Opioid Use Disorder

Opioid use disorder (OUD) is a substance use disorder characterized by pathologic consumption of opioids. Opioids are central nervous system depressants that are used medically as potent analgesics. However, they are often misused for their euphoric effects. Features of opioid intoxication include respiratory depression, drowsiness, and pinpoint pupils. Intoxication can be managed with administration of naloxone. If discontinued, patients may develop withdrawal symptoms such as irritability, piloerection, and stomach cramps. Withdrawal may be managed by methadone or buprenorphine. Chronic OUD is managed with psychotherapy as well as medications. Prognosis is poor without adequate management and prevention of relapse and overdose.

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Definition and Epidemiology


Opioid use disorder (OUD) is the chronic (> 12 months) maladaptive use of opioids. The most common substances in OUD are prescription pills such as morphine, codeine, oxycodone, and hydrocodone, and IV forms such as heroin and fentanyl.

  • Intoxication: 
    • High amounts of use can lead to sedation and respiratory depression.
    • Other symptoms include psychomotor retardation, slurred speech, and myosis.
    • Delirium and opioid-induced psychotic disorders may also occur.
  • Withdrawal: 
    • Development of a substance-specific syndrome due to the cessation (or reduction) of substance use
    • Patients experience physical (nausea, diarrhea, chills, and body aches) and/or psychological symptoms (craving or perceived need to use the substance). 
    • Symptoms are usually at their worst 2–3 days after last use.
  • Tolerance: the need to increase the dose of the substance to achieve the desired effect (= diminished effect if using the same amount of the substance)


  • Opioid medications are the most commonly misused prescription medication class.
  • Peak age of OUD is between the late 30s and 40s.
  • Men:women ratio is 3:1. 
  • In 2019, close to 50,000 Americans died from drug overdoses involving any opioid.
  • Illegal synthetic opioids have contributed to an increase in opioid overdose deaths in recent years.


Types of opioids

  • Natural: morphine, codeine
  • Semi-synthetic: oxycodone, hydrocodone, heroin
  • Synthetic: fentanyl, tramadol, methadone

Pharmacological properties

  • Opioids stimulate mu, kappa, and delta receptors. 
  • Addiction to opioids happens due to their effects on the dopaminergic system, which mediates their addictive and rewarding properties.
  • Heroin is very lipophilic → enters CNS rapidly → metabolized to 6-monoacetylmorphine → attaches to opioid receptors more strongly than morphine → results in intoxication symptoms more quickly

Clinical Presentation and Diagnosis

Opioid intoxication


  • Respiratory depression: may progress to coma or death in overdose
  • CNS: euphoria, drowsiness, slurred speech, seizures
  • GI: nausea/vomiting, constipation, decreased gag reflex
  • Ophthalmologic:
    • Miosis 
      • Found in almost 50% of patients
      • Absence of pinpoint pupils does not exclude the diagnosis of opioid intoxication!
    • Meperidine causes mydriasis.

Diagnosis is based on history and physical exam, and can be supported by urine drug screen:

  • Urine drug screen by itself does not confirm a diagnosis of OUD. 
  • Only detects morphine, codeine, and heroin 
  • Eating large amounts of poppy seed bagels or muffins can result in false-positive urine drug screens.

Opioid withdrawal

The Clinical Opioid Withdrawal Scale (COWS) helps in determining the severity of withdrawal and assesses the following symptoms:

  • Resting pulse rate (tachycardia)
  • GI upset (stomach cramps to diarrhea)
  • Sweating 
  • Tremor
  • Restlessness
  • Yawning
  • Pupil size (mydriasis)
  • Anxiety or irritability
  • Bone or joint aches
  • Gooseflesh skin
  • Runny nose or tearing

For diagnosis, a detailed history of opioid use, including last use, must be obtained.

Management and Complications

Opioid intoxication

  • ABCDE assessment (Airway, Breathing, Circulation, Disability, Exposure): to ensure patient safety.
  • Administration of naloxone (short-acting competitive opioid antagonist):
    • Results in improving respiratory depression
    • May cause severe withdrawal if last heroin use was less than 7 days ago
  • If patient doesn’t improve after naloxone: Start ventilatory support and look for other substances causing CNS depression.
  • Naloxone may need to be administered multiple times. 
  • Patients should always be monitored after administration of naloxone due to its short half-life.

Opioid withdrawal

Treatment of opioid withdrawal depends on the severity of symptoms.

Symptom relief:

  • Clonidine: alpha-2 agonist, decreases autonomic signs and symptoms of withdrawal
  • NSAIDs for pain
  • Dicyclomine for abdominal cramps
  • All of these drugs are inferior to medications for treatment of opioid dependence (see table below).

Medications for opioid use disorder

  • Methadone: 
    • Synthetic long-acting opioid agonist 
    • Used to suppress withdrawal symptoms  
    • Research has shown that methadone is associated with decreased mortality from OUD as well as decreased rate of infectious sequelae of injection drug use.
    • QT interval–prolonging drug with the potential for lethal overdose 
  • Buprenorphine: 
    • Partial opioid agonist used for opioid dependence
    • Used to suppress withdrawal symptoms
    • Unlike methadone, buprenorphine has no narcotic effect. 
    • Addition of naloxone eliminates potential for misuse. 
      • Subutex is the trade name for buprenorphine.
      • Suboxone is the trade name for buprenorphine-naloxone. 
    • Disadvantage: the precipitation of withdrawal symptoms if there was no period of abstinence prior to initiation
  • Naltrexone:
    • Long-acting competitive opioid antagonist 
    • Used only after detoxification to prevent relapse
    • While naltrexone has few side effects, patients who relapse are at higher risk of overdose due to decreased tolerance.
Table: Summary of medications for opioid use disorder
MedicationProperties and administrationAdvantagesDiasdvantages
  • Full opioid receptor agonist
  • Administration: most commonly sublingual and oral
  • Once daily
  • Decreases morbidity and mortality
  • Can be used in pregnancy
Might cause QT prolongation
  • Partial opioid receptor agonist
  • Administration: most commonly sublingual and buccal films
  • Available as sublingual preparation (safer)
  • Mixed with naloxone to avoid any euphoric effects → prevents potential for opioid misuse when injected instead of taken orally
Requires abstinence from opioids prior to initiation


Injection drug use–related infections:

  • IV use of opioids is common among those with severe OUD. 
  • Unsanitary use of injection equipment increases risk of infections: 
    • Abscesses
    • Bacteremia
    • Endocarditis
    • Osteomyelitis 
  • People who inject drugs are at higher risk of bloodborne infectious viruses, notably HIV and hepatitis B and C. 
  • Harm-reduction practices, such as needle exchanges, are critical to reducing the risk of complications.


  • As with any other substance use disorders, relapse or remission of OUD is common.
  • Relapse especially after discharge from hospital is often associated with fatal overdosing due to decreased tolerance.
  • All patients with OUD must be advised to obtain naloxone for overdose prevention.

Differential Diagnosis

  • Hypoglycemia: a state of low blood glucose levels (< 70 mg/dL) most common in those with diabetes or heavy alcohol ingestion. Symptoms can be vague and nonspecific, including confusion, changes in mental status, and somnolence, similar to opioid intoxication. Diagnosis is quickly made using fingerstick glucose test or basic metabolic panel. Management is replenishing glucose via oral or IV route. 
  • Sedatives and hypnotics intoxication: Sedatives and hypnotics agents include benzodiazepines (BDZ), barbiturates, and non-BDZ. Medically, these substances are used as anxiolytic, hypnotics, anticonvulsant medications, and muscle relaxants. Symptoms include ataxia, short-term memory loss, and respiratory depression, similar to opioid intoxication. History and urine drug screen can distinguish sedative and hypnotic use from OUD; however, opioids are often taken with sedatives and hypnotics, resulting in synergistic effects. Treatment is supportive care, being wary of aspiration, respiratory failure, and cardiac arrhythmias.
  • Alcohol withdrawal: alcohol abuse is the most common substance abuse in the United States. Withdrawal symptoms occur after cessation or reduction in those with severe, chronic alcohol use. Clinically presents with tremors, nausea, psychomotor agitation, anxiety, and, in severe cases, seizures and hallucinations. Diagnosis is clinical and can be supported by using the Clinical Institute Withdrawal Assessment (CIWA) of Alcohol scale. Unlike opioid withdrawal, alcohol withdrawal can be fatal. Management includes benzodiazepines as well as supportive care. 


  1. Strain, E. (2020). Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis. UpToDate. Retrieved February 16, 2021, from https://www.uptodate.com/contents/opioid-use-disorder-epidemiology-pharmacology-clinical-manifestations-course-screening-assessment-and-diagnosis 
  2. Strain, E. (2020). Pharmacotherapy for opioid use disorder. UpToDate. Retrieved February 16, 2021, from https://www.uptodate.com/contents/pharmacotherapy-for-opioid-use-disorder 
  3. Sadock, B. J., Sadock, V. A., & Ruiz, P. (2014). Kaplan and sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (11th ed.). Chapter 20, Substance use and addictive disorders, pages 659-666. Philadelphia, PA: Lippincott Williams and Wilkins.
  4. Thompson, A. (2021). Clinical management of drug use disorders. DeckerMed Medicine. Retrieved February 16, 2021. doi:10.2310/im.13042
  5. Kumar R, Viswanath O, Saadabadi A. Buprenorphine. [Updated 2020 Oct 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK459126/
  6. Wesson, D. R., & Ling, W. (2003). The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs, 35(2), 253–9.

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