longer available for abuse, the drug was replaced on the street first by heroin and then by other illicit opioids including fentanyl. The researcher found that the areas most exposed to the reformulated OxyContin had a greater rise in child suicides. The researcher suggests that the problem was not an increase in illicit opioid use by children, but rather higher propensities to suicide risk factors such as increasing rates of child neglect and altered household living arrangements — drug use by parents and caregivers. The researcher also documents the decline in living conditions for children during this period. The article documents suicide rates from the National Vital Statistics System Multiple Cause of Death database. Powell, D. (2023, Dec 1). Growth in suicide rates among children during the illicit opioid crisis. Demography, 60(6), 1843–1875. http://doi.org/10.1215/00703370‐11077660.

Comparing the effects of decreasing prescription opioid shipments and the release of an abuse deterrent OxyContin formulation on opioid overdose fatalities in WV: an interrupted time series study

IntroductionThe 2010 release of an abuse deterrent formulation (ADF) of OxyContin, a brand name prescription opioid, has been cited as a major driver for the reduction in prescription drug misuse and the associated increasing illicit opioid use and overdose rates. However, studies of this topic often do not account for changes in supplies of other prescription opioids that were widely prescribed before and after the ADF OxyContin release, including generic oxycodone formulations and hydrocodone. We therefore sought to compare the impact of the ADF OxyContin release to that of decreasing prescription opioid supplies in West Virginia (WV).MethodsOpioid tablet shipment and overdose data were extracted from The Washington Post ARCOS (2006–2014) and the WV Forensic Drug Database (2005–2020), respectively. Locally estimated scatterplot smoothing (LOESS) was used to estimate the point when shipments of prescription opioids to WV began decreasing, measured via dosage units and morphine milligram equivalents (MMEs). Interrupted time series analysis (ITSA) was used to compare the impact LOESS-identified prescription supply changes and the ADF OxyContin release had on prescription (oxycodone and hydrocodone) and illicit (heroin, fentanyl, and fentanyl analogues) opioid overdose deaths in WV. Model fit was compared using Akaike Information Criteria (AIC).ResultsThe majority of opioid tablets shipped to WV from 2006 to 2014 were generic oxycodone or hydrocodone, not OxyContin. After accounting for a 6-month lag from ITSA models using the LOESS-identified change in prescription opioid shipments measured via dosage units (2011 Q3) resulted in the lowest AIC for both prescription (AIC = -188.6) and illicit opioid-involved overdoses (AIC = -189.4), indicating this intervention start date resulted in the preferred model. The second lowest AIC was for models using the ADF OxyContin release as an intervention start date.DiscussionWe found that illicit opioid overdoses in WV began increasing closer to when prescription opioid shipments to the state began decreasing, not when the ADF OxyContin release occurred. Similarly, the majority of opioid tablets shipped to the state for 2006–2014 were generic oxycodone or hydrocodone. This may indicate that diminishing prescription supplies had a larger impact on opioid overdose patterns than the ADF OxyContin release in WV.

The dynamics of heroin and illicit opioid use disorder, casual use, treatment, and recovery: A mathematical modeling analysis.

A leading crisis in the United States is the opioid use disorder (OUD) epidemic. Opioid overdose deaths have been increasing, with over 100,000 deaths due to overdose from April 2020 to April 2021. This paper presents a mathematical model to address illicit OUD (IOUD), initiation, casual use, treatment, relapse, recovery, and opioid overdose deaths within an epidemiological framework. Within this model, individuals remain in the recovery class unless they relapse back to use and due to the limited availability of specialty treatment facilities for individuals with OUD, a saturation treatment function was incorporated. Additionally, a casual user class and its corresponding specialty treatment class were incorporated. We use both heroin and all-illicit opioids datasets to find parameter estimates for our models. Bistability of equilibrium solutions was found for realistic parameter values for the heroin-only dataset. This result implies that it would be beneficial to increase the availability of treatment. An alarming effect was discovered about the high overdose death rate: by 2046, the disorder-free equilibrium would be the only stable equilibrium. This consequence is concerning because it means the epidemic would end due to high overdose death rates. The IOUD model with a casual user class, its sensitivity results, and the comparison of parameters for both datasets, showed the importance of not overlooking the influence that casual users have in driving the all-illicit opioid epidemic. Casual users stay in the casual user class longer and are not going to treatment as quickly as the users of the heroin epidemic. Another result was that the users of the all-illicit opioids were going to the recovered class by means other than specialty treatment. However, the change in the relapse rate has more of an influence for those individuals than in the heroin-only epidemic. The results above from analyzing this model may inform health and policy officials, leading to more effective treatment options and prevention efforts.

Three noteworthy idiosyncrasies related to Canada's opioid-death crisis, and implications for public health-oriented interventions.

Canada has been experiencing a prolonged public health-crisis of high rates of overdose deaths caused by exceptionally potent/toxic, illicit opioid use. While many key features of this drug death epidemic are well-documented, several idiosyncratic aspects with relevance for public health-oriented interventions are not adequately recognised. These include: (i) the discrepant opioid patterns pan-Canada, with large majorities of opioid deaths caused by illicit fentanyl drugs in Western, but not Eastern regions where prescription-type opioid prevail; (ii) the environments of overdose deaths, where vast majorities occur in 'residential' or other shelter-type settings, presenting barriers for emergency interventions rather than health protection; and (iii) shifting drug use modes, where now majorities of overdose deaths are associated with drug 'inhalation' (instead of 'injection') in contexts of potent/toxic drug supply. We briefly describe these factors and related implications for intervention programming towards an improved response to the drug death-crisis.

Initiation and rapid titration of methadone and slow-release oral morphine (SROM) in an acute care, inpatient setting: a case series

BackgroundMethadone titration in an outpatient setting typically involves initiation with subtherapeutic doses with slow titration to mitigate the risks of respiratory depression and overdose. In pregnancy, and generally, subtherapeutic doses of methadone and slow titrations are associated with poorer outcomes in terms of treatment retention and ongoing illicit opioid use. We aim to describe rapid titration of OAT in an inpatient setting for pregnant injection opioid users with high opioid tolerance secondary to a fentanyl-based illicit drug supply.MethodsRetrospective case series of patients admitted to a tertiary center with a primary indication of opioid withdrawal and treatment for severe opioid use disorder in pregnancy. ResultsTwelve women received rapid methadone titrations with or without slow-release oral morphine for opioid use disorder during a total of fifteen hospital admissions. All women included in the study were active fentanyl users (12/12). Methadone dosing was increased rapidly with no adverse events with a median dose at day 7 of 65 mg (IQR 60–70 mg) and median discharge dose of 85 mg (IQR 70–92.5 mg) during their admission for titration. Slow-release oral morphine was used in half of the titration admissions (8/15) with a median dose of 340 mg (IQR 187.5–425 mg) at discharge. The median length of admission was 12 days (IQR 9.5–15).ConclusionsA rapid titration of methadone was completed in an inpatient setting with or without slow-release oral morphine, without adverse events showing feasibility of this protocol for a pregnant population in an inpatient setting. Patients achieved therapeutic doses of methadone (and/or SROM) faster than outpatient counterparts with no known adverse events.

Cost-effectiveness of full and partial opioid agonists for opioid use disorder in outpatient settings: United States healthcare sector perspective

IntroductionStudies show that medications for opioid use disorder (MOUD) reduce illicit opioid use, emergency healthcare services, opioid-related overdose, and death. However, few studies have investigated the long-term cost-effectiveness of MOUD in office-based opioid treatment (OBOT) and opioid treatment program (OTP) settings. We aimed to estimate the cost, utility, quality-adjusted life years gained (QALYs), and incremental cost-effectiveness ratios (ICERs) of three MOUD compared to each other and counseling without medication from a US healthcare sector perspective. MethodsOur study developed a Markov model to conduct a cost-effectiveness analysis of counseling and three MOUD in the OBOT and OTP settings: sublingual buprenorphine/naloxone (BUPNX), buprenorphine extended-release (XR-BUP) injection, and oral methadone. The model included five health states representing combinations of receiving or off treatment while either using or not actively using illicit opioids, and death. The cycle length was one month; the time-horizon was ten years. The study obtained model inputs from systematic reviews of published literature and public data. A 3 % annual discount rate was applied to cost and utility calculation. The primary outcomes included total costs, life-years (LYs), QALYs, and ICERs. We also conducted a scenario analysis using a hypothetical OBOT outpatient setting with methadone. ResultsIn the base-case OBOT setting, the total costs and QALYs, respectively, were counseling $22,848, 5.60; BUPNX $29,875, 5.82; and XR-BUP $63,936, 5.87. ICERs were $32,345/QALY (BUPNX vs. counseling) and $625,858/QALY (XR-BUP vs BUPNX). In the OTP setting, the total costs of counseling, methadone, BUPNX, and XR-BUP were $20,124, $27,000, $33,500, and $75,272, respectively. QALYs of methadone were 5.86. QALYs of counseling, BUPNX, and XR-BUP remained the same as in the OBOT setting. Incremental ICERs were $26,714/QALY (methadone vs counseling) and $3,337,623/QALY (XR-BUP vs methadone). BUPNX was dominated by methadone. In the scenario analysis, BUPNX was also dominated by methadone. ConclusionsOutpatient MOUD resulted in important gains in quality of life and life expectancy. In both OBOT and OTP settings, XR-BUP was not cost-effective. BUPNX was cost-effective in the OBOT setting, while it was dominated by methadone in the OTP setting. The cost-effectiveness of BUPNX and XR-BUP could be enhanced if the costs of these medications were reduced.

Health-care resource use among patients who use illicit opioids in England, 2010-20: A descriptive matched cohort study.

People who use illicit opioids have higher mortality and morbidity than the general population. Limited quantitative research has investigated how this population engages with health-care, particularly regarding planned and primary care. We aimed to measure health-care use among patients with a history of illicit opioid use in England across five settings: general practice (GP), hospital outpatient care, emergency departments, emergency hospital admissions and elective hospital admissions. This was a matched cohort study using Clinical Practice Research Datalink and Hospital Episode Statistics. Primary and secondary care practices in England took part in the study. A total of 57 421 patients with a history of illicit opioid use were identified by GPs between 2010 and 2020, and 172 263 patients with no recorded history of illicit opioid use matched by age, sex and practice. We estimated the rate (events per unit of time) of attendance and used quasi-Poisson regression (unadjusted and adjusted) to estimate rate ratios between groups. We also compared rates of planned and unplanned hospital admissions for diagnoses and calculated excess admissions and rate ratios between groups. A history of using illicit opioids was associated with higher rates of health-care use in all settings. Rate ratios for those with a history of using illicit opioids relative to those without were 2.38 [95% confidence interval (CI) = 2.36-2.41] for GP; 1.99 (95% CI = 1.94-2.03) for hospital outpatient visits; 2.80 (95% CI = 2.73-2.87) for emergency department visits; 4.98 (95% CI = 4.82-5.14) for emergency hospital admissions; and 1.76 (95% CI = 1.60-1.94) for elective hospital admissions. For emergency hospital admissions, diagnoses with the most excess admissions were drug-related and respiratory conditions, and those with the highest rate ratios were personality and behaviour (25.5, 95% CI = 23.5-27.6), drug-related (21.2, 95% CI = 20.1-21.6) and chronic obstructive pulmonary disease (19.4, 95% CI = 18.7-20.2). Patients who use illicit opioids in England appear to access health services more often than people of the same age and sex who do not use illicit opioids among a wide range of health-care settings. The difference is especially large for emergency care, which probably reflects both episodic illness and decompensation of long-term conditions.

In Case You Haven't Heard…

You've heard it from the pro‐legalization advocates for years: Cannabis reduces illicit drug use. No, it doesn't, as studies have shown, most recently one published Nov. 29 in the American Journal of Psychiatry. For the study, “The Long‐Term Relationship Between Cannabis and Heroin Use: An 18‐ to 20‐year Follow‐Up of the Australian Treatment Outcome Study (ATOS),” researchers from the University of Sydney in Australia followed 615 people with heroin dependence for more than 20 years; many of the users also used cannabis. There was no evidence that illicit opioid use was reduced.

Experiences of serious depression and serious anxiety among individuals receiving injectable opioid agonist treatment (iOAT)

BackgroundThis study aims to provide evidence of factors that impact participant reported serious depression and serious anxiety among individuals receiving injectable opioid agonist treatment (iOAT). MethodsData from an 18-month longitudinal retrospective cohort of individuals receiving iOAT was utilized. The outcomes of serious depression and serious anxiety were ascertained via self-report in the European Addiction Severity Index. Two Generalized Linear Mixed Models were formulated using Penalized Quasi-Likelihood method. ResultsAnalyses included 131 participants. Average age was 49.04 years, 31 % self-identified as female, and 30 % self-identified as Indigenous. Adjusted analysis identified the importance of poorer physical health (AOR:1.06; 95 % CI: 1.03, 1.08), illicit opioid use (AOR: 1.03; 95 %CI: 1.01, 1.06), emotional abuse (AOR: 2.01; 95 % CI: 1.17, 3.44), and social isolation (AOR: 1.95; 95 % CI: 1.06, 3.58) with serious depression. Adjusted analysis of serious anxiety identified associations with age (AOR: 0.95; 95 % CI: 0.92, 0.98), illicit benzodiazepine use (AOR:1.31 95 % CI: 1.06, 1.61), poorer physical health (AOR: 1.05; 95 % CI: 1.03, 1.07), and social problems (AOR: 2.09; 95 % CI: 1.18, 3.71). LimitationsGeneralizability of study findings may be limited given the criteria used to enroll participants and to define depression and anxiety. ConclusionDepression and anxiety are highly prevalent among clients receiving iOAT. While both disorders share several factors, there are distinct characteristics associated with each outcome. These include poorer physical health, experiences of abuse, illicit substance use, and social problems. Understanding factors that influence depression and anxiety in iOAT can assist providers in supporting iOAT clients' mental health and developing individualized care plans.

Growth in Suicide Rates Among Children During the Illicit Opioid Crisis

This article documents child suicide rates from 1980 to 2020 in the United States using the National Vital Statistics System Multiple Cause of Death database. After generally declining for decades, suicide rates among children aged 10–17 accelerated from 2011 to 2018 in an unprecedented rise in both duration and magnitude. I consider the role of the illicit opioid crisis in driving this mental health crisis. In August 2010, an abuse-deterrent version of OxyContin was introduced and the original formulation was removed from the market, leading to a shift to illicit opioids and stimulating growth in illicit opioid markets. Areas more exposed to reformulation—as measured by pre-reformulation rates of OxyContin misuse in the National Survey on Drug Use and Health—were more affected by the transition to illicit opioids and experienced sharper growth in child suicide rates. The evidence suggests that children's illicit opioid use did not increase, implying that the illicit opioid crisis engendered higher suicide propensities by increasing suicidal risk factors for children, such as increasing rates of child neglect and altering household living arrangements. In complementary analyses, I document how living conditions declined for children during this time period.

The Long-Term Relationship Between Cannabis and Heroin Use: An 18- to 20-year Follow-Up of the Australian Treatment Outcome Study (ATOS).

Cannabis use is common among individuals with opioid use disorder, but it remains unclear whether cannabis use is associated with an increase or a reduction in illicit opioid use. To overcome limitations identified in previous longitudinal studies with limited follow-ups, the authors examined a within-person reciprocal relationship between cannabis and heroin use at several follow-ups over 18 to 20 years. The Australian Treatment Outcome Study (ATOS) recruited 615 people with heroin dependence in 2001 and 2002 and reinterviewed them at 3, 12, 24, and 36 months as well as 11 and 18-20 years after baseline. Heroin and cannabis use were assessed at each time point using the Opiate Treatment Index. A random-intercept cross-lagged panel model analysis was conducted to identify within-person relationships between cannabis use and heroin use at subsequent follow-ups. After accounting for a range of demographic variables, other substance use, and mental and physical health measures, an increase in cannabis use 24 months after baseline was significantly associated with an increase in heroin use at 36 months (estimate=0.21, SE=0.10). Additionally, an increase in heroin use at 3 months and 24 months was significantly associated with a decrease in cannabis use at 12 months (estimate=-0.27, SE=0.09) and 36 months (estimate=-0.22, SE=0.08). All other cross-lagged associations were not significant. Although there was some evidence of a significant relationship between cannabis and heroin use at earlier follow-ups, this was sparse and inconsistent across time points. Overall, there was insufficient evidence to suggest a unidirectional or bidirectional relationship between the use of these substances.

Characterizing prescription opioid, heroin, and fentanyl initiation trajectories: A qualitative study

We understand the current crisis of overdose deaths to be driven by widespread opioid use, characterized by distinct ‘waves’ of drug use. The first wave was driven by prescription opioids, the second by heroin, and the third by illicit, non-pharmaceutical fentanyl and fentanyl analogues (henceforth, fentanyl). The purpose of this study is to describe opioid initiation within each of the three waves from the perspective of people who use illicit opioids, with a focus on emerging pathways into fentanyl use. The authors recruited sixty people reporting past-30-day illicit opioid use in Dayton, Ohio. Participants completed a brief survey and a semi-structured in-depth qualitative interview, conducted from March to November 2020 with a total of 13 in-person and 47 virtual interviews. The qualitative interviews were transcribed in their entirety and analyzed thematically using NVivo 12. We noted supply-side changes as influencing trajectories in all three waves. However, we also noted differences in the experiences of prescription opioid and heroin initiation, with these trajectories influenced by pharmacological effects, pain management, curiosity, intergenerational use, pricing, and peers. In comparison, most participants were unaware that they were initiating fentanyl, and many reported overdosing with their first use of fentanyl. We identified a trajectory into fentanyl with limited to no prior heroin use among a few participants. The increased risk of overdose with initiation into fentanyl use further emphasizes the need for an expansion of naloxone distribution and the implementation of more comprehensive measures, such as overdose prevention centers, drug testing, and a safer supply. Further research on the dynamics of the ongoing overdose death crisis in the era of fentanyl and the 4th wave of the overdose crisis is critical in developing responsive prevention and intervention strategies.

Subthreshold opioid use disorder prevention (STOP) trial: a cluster randomized clinical trial: study design and methods

BackgroundPreventing progression to moderate or severe opioid use disorder (OUD) among people who exhibit risky opioid use behavior that does not meet criteria for treatment with opioid agonists or antagonists (subthreshold OUD) is poorly understood. The Subthreshold Opioid Use Disorder Prevention (STOP) Trial is designed to study the efficacy of a collaborative care intervention to reduce risky opioid use and to prevent progression to moderate or severe OUD in adult primary care patients with subthreshold OUD.MethodsThe STOP trial is a cluster randomized controlled trial, randomized at the PCP level, conducted in 5 distinct geographic sites. STOP tests the efficacy of the STOP intervention in comparison to enhanced usual care (EUC) in adult primary care patients with risky opioid use that does not meet criteria for moderate-severe OUD. The STOP intervention consists of (1) a practice-embedded nurse care manager (NCM) who provides patient participant education and supports primary care providers (PCPs) in engaging and monitoring patient-participants; (2) brief advice, delivered to patient participants by their PCP and/or prerecorded video message, about health risks of opioid misuse; and (3) up to 6 sessions of telephone health coaching to motivate and support behavior change. EUC consists of primary care treatment as usual, plus printed overdose prevention educational materials and an educational video on cancer screening. The primary outcome measure is self-reported number of days of risky (illicit or nonmedical) opioid use over 180 days, assessed monthly via text message using items from the Addiction Severity Index and the Current Opioid Misuse Measure. Secondary outcomes assess other substance use, mental health, quality of life, and healthcare utilization as well as PCP prescribing and monitoring behaviors. A mixed effects negative binomial model with a log link will be fit to estimate the difference in means between treatment and control groups using an intent-to-treat population.DiscussionGiven a growing interest in interventions for the management of patients with risky opioid use, and the need for primary care-based interventions, this study potentially offers a blueprint for a feasible and effective approach to improving outcomes in this population.Trial Registration: Clinicaltrials.gov, identifier NCT04218201, January 6, 2020.

Abstract 11708: Examining the Impact of Social Determinants of Health in Cardiovascular Disease Risk Factors: Insights From an Implementation Study in a Rural Primary Care Clinic

Introduction: The social determinants of health (SDoH) are associated with uncontrolled cardiovascular disease (CVD) risk factors and warrant attention. Methods: We describe methods and cross-sectional results of the SDoH screening and referral system at a resident-run primary care clinic at Cayuga Medical Center (total 30 residents ~539 patients seen/month with 12% no shows) starting from Nov 2019. Eight domains of SDoH including food security, utility, housing, childcare, finances, transportation, literacy, and social support were selected based on local county data and focus group discussions. We developed an annual screening tool and referral system integrated into the electronic medical record for any SDoH positive patients to the community health and social workers (CHW/SW), who facilitated access to community resources. Patient education about available community resources, regular follow-up visits with the physician and CHW/SW, and periodic SDoH screening were other key components. Results: Among 741 patients (Hypertension and Diabetes), 607 (82%) patients underwent SDoH screening (Table). 200 (33%) patients had at least one domain of SDoH (SDoH +) and received SDoH interventions whereas, 407 (67%) did not have any SDoH. The three most common SDoH were lack of social support (61%), transportation (35%) and finance issues (25%). Patients in the SDoH+ group were younger, with higher percentage of non-White race/ethnicity, unemployment, disability, living alone, current smokers, illicit substance use, anxiety, depression, obesity, and opioid use with statistical significance. However, there were no significant differences in CVD risk factors like SBP (138.3 vs 138.4 mmHg), DBP (84 vs 83 mmHg), HbA1c (6.4 vs 6.2) and LDL-c (103.7 vs 101.5 mg/dL). Conclusions: In addition to controlling standard CVD risk factors, implementation of SDoH routine screening and referral system in a primary care clinic may help in mitigating CVD burden as seen in our study.

Low-dose Induction of Buprenorphine in Pregnancy: A Case Series.

Because of a risk of precipitated withdrawal occurring from buprenorphine induction in people who use fentanyl, low-dose inductions are becoming increasingly common. However, little evidence exists on the use of this method in pregnant people. We conducted a case series of all pregnant people treated for opioid use disorder with low-dose buprenorphine induction at the University of Maryland Medical Center between January 1, 2021, and August 22, 2022. Primary outcome was completion of induction regimen. Secondary outcomes were self-report of withdrawal, continuation of buprenorphine until delivery, and return to or continuation of illicit opioid use. Six pregnant people were prescribed a total of 10 buprenorphine inductions. Five of the 6 pregnant people (83.3%) completed at least 1 induction, none of whom experienced precipitated withdrawal. Two of 6 (33.3%) continued buprenorphine until the time of delivery, and 1 of 6 (16.7%) abstained from illicit opioid use. The low-dose buprenorphine induction regimen described was successful in 5 of 6 pregnant individuals. Further research, particularly regarding continuation rates, is needed.

Associations between stimulant use and return to illicit opioid use following initiation onto medication for opioid use disorder.

The aim of this study was to estimate how ongoing stimulant use affects return to illicit opioid use after initiation onto medication for opioid use disorder (MOUD). This was a secondary analysis of pooled data from two clinical trials comparing buprenorphine (BUP-NX) and extended-release naltrexone (XR-NTX). Thirteen opioid treatment programs and HIV clinics across 10 states in the United States from 2014 to 2019 took part in this study. A total of 528 participants who initiated MOUD as part of trial participation were included. Nearly half (49%) were between 30 and 49 years of age, 69% were male and 66% were non-Hispanic White. The primary outcome was first self-reported day of non-prescribed opioid use following MOUD initiation, and the exposure of interest was daily stimulant use (methamphetamine, amphetamines or cocaine). Both were defined using time-line follow-back. Among participants reporting at least 1day of illicit opioid use, we also examined relapse to ongoing use, defined as (1) 7days of continuous opioid use or (2) 4 consecutive weeks with self-reported opioid use, one or more positive urine drug screens (UDS) for opioids or one or more missing UDS. Forty-seven per cent of participants reported stimulant use following MOUD initiation, 58% returned to illicit opioid use and 66% of those relapsed to ongoing use. Stimulant use was strongly associated with increased risk of misusing opioids after MOUD initiation when measured daily [adjusted hazard ratio (aHR) = 9.23, 95% confidence interval (CI) = 6.80-12.50, P < 0.001] and over a 7-day period (aHR = 1.27 for each additional day, CI = 1.18-1.37, P < 0.001). Using stimulants weekly or more often was associated with increased likelihood of relapse to ongoing opioid use compared with less than weekly or no stimulant use (adjusted odds ratio = 2.30, CI = 1.05-5.39, P = 0.044). People initiated on medication for opioid use disorder who subsequently use stimulants appear to be more likely to return to and continue using non-prescribed opioids compared with those without stimulant use. The association appears to be stronger among patients who initiate buprenorphine compared with those who initiate extended-release naltrexone.

A randomized, parallel group, pragmatic comparative-effectiveness trial comparing medication-assisted treatment induction methods in primary care practices: The HOMER study protocol.

Opioid use disorder (OUD) represents a public health crisis in the United States. Medication for opioid use disorder (MOUD) with buprenorphine in primary care is a proven OUD treatment strategy. MOUD induction is when patients begin withdrawal and receive the first doses of buprenorphine. Differences between induction methods might influence short-term stabilization, long-term maintenance, and quality of life. This paper describes the protocol for a study designed to: (1) compare short-term stabilization and long-term maintenance treatment engagement in MOUD in patients receiving office, home, or telehealth induction and (2) identify clinically-relevant practice and patient characteristics associated with successful long-term treatment. The study design is a randomized, parallel group, pragmatic comparative effectiveness trial of three care models of MOUD induction in 100 primary care practices in the United States. Eligible patients are at least 16 years old, have been identified by their clinician as having opioid dependence and would benefit from MOUD. Patients will be randomized to one of three induction comparators: office, home, or telehealth induction. Primary outcomes are buprenorphine medication-taking and illicit opioid use at 30, 90, and 270 days post-induction. Secondary outcomes include quality of life and potential mediators of treatment maintenance (intentions, planning, automaticity). Potential moderators include social determinants of health, substance use history and appeal, and executive function. An intent to treat analysis will assess effects of the interventions on long-term treatment, using general/generalized linear mixed models, adjusted for covariates, for the outcomes analysis. Analysis includes practice- and patient-level random effects for hierarchical/longitudinal data. No large-scale, randomized comparative effectiveness research has compared home induction to office or telehealth MOUD induction on long-term outcomes for patients with OUD seen in primary care settings. The results of this study will offer primary care providers evidence and guidance in selecting the most beneficial induction method(s) for specific patients.

Risks of returning to opioid use at treatment entry and early in opioid use disorder treatment: Role of non-opioid substances

ObjectivePatients in treatment with medications for opioid use disorder (MOUD) often report use of other substances in addition to opioids. Few studies exist that examine the relationship between use at treatment entry and early non-opioid use in opioid treatment outcome. MethodologyWe combined and harmonized three randomized, controlled MOUD clinical trials from the National Institutes of Drug Abuse (NIDA) Clinical Trials Network (CTN) (N=2197) and investigated the association of non-opioid substance use at treatment entry and during early treatment with a return to opioid use. The trials compared MOUD treatment (buprenorphine, methadone, extended-release naltrexone) in populations with opioid use disorder (OUD). Non-opioid substances were identified through harmonizing self-reported use. The primary outcomes were markers of return to opioid use by 12 weeks. ResultsWhen treatment cohorts were adjusted, no association between self-reported treatment entry use of non-opioid substances and week-12 opioid use was detected. During the first month of treatment, higher use of cocaine (OR 1.41 [1.18–1.69]) and amphetamine (OR 1.70 [1.27–2.26]) was found to be associated with higher likelihood of illicit opioid use by week 12. Exploratory analyses of potential treatment cohort-by-predictor interactions showed that those with heavier cocaine use had a lower rate of returning to opioid use in the extended-release naltrexone group than in the methadone group. ConclusionSubstance use other than opioids at treatment entry is not associated with relapse. Use of cocaine or amphetamines during the first few weeks of MOUD treatment may signal a worse outcome, suggesting a need for additional interventions.

Buprenorphine and methadone differentially alter early brain development in human cortical organoids

Buprenorphine (BUP) and methadone (MTD) are used for medication-assisted treatment (MAT) in opioid use disorder. Although both medications show improved maternal and neonatal outcomes compared with illicit opioid use during pregnancy, BUP has exhibited more favorable outcomes to newborns than MTD. The underlying cellular and molecular mechanisms for the difference between BUP and MTD are largely unknown. Here, we examined the growth and neuronal activity in human cortical organoids (hCOs) exposed to BUP or MTD. We found that the growth of hCOs was significantly restricted in the MTD-treated but not in the BUP-treated hCOs and BUP attenuated the growth-restriction effect of MTD in hCOs. Furthermore, a κ-receptor agonist restricted while an antagonist alleviated the growth-restriction effect of MTD in hCOs. Since BUP is not only a μ-agonist but a κ-antagonist, the prevention of this growth-restriction by BUP is likely due to its κ-receptor-antagonism. In addition, using multielectrode array (MEA) technique, we discovered that both BUP and MTD inhibited neuronal activity in hCOs but BUP showed suppressive effects only at higher concentrations. Furthermore, κ-receptor antagonist nBNI did not prevent the MTD-induced suppression of neuronal activity in hCOs but the NMDA-antagonism of MTD (that BUP lacks) plays a role in the inhibition of neuronal activity. We conclude that, although both MTD and BUP are μ-opioid agonists, a) the additional κ-receptor antagonism of BUP mitigates the MTD-induced growth restriction during neurodevelopment and b) the lack of NMDA antagonism of BUP (in contrast to MTD) induces much less suppressive effect on neural network communications.