The Origins and Promise of Methadone Maintenance Treatment

Methadone is an opioid used in medical detox. Methadone maintenance (MMT) reduces the use of heroin and other opioids. Still, it is one of the most closely regulated medical treatments in the United States and also one of the most stigmatized, controversial, misunderstood, and effective medications. Approximately 400,000 people in the United States are treated with methadone yearly for opioid use disorder (OUD), yet as buprenorphine has become more widely used and prescribed, MMT remains stigmatized as a cheap opioid replacement treatment for poor or low-income people.

Methadone may only be dispensed through federally-regulated opioid treatment programs (OTPs), often requiring community clinic visits rather than to provider’s private offices, hospitals, and clinics.

The 1960s: Methadone As a New Treatment for Heroin Addiction

Methadone treatment for heroin addicts was spearheaded by the pioneering work of Vincent Dole, M.D., and Marie Nyswander, M.D., and researcher Mary Jeanne Kreek, M.D. Before their efforts, opioid addiction was perceived as an untreatable moral failing rather than an acquired disease. Dole, an internist and researcher at Rockefeller University, and Nyswander, a psychiatrist experienced in addiction treatment, were among the first to treat opioid dependence as a chronic, relapsing condition manageable with medication and therapy.

In 1964, Dole and Nyswander initiated their groundbreaking study using MMT to treat heroin addiction. The duo hypothesized methadone could stabilize individuals by replacing the missing opioids, mitigating withdrawal symptoms and cravings without producing the euphoric effects associated with heroin. At the same time, treatment helped them reintegrate into society.

Mary Jeanne Kreek, MD

Source: Rockefeller University

Mary Jeanne Kreek

Mary Jeanne Kreek. M.D., Dole, and Marie Nyswander found individuals with chronic heroin use were no longer able to obtain a high (euphoria) from heroin but were compelled to use it to avoid withdrawal and “function." Kreek's research was instrumental in shifting perceptions from opioid addiction as a behavioral issue to seeing the disorder as an acquired brain or neurobiological disorder, manageable with medication and rehabilitation.

“Addictions are diseases, they are diseases of the brain,” said Kreek. “They are not criminal behaviors, and they are not weaknesses. They, however, do respond to treatments—and it’s unfortunate that we have tools available to treat opiate addiction, but we’re not using them.”

Other MMT Pioneers: Herbert Kleber, Charles O’Brien, and Tom McLellan

The late Herbert Kleber, M.D., was another key figure in MMT. Kleber, who trained under Dole and Nyswander, advocated evidence-based approaches to addiction treatment. In the 1970s, Kleber directed the Substance Abuse Division at Yale University, where we researched the effectiveness of methadone maintenance, adding psychotherapy to MMT, treating concurrent depression, and then-experimental treatments like naltrexone.

Charles O'Brien MD, PhD , The Charles O'Brien Center for Addiction Treatment at the University of Pennsylvania Health System

Source: University of Pennsylvania School of Medcine

Charles O'Brien, MS, Ph.D., and Tom McLellan, Ph.D., helped solidify methadone's role as a safe and effective treatment for OUDs. O'Brien and McLellan were instrumental in developing protocols optimizing methadone dosing and administration, adding relapse prevention to MMPs, and strategies to reduce relapse. O'Brien's Penn addiction group demonstrated efficacy for Naltrexone as well. McLellan championed treatment plans, like those utilized in private drug rehabs, tailored to individual diagnoses and needs.

Methadone in the '70s to the Century’s End

In 1970, the federal government faced two major heroin-related problems: heroin use and associated crime were increasing, especially in urban areas, and secondly. Returning soldiers in Vietnam had been using heroin, and it was feared this could lead to a crime wave. MMT was seen as an option for both.

By 1972, the Food and Drug Administration (FDA) and the Drug Enforcement Administration (DEA) instituted regulations designed primarily to prevent methadone from being diverted to the street. Patients were required to receive medication under close supervision only at federally approved clinics and submit to regular urine testing.

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MMT devolved from a promising treatment for anyone with an OUD, as proposed by Dole, Nyswander, and Kreek, to a niche urban public program. Private patients voted with their feet going elsewhere, led by trend-setting celebrities with OUD.

COVID Strengthens Calls for MMT Changes

During the COVID-19 pandemic, temporary changes allowed for more take-home doses of methadone and telemedicine, highlighting that regulations can adapt to public health needs. The frequency of required clinic visits was reduced; for example, one study showed that patients receiving medication for two weeks rather than weekly doubled from 22% before COVID to 53% afterward. Researchers discovered regulatory relaxations did not lead to increases in methadone-related overdoses, diversion, or misuse.

The Methadone Situation Today

Both methadone and buprenorphine (the most prescribed and popular OUD treatment medication) are associated with reduced overdose and are used as first-line treatments for OUD. Any provider with a DEA registration Schedule III authority can prescribe buprenorphine and treat the OUD patient in a private office or clinic. In 2122 alone, buprenorphine was prescribed >16 million times. Unfortunately, methadone cannot be prescribed like this.

With the fentanyl crisis causing relapses, overdoses, deaths, and withdrawal distress, there have been calls to re-examine the feasibility of relaxing methadone restrictions. The National Institute on Drug Abuse (NIDA) has also recommended methadone be actively supported as a viable option for OUDs and that rigid restrictions be relaxed. Nora Volkow, director of NIDA, recently called to provide MMT in primary care settings and make it available in mobile units and pharmacies. Analysis of experiences during COVID-19 with changes in policy and practices of MMT support allowing MMT to become more commonly used, as are other treatment medications such as buprenorphine, naltrexone, long-acting injectable naltrexone, and long-acting injectable buprenorphine. It’s not only the poor and unemployed who may benefit from methadone therapy but also many others trapped in dependency on opioids.

Summary

Opioid use disorders and overdose deaths were rare in the 1960s when MMT was invented. Today, fentanyl has replaced heroin, OUD affects 2.1 million, and in 2023 alone, 108,300 people in the United States died of drug overdoses. It’s time to take another look at methadone.

Attitudes toward opioids, OUD, and methadone, in particular, have evolved. Research supports MMT treatment as an important option for preventing opioid-fentanyl overdose relapse and treating addictions to fentanyl and other opioids.