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Opioids relieve pain but are dangerous and highly addictive. In a recent 12-month period, there were 109,600 USA drug-overdose deaths, with 70% linked to opioids. In 2023, 5.7 million people in the U.S. 12 years and older had an opioid use disorder (OUD).
Despite high numbers of opioid abusers needing treatment, most don’t receive it. Some can’t find it, others delay treatment, and others refuse it. In 2022, only about 25% of U.S. adults with OUDs received medication-assisted treatment (MAT) like methadone or buprenorphine.
Some people with OUD receive methadone at one of the 1,500 methadone maintenance treatment (MMT) clinics in the United States. Drs. Vincent Dole and Marie Nyswander pioneered MMT, conceptualizing OUD as a chronic, metabolic disease in the mid-1960s. They argued long-term medication was a necessary medical treatment for OUD, just as insulin is for type 1 diabetes. Drawing on Dole’s background in endocrinology and metabolism, the researchers theorized OUD caused permanent changes in brain and body chemistry. They called this a “persistent derangement” of the opioid receptor system. This defect, they believed, was the source of intense, persistent cravings leading to relapse even after addicts detoxified from the drug.
Instead of seeing addiction as an intractable character flaw, they argued it should be treated as a medical condition. They found methadone could stabilize the “metabolic defect” by suppressing cravings and blocking the euphoric effects of other opioids, enabling individuals to function normally. In 1976, Dole and Nyswander addressed the common criticism that MMT was merely substituting one opioid drug for another. They wrote that critics failed to consider the “analogous long-term use of other medications such as insulin and digitalis in medical practice.” By proving that MMT could help formerly addicted people return to school, get jobs, and reintegrate into society, their research provided a powerful rebuttal to the moralistic view of addiction.
Methadone is a long-acting, orally administered opioid that doesn’t provide the euphoric rush of other opioids, but is safe and effective as a treatment for OUD and prevents withdrawal symptoms. Some experts (including me) believe addiction physicians should be allowed to prescribe methadone, like they prescribe buprenorphine, to be filled at local pharmacies.
After Treatment Stops
Even when buprenorphine or methadone is used for an OUD, it’s important to consider what happens to people if treatment ends. In a recent New England Journal of Medicine paper, A. Thomas McLellan, Ph.D., Professor at the University of Pennsylvania, and Nora D. Volkow, M.D., Director of the National Institute on Drug Abuse, proposed a patient-level “cascade of care” for OUD with three sequential goals: Protection → Remission → Recovery.
McLellan and Volkow argue that recovery can occur while individuals stay on medication-assisted treatment with methadone or buprenorphine. They contend that abstinence is neither necessary nor sufficient for recovery from an OUD. They also argue that abruptly stopping medication treatment for lack of progress or other reasons is dangerous.
Benjy Primm, MD, Herb Kleber, MD, and I have long agreed, arguing for broad patient access to methadone and buprenorphine. I reviewed in detail the successes of methadone maintenance treatment since its initiation in the 1960s. Approximately 400,000 people in the United States are treated with methadone yearly for OUD, yet buprenorphine is more widely prescribed.
After diagnosis or intervention, the first goal should be to focus on overdose protection. That means as soon as the OUD diagnosis is made, medication treatment should be started, to prevent overdose as well as risks for infection with HIV and other diseases from dirty needles to inject drugs. Treatment with methadone or buprenorphine focuses on preventing overdose, preserving life, and keeping people in the program.
Ideally, the person with OUD has a remission of addiction or a significant, sustained reduction in OUD symptoms. This result would occur because of daily MAT dosing as well as engaging the person in psychosocial rehabilitation support.
It’s important to understand opioids induce changes in the brain not reversible by abstinence. The main problem occurs when people with OUDs go off treatment. The overdose mortality risk is 3–4x higher after detox, compared to when retained on buprenorphine or methadone; retention alone is strongly protective. In contrast, after discontinuation of opioid treatment drugs, the relapse risk rebounds quickly—especially in the first month, when even a previously low dose of the drug can kill users because of their now much-lower tolerance to the drug.
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Within this system, remission is possible, and the individual may have a sustained, stable recovery after 12 months. With opioid use disorders, in contrast to addiction with cocaine, methamphetamine, cannabis, or even alcohol, there should be a clear initial treatment focus, which, above all else, prevents overdose deaths.
Why So Many People With OUDs Say No to MAT-Providers
Several factors limit access to medications for OUD. According to a CDC study, approximately 43% of adults needing OUD treatment did not agree they needed it. I see MMT retention as life-saving, but they may view it as continued chemical slavery. They may also choose buprenorphine because it’s easier to stop taking than methadone. Physician and program preferences can play a role, too.
The recent McLellan/Volkow NEJM article is a reminder that Dole and Nyswander were correct in suggesting we didn’t (and still don’t) have a way to reverse opioids’ effects on the brain. We need to finally reject time-limited detox for OUD as a primary treatment goal and not stop medication with imperfect progress. Patients should be referred to higher-intensity residential services if needed.
Brian Fuerlein, MD, PhD, notes in the Yale Emergency Room that many patients are rescued with Narcan, leave, and refuse other treatment. Doctors try to use this teachable moment to engage the person, family, and other loved ones in an intervention to start buprenorphine immediately. It’s unclear what to do about treatment refusal and early dropouts, other than establishing rapport and trust, and working together to reduce overdoses among persons unready for treatment.
Conclusions
Dole and Nyswander theorized in the 1960s that OUD was a chronic “metabolic disease” involving permanent physiological changes. They concluded abstinence was unrealistic because the metabolic deficiency would persist. Therefore, they advocated for MMT as a long-term, often life-long treatment to stabilize this condition. There is no arbitrary time limit, and treatment should continue as long as it’s beneficial to the patient and recovery doesn’t require tapering of opioids. We need to face reality, confront the conditions experienced by people addicted to opioids, and help them stay alive, adapt, and recover.
We don’t have treatments like penicillin for strep throat. Relapse is common, residual problems often persist, and treatment-resistant opioid use disorder is also reported.
