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Opioid use disorder (OUD) is a chronic disease characterized by physical and psychological dependence on prescription and/or illicit opioids. The prevalence of OUD in the United States has risen sharply in recent decades. Core clinical features of OUD are a persistent pattern of maladaptive behaviors related to the pursuit and use of opioids, including use despite adverse consequences and a preoccupation with obtaining opioids. Diagnosis is based on DSM-5 criteria. Medication-assisted treatment is the cornerstone of management, combining medications for opioid use disorder (MOUD) with individualized psychosocial treatment. Long-acting opioid agonists (i.e., methadone or buprenorphine) are most commonly used and have comparable long-term outcomes for addressing cravings and opioid withdrawal syndrome (OWS) and reducing the risk of overdose. Naltrexone may be appropriate for patients trying to abstain from opioid use. OUD is a highly stigmatized lifelong condition that requires a strong therapeutic alliance and patient-centered approach to address relapses, comorbid conditions (e.g., PTSD, infectious complications of injecting drugs), and other circumstances that may impact treatment adherence.
Opioid agonists bind at κ-, δ-, and μ-opioid receptors throughout the body. Clinical features of OUD (e.g., physical dependence and compulsive use) result from repeated stimulation of μ-opioid receptors in the brain.
Acute use 
- Opioids bind to μ-opioid receptors in the locus coeruleus → inhibition of cAMP → ↓ norepinephrine release
- ↑ Dopamine in reward circuits → euphoria
Long-term use 
- Dependence: absent or diminished stimulation of μ-opioid receptors → ↑ norepinephrine levels → OWS
Opioid cessation 
- Tolerance, dependence, craving, compulsive use
- Social impairment (e.g., unable to fulfill family, work, or school obligations)
- Opioid-induced disorders, e.g.:
- Opioid-induced neurotoxicity
DSM-5 diagnostic criteria for opioid use disorder 
- Taking larger amounts of opioids and for longer than intended
- Inability to reduce opioid intake despite a desire to do so
- Spending excessive time obtaining, using, or recovering from opioids
- Craving or having a strong desire to use opioids
- Failing to fulfill family, work, or school obligations as a result of opioid use
- Continued use of opioids despite negative social or interpersonal consequences
- Stopping or limiting important social, work, or leisure activities as a result of opioid use
- Repeated opioid use in physically hazardous situations
- Continued opioid use despite knowledge of its personal harm (physical and/or psychological)
- One or both of the following manifestations of tolerance:
- One or both of the following manifestations of withdrawal:
- OUD: ≥ 2 criteria occurring within a 12-month period
- Exceptions: Physical dependence (i.e., the presence of tolerance and/or withdrawal) is not considered a criterion in patients solely using opioids under appropriate medical supervision.
- Mild: 2–3 criteria
- Moderate: 4–5 criteria
- Severe: 6–7 criteria
- Identify and treat .
- Perform a comprehensive .
- Offer , i.e.:
- Utilize person-centered language, motivational interviewing, and harm reduction strategies. 
- Refer to an addiction medicine specialist as needed.
Do not withhold MOUD from patients who decline a psychosocial evaluation or if comprehensive addiction treatment is unavailable. 
Medication for opioid use disorder (MOUD) 
MOUD involves the treatment of OUD with a long-acting opioid agonist (i.e., methadone or buprenorphine) or antagonist (i.e., naltrexone). See “Management of opioid withdrawal” for details on initiating treatment for OWS.
- Higher success rates than abstinence-based treatment
- Initiate under medical supervision
- Continue for as long as the patient benefits from treatment.
- The process of initiating MOUD to determine an effective treatment dose
- See “Methadone induction” and “Buprenorphine induction” in “Opioid withdrawal.”
- Induction regimens vary but are generally similar to those used to treat OWS.
- See “Methadone induction” and “Buprenorphine induction” in “Opioid withdrawal” for dosages.
Opioid antagonist therapy
- Indication: maintenance therapy for patients who have completed opioid withdrawal and want to abstain from opioid use
- Treatment options
- Primary prevention: Early recognition and treatment of physical dependence may prevent the development of OUD. 
- Relapse prevention
- HIV prevention: Offer HIV PrEP to HIV-negative . 
- ; needle exchange services