Opioid Use Disorder

Clinical picture

• Use escalates from prescribed or recreational opioids to daily dosing that prevents withdrawal, with most of the day spent obtaining and using.
• Intoxication brings miosis, sedation, slurred speech, and constipation, while overdose adds respiratory depression, cyanosis, and pinpoint pupils.
• Withdrawal begins 8 to 12 hours after short-acting opioids with lacrimation, rhinorrhea, yawning, myalgias, diarrhea, piloerection, and dysphoria.
• Withdrawal is rarely life-threatening but is intensely aversive, and fear of it sustains use more powerfully than the pursuit of euphoria.
• Injection use brings abscesses, cellulitis, endocarditis, hepatitis C, and HIV, so look for track marks and unexplained fevers or murmurs.
• Presentation often follows a crisis such as nonfatal overdose, incarceration, pregnancy, or an infection requiring hospital admission.

Criteria snapshot

• Requires at least 2 of 11 criteria in a 12-month period across impaired control, social impairment, risky use, and pharmacologic features.
• Severity is graded mild 2-3, moderate 4-5, or severe 6 or more, and most patients presenting to treatment meet the severe threshold.
• Tolerance and withdrawal are excluded from the count when opioids are taken as prescribed under appropriate medical supervision for pain.
• Craving is an explicit criterion and a practical treatment target that should be measured by self-report during induction and stabilization.
• Remission specifiers apply while a patient is on maintenance medication, since taking buprenorphine or methadone is not itself a criterion.

Neurobiology

• Mu-opioid receptor agonism in the ventral tegmental area disinhibits dopaminergic projections to the nucleus accumbens, producing reinforcement.
• Locus coeruleus noradrenergic rebound after chronic mu suppression generates the autonomic storm that characterizes opioid withdrawal.
• Neuroadaptation includes receptor desensitization, upregulated cAMP signaling, and blunted endogenous endorphin and enkephalin tone.
• Prefrontal hypofunction with amygdala and habenula hyperreactivity sustains compulsive use despite intact knowledge of the harms involved.
• Heritability approaches 50%, and OPRM1 A118G and stress-axis variants modestly shift risk, analgesic response, and dose requirements.
• Loss of tolerance after abstinence, combined with illicit fentanyl contamination, drives the sharp overdose spike after jail release or detox.

Psychology

• Negative reinforcement predominates: use terminates withdrawal, physical pain, and emotional distress, which powerfully strengthens the behavior.
• Early adversity and chronic pain are frequent antecedents, with opioids serving as an affect-regulation strategy when alternatives are absent.
• Delay discounting is steep, so immediate relief consistently outweighs the delayed cost of overdose, lost custody, or lost relationships.
• Identity, social network, and daily structure become organized around use, so recovery means rebuilding roles rather than only stopping the drug.
• Internalized stigma, including stigma about medication treatment itself, is a leading driver of premature discontinuation and dropout.

Differential & comorbidity

• Distinguish physical dependence from opioid use disorder, since dependence alone in an appropriately treated pain patient is not a diagnosis.
• Screen for stimulant, benzodiazepine, and alcohol co-use, all of which sharply increase respiratory depression and fatal overdose risk.
• Comorbidity with depression, PTSD, ADHD, chronic pain, and personality pathology is high, so treat concurrently rather than sequentially.
• Hepatitis C, HIV, infective endocarditis, and skin and soft tissue infections require routine screening and integrated medical care.
• Suicide risk is markedly elevated and overdose intent is often ambiguous, so assess intent directly and repeatedly at every visit.

Pharmacologic treatment

• Buprenorphine 8-24 mg/day is first-line partial agonist therapy with a ceiling on respiratory depression, and no special waiver is required.
• Induce at moderate withdrawal (COWS 8-12) to avoid precipitated withdrawal, or use a low-dose cross-taper when fentanyl exposure is likely.
• Methadone 60-120 mg/day through an opioid treatment program has the strongest retention data; monitor QTc and CYP3A4 interactions.
• Naltrexone XR 380 mg IM monthly requires 7 to 10 opioid-free days, and induction failure substantially limits its real-world uptake.
• Prescribe take-home naloxone to every patient and household, and counsel that medication reduces all-cause mortality by roughly 50%.

Psychotherapy

• Contingency management with escalating incentives has the strongest behavioral evidence for reducing use and improving retention.
• CBT with relapse prevention adds benefit to medication but does not substitute for it, since medication alone outperforms therapy alone.
• Motivational interviewing resolves ambivalence about starting medication and addresses internalized treatment stigma directly.
• Counseling should be offered and made accessible but never mandated as a condition of receiving buprenorphine or methadone.
• Family work and community reinforcement and family training (CRAFT) improve engagement of reluctant or ambivalent patients.

Adjunct options

• Syringe services, fentanyl test strips, and never-use-alone lines reduce infection and overdose deaths without increasing drug use.
• Recovery housing, peer recovery coaches, and mutual-help groups that accept medication, such as Medication-Assisted Recovery Anonymous, aid retention.
• Apply ASAM criteria for level of care, and use hospital bridge programs to start medication before discharge from acute care.
• Monitor with urine drug testing that includes fentanyl and xylazine, used therapeutically to guide care rather than punitively.
• In pregnancy, buprenorphine or methadone are standard; do not attempt withdrawal, and plan for neonatal opioid withdrawal syndrome.

Clinical pearls

• Buprenorphine and methadone cut mortality by about half; withholding them is riskiest.
• Never taper a pregnant patient off buprenorphine or methadone; maintain the dose.
• Overdose risk spikes after jail release or detox because tolerance is lost.