Written by Elizabeth Cairns, Mobilize Recovery Special Projects and Michael Masiowski, MD, reviewed by Code Recover Clinician Advisors, August 2026

Dr. Lindsey Jennings talks about how to start a patient on buprenorphine in the ED.

Medication for Opioid Use Disorder (MOUD) is the most effective tool for improving outcomes in OUD patients. The landmark trial establishing this in the emergency setting was published in JAMA in 2015: D'Onofrio and colleagues randomized 329 ED patients with opioid dependence to one of three arms — referral to treatment, a brief intervention with facilitated referral, or ED-initiated buprenorphine with continuation in primary care. At 30 days, 78% of patients who received ED-initiated buprenorphine were still engaged in treatment, compared to 37% of those given a referral alone. (source) The three medications approved to treat OUD — buprenorphine, methadone, and naltrexone — differ in mechanism, regulatory structure, and practicality in the ED, but the evidence supporting medication over referral alone is not in dispute.

Buprenorphine is a partial agonist that binds to the opioid receptors, blocking cravings and preventing withdrawal without producing a significant high. Its high affinity for the mu-opioid receptor makes it safer than full agonists and ideal for ED induction.

Buprenorphine's ceiling effect makes respiratory depression far less likely than with full agonists, and clinically meaningful respiratory suppression is rare when used as directed. That protection is reduced, however, when buprenorphine is combined with benzodiazepines or other sedatives — a combination that carries an FDA boxed warning. Importantly, the FDA has been explicit that this risk should not be a reason to withhold MOUD from patients who take benzodiazepines; the risk of untreated OUD is greater, and careful monitoring, not avoidance, is the appropriate response. (source)

Methadone is a full opioid agonist that occupies the same mu-opioid receptors as heroin or fentanyl, suppressing withdrawal and cravings without producing the same euphoria when taken as prescribed. Vincent Dole and Marie Nyswander first reported methadone maintenance as a treatment for heroin addiction in JAMA in 1965, (source) and for decades afterward methadone was the mainstay of pharmacologic OUD treatment, well before buprenorphine came along. Methadone is dispensed daily at licensed opioid treatment programs (OTPs), with patients earning take-home doses over time as they stabilize — a structure rooted in its overdose and diversion risk as a full agonist. (source)

Because of this strict regulation, methadone generally cannot be "started" in the ED for long-term OUD treatment. (source) However, under the federal "three-day rule," an ED clinician can dispense up to a three-day supply to relieve acute withdrawal while arranging a transition to ongoing care at an OTP — a practical bridge that keeps a patient stable during the gap between the ED visit and their first clinic appointment. (source)

Naltrexone (not to be confused with overdose reversal agent naloxone) is a full antagonist that requires a patient to be 7–10 days opioid-free, making it difficult to initiate in an acute ED setting. Once detox is complete, the monthly injectable formulation has been shown to control opioid cravings and prevent return to use. (source) Naltrexone is also FDA-approved for treatment of alcohol use disorder.

For the ED clinician, buprenorphine is the primary tool — the only one of the three that can be initiated on the spot, in a single visit, for a patient in moderate withdrawal. This approach is now considered best practice and standard of care. (source)

Dr. Nasir Naqvi talks about MOUD, including buprenorphine induction.

The Myth of "Substituting One Drug for Another"

Dr. Arianna Campbell talks about the importance of listening to the evidence about MOUD, not the myths.

Arguments against treating OUD with medications—often dismissed as merely "substituting one drug for another"—are rooted in stigma, misinformation, and a misunderstanding of the physiological basis of addiction. Critics, including some healthcare providers and recovery community members, fear continued dependency, diversion of medication, and potential impairment. This misconception exists despite robust evidence that MOUD reduces mortality: a systematic review and meta-analysis of cohort studies found that all-cause and overdose mortality are substantially lower during opioid agonist treatment than out of it. (source)

Arguments against this substitution mindset and in favor of MOUD include:

• Dependence: Critics argue that because patients depend on the medication, they are not truly in recovery. However, experts distinguish between physical dependence (the body needing medication to function normally) and addiction (compulsive drug seeking despite harm). MOUD restores brain function, allowing patients to live productive lives, whereas illicit opioid use is linked to dysfunction and overdose.
• Abstinence: Some believe that total abstinence is the only path to recovery and that medication is incompatible with abstinence. In fact, MOUD stabilizes the patient without a high, allowing them to begin the social and emotional work of recovery. SAMHSA is explicit on this point: patients taking FDA-approved medication to treat OUD can be considered in recovery. (source)
• Safety: While illicit opioid use is often unsupervised and carries a high risk of overdose, methadone and buprenorphine are approved, evidence-based treatments that prevent withdrawal and cravings without causing impairment, when taken as prescribed. Both medications have excellent safety profiles. (source)
• Diversion: Critics cite the risk of buprenorphine being diverted to the illegal drug market. However, a review of 17 studies found that most people using non-prescribed buprenorphine do so to manage withdrawal symptoms or to maintain abstinence from other opioids — not to get high. (source) In one survey of people using opioids non-medically, only 12% reported using diverted buprenorphine to get high, while 40% used it to manage withdrawal and 39% to self-treat their opioid use disorder. (source) Diversion, in other words, is largely a symptom of inadequate access to treatment — not evidence against providing it.
• "Opening the Floodgates": Some providers fear that offering MOUD in the ED will attract a difficult, unmanageable patient population. In fact, MOUD is the gold standard of care and offers improved outcomes for what historically has been a difficult-to-treat patient population. ED-initiated buprenorphine has also been shown to be cost-effective compared with referral alone. (source)