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IntroductionThe Coronavirus Disease 2019 (COVID-19) pandemic has had devastating consequences for persons with opioid use disorder (OUD). Yet, little is known about how people seeking treatment for OUD perceive the risks of COVID-19 and how their perception interplays with their health behaviours.MethodsIn-depth interviews were conducted from September 2021 to March 2022 with 32 patients seeking medication treatment for OUD (MOUD) in Southern California. All interviews were conducted virtually and lasted between one and two hours. Interviews were recorded and transcribed verbatim. Two qualitative researchers independently conducted a content analysis of the transcripts to identify themes.ResultsThree primary themes were identified: (1) perceptions and beliefs about COVID-19 susceptibility and severity; (2) perceptions of COVID-19 risk compared to substance use behaviours; and (3) vaccine hesitancy. Participants were mixed in their beliefs of susceptibility to contracting COVID-19 and the severity of the disease if contracted. Some participants reported taking precautions to mitigate their chances of acquiring COVID-19, and other participants reported that COVID was not a big concern as substance use took priority. For many of the participants, COVID-19 concerns were overshadowed by the risk of overdosing on substances and other risky substance use behaviour. Most of the participants (n = 23; 72%) had received at least one COVID-19 vaccine by the time of the interview, but over half (n = 19; 59%) expressed vaccine hesitancy. Vaccine hesitancy was driven by concerns about the unknown long-term side effects and potential interactions of the vaccine with MOUD.ConclusionsOur study provides insight into COVID-19 prevention measures as well as vaccination perceptions and hesitancy among people who received treatment for OUD.Key messagesParticipants expressed diverse perceptions of the seriousness of COVID-19, with some taking precautions to mitigate their chances of acquiring COVID-19 and others perceiving that the risk of contracting COVID-19 was less than the risk of overdosing.Substance use, social isolation, vaccine hesitancy and COVID-19 risk behaviours should be studied as co-occurring phenomena that have potentially overlapping relationships that can influence behaviours that impact health and well-being.

BackgroundThe COVID-19 pandemic has changed the landscape of healthcare service delivery. This review aims to describe telemedicine-delivered substance use disorder (SUD) treatments and services along the cascade of care in the U.S. after the start of the COVID-19 pandemic.MethodsA literature review was conducted on PubMed, Embase, Web of Science, and Cochrane Library (Wiley). English-language articles that describe any healthcare services for patients with SUDs using telemedicine in the U.S. since the onset of the COVID-19 pandemic were identified (N = 33). We narratively summarized telemedicine-based service provision along the cascade of SUD care, such as screening/assessment, prescription, monitoring, recovery support, and other services.ResultsSoon after the onset of COVID-19 and mandated restrictions, cadres of healthcare providers from different specialties mobilized to ramp up video- and audio-based services to remotely treat patients with SUDs. Medication prescription (48.5%) and individual counseling (39.4%) were the most frequently reported services delivered via telemedicine. Other steps of SUD care delivered by telemedicine characterized in our review included SUD screening and assessment (30.3%), induction (21.2%), medication management (27.3%), monitoring (27.3%), recovery support (15.2%), and referral (24.2%). Feasibility issues and challenges to implementing telemedicine included patients' lack of access to technology and health insurance coverage, providers' capacity limits and concerns, and clinics' financial and office-space constraints.ConclusionThe COVID-19 pandemic has offered a window of opportunity to advance telemedicine expertise by formalizing clinical guidance and routinizing provider in-service training in virtual SUD treatment. Findings suggest enhanced efforts to reduce disparities in telemedicine-based services.

PurposeTo examine characteristics associated with disparities in digital access (i.e., access to high-speed Internet via a computer or smartphone) in American rural and urban households given that digital access has a direct impact on access to telemedicine-based services.MethodsUsing the 2019 American Community Survey, we analyzed the proportions of geographic area, race/ethnicity, and socioeconomic status according to device and high-speed Internet access. Maximum likelihood logit estimators estimated how these factors influenced device and high-speed Internet access.FindingsOf 105,312,959 households, 32.29% were without a desktop or laptop computer with high-speed Internet (WDW), 21.51% were without a smartphone with a data plan for wireless Internet (WSW), and 14.02% were without any digital access (WDA). Nonmetropolitan households were significantly more likely to be WDA than metropolitan households (odds ratio [OR] = 1.87; 95% confidence interval [CI]: 1.83-1.91). Relative to non-Hispanic Whites, non-Hispanic Blacks (OR = 1.60; 95% CI: 1.56-1.64), American Indian or Alaska natives (OR = 2.00; 95% CI: 1.82-2.19), or Hispanics (OR = 1.70; 95% CI: 1.66-1.74) were significantly more likely to be WDA. When compared to households with private health insurance coverage, households WDA were significantly more likely to have no insurance (OR = 2.44; 95% CI: 2.36-2.53) or public insurance coverage (OR = 3.78; 95% CI: 3.70-3.86). Households with any digital access reported higher income and more family members living at home. Using the same predictors, similar findings were reported for households WDW or WSW.ConclusionsSignificant disparities in digital access exist among nonmetropolitan households, racial/ethnic minority households, and lower-income households. The lack of digital access has implications for the accessibility of health care services via telemedicine and thus could exacerbate health disparities.

BackgroundThe COVID-19 pandemic has had a profound impact on the U.S. health care system, including addiction treatment. The objective of this study is to describe the impact of COVID on the delivery of treatment for substance use disorders (SUDs) from the perspectives of service providers.MethodsBetween May and September 2020, 61 service providers from 16 SUD treatment sites in California participated in virtual focus groups that lasted about an hour. We recorded the discussions and transcribed them verbatim. Two qualitative analysts independently conducted content analysis to identify themes from the transcripts.ResultsAt the beginning of the pandemic, service providers observed a slight decrease in patient admissions, followed by an uptick in patient flow due to increased mental health issues, alcohol use, and relapse. Many of the clinics adopted flexible service delivery modes, such as curbside dosing and extended take-home medication, to enable social distancing in clinic settings. Approximately half of the clinic encounters offered telemedicime, and a considerable proportion of patients preferred to use telephone-based services rather than video-based services. Internet instability and technical difficulties limited the use of telemedicine among their patients.ConclusionCOVID has been challenging for SUD treatment, but health care systems rapidly reacted with adjustments that may result in long-term changes in SUD service delivery. Telemedicine-based services have played a major role in ensuring uninterrupted patient care. Providers need organizational, technical, and logistical support to improve and sustain telemedicine services that increase access to quality care for their patients.

AimsTo investigate whether reduction in opioid use differs when treated by either buprenorphine-naloxone (BUP) or methadone (MET) among adults with comorbid opioid use disorder (OUD) and mental disorders.Design, setting and participantsIn a randomized controlled trial, adults with OUD were randomized to 24 weeks of either BUP or MET treatment and were followed up in 3-yearly assessments. The present secondary analyses were based on 597 participants who completed all assessments.MeasurementsThe outcome measure was the number of days of using opioids per month during the follow-up period. The Mini-International Neuropsychiatric Interview (MINI) was used to classify participants into three groups: life-time mood disorder (n = 302), life-time mental disorder other than mood disorder (n = 114) and no mental disorder (n = 181). Medication treatment (BUP, MET, no treatment) during the follow-up period was a time-varying predictor.FindingsBased on zero-inflated Poisson (ZIP) mixed regression analysis, it was found that relative to no treatment, opioid use during the follow-up was significantly reduced by BUP [odds ratio (OR) = 0.12, 95% confidence interval (CI) = 0.07-0.21 for any use; risk ratio (RR) = 0.77, 95% CI =0.66-0.89 for days of use] and by MET [OR = 0.33, 95% CI = 0.25-0.45 for any use; RR = 0.78, 95% CI = 0.72-0.84 for days of use]. Relative to MET, BUP was associated with a lower likelihood of any opioid use among participants with mood disorders (OR = 0.52, 95% CI = 0.36-0.74) and for participants without mental disorder (OR = 0.37, 95% CI = 0.21-0.66) and fewer number of days using opioids (RR = 0.37, 95% CI = 0.25-0.56) among participants with other mental disorders.ConclusionsAmong adults with comorbid opioid use disorder and mental disorders, treatment with buprenorphine-naloxone produced greater reductions in opioid use than treatment with methadone.

ObjectiveCoprescription of opioids and benzodiazepines (BDZ) is associated with adverse outcomes, including greater healthcare utilization and overdose risk. This study aims to examine opioid and BDZ coprescription, dosing, and mortality among patients with and without opioid use disorder (OUD) in a large healthcare system.MethodsUsing data from the California state Prescription Drug Monitoring Program during 2010 to 2014 linked with a large healthcare system electronic health record database and mortality records from the Centers for Disease Control National Death Index, this study examined 5202 patients (1978 with OUD, 3224 controls). Multiple logistic regression analyses were conducted to examine relationships between most recent BDZ and opioid prescription, and their interaction with respect to mortality.ResultsAbout 10.5% of the sample died on or before December 31, 2014. About 17.7% were prescribed BDZ during the final month of observation. Individuals with OUD were prescribed higher average BDZ and opioid doses than those without OUD. After adjusting for covariates, increased prescribed doses of BDZ (odds ratio [OR]=1.34, 95%CI: 1.15-1.55 per 10 mg/d increment) and opioids (OR = 1.04, 95%CI: 1.02-1.05 per 10 mg/d increment) were positively associated with mortality. Non-OUD patients who received both BDZ and opioid prescriptions had a higher mortality than those who received only BDZ or opioids (The ratio of odds ratio (ROR) = 3.83, 95%CI: 1.78-8.21).ConclusionsStudy findings highlight significant mortality associated with the coprescription of opioids and BDZ in a general healthcare setting. Further research is needed to elucidate factors associated with mortality among non-OUD patients who are co-prescribed opioids and BDZ.

ObjectivesBoth COVID-19 deaths and opioid overdose deaths continue to increase in the United States. Little is known about the characteristics of counties with high rates of mortality for both.MethodsWe analyzed county-level data on COVID-19 mortality from January 1 to May 31, 2020, and on opioid overdose mortality during 2014-2018. The outcome variable, "high-risk county" was a binary indicator of high mortality rates (above 75% quartile) for both COVID-19 and opioid overdose. We conducted geospatial logistic regression models separately for urban and rural counties to identify social determinants of health associated with being a high-risk county.ResultsAfter adjusting for other covariates, the overall mortality rate of COVID-19 is higher in counties with larger population size and a higher proportion of racial/ethnic minorities, although counties with high rates of opioid overdose mortality have lower proportions of racial/ethnic minorities, a higher proportion of females, and are more economically disadvantaged. Significant predictors of rural counties with high mortality rates for both COVID-19 and opioid overdose include higher proportions of Blacks (Adjusted odds ratio [aOR], 1.04; 95%CI, 1.01-1.07), American Indians and Alaska Natives (aOR, 1.07; 95%CI, 1.02-1.13), and two or more races (aOR, 1.34; 95%CI, 1.13-1.60). Additional predictors for high-risk urban counties include population density (aOR, 1.12; 95%CI, 1.04-1.22) and higher unemployment rates during the COVID-19 pandemic (aOR, 1.23; 95%CI, 1.07-1.41).ConclusionsRural counties with high proportions of racial/ethnic minorities and urban counties with high unemployment rates are at high mortality risk for COVID-19 and opioid overdose.

Telemedicine (TM) enabled by digital health technologies to provide medical services has been considered a key solution to increasing health care access in rural communities. With the immediate need for remote care due to the COVID-19 pandemic, many health care systems have rapidly incorporated digital technologies to support the delivery of remote care options, including medication treatment for individuals with opioid use disorder (OUD). In responding to the opioid crisis and the COVID-19 pandemic, public health officials and scientific communities strongly support and advocate for greater use of TM-based medication treatment for opioid use disorder (MOUD) to improve access to care and have suggested that broad use of TM during the pandemic should be sustained. Nevertheless, research on the implementation and effectiveness of TM-based MOUD has been limited. To address this knowledge gap, the National Drug Abuse Treatment Clinical Trials Network (CTN) funded (via the NIH HEAL Initiative) a study on Rural Expansion of Medication Treatment for Opioid Use Disorder (Rural MOUD; CTN-0102) to investigate the implementation and effectiveness of adding TM-based MOUD to rural primary care for expanding access to MOUD. In preparation for this large-scale, randomized controlled trial incorporating TM in rural primary care, a feasibility study is being conducted to develop and pilot test implementation procedures. In this commentary, we share some of our experiences, which include several challenges, during the initial two-month period of the feasibility study phase. While these challenges could be due, at least in part, to adjusting to the COVID-19 pandemic and new workflows to accommodate the study, they are notable and could have a substantial impact on the larger, planned pragmatic trial and on TM-based MOUD more broadly. Challenges include low rates of identification of risk for OUD from screening, low rates of referral to TM, digital device and internet access issues, workflow and capacity barriers, and insurance coverage. These challenges also highlight the lack of empirical guidance for best TM practice and quality remote care models. With TM expanding rapidly, understanding implementation and demonstrating what TM approaches are effective are critical for ensuring the best care for persons with OUD.

BackgroundIndividuals treated for opioid use disorder (OUD) have high rates of psychiatric disorders potentially diminishing treatment outcomes. We examined long-term treatment experiences and outcomes by type of psychiatric disorder among participants who participated in the Starting Treatment with Agonist Replacement Therapies (START) study and its follow-up study.MethodsWe categorized the 593 participants who completed the Mini-International Neuropsychiatric Interview (MINI) during the START follow-up study into four mutually exclusive groups to indicate current psychiatric diagnosis: 1) bipolar disorder (BPD; n = 51), 2) major depressive disorder (MDD; n = 85), 3) anxiety disorder (AXD; n = 121), and 4) no comorbid mental disorder (NMD; n = 336). We compared participants' baseline characteristics and treatment outcomes.ResultsGroups with mental disorders had worse substance use outcomes and poorer psychosocial functioning than the NMD group. Participants with BPD had significantly more self-reported days using opioids (Mean: 8.6 for BPD vs. 3.4 days for NMD, p < 0.01) and heroin (Mean: 6.4 for BPD vs. 2.0 for MDD, 3.1 days for NMD, p < 0.05) in the 30 days prior to the final interview. Compared to patients without mental disorders, patients with MDD spent more time engaged with OUD pharmacotherapy during the ∼16-month period between MINI and final interview (mean: 71.6 % vs. 50.6 %; p < 0.001).ConclusionsOur results show that treatment outcomes in individuals with OUD vary by psychiatric comorbidity groups, which supports the need for mental health assessment and treatment for psychiatric conditions in the context of pharmacotherapy for patients with OUD.

Cannabis is the most widely used psychoactive substance after alcohol and tobacco; 4% of the global adult population (200 million people) endorses its use (Figure 1). Cannabis use disorder (CUD) [...]

Background and aimsAs treatment for opioid use disorder (OUD) expands within general healthcare settings such as primary care, mechanisms to facilitate decision-making processes are increasingly necessary. Decision aids have the capacity to bolster existing resources in diverse treatment settings by increasing knowledge of treatment options and facilitating shared decision making. The aim of this study is to develop and test a patient decision aid for medication treatment for opioid use disorder (PtDA-MOUD) that assists individuals with OUD in making informed decisions about treatment at the time of initial clinical visit. Use of the PtDA-MOUD will be further tested in diverse treatment settings within the California Hub and Spoke System developed under the SAMHSA State Targeted Response to the Opioid Crisis grants.MethodsThe PtDA-MOUD was iteratively developed with input from a scientific expert panel and both patient and provider focus groups, incorporating International Patient Decision Aid Standards. Thirty-six patients with OUD entering treatment pilot tested the PtDA and completed assessments, and results from clinical records were compared with matched controls who did not receive the PtDA. A clinical profile based on assessment data was created for use within the clinical visit.ResultsThe developed decision aid provides information on MOUD and captures patient characteristics relevant to medication treatment decisions. Feedback indicated that the PtDA-MOUD was feasible to implement and useful. Though the small sample size limited the ability to detect significant differences (p > .05), a greater number of individuals who reviewed the PtDA (37%) were inducted on MOUD than controls (11%) and received MOUD for more days (M = 14.0, SD = 24.7) than controls (M = 8.4; SD = 22.5). Moreover, the difference in means for days receiving MOUD had an approximately medium effect size (r = 0.25).ConclusionsPatient perceptions of the decision aid were favorable and it showed promise as a tool in the OUD treatment process. Pilot testing results suggested preliminary positive effects on MOUD initiation. Future phases of this study will further investigate the usefulness of this tool. ClinicalTrials.govIdentifier:NCT03394261.

Studies on the relationships between marijuana use and quality of life have reported mixed findings. Based on a survey of 123 marijuana users conducted in Los Angeles during 2017-2018, we investigated the relationships between marijuana use frequency, severity of marijuana-related problems, and health-related quality of life (HRQoL). Results indicated that (1) marijuana use frequency was positively related to severity of marijuana-related problems; (2) severity of marijuana-related problems was negatively related to mental domain of HRQoL but was not significantly related to physical domain of HRQoL; and (3) marijuana use frequency was positively associated with mental health symptoms and physical health conditions, and both in turn were negatively linked to mental and physical domains of HRQoL, respectively. Reduction of marijuana-related problems and mitigation of mental and physical health problems may improve HRQoL among marijuana users. The study findings may contribute to developing treatment interventions for marijuana use that simultaneously address marijuana-related problems and associated mental and physical issues.

ObjectivePrescription Drug Monitoring Programs (PDMPs) are intended to help reduce prescription drug misuse and opioid overdose, yet little is known about the longitudinal patterns of opioid prescribing that may be associated with mortality. This study investigated longitudinal opioid prescribing patterns among patients with opioid use disorder (OUD) and without OUD in relation to mortality using PDMP data.MethodsGrowth modeling was used to examine opioid prescription data from the California PDMP for a 4-year period before death or a comparable period ending in 2014 for those remaining from a sample of 7728 patients (2576 with OUD, and 5152 matched non-OUD controls) treated in a large healthcare system.ResultsCompared to controls, individuals with OUD (alive and deceased) had received significantly more opioid prescriptions, greater number of days' supply, and steeper increases of opioid dosages over time. For morphine equivalents (ME, in grams), the interaction of OUD and mortality was significant at both intercept (β = 10.4, SE = 4.4, P

Opioid use disorder (OUD) is a chronic, relapsing condition with severe negative health consequences. Previous studies have reported that 5-year opioid abstinence is a good predictor of reduced likelihoods of relapse, but factors that shape long-term opioid abstinence are poorly understood. The present study is based on data from a prospective study of 699 adults with OUD who had been randomized to either methadone or buprenorphine/naloxone and who were followed for at least 5 years. During the 5 years prior to the participants' last follow-up interview, 232 (33.2%) had achieved 5-year abstinence from heroin. Of those 232, 145 (20.7% of the total) had remained abstinent from both heroin and other opioids (e.g., hydrocodone, oxycodone, other opioid analgesics, excluding methadone or buprenorphine). Compared to non-abstinent individuals, those in both categories of opioid abstinence had lower problem severity in health and social functioning at the final follow-up. Logistic regression results indicated that cocaine users and injection drug users were less likely to achieve 5-year heroin abstinence, whereas Hispanics (vs. whites) and those treated in clinics on the West Coast (vs. East) were less likely to achieve 5-year abstinence from heroin and other opioids. For both abstinence category groups, abstinence was positively associated with older age at first opioid use, lower impulsivity, longer duration of treatment for OUD, and greater social support. Reducing cocaine use and injection drug use and increasing social support and retention in treatment may help maintain long-term abstinence from opioids among individuals treated with agonist pharmacotherapy.

Treatment for substance use disorders has traditionally been abstinence-oriented, but evaluating the merits of low-level cannabis use as potential treatment endpoint may identify benefits that are clinically relevant for treatment-seeking individuals who do not attain abstinence. This study explores if reduction in cannabis use to a lower level of use is related to improved physical health, mental health, and perceived cognitive functions. Study participants with a history of problematic cannabis use (n = 111) completed assessments. Regression models were used to explore the relationship between past 30-day cannabis use levels (abstinent [57%], low use [22%] defined as less than or equal to 3 days per week, and heavy use [22%] defined as 4 or more days of use per week) and functional status in physical health, mental health, and cognition. Compared to heavy users, both abstinent and low-use individuals were similarly associated with better global health, appetite, and depression outcomes. Abstinent users also reported improved sleep, anxiety, and self-reported cognitive functioning relative to heavy users. Thus, reduction in cannabis use to lower levels is associated with beneficial outcomes important to health and other areas of functioning in individuals with problematic cannabis use.

Background: The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. Methods: Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. Results: MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. Conclusion: Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance. [ABSTRACT FROM AUTHOR]

AimsThis study examined the longitudinal association between reductions in cannabis use and changes in anxiety, depression, sleep quality, and quality of life.MethodsSecondary analyses were conducted based on data from a cannabis use disorder medication trial in 302 adults (ages 18-50). Changes in symptoms of anxiety and depression, sleep quality, and quality of life were assessed in relation to changes in cannabis use during the 12-week trial of treatment.ResultsBased on the slope of individual cannabis use trajectory, the sample was classified into two groups (Cannabis Use Reduction, n=152 vs. Cannabis Use Increase, n=150) which was included as a binary covariate in subsequent modeling. Controlling for demographics (age, gender, race/ethnicity), treatment condition, and time-varying tobacco and alcohol use, separate latent growth curve models showed a significant association between the Cannabis Use Reduction group and improvement (i.e., lower values in slope) in anxiety (β=-0.09, SE=0.04; p

BackgroundCannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults.MethodsIn a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18-50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants.ResultsThere was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio=1.00, 95% confidence interval 0.63-1.59, p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group.ConclusionsIn contrast with prior findings in adolescents, there is no evidence that NAC 1200mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors.

ObjectivesElevated mortality has been observed among individuals with opioid use disorder (OUD) treated in addiction specialty clinics or programs. Information about OUD patients in general healthcare settings is needed in light of the current effort to integrate addiction services into primary healthcare systems. This study examined mortality rates, causes of death, and associated risk factors among patients with OUD in a large general healthcare system.MethodsMortality data were linked with electronic health records of 2576 OUD patients cared for in a large university health system from 2006 to 2014.ResultsThere were 465 deaths confirmed (18.1% of the study participants), corresponding to a crude mortality rate of 48.6 per 1000 person-years and standardized mortality ratio of 10.3 (95% confidence interval [CI] 9.4-11.3). Drug overdose and disorder (19.8%), cardiovascular diseases (17.4%), cancer (16.8%), and infectious diseases (13.5%, including 12% hepatitis C virus [HCV]) were the leading causes of death. HCV (hazard ratio [HR] 1.99, 95% CI 1.62-2.46) and alcohol use disorder (HR 1.27, 95% CI 1.05-1.55) were 2 clinically important indicators of overall mortality risk. Tobacco use disorder (adjusted HR [AHR] 2.58, 95% CI 1.60-4.17) was associated with increased risk of cardiovascular death, HCV infection (AHR 2.55, 95% CI 1.52-4.26) with cancer mortality risk, and HCV (AHR 1.92, 95% CI 1.03-3.60) and alcohol use disorder (AHR 5.44, 95% CI 2.95-10.05) with liver-related mortality risk.ConclusionsPatients with OUD in a general healthcare system demonstrated alarmingly high morbidity and mortality, which challenges healthcare systems to find innovative ways to identify and treat patients with substance use disorder.

PurposeTo examine the prevalence of comorbid chronic pain among patients with opioid use disorder (OUD) and to compare other comorbidities (substance use disorder (SUD), mental health disorders, health/disease conditions) among patients in four categories: no chronic pain (No Pain), OUD prior to pain (OUD First), OUD and pain at the same time (Same Time), or pain condition prior to OUD (Pain First).MethodsUsing an electronic health record (EHR) database from 2006-2015, the study assessed 5307 adult patients with OUD in a large healthcare system; 35.6% were No Pain, 9.7% were OUD First, 14.9% were Same Time, and 39.8% were Pain First.ResultsMost OUD patients (64.4%) had chronic pain conditions, and among them 61.8% had chronic pain before their first OUD diagnosis. Other SUDs occurred more frequently among OUD First patients than among other groups in terms of alcohol (33.4% vs. 25.4% for No Pain, 20.7% for Same Time, and 20.3% for Pain First), cocaine (19.0%, vs. 13.8%, 9.4%, 7.1%), and alcohol or drug-induced disorders. OUD First patients also had the highest rates of HIV (4.7%) and hepatitis C virus (HCV; 28.2%) among the four groups. Pain First patients had the highest rates of mental disorder (81.7%), heart disease (72.0%), respiratory disease (68.4%), sleep disorder (41.8%), cancer (23.4%), and diabetes (19.3%).ConclusionsThe alarming high rates of chronic pain conditions occurring before OUD and the associated severe mental health and physical health conditions require better models of assessment and coordinated care plans to address these complex medical conditions.

In light of the known associations between stress, negative affect, and relapse, mindfulness strategies hold promise as a means of reducing relapse susceptibility. In a pilot randomized clinical trial, we evaluated the effects of Mindfulness Based Relapse Prevention (MBRP), relative to a health education control condition (HE) among stimulant dependent adults receiving contingency management. All participants received a 12-week contingency management (CM) intervention. Following a 4-week CM-only lead in phase, participants were randomly assigned to concurrently receive MBRP (n=31) or HE (n=32). Stimulant dependent adults age 18 and over. A university based clinical research center. The primary outcomes were stimulant use, measured by urine drug screens weekly during the intervention and at 1-month post-treatment, negative affect, measured by the Beck Depression Inventory and Beck Anxiety Inventory, and psychiatric severity, measured by the Addiction Severity Index. Medium effect sizes favoring MBRP were observed for negative affect and overall psychiatric severity outcomes. Depression severity changed differentially over time as a function of group, with MBRP participants reporting greater reductions through follow-up (p=0.03; Effect Size=0.58). Likewise, the MBRP group evidenced greater declines in psychiatric severity, (p=0.01; Effect Size=0.61 at follow-up). Among those with depressive and anxiety disorders, MBRP was associated with lower odds of stimulant use relative to the control condition (Odds Ratio= 0.78, p=0.03 and OR=0.68, p=0.04). MBRP effectively reduces negative affect and psychiatric impairment, and is particularly effective in reducing stimulant use among stimulant dependent adults with mood and anxiety disorders.

AimsTo examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.MethodsThis multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York and Washington DC, USA to one of three conditions provided with XR-NTX: 4 mg/day BUP (BUP4, n = 100), 16 mg/day BUP (BUP16, n = 100, or no buprenorphine (placebo; PLB, n = 102). Participants received pharmacotherapy for 8 weeks, with three clinic visits per week. Cognitive behavioral therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention and adverse events.ResultsNo group differences were found between groups for the primary outcome (BUP4 versus PLB, P = 0.262; BUP16 versus PLB, P = 0.185). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB [P = 0.022, odds ratio (OR) = 1.71] but not for BUP4 (P = 0.105, OR = 1.05). No secondary outcome differences across groups were found for adherence, retention or adverse events.ConclusionsBuprenorphine + naloxone, used in combination with naltrexone, may be associated with reductions in cocaine use among people who meet DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.

ObjectivesThis 2-stage open-label pilot study evaluated the safety and potential efficacy of naltrexone + bupropion as a pharmacotherapy for methamphetamine (MA) use disorder.MethodsThe study was conducted in 2 stages of recruitment across 3 sites; 20 participants were enrolled in stage 1 and 29 participants were enrolled in stage 2. Eight weeks of open-label pharmacotherapy with a combination of extended-release injectable naltrexone (XR-NTX; Vivitrol) plus extended-release oral bupropion (BRP; Wellbutrin XL) were provided with a smartphone-assisted medication adherence platform. Participants met Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for severe MA use disorder, self-reported ≥20 days of MA use in the 30 days prior to consent, and submitted 3 MA-positive urine drug screens (UDS) out of 4 collected during screening. Participants attended clinic twice weekly for observed BRP dosing, UDS testing, assessments, and medical management; XR-NTX was administered at weeks 1 and 5. A BRP taper and follow-up visit occurred in week 9.ResultsAnalyses evaluated effects of XR-NTX + BRP to determine the number of "responders" according to a statistically predefined response criterion (6 of 8 MA-negative UDS during the last 4 weeks of medication). The 2-stage design required that stage 1 yield ≥3 responders to continue to stage 2; 11 of the 49 participants met responder criteria across both stages (5 in stage 1, 6 in stage 2).ConclusionsUnder the statistical analysis plan, study "success" required ≥9 responders. With 11 responders, the study demonstrated sufficient potential of naltrexone plus bupropion as a combination pharmacotherapy for MA use disorder to warrant further study.

Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BPND)) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n=10) or one that received equal-time health education training (n=9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [(18)F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BPND. At baseline, striatal D2/D3 BPND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BPND, whereas those in the education group did not. There were no changes in D2/D3 BPND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.

BackgroundEffective pharmacotherapies to treat methamphetamine (MA) dependence have not been identified, and behavioral therapies are marginally effective. Based on behavioral studies demonstrating the potential efficacy of aerobic exercise for improving depressive symptoms, anxiety, cognitive deficits, and substance use outcomes, the study described here is examining exercise as a potential treatment for MA-dependent individuals.MethodsThis study is randomizing 150 participants with MA dependence at a residential treatment facility for addictive disorders to receive either a thrice-weekly structured aerobic and resistance exercise intervention or a health education condition. Recruitment commenced in March, 2010. Enrollment and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates.ConclusionsSeeking evidence for a possibly effective adjunct to traditional behavioral approaches for treatment of MA dependence, this study is assessing the ability of an 8-week aerobic and resistance exercise protocol to reduce relapse to MA use during a 12-week follow-up period after discharge from residential-based treatment. The study also is evaluating improvements in health and functional outcomes during and after the protocol. This paper describes the design and methods of the study.

Purpose: To investigate the prevalence of opioid use disorder (OUD) and medication treatment for OUD (MOUD) receipt in rural primary care settings and identify characteristics associated with MOUD among patients with OUD. Methods: Secondary analyses based on electronic health records of all adult patients who visited 1 of the 6 rural primary care clinic sites from October 2019 to January 2021. Mixed effects logistic regression was conducted to assess MOUD receipt (Y/N) in relation to patient characteristics (eg, demographics, other substance use disorders [SUDs], mental health disorders, and chronic pain) and the number of MOUD prescribers per clinic. Findings: The prevalence of OUD varied from 0.7% to 8.2% (Mean [SD] = 3.3% [95% CI: 0.4, 6.1]) among 36,762 primary care patients across 6 clinic sites. Among 1,164 patients with OUD, on average 50.1% received MOUD (95% CI: 28.0, 72.3). Patients in clinics with more than 3 MOUD prescribers had more than 3 times the odds of receiving MOUD (OR = 3.42; 95% CI, 1.22‐9.62) as those in clinics with fewer than 3 prescribers. MOUD was positively associated with younger age (18‐30 [OR = 6.97; 95% CI, 3.37‐14.42], 31‐64 [OR = 5.03; 95% CI, 2.64‐9.57], relative to those 65 and older), having other co‐occurring SUDs (OR = 3.77; 95% CI, 2.57‐5.52), being male (OR = 1.50; 95% CI, 1.12‐2.01), and negatively associated with having chronic pain disorders (OR = 0.69; 95% CI, 0.50‐0.94). Conclusions: The prevalence of OUD and MOUD are high but vary considerably across rural primary care clinics; primary care MOUD prescribers play a key role on MOUD access in rural settings. [ABSTRACT FROM AUTHOR]

Background and Aims: International Classification of Diseases (ICD) diagnosis codes are often used in research to identify patients with opioid use disorder (OUD), but their accuracy for this purpose is not fully evaluated. This study describes application of ICD‐10 diagnosis codes for opioid use, dependence and abuse from an electronic health record (EHR) data extraction using data from the clinics' OUD patient registries and clinician/staff EHR entries. Design: Cross‐sectional observational study. Setting: Four rural primary care clinics in Washington and Idaho, USA. Participants: 307 patients. Measurements This study used three data sources from each clinic: (1) a limited dataset extracted from the EHR, (2) a clinic‐based registry of patients with OUD and (3) the clinician/staff interface of the EHR (e.g. progress notes, problem list). Data source one included records with six commonly applied ICD‐10 codes for opioid use, dependence and abuse: F11.10 (opioid abuse, uncomplicated), F11.20 (opioid dependence, uncomplicated), F11.21 (opioid dependence, in remission), F11.23 (opioid dependence with withdrawal), F11.90 (opioid use, unspecified, uncomplicated) and F11.99 (opioid use, unspecified with unspecified opioid‐induced disorder). Care coordinators used data sources two and three to categorize each patient identified in data source one: (1) confirmed OUD diagnosis, (2) may have OUD but no confirmed OUD diagnosis, (3) chronic pain with no evidence of OUD and (4) no evidence for OUD or chronic pain. Findings F11.10, F11.21 and F11.99 were applied most frequently to patients who had clinical diagnoses of OUD (64%, 89% and 79%, respectively). F11.20, F11.23 and F11.90 were applied to patients who had a diagnostic mix of OUD and chronic pain without OUD. The four clinics applied codes inconsistently. Conclusions: Lack of uniform application of ICD diagnosis codes make it challenging to use diagnosis code data from EHR to identify a research population of persons with opioid use disorder. [ABSTRACT FROM AUTHOR]