Medication-Assisted Treatment for Opioid Use Disorder

Number: 1104

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses medication-assisted treatment for opioid use disorder.

1. Medical Necessity

   Subject to applicable benefit plan terms and limitations, Aetna considers medication-assisted therapy for opioid use disorder (MAT OUD; MOUD) medically necessary when all of the following criteria are met:

   1. General Requirements

      1. Member has a diagnosis of opioid use disorder (OUD) per DSM-5-TR criteria; and
      2. Member is able to provide informed consent (Note: for members less than 18 years of age, consent of a parent or legal guardian has been given except in
         States where State law grants persons under 18 years of age the ability to consent to an opioid treatment program [OTP] without the consent of another); and
      3. Methadone treatment is provided through a licensed OTP with a designated medical director responsible for clinical oversight (includes all dosing decisions and the overall medical and behavioral health services of the program); and
      4. Treatment is prescribed and overseen by a licensed clinician performing within the scope of practice, with documentation supporting medical necessity (see Program Requirements below); and
      5. Treatment is provided in a licensed outpatient setting permitted under state law (includes community clinics, primary care, behavioral health practices, or other outpatient setting); and
      6. If the member is pregnant, the individual should be co-managed by an obstetrician; and
      7. Mobile OTP services meets applicable federal and state regulatory requirements; and
         

   2. Program Requirements

      1. The MAT OUD program is certified by the Substance Abuse and Mental Health Services Administration (SAMHSA) and accredited by an independent, SAMHSA-approved accrediting body to ensure quality care and compliance with federal standards (e.g., The Joint Commission [TJC] or Commission on Accreditation of Rehabilitation Facilities [CARF]), along with inclusion on the Centers for Medicare & Medicaid Services (CMS) roster; and
      2. The MAT OUD program employs a state-approved, qualified health professional (QHP) (licensed practical nurse [LPN], licensed vocational nurse [LVN], registered nurse [RN], pharmacist, psychiatrist, etc.) licensed to dispense controlled medications classified as Schedule II or III; and
      3. Within a MAT OUD program, the physician or medical director is responsible for the medical care of members. However, they may appoint a QHP, such as an NP or PA, to provide direct medical care to individuals under their supervision, as permitted by state law and within their scope of practice; and
      4. A comprehensive clinical evaluation (including medical, psychiatric, and substance use history) is completed prior to or at initiation of treatment by the physician or QHP (e.g., NP, PA) (Note: if evaluation is conducted by a non-physician, the physician must oversee and assume ultimate responsibility for the evaluation and treatment decisions); and clinical documentation includes all of the following:
         
         
         1. Diagnosis of OUD using criteria from the DSM-5 TR; and
         2. Opioid use history and withdrawal symptoms; and
         3. Co-morbid medical and psychiatric conditions, including, but not limited to the following:
            
            
            1. Cardiac conditions
            2. Chronic pain
            3. Infectious disease screening (tuberculosis, HIV, viral hepatitis and syphilis)
            4. Inpatient/outpatient treatments
            5. Liver disease
            6. Pregnancy testing (if applicable)
            7. Respiratory status
            8. Substance use and overdose history; and

         4. Medication reconciliation, including potential drug interactions; and
            

      5. Initial and ongoing assessment of withdrawal symptoms with standardized tools (e.g., Clinical Opioid Withdrawal Scale/COWS; Subjective Opioid Withdrawal Scale/SOWS) to determine safe timing for initiation of treatment and medication dosage adjustments; and
      6. Appropriate laboratory serologies and psychosocial assessments are conducted within 14 days of program admission; and
      7. Urine toxicology testing results, accompanied by the physician/QHP's signature and documentation of necessity, and
         
         
         1. Testing is in accordance with CPB 0965 - Drug Testing in Pain Management and Substance Use Disorder Treatment and state/federal regulations; and
         2. Providers provide rationale for individualized definitive urine testing, documentation of results and description of how results determine the direction of further treatment; and
            
      8. Medication dosing and changes are documented by the treating clinician; and
      9. The member is provided education regarding harm reduction, including, but not limited to the following:
         
         
         1. Overdose prevention and reversal support (e.g., access to opioid antagonist naloxone or nalmefene)
         2. HIV (human immunodeficiency virus), hepatitis B virus (HBV), and hepatitis C virus (HCV)
         3. Bacterial and fungal infections
         4. Sexually transmitted infections (STIs)/sexually transmitted diseases (STDs); and
            
      10. An annual physical assessment is documented in member's chart (Note: If the assessment has not been completed within the past year, or if member is new to the MAT OUD program, the assessment should be conducted as art of the admission process); and
      11. The QHP (e.g., MD, NP, PA), practicing within their scope as permitted by state law, will provide psychiatric consultation or referral to behavioral health or psychiatric services when clinically indicated.

2. Policy Limitations and Exclusions 

   Some plans may have limitations or exclusions applicable to these services. Please refer to the member's benefit plan for applicable details. 

3. Related Policies 

   • CPB 0237 - Chronic Pain Rehabilitation Programs
   • CPB 0300 - Hair Analysis - for drug testing by hair analysis
   • CPB 0608 - Salivary Tests - for drug testing by oral fluid analysis
   • CPB 0910 - Extended-Release Buprenorphine Injectables
   • CPB 0965 - Drug Testing in Pain Management and Substance Use Disorder Treatment

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
80305	Drug test(s), presumptive, any number of drug classes, any number of devices or procedures; capable of being read by direct optical observation only (eg, utilizing immunoassay [eg, dipsticks, cups, cards, or cartridges]), includes sample validation when performed, per date of service
80306	Drug test(s), presumptive, any number of drug classes, any number of devices or procedures; read by instrument assisted direct optical observation (eg, utilizing immunoassay [eg, dipsticks, cups, cards, or cartridges]), includes sample validation when performed, per date of service
80307	Drug test(s), presumptive, any number of drug classes, any number of devices or procedures; by instrument chemistry analyzers (eg, utilizing immunoassay [eg, EIA, ELISA, EMIT, FPIA, IA, KIMS, RIA]), chromatography (eg, GC, HPLC), and mass spectrometry either with or without chromatography, (eg, DART, DESI, GC-MS, GC-MS/MS, LC-MS, LC-MS/MS, LDTD, MALDI, TOF) includes sample validation when performed, per date of service
HCPCS codes covered for indications listed in the CPB:
G2067	Medication assisted treatment, methadone; weekly bundle including dispensing and/or administration, substance use counseling, individual and group therapy, and toxicology testing, if performed (provision of the services by a medicare-enrolled opioid treatment program)
G2068	Medication assisted treatment, buprenorphine (oral); weekly bundle including dispensing and/or administration, substance use counseling, individual and group therapy, and toxicology testing if performed (provision of the services by a medicare-enrolled opioid treatment program)
G2069	Medication assisted treatment, buprenorphine (injectable) administered on a monthly basis; bundle including dispensing and/or administration, substance use counseling, individual and group therapy, and toxicology testing if performed (provision of the services by a medicare-enrolled opioid treatment program)
G2073	Medication assisted treatment, naltrexone; weekly bundle including dispensing and/or administration, substance use counseling, individual and group therapy, and toxicology testing if performed (provision of the services by a medicare-enrolled opioid treatment program)
G2074	Medication assisted treatment, weekly bundle not including the drug, including substance use counseling, individual and group therapy, and toxicology testing if performed (provision of the services by a medicare-enrolled opioid treatment program)
G2075	Medication assisted treatment, medication not otherwise specified; weekly bundle including dispensing and/or administration, substance use counseling, individual and group therapy, and toxicology testing, if performed (provision of the services by a medicare-enrolled opioid treatment program)
Other HCPCS codes related to the CPB:
G0480	Drug test(s), definitive, utilizing (1) drug identification methods able to identify individual drugs and distinguish between structural isomers (but not necessarily stereoisomers), including, but not limited to gc/ms (any type, single or tandem) and lc/ms (any type, single or tandem and excluding immunoassays (e.g., ia, eia, elisa, emit, fpia) and enzymatic methods (e.g., alcohol dehydrogenase)), (2) stable isotope or other universally recognized internal standards in all samples (e.g., to control for matrix effects, interferences and variations in signal strength), and (3) method or drug-specific calibration and matrix-matched quality control material (e.g., to control for instrument variations and mass spectral drift); qualitative or quantitative, all sources, includes specimen validity testing, per day; 1-7 drug class(es), including metabolite(s) if performed
G0481	Drug test(s), definitive, utilizing (1) drug identification methods able to identify individual drugs and distinguish between structural isomers (but not necessarily stereoisomers), including, but not limited to gc/ms (any type, single or tandem) and lc/ms (any type, single or tandem and excluding immunoassays (e.g., ia, eia, elisa, emit, fpia) and enzymatic methods (e.g., alcohol dehydrogenase)), (2) stable isotope or other universally recognized internal standards in all samples (e.g., to control for matrix effects, interferences and variations in signal strength), and (3) method or drug-specific calibration and matrix-matched quality control material (e.g., to control for instrument variations and mass spectral drift); qualitative or quantitative, all sources, includes specimen validity testing, per day; 8-14 drug class(es), including metabolite(s) if performed
G0482	Drug test(s), definitive, utilizing (1) drug identification methods able to identify individual drugs and distinguish between structural isomers (but not necessarily stereoisomers), including, but not limited to gc/ms (any type, single or tandem) and lc/ms (any type, single or tandem and excluding immunoassays (e.g., ia, eia, elisa, emit, fpia) and enzymatic methods (e.g., alcohol dehydrogenase)), (2) stable isotope or other universally recognized internal standards in all samples (e.g., to control for matrix effects, interferences and variations in signal strength), and (3) method or drug-specific calibration and matrix-matched quality control material (e.g., to control for instrument variations and mass spectral drift); qualitative or quantitative, all sources, includes specimen validity testing, per day; 15-21 drug class(es), including metabolite(s) if performed
G0483	Drug test(s), definitive, utilizing (1) drug identification methods able to identify individual drugs and distinguish between structural isomers (but not necessarily stereoisomers), including, but not limited to gc/ms (any type, single or tandem) and lc/ms (any type, single or tandem and excluding immunoassays (e.g., ia, eia, elisa, emit, fpia) and enzymatic methods (e.g., alcohol dehydrogenase)), (2) stable isotope or other universally recognized internal standards in all samples (e.g., to control for matrix effects, interferences and variations in signal strength), and (3) method or drug-specific calibration and matrix-matched quality control material (e.g., to control for instrument variations and mass spectral drift); qualitative or quantitative, all sources, includes specimen validity testing, per day; 22 or more drug class(es), including metabolite(s) if performed
ICD-10 codes covered if selection criteria are met:
F11.10-F11.99	Opioid related disorders

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Background

Medication-assisted treatment (MAT), also known as medications for opioid use disorder (MOUD), combines U.S. Food and Drug Administration (FDA)-approved pharmacologic therapies with psychosocial support to reduce opioid cravings, prevent withdrawal symptoms, and block the effects of opioids. This approach is endorsed by multiple national and international organizations, including the Substance Abuse and Mental Health Services Administration (SAMHSA), the American Society of Addiction Medicine (ASAM), the National Institute on Drug Abuse (NIDA), the Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO), the American Medical Association (AMA), and the American Psychiatric Association (APA). Goals of treatment are broad with an emphasis on improving health, maintaining sobriety, and decreasing the negative psychosocial effects of opioid use. 

Opioid use disorder (OUD) remains a significant public health concern in the United States. Recent estimates indicate that approximately 5.7 to 6.1 million individuals aged 12 years and older have OUD, with an additional approximately 9 million individuals misusing opioids annually (SAMHSA, 2023; SAMHSA, 2024). In 2022, approximately 9.3 million adults (3.7%) required treatment for OUD (Dowell et al., 2024). Opioid-related mortality is substantial, with nearly 80,000 opioid-involved overdose deaths reported among approximately 105,000 total drug overdose deaths in 2023 (CDC, 2025). Although provisional data suggest a decline in overdose deaths between 2023 and 2024, mortality remains elevated compared to prior decades (CDC, 2025; Saunders et al., 2026). Despite the availability of effective treatment, a minority of individuals with OUD receive care; in 2021, approximately 2.5 million U.S. adults had past-year OUD, yet only about 22% received medications for OUD, reflecting persistent gaps in access to evidence-based treatment (Jones et al., 2023; NIDA, 2023).

Despite the relatively low proportion of individuals receiving treatment, the use of MOUD has increased over time, with evidence demonstrating expanded access and uptake of treatment, including methadone and buprenorphine, in association with policy changes such as Medicaid expansion (Gupta et al., 2025; Siegel et al., 2026). While MOUD is used to treat opioid use disorder broadly, the current landscape is increasingly driven by illicit synthetic opioids, particularly fentanyl and its analogs, which now dominate the drug supply and are closely associated with recent increases in overdose mortality (Saunders et al., 2026; Zhu, 2025). Polysubstance use, including co-use of opioids with stimulants and other agents, has further contributed to the evolving and more complex overdose epidemic (AMA, 2025). Medications for opioid use disorder, including methadone, buprenorphine, and naltrexone, have demonstrated effectiveness in reducing morbidity and mortality, with evidence from systematic reviews and meta-analyses showing decreased risk of all-cause and overdose-related death among individuals receiving treatment. These findings have supported ongoing efforts to expand access to evidence-based pharmacologic treatment for individuals with opioid use disorder (Santo et al., 2021; Harris et al., 2026).

MOUD have distinct mechanisms of action but act on opioid receptors and related neural pathways involved in reward and dependence. Opioids exert their effects primarily through mu-opioid receptors, which play a central role in modulating pain perception, reward, and withdrawal processes (Kosten & George, 2002; Zhang et al., 2022). Chronic opioid exposure is associated with neuroadaptive changes in brain structure and function that contribute to dependence, craving, and compulsive opioid use (Kosten & George, 2002). Medications such as methadone, buprenorphine, and naltrexone act on these same receptor systems with differing pharmacologic properties, and have been shown to reduce craving, alleviate withdrawal symptoms, and decrease relapse risk (Harris et al., 2026; Nguyen et al., 2022). These effects support stabilization of dysregulated neurobiologic processes associated with opioid use disorder (Harris et al., 2026).

Use of MOUD has been associated with reductions in morbidity and mortality, including improved survival among individuals with opioid use disorder. Multiple studies have demonstrated that treatment with methadone or buprenorphine is associated with decreased risk of overdose and all-cause mortality, with evidence from systematic reviews and meta-analyses showing substantial reductions in mortality among individuals receiving opioid agonist therapy compared with no medication treatment (Harris et al., 2026; Santo et al., 2021). Randomized clinical trials and systematic reviews have demonstrated that methadone and buprenorphine are more effective than non-pharmacologic approaches in reducing illicit opioid use and improving treatment retention (Mattick et al., 2014). In addition to mortality benefits, treatment with MOUD has been associated with reductions in opioid use, decreased risk of overdose, and improvements in overall health outcomes (Harris et al., 2026). Among pregnant individuals with opioid use disorder, MOUD improves maternal and neonatal outcomes, with methadone and buprenorphine considered standard of care; available evidence suggests differences in neonatal outcomes and treatment retention across medications (Harris et al., 2026).

In a systematic review, Palmateer et al. (2022) reviewed evidence published between 2011 and 2020 on the effectiveness of harm reduction interventions for preventing HIV and hepatitis C virus (HCV) transmission and reducing injecting risk behaviour (IRB) and injection frequency among people who inject drugs. The review updated a 2011 review of reviews using an overview of systematic reviews and supplementary searches for primary studies, with database searches conducted in Medline, CINAHL, the Cochrane Library, EMBASE, PsycINFO, and Web of Science. The population of interest was people who inject drugs, as explicitly defined in included reviews and studies. Outcomes assessed included HIV infection, HCV infection and reinfection, IRB, and injection frequency. The authors screened 8513 reviews and 7133 primary studies, identifying 27 relevant reviews and 61 relevant primary studies. The level of evidence was classified as sufficient for opioid agonist therapy (OAT) for HIV, HCV, and IRB outcomes; for needle and syringe programmes (NSP) for HIV transmission and IRB; and for combined OAT and NSP for HCV transmission, with reported pooled effect estimates including a 50% reduction in primary HCV infection risk with OAT (risk ratio 0.50, 95% confidence interval 0.40–0.63) and a 74% reduction in HCV risk with combined OAT and high-coverage NSP (risk ratio 0.26, 95% confidence interval 0.07–0.89). The review reported sufficient evidence for some additional interventions in specific outcomes or settings, including psychosocial interventions for reducing IRB and pharmacy-based NSP for IRB, while evidence remained insufficient or absent for heroin-assisted treatment, pharmacological treatment for stimulant dependence, contingency management, technology-based interventions, low dead space syringes, and drug consumption rooms for HIV or HCV outcomes. The authors concluded that evidence had strengthened since 2011 for OAT, NSP, and their combination in reducing HIV, HCV, and injecting risk behaviors, while substantial gaps in evidence persisted for several other harm reduction interventions.

The overall goal of treatment with MOUD is to reduce relapse risk through alleviation of withdrawal symptoms, reduction of opioid craving, and stabilization of underlying neurobiologic processes associated with opioid use disorder. Evidence demonstrates that MOUD is more effective than non-pharmacologic approaches in reducing illicit opioid use and improving retention in treatment (Mattick et al., 2014). In addition to these treatment effects, MOUD has been associated with reductions in opioid use, decreased risk of overdose, and improvements in overall health outcomes (Harris et al., 2026). Observational studies have also suggested that treatment with MOUD may be associated with reductions in some measures of criminal justice involvement, although findings across populations vary (NIH, 2022).

MOUD include three primary agents: methadone, buprenorphine, and naltrexone, all of which are approved by the U.S. Food and Drug Administration for the treatment of opioid use disorder. These medications have distinct mechanisms of action but each act on opioid receptor systems to reduce opioid use and support recovery. Methadone and buprenorphine function as opioid agonist therapies, while naltrexone is an opioid antagonist, resulting in differing effects on opioid receptor activation and blockade. Depending on the agent used, these medications reduce or block the euphoric effects of opioids, alleviate withdrawal symptoms, and decrease opioid craving (Harris et al., 2026). These medications are approved for and commonly used in long-term (maintenance) treatment of opioid use disorder (Harris et al., 2026).

Medication Overview

Methadone for OUD

Methadone is a full opioid agonist that acts at mu-opioid receptors and is administered in a controlled clinical setting for the treatment of opioid use disorder (OUD). Through its pharmacologic activity, methadone reduces withdrawal symptoms and opioid craving, supporting stabilization and engagement in ongoing treatment (Kosten & George, 2002; Volkow & Blanco, 2020). Evidence from systematic reviews demonstrates that methadone maintenance therapy is more effective than non-pharmacologic approaches, including psychosocial treatment alone, in reducing illicit opioid use and improving treatment retention. Comparative analyses indicate that methadone may be associated with slightly higher retention rates than buprenorphine in some populations, although differences are reduced when higher buprenorphine doses are used (Mattick et al., 2014). These medications are considered first-line therapy for OUD and are associated with reductions in opioid use, overdose risk, and overall morbidity and mortality (Harris et al., 2026).

In the United States, access to methadone is highly regulated and generally limited to certified opioid treatment programs, which can create barriers for patients, particularly in areas with limited program availability. Treatment typically begins with supervised daily dosing, with take-home doses permitted based on clinical stability. Federal policy allows limited exceptions, including short-term administration for withdrawal management and hospital-based use, and recent regulatory changes have expanded flexibility in take-home dosing and telehealth evaluation (SAMHSA, 2021; NASADA, 2022). Despite these changes, geographic limitations, program availability, and state-level regulatory variation continue to affect patient access and adherence, and increased distance to treatment facilities has been associated with missed dosing and reduced engagement in care. Efforts to expand access, including mobile treatment units and alternative dispensing models, have been implemented to improve treatment availability and continuity of care.

Methadone is a long-acting full opioid agonist used for the treatment of opioid use disorder and is administered through federally regulated opioid treatment programs. Initial dosing is conservative due to the risk of accumulation and respiratory depression. Federal regulations limit the initial dose to no more than 30 mg, with a total first-day dose not exceeding 40 mg. Maintenance dosing is individualized based on clinical response, with typical therapeutic ranges reported between 60 and 120 mg per day; doses ≥80 mg/day are commonly observed in clinical practice to suppress withdrawal symptoms and opioid craving. Dose titration is gradual due to methadone’s long and variable half-life, with increases of approximately 5 to 10 mg generally made every 3 to 7 days to minimize risk of accumulation and toxicity. Methadone has been associated with dose-dependent QT interval prolongation; clinical guidance recommends consideration of electrocardiographic monitoring in patients with cardiac risk factors and at higher doses (e.g., >100 mg/day). There is no defined maximum maintenance dose; however, higher doses require careful monitoring for sedation, respiratory depression, and cardiac effects, with dosing guided by individualized clinical assessment rather than fixed thresholds (Chou et al., 2014; SpecGx, 2025; SAMHSA, 2021; SAMHSA, 2026).

Naltrexone

Naltrexone is an opioid receptor antagonist approved for the treatment of OUD. It is available as an oral formulation taken daily or as an extended-release injectable formulation administered intramuscularly once monthly. Its mechanism involves competitive blockade of mu-opioid receptors, thereby preventing the euphoric and reinforcing effects of opioids. Initiation requires patients to be fully opioid-free (at least 7 to 10 days) to avoid precipitated withdrawal, with recommended abstinence periods varying by opioid type. Oral naltrexone is limited by poor adherence, whereas extended-release naltrexone demonstrates improved treatment retention, reduced opioid use, and decreased cravings compared with nonpharmacologic treatment or placebo in studied populations. Appropriate candidates include individuals who are highly motivated, those leaving controlled environments such as incarceration or residential treatment, or those who prefer a non-agonist approach. Contraindications include current physiologic opioid dependence, acute hepatitis, liver failure, or hypersensitivity. Risks include hepatotoxicity, injection site reactions for the extended-release formulation, and increased risk of opioid overdose if patients attempt to override receptor blockade or resume opioid use after discontinuation due to reduced tolerance (SAMHSA, 2021).

In the treatment of OUD, naltrexone is generally best suited for patients who have completed detoxification and prefer a non-opioid treatment option. It may be considered in individuals who cannot or do not wish to receive opioid agonist therapy. However, because naltrexone does not alleviate withdrawal symptoms and may have less direct effect on cravings compared with agonist therapies, its effectiveness depends on adherence and engagement in comprehensive treatment, including counseling and behavioral support (SAMHSA, 2025).

Oral naltrexone is typically administered at a dose of 50 mg daily; however, its effectiveness is limited by adherence challenges, as missed doses reduce receptor blockade (Singh & Saadabadi, 2023; SpecGx, 2023). The extended-release injectable formulation (e.g., Vivitrol) is administered as 380 mg IM every four weeks (or once monthly) following detoxification and provides sustained opioid receptor blockade over the dosing interval (Alkermes, 2026; SAMHSA, 2025). Randomized controlled trial evidence supports the efficacy of monthly extended-release naltrexone in maintaining opioid abstinence compared with placebo following detoxification (Krupitsky et al., 2011).

Buprenorphine (+/- Naloxone) for OUD 

Buprenorphine is a partial opioid agonist approved for the treatment of opioid use disorder (OUD) and is distinct in that it can be prescribed in office-based settings, thereby improving access to care. It binds with high affinity to μ-opioid receptors, reducing withdrawal symptoms and opioid cravings while producing less euphoria and respiratory depression compared with full opioid agonists due to its partial agonist activity and ceiling effect. Its high receptor affinity allows it to displace other opioids, which may precipitate withdrawal if initiated before the onset of moderate withdrawal symptoms; therefore, induction is recommended when objective signs of withdrawal are present.

Buprenorphine is commonly co-formulated with naloxone to reduce misuse potential. Naloxone has minimal sublingual bioavailability when administered as directed but becomes pharmacologically active if injected, where it acts as an opioid antagonist that can precipitate acute withdrawal, thereby deterring parenteral misuse.

Buprenorphine is available as a monoproduct and in combination with naloxone. The combination product is generally preferred due to its abuse-deterrent properties, while the monoproduct may be used in selected clinical scenarios such as pregnancy. Formulations include sublingual tablets and films for daily administration, as well as extended-release injectable or implantable formulations that provide sustained drug delivery and may improve adherence and reduce diversion.

Evidence supports buprenorphine as a first-line pharmacologic treatment for OUD due to its effectiveness in reducing opioid use and associated risks. Optimal outcomes occur when medication therapy is combined with counseling, psychosocial support, and ongoing monitoring as part of a comprehensive treatment program.

Buprenorphine is initiated when a patient is in mild-to-moderate opioid withdrawal to reduce the risk of precipitated withdrawal, with clinical assessment often supported by standardized tools such as the Clinical Opiate Withdrawal Scale (COWS), an 11-item instrument used to quantify withdrawal severity (Wesson & Ling, 2003). In clinical practice, thresholds such as a COWS score greater than 8 are commonly used to indicate adequate withdrawal for safe initiation, although timing should be individualized based on patient presentation (Weinstein et al., 2023). Initial dosing typically begins with approximately 2 to 4 mg and is titrated based on withdrawal symptoms and clinical response. Maintenance dosing is individualized to suppress withdrawal symptoms and cravings, with most patients stabilized within a range of approximately 4 to 24 mg/day; dosing adjustments are guided by symptom control rather than fixed thresholds. Buprenorphine demonstrates a ceiling effect on respiratory depression, and doses above 24 mg/day generally do not produce proportionally increased pharmacologic effects, although higher doses may be used in select cases based on clinical judgment (SAMHSA, 2024). The medication is commonly administered once daily as a sublingual film or tablet, although split dosing may be considered in specific clinical scenarios (Indivior, 2025). Extended-release formulations, including monthly injectable products, are administered per product labeling following stabilization and provide sustained drug exposure, which may improve adherence and reduce diversion risk (Lofwall et al., 2018; SAMHSA, 2024).

SAMHSA Federal Guidelines for Opioid Treatment Programs

The Substance Abuse and Mental Health Services Administration (SAMHSA) published the "Federal Guidelines for Opioid Treatment Programs" to describe the implementation of revised federal regulations governing opioid treatment programs (OTPs) under 42 CFR part 8. The Guidelines outlined minimum federal standards for certification, accreditation, clinical services, and patient protections within OTPs and described the delivery of medications for opioid use disorder (MOUD) as part of comprehensive, patient‑centered care. The document addressed admission criteria, assessment requirements, medication administration, counseling, overdose prevention, and continuity of care, with an emphasis on reducing barriers to treatment, promoting patient safety, and supporting long‑term engagement in care (SAMHSA, 2026).

Medications for Opioid Use Disorder (MOUD)

Medications for the treatment of opioid use disorder (MOUD) are medications approved by the Food and Drug Administration for use in the treatment of OUD and include methadone, buprenorphine, and naltrexone. In the same way that medications are used to treat long‑term, chronic health conditions, medications can also be used to treat opioid use disorder. Short‑term withdrawal management by itself is associated with extremely high recurrence and overdose risks, while the reduction in mortality and increased recovery benefits associated with MOUD are enhanced when these medications are part of a long‑term, chronic disease management plan that supports people with opioid use disorder taking their medication for as long as it helps them.

Opioid Treatment Programs (OTPs)

Opioid treatment programs (OTPs) are federally certified, registered, and accredited entities that provide comprehensive services for people with opioid use disorder and other related substance use disorders and related physical and mental health conditions through a multidisciplinary team of healthcare professionals. OTPs dispense and administer methadone and increasingly also buprenorphine and naltrexone and offer medical care and non‑pharmacological behavioral health services such as counseling, peer support, care management, and referrals to community recovery organizations.

Federal Regulations Governing OTPs

The regulations in 42 CFR part 8 establish the procedures by which the Secretary of the U.S. Department of Health and Human Services determines whether a program is qualified to dispense opioid agonist medications for the treatment of opioid use disorder. These regulations establish minimum acceptable standards for the operation of opioid treatment programs, require certification and accreditation, and govern the dispensing and administration of methadone and buprenorphine in accordance with the Controlled Substances Act.

Criteria for Admission to Treatment

Admission to an opioid treatment program (OTP) requires that a patient meets specific criteria. A patient must have a diagnosis of moderate to severe OUD, have active moderate to severe OUD or OUD in remission, or be at high risk for recurrence of use or overdose. These criteria may exist independently or in combination, including for individuals with mild OUD when there is a risk of overdose.

The diagnosis of OUD is characterized by signs and symptoms associated with compulsive, persistent use of opioids despite harmful consequences. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) outlines 11 diagnostic criteria used to establish the diagnosis and determine severity. Severity classification is based on the number of criteria met, with 2 to 3 criteria indicating mild OUD, 4 to 5 criteria defining moderate OUD, and 6 or more symptoms indicating severe OUD. However, tolerance and withdrawal are not counted for individuals taking opioids solely under appropriate medical supervision.

Patients receiving methadone or buprenorphine may achieve remission or a lower severity classification based on the remaining diagnostic criteria, and reductions in the frequency or amount of use may reflect changes in severity over time. The admission evaluation requires a comprehensive history and examination, particularly in the context of high-potency synthetic opioids. It incorporates a patient-centered, shared decision-making approach, where the practitioner reviews available medications, risks, and benefits, while the patient provides information regarding treatment goals, preferences, and prior history. This process continues through a full examination and psychosocial assessment, with documentation of findings and informed consent included in the patient record.

The revised regulations eliminate the requirement that patients have an opioid addiction history of one year or longer and remove the requirement that people under age 18 have documented unsuccessful withdrawal attempts. Admission is based on a determination that the individual meets diagnostic criteria for moderate to severe opioid use disorder, has opioid use disorder in remission, or is at high risk for recurrence or overdose, and that the individual voluntarily chooses treatment with informed consent.

An opioid treatment program must maintain procedures designed to ensure that patients are admitted by qualified personnel using accepted medical criteria and that the decision is documented in the patient’s clinical record. Admission requires confirmation that the patient meets criteria for opioid use disorder or is at high risk for overdose and that the patient voluntarily chooses treatment with medications for opioid use disorder with informed consent.

Role of the Medical Director

The medical director is a physician licensed to practice medicine in the jurisdiction in which the opioid treatment program is located and assumes responsibility for all medical and behavioral health services provided by the program, including their administration. Although responsibilities may be delegated to authorized practitioners, such delegation does not eliminate the medical director’s responsibility for ensuring compliance with federal, state, and local laws and regulations and for overseeing clinical quality and patient safety.

Informed Consent and Patient Rights

Informed consent requires opioid treatment program staff to explain treatment procedures, medication risks and benefits, alternative treatments, patient responsibilities, and the right to refuse treatment in a manner the patient can understand. Programs must implement policies that protect patients’ rights to dignity, privacy, confidentiality, and the ability to file grievances without fear of retaliation and ensure protection from discrimination under applicable federal laws.

Initial and Periodic Physical and Behavioral Health Assessment

Each patient admitted to an opioid treatment program must receive a physical and behavioral health assessment within 14 calendar days following admission and periodically thereafter. The assessment includes screening for imminent risk of harm, evaluation of substance use and co‑occurring conditions, and development and regular updating of a patient‑centered care plan that reflects treatment response and evolving recovery goals.

Counseling and Recovery Support Services

Opioid treatment programs must provide substance use disorder counseling and psychoeducation as clinically necessary and mutually agreed upon, including overdose prevention education and recovery‑oriented counseling. Patient refusal of counseling does not preclude receipt of medications for opioid use disorder, and programs must offer or link patients to vocational, educational, and recovery support services when requested or clinically indicated.

Drug Testing

Per 42 CFR Part 8, drug testing is required at a minimum frequency of eight times per year and must use FDA‑authorized tests for substances that may affect patient safety or treatment. Drug testing is intended to support patient recovery and inform clinical decision‑making and must not be used in a punitive manner or as the sole basis for treatment decisions.

Drug testing is a component of ongoing assessment in opioid treatment programs (OTPs), and panels typically include testing for opioids (e.g., fentanyl, methadone and its metabolites, and buprenorphine and its metabolites), as well as benzodiazepines, cocaine, and amphetamines, with the option to include barbiturates, delta-9-tetrahydrocannabinol, and alcohol metabolites based on clinical indication. Selection of substances for testing may be individualized according to patterns of drug use in the community, patient-reported substance use, and assessed risk. It is recommended that presumptive (screening) test panels include benzodiazepines, barbiturates, and alcohol, often assessed through ethyl glucuronide, as alcohol is the most widely used mood-altering substance and benzodiazepines and barbiturates are commonly prescribed; when used in combination with opioids, these substances can result in additive respiratory depression with detrimental effects, making their detection an important component of “ongoing assessment, care planning, medication management, and patient safety.” If detected, clinicians should evaluate the reasons for use and coordinate with external prescribers as appropriate, and these agents should not be abruptly discontinued due to risk of seizure and adverse events. Point-of-care (POC) drug testing may be used to assess a limited range of substances using immunoassay technologies; however, such testing may be insufficient for definitive clinical management or nonclinical purposes, and confirmatory laboratory-based testing (e.g., gas chromatography–mass spectrometry or liquid chromatography–mass spectrometry) may be required when results are inconsistent with clinical findings or when false positive or false negative results are suspected. Testing approaches and specimen type should be determined on a patient-by-patient basis, with consideration of less invasive methods, and programs should comply with applicable federal and state requirements related to drug testing.

Medication Administration, Dispensing, and Use

Medications for opioid use disorder must be administered or dispensed only by appropriately licensed and registered practitioners and in accordance with FDA‑approved labeling. Methadone, buprenorphine, and naltrexone are the approved medications, and dosing decisions must be individualized, documented, and based on clinical judgment to balance therapeutic benefit and patient safety.

Withdrawal Management

Withdrawal management refers to the dispensing of medications for opioid use disorder in decreasing doses to alleviate withdrawal symptoms and is distinct from continuous medication treatment. Withdrawal management is associated with a high risk of recurrence and overdose, and patient‑centered, informed‑consent‑based approaches with careful planning and follow‑up are emphasized.

Supporting Pregnant or Postpartum Women

Pregnant patients seeking treatment for opioid use disorder are considered a priority for enrollment in opioid treatment programs, and methadone and buprenorphine are part of evidence‑based treatment strategies during pregnancy. Programs must maintain policies that address prenatal care, reproductive health services, overdose prevention education, and continuity of care during pregnancy and the postpartum period, with medically supervised withdrawal not recommended due to high risk of return to opioid use.

Supporting People Under Age 18

Except in states where individuals under age 18 may consent to treatment without parental involvement, admission requires written consent from a parent, legal guardian, or responsible adult. The revised regulations remove prior requirements for unsuccessful withdrawal attempts and emphasize age‑appropriate, trauma‑informed care and assessment to determine whether medications for opioid use disorder are clinically appropriate.

Overdose Prevention and Infectious Disease Prevention

The revised regulations promote integration of overdose prevention and infectious disease prevention services, including overdose education, naloxone distribution, infectious disease testing, and risk mitigation strategies. These services are intended to reduce overdose risk, prevent transmission of HIV and viral hepatitis, and support patient safety as part of comprehensive opioid use disorder treatment.

Continuity of Care

Continuity of care includes transition planning, guest dosing arrangements, medication continuity during emergencies, and coordination with other healthcare providers and community resources. Opioid treatment programs are expected to implement policies that ensure uninterrupted access to medications and services during transitions, temporary absences, or program closures.

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Glossary of Terms

For a list of applicable definitions and terms, see Title 42: Code of Federal Regulations.

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References