By Nora D. Volkow, MD

Director, National Institute on Drug Abuse (NIDA) at the National Institutes of HealthNIDA is the world’s largest funder of scientific research on the health aspects of drug use and addiction. 

Over the past several years, the increasing prevalence of fentanyl in the drug supply has created an unprecedented overdose death rate and other devastating consequences. People with an opioid use disorder (OUD) urgently need treatment not just to protect them from overdosing but also to help them achieve recovery, but highly effective medications like buprenorphine and methadone remain underused. Amid this crisis, it is critical that methadone be made more accessible, as it may hold unique clinical advantages in the age of fentanyl.  

Growing evidence suggests that methadone is as safe and effective as buprenorphine for patients who use fentanyl. In a 2020 naturalistic follow-up study, 53% of patients admitted to methadone treatment who tested positive for fentanyl at intake were still in treatment a year later, compared to 47% for patients who tested negative. Almost all (99%) of those retained in treatment achieved remission. An earlier study similarly found that 89% of patients who tested positive for fentanyl at methadone treatment intake and who remained in treatment at 6 months achieved abstinence.  

Methadone may even be preferable for patients considered to be at high risk for leaving OUD treatment and overdosing on fentanyl. Comparative effectiveness evidence is emerging which shows that people with OUD in British Columbia given buprenorphine/naloxone when initiating treatment were 60% more likely to discontinue treatment than those who received methadone.i More research is needed on optimal methadone dosing in patients with high opioid tolerance due to use of fentanyl, as well as on induction protocols for these patients. It is possible that escalation to a therapeutic dose may need to be more rapid. 

It remains the case that only a fraction of people who could benefit from medication treatment for OUD (MOUD) receive it, due to a combination of structural and attitudinal barriers. A study using data from the National Survey on Drug Use and Health (NSDUH) from 2019 (pre-pandemic) found that only slightly more than a quarter (27.8%) of people who needed OUD treatment in the past year had received medication to treat their disorder. But a year into the pandemic, in 2021, the proportion had dropped to just 1 in 5.  

Efforts have been made to expand access to MOUD. For instance, in 2021, the U.S. Department of Health and Human Services (HHS) advanced the most comprehensive Overdose Prevention Strategy to date. Under this strategy, in 2023, HHS eliminated the X-waiver requirement for buprenorphine. But in the fentanyl era, expanded access to methadone too is essential, although there are even greater attitudinal and structural barriers to overcome with this medication. People in methadone treatment, who must regularly visit an opioid treatment program (OTP), face stigma from their community and from providers. People in rural areas may have difficulty accessing or sticking with methadone treatment if they live far from an OTP. 

SAMHSA’s changes to 42 CFR Part 8 (“Medications for the Treatment of Opioid Use Disorder”) on January 30, 2024 were another positive step taken under the HHS Overdose Prevention Strategy. The new rule makes permanent the increased take-home doses of methadone established in March 2020 during the COVID pandemic, along with other provisions aimed to broaden access like the ability to initiate methadone treatment via telehealth. Studies show that telehealth is associated with increased likelihood of receiving MOUD and that take-home doses increase treatment retention. 

Changes implemented during the COVID pandemic have not been associated with adverse outcomes. An analysis of CDC overdose death data from January 2019 to August 2021 found that the percentage of overdose deaths involving methadone relative to all drug overdose deaths declined from 4.5% to 3.2% in that period. Expanded methadone access also was not associated with significant changes in urine drug test results, emergency department visits, or increases in overdose deaths involving methadone. An analysis of reports to poison control centers found a small increase in intentional methadone exposures in the year following the loosening of federal methadone regulations, but no significant increases in exposure severity, hospitalizations, or deaths.  

Patients themselves reported significant benefits from increased take-home methadone and other COVID-19 protocols. Patients at one California OTP in a small qualitative study reported increased autonomy and treatment engagement. Patients at three rural OTPs in Oregon reported increased self-efficacy, strengthened recovery, and reduced interpersonal conflict. 

The U.S. still restricts methadone prescribing and dispensing more than most other countries but worries over methadone’s safety and concerns about diversion have made some physicians and policymakers hesitant about policy changes that would further lower the guardrails around this medication. Methadone treatment, whether for OUD or pain, is not without risks. Some studies have found elevated rates of overdose during the induction and stabilization phase of maintenance treatment, potentially due to starting at too high a dose, escalating too rapidly, or drug interactions.  

Although increased prescribing of methadone to treat pain two decades ago was associated with diversion and a rise in methadone overdoses, overdoses declined after 2006, along with methadone’s use as an analgesic, even as its use for OUD increased. Most methadone overdoses are associated with diversion and, less often, prescription for chronic pain; currently, 70 percent of methadone overdoses involve other opioids (like fentanyl) or benzodiazepines.ii  

Recent trials of models of methadone dispensing in pharmacies and models of care based in other settings than OTPs have not supported concerns that making methadone more widely available will lead to harms like overdose. In two feasibility studies, stably maintained patients from OTPs in Baltimore, Maryland and Raleigh, North Carolina who received their methadone from a local pharmacy found this model to be highly satisfactory, with no positive urine screens, adverse events, or safety issues. An older pilot study in New Mexico found that prescribing methadone in a doctor’s office and dispensing in a community pharmacy, as well as methadone treatment delivered by social workers, produced better outcomes than standard care in an OTP for a sample of stably maintained female methadone patients.  

Critics of expanded access to methadone outside OTPs sometimes argue that the medication should not be offered without accompanying behavioral treatment. Data suggest that counseling is not essential. In waitlist studies, methadone treatment was effective at reducing opioid use on its own, and patients stayed in treatment. However, counseling may have benefits or even be indispensable for some patients to help them improve their psychosocial functioning and reduce other drug use. How to personalize the intensity and the level of support needed is a question that requires further investigation.  

Over the past two decades, the opioid crisis has accelerated the integration of addiction care in the U.S. with mainstream medicine. Yet methadone, the oldest and still one of the most effective medications in our OUD treatment toolkit, remains siloed. In the current era of powerful synthetic opioids like fentanyl dominating the statistics on drug addiction and overdose, it is time to make this effective medication more accessible to all who could benefit. The recent rules making permanent the COVID-19 provisions are an essential step in the right direction, but it will be critical to pursue other ways that methadone can safely be made more available to a wider range of patients with OUD. Although more research would be of value, the initial evidence suggests that providing methadone outside of OTPs is feasible, acceptable, and leads to good outcomes.