Addressing opioid overdose deaths: The vision for the HEALing communities study.

The United States is facing two devastating public health crises- the opioid epidemic and the COVID-19 pandemic. Within this context, one of the most ambitious implementation studies in addiction research is moving forward. Launched in May 2019, the HEALing Communities Study (HCS) was developed by the National Institutes of Health (NIH) and the Substance Abuse and Mental Health Services Administration (SAMHSA) as part of the Helping to End Addiction Long-termSM Initiative (National Institutes of Health, 2020). The goal for this research was to reduce opioid overdose deaths by 40 % in three years by enhancing and integrating the delivery of multiple evidence-based practices (EBPs) with proven effectiveness in reducing opioid overdose deaths across health care, justice, and community settings. This paper describes the initial vision, goals, and objectives of this initiative; the impact of COVID-19; and the potential for knowledge to be generated from HCS at the intersection of an unrelenting epidemic of opioid misuse and overdoses and the ravishing COVID-19 pandemic.

Characteristics and current clinical practices of opioid treatment programs in the United States.

BACKGROUND: Given rising rates of opioid use disorder (OUD) and related consequences, opioid treatment programs (OTPs) can play a pivotal role in the U.S. opioid crisis. There is a paucity of recent research to guide how best to leverage OTPs in the opioid response. METHODS: We conducted a national survey of U.S. OTPs using a 46-question electronic survey instrument covering three domains: 1) OTP characteristics; 2) services offered; and 3) current clinical practices. Descriptive statistics and multivariable logistic regression examined variables in these domains. RESULTS: Among responding OTPs, 32.4% reported using all three medications for OUD treatment; 95.8% used methadone, 61.8% used buprenorphine, and 43.9% used naltrexone. The mean (SD) number of patients currently receiving methadone was 383 (20.4), buprenorphine 51 (7.0), extended-release naltrexone 6 (1.0). Viral hepatitis testing was provided by 60.9% of OTPs, 15.3% provided hepatitis B vaccination, 14.9% provided hepatitis A vaccination, and 12.6% provided medication treatment for hepatitis C virus infection. HIV testing was provided by 60.7% of OTPs, 9.5% provided pre-exposure prophylaxis, and 8.4% provided medication treatment for HIV. OTP characteristics associated with using all three forms of medications for OUD included: providing medication for alcohol use disorder (aOR = 5.24, 95% CI:2.99-9.16), providing telemedicine services (aOR = 3.82, 95% CI:2.14-6.84), and directly providing naloxone to patients (aOR = 2.57, 95% CI:1.53-4.29). Multiple barriers to providing buprenorphine and extended-release naltrexone were identified. CONCLUSIONS: Efforts are needed to increase availability of all medications approved to treat OUD in OTPs, integrate infectious disease-related services, and expand the reach of OTPs in the U.S.

Associations of Parental Marijuana Use With Offspring Marijuana, Tobacco, and Alcohol Use and Opioid Misuse.

Importance: Marijuana use is increasing among adults and often co-occurs with other substance use; therefore, it is important to examine whether parental marijuana use is associated with elevated risk of substance use among offspring living in the same household. Objective: To examine associations of parental marijuana use with offspring marijuana, tobacco, and alcohol use and opioid misuse. Design, Setting, and Participants: This cross-sectional study used survey data from the 2015 through 2018 National Surveys on Drug Use and Health (NSDUH), which provide nationally representative data on adolescents or young adults living with a parent (the mother or the father). Annual average percentages were based on survey sampling weights. Final analyses were conducted September 21 through 23, 2019. Exposures: Parental marijuana use status. Main Outcomes and Measures: Offspring self-reported use of marijuana, tobacco, or alcohol or misuse of opioids. Results: Survey respondents included 24 900 father-offspring or mother-offspring dyads sampled from the same household. Among mothers living with adolescent offspring, 8.2% (95% CI, 7.3%-9.2%) had past-year marijuana use, while 7.6% (95% CI, 6.2%-9.2%) of mothers living with young adult offspring had past-year marijuana use. Among fathers living with adolescent offspring, 9.6% (95% CI, 8.5%-10.8%) had past-year marijuana use, and 9.0% (95% CI, 7.4%-10.9%) of fathers living with young adult offspring had past-year marijuana use. Compared with adolescents whose mothers never used marijuana, adjusted relative risk (ARR) of past-year marijuana use was higher among those whose mothers had lifetime (without past-year) marijuana use (ARR, 1.3; 95% CI, 1.1-1.6; P = .007), less than 52 days of past-year marijuana use (ARR, 1.7; 95% CI, 1.1-2.7; P = .02), or 52 days or more of past-year marijuana use (ARR, 1.5; 95% CI, 1.1-2.2; P = .02). Compared with young adults whose mothers never used marijuana, adjusted risk of past-year marijuana use was higher among those whose mothers had lifetime (without past-year) marijuana use (ARR, 1.4; 95% CI, 1.1-1.7; P = .001), less than 52 days of past-year marijuana use (ARR, 1.5; 95% CI, 1.0-2.3; P = .049), or 52 days or more of past-year marijuana use (ARR, 1.8; 95% CI, 1.3-2.5; P = .002). Compared with adolescents whose fathers never used marijuana, adolescents whose fathers had less than 52 days of past-year marijuana use were more likely to use marijuana (ARR, 1.8; 95% CI, 1.2-2.7; P = .006). Compared with young adults whose fathers never used marijuana, young adults whose fathers had 52 days or more of past-year marijuana use were more likely to use marijuana (ARR, 2.1; 95% CI, 1.6-2.9; P < .001). Compared with their peers whose parents never used marijuana and after adjusting for covariates, the adjusted risk of past-year tobacco use was higher among adolescents whose mothers had lifetime marijuana use (ARR, 1.3; 95% CI, 1.0-1.6; P = .03), less than 52 days of past-year marijuana use (ARR, 1.5; 95% CI, 1.0-2.1; P = .04), or 52 days or more of past-year marijuana use (ARR, 1.6; 95% CI, 1.1-2.3; P = .03); adolescents whose fathers had lifetime marijuana use (ARR, 1.5; 95% CI, 1.1-1.9; P = .004) or 52 days or more of past-year marijuana use (ARR, 1.8; 95% CI, 1.2-2.7; P = .006); young adults whose mothers had lifetime marijuana use (ARR, 1.2; 95% CI, 1.0-1.4; P = .04); and young adults whose fathers had 52 days or more of past-year marijuana use (ARR, 1.4; 95% CI, 1.0-1.9; P = .046). Compared with their peers whose parents had no past marijuana use and after adjusting for covariates, risk of past-year alcohol use was higher among adolescents whose mothers had lifetime marijuana use (ARR, 1.2; 95% CI, 1.1-1.4; P = .004), less than 52 days of past-year marijuana use (ARR, 1.5; 95% CI, 1.2-1.9; P = .002), or 52 days or more of past-year marijuana use (ARR, 1.3; 95% CI, 1.0-1.7; P = .04). After adjusting for covariates, parental marijuana use was not associated with opioid misuse by offspring. Conclusions and Relevance: In this cross-sectional study, parental marijuana use was associated with increased risk of substance use among adolescent and young adult offspring living in the same household. Screening household members for substance use and counseling parents on risks posed by current and past marijuana use are warranted.

Co-occurring substance use and mental disorders among adults with opioid use disorder.

BACKGROUND: Co-occurring substance use and mental disorders among people with opioid use disorder (OUD) increase risk for morbidity and mortality. Addressing these co-occurring conditions is critical for improving treatment and health outcomes. There is limited recent research on the prevalence of co-occurring disorders, demographic characteristics associated with co-occurring disorders, and receipt of mental health and substance use treatment services among those with OUD. This limits the development of targeted and resourced policies and clinical interventions. METHODS: Using 2015-2017 National Survey on Drug Use and Health data, prevalence of co-occurring substance use and mental disorders and receipt of mental health and substance use treatment services was estimated for adults aged 18-64 with OUD. Multivariable logistic regression assessed demographic and substance use characteristics associated with past-year mental illness (AMI) and serious mental illness (SMI) among adults with OUD as well as treatment receipt. RESULTS: Among adults with OUD, prevalence of specific co-occurring substance use disorders ranged from 26.4% (95% CI:23.6%-29.4%) for alcohol to 10.6% (95% CI:8.6%-13.0%) for methamphetamine. Prevalence of AMI was 64.3% (95% CI:60.4%-67.9%) and SMI was 26.9% (95% CI:24.2%-29.8%). Receiving both mental health and substance use treatment services in the past year was reported by 24.5% (95% CI:21.5%-29.9%) of adults with OUD and AMI and 29.6% (95% CI:23.3%-36.7%) of adults with OUD and SMI. CONCLUSIONS: Co-occurring substance use and mental disorders are common among adults with OUD. Expanding access to comprehensive service delivery models that address the substance use and mental health co-morbidities of this population is urgently needed.

Characteristics and prescribing practices of clinicians recently waivered to prescribe buprenorphine for the treatment of opioid use disorder.

BACKGROUND AND AIMS: Expanding access to medication-assisted treatment with buprenorphine is a cornerstone of the opioid crisis response, yet buprenorphine remains underutilized. Research has identified multiple barriers to prescribing buprenorphine. This study aimed to examine clinician characteristics, prescribing practices and barriers and incentives to prescribing buprenorphine among clinicians with a federal Drug Addiction Treatment Act of 2000 (DATA) waiver to prescribe buprenorphine for opioid use disorder treatment. DESIGN: Electronic survey of 4225 clinicians conducted between March and April 2018. SETTING: United States. PARTICIPANTS: Clinicians obtaining an initial federal DATA waiver or an increase in authorized patient limit to prescribe buprenorphine for opioid use disorder treatment in 2017. MEASUREMENTS: Descriptive statistics and multivariable logistic regression examined clinician characteristics, prescribing practices and primary barriers and incentives to prescribing buprenorphine or prescribing at or near the authorized patient limit. FINDINGS: Among respondents, 75.5% had prescribed buprenorphine since obtaining a DATA waiver; the mean (standard deviation) number of patients treated in the past month was 26.6 (40.3), and 13.1% of providers were prescribing at or near their patient limit in the past month. Lack of patient demand, cited by 19.4% of clinicians, was the most common primary barrier to prescribing buprenorphine or prescribing to the authorized patient limit, followed by time constraints in practice (14.6%) and insurance reimbursement, prior authorization or other insurance requirements (13.2%). Increased patient demand (22.2%), institutional support for buprenorphine treatment (12.5%) and increased reimbursement (12.2%) were the most endorsed primary incentives for buprenorphine prescribing. Multivariable logistic regression models identified multiple clinician characteristics associated with buprenorphine prescribing and prescribing at or near the authorized patient limit. CONCLUSIONS: US clinicians recently waivered to prescribe buprenorphine for opioid use disorder treatment appear to prescribe well below their patient limit, and many do not prescribe at all.

Relationship Between Recency and Frequency of Youth Cannabis Use on Other Substance Use.

PURPOSE: To assess the relationship between lifetime, past-year, and frequent past-year cannabis use on use of other substances among youth in order to inform prevention initiatives. METHODS: Data are from 27,900 youth aged 12-17 participating in the 2015-2016 National Surveys on Drug Use and Health. Multivariable multinomial logistic regression assessed the relationship between levels of youth cannabis use and past-year use of other substances compared to youth with no lifetime cannabis use. RESULTS: Prevalence of lifetime cannabis use among youth was 15.4%; 3.0% reported lifetime but not past-year use, 10.3% reported past-year use <200 days, and 2.1% reported past-year use ≥200 days. Past-year tobacco and alcohol use, and past-year misuse of prescription sedatives or tranquilizers, stimulants, and opioids were associated with increased adjusted relative risk ratios across all levels of cannabis use compared to youth reporting no lifetime cannabis use. Increased adjusted relative risk ratios across all levels of cannabis use were seen among youth aged 14-15 and 16-17 compared to 12-17 and among non-Hispanic blacks and Hispanics compared to non-Hispanic whites. CONCLUSIONS: Cannabis use is prevalent among youth and associated with other substance use. Efforts to scale up prevention programming and science-based messaging on risks of substance use are needed.

Access to treatment for opioid use disorders: Medical student preparation.

The current opioid epidemic requires new approaches to increasing access to treatment for patients with opioid use disorders and to improve availability of medication assisted treatment. We propose a model where medical students complete the necessary training to be eligible for the waiver to prescribe opioid medications to treat these disorders by the time of medical school graduation. This plan would increase the number of Drug Abuse Treatment Act of 2000 (DATA 2000) waivered physicians who could gain additional experience in treating substance use disorders during residency and provide the access to clinical care needed for individuals suffering with opioid use disorder. (Am J Addict 2017;26:316-318).

Adapting Screening, Brief Intervention, and Referral to Treatment for Alcohol and Drugs to Culturally Diverse Clinical Populations.

OBJECTIVES: To review the literature on the screening, brief intervention, and referral to treatment (SBIRT) approach to alcohol and drug use with racial and ethnic subgroups in the United States and to develop recommendations for culturally competent SBIRT practice. METHODS: Articles reporting on the use of SBIRT components (screening, brief intervention, referral to treatment) for alcohol and drug use were identified through a comprehensive literature search of PubMed from 1995 to 2015. RESULTS: A synthesis of the published literature on racial and ethnic considerations regarding SBIRT components (including motivational interviewing techniques) was created using evidence-based findings. Recommendations on culturally competent use of SBIRT with specific ethnic groups are also described. CONCLUSIONS: On the basis of the literature reviewed, SBIRT offers a useful set of tools to help reduce risky or problematic substance use. Special attention to validated screeners, appropriate use of language/literacy, trust building, and incorporation of patient and community health care preferences may enhance SBIRT acceptability and effectiveness. PRACTICE IMPLICATIONS: Providers should consider the implications of previous research when adapting SBIRT for diverse populations, and use validated screening and brief intervention methods. The accompanying case illustration provides additional information relevant to clinical practice.

Medicaid coverage of medications to treat alcohol and opioid dependence.

Substance use disorders affect 12% of Medicaid beneficiaries. The prescription drug epidemic and growing need for treatment of alcohol and opioid dependence have refocused states' attention on their provision of substance use disorder treatment services, including medications. This study characterized how Medicaid programs cover these treatment medications. Data were from 2013 Medicaid pharmacy documents, 2011 and 2012 Medicaid state drug utilization records, and a 2013 American Society of Addiction Medicine survey. Results showed that only 13 state Medicaid programs included all medications approved for alcohol and opioid dependence on their preferred drug lists. The most commonly excluded were extended-release naltrexone (19 programs), acamprosate (19 programs), and methadone (20 programs). For combined buprenorphine-naloxone, 48 Medicaid programs required prior authorization, and 11 programs used 1- to 3-year lifetime treatment limits. Given the chronic nature of substance use disorders and the overwhelming evidence supporting ongoing coverage for many of these medications, states may want to reexamine substance use disorder benefits.

N-acetyl-S-(N,N-diethylcarbamoyl) cysteine in rat nucleus accumbens, medial prefrontal cortex, and in rat and human plasma after disulfiram administration.

Disulfiram (DSF), a treatment for alcohol use disorders, has shown some clinical effectiveness in treating addiction to cocaine, nicotine, and pathological gambling. The mechanism of action of DSF for treating these addictions is unclear but it is unlikely to involve the inhibition of liver aldehyde dehydrogenase (ALDH2). DSF is a pro-drug and forms a number of metabolites, one of which is N-acetyl-S-(N,N-diethylcarbamoyl) cysteine (DETC-NAC). Here we describe a LCMS/MS method on a QQQ type instrument to quantify DETC-NAC in plasma and intracellular fluid from mammalian brain. An internal standard, the N,N-di-isopropylcarbamoyl homolog (MIM: 291>128) is easily separable from DETC-NAC (MIM: 263>100) on C18 RP media with a methanol gradient. The method's linear range is 0.5-500 nM from plasma and dialysate salt solution with all precisions better than 10% RSD. DETC-NAC and internal standards were recovered at better than 95% from all matrices, perchloric acid precipitation (plasma) or formic acid addition (salt) and is stable in plasma or salt at low pH for up to 24 h. Stability is observed through three freeze-thaw cycles per day for 7 days. No HPLC peak area matrix effect was greater than 10%. A human plasma sample from a prior analysis for S-(N,N-diethylcarbamoyl) glutathione (CARB) was found to have DETC NAC as well. In other human plasma samples from 62.5 mg/d and 250 mg/d dosing, CARB concentration peaks at 0.3 and 4 nM at 3 h followed by DETC-NAC peaks of 11 and 70 nM 2 h later. Employing microdialysis sampling, DETC-NAC levels in the nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and plasma of rats treated with DSF reached 1.1, 2.5 and 80 nM at 6h. The correlation between the appearance and long duration of DETC-NAC concentration in rat brain and the persistence of DSF-induced changes in neurotransmitters observed by Faiman et al. (Neuropharmacology, 2013, 75C, 95-105) is discussed.