Extreme opioid tolerance among illicit fentanyl users may be a major reason methadone induction has become more difficult in the fentanyl era, according to a study published June 9 in the Drug and Alcohol Dependence.
Researchers from University of California Los Angeles and University of California San Diego analyzed the purity of 509 fentanyl samples collected between September 2023 and January 2026 through Drug Checking Los Angeles, a community-based drug checking program, using liquid chromatography mass spectrometry. They also followed 47 participants who reported regular fentanyl use over a 30-day period to assess consumption patterns and routes of administration.
Here are four things to know:
- Typical illicit fentanyl users consume an average of nearly 9,000 milligrams of morphine equivalent (MME) daily. A high-end methadone dose of 180 milligrams equals only 846 MME, a small fraction of that intake.
- Researchers said the mismatch helps explain persistently low national uptake of medications for opioid use disorder despite methadone and buprenorphine being the best evidence-based treatments, according to the study.
- The typical illicit fentanyl product from Los Angeles tested just 12.47% pure, meaning a $100 gram of street product contains roughly 125 milligrams of active fentanyl. Among 47 survey respondents who reported regular use, average daily consumption was 1.07 grams of raw product, and 97.87% reported smoking or vaporizing as their primary route.
- Researchers said clinicians may need to consider higher induction and maintenance doses of methadone, or augmenting treatment with agents like slow-release oral morphine, to improve patient retention in medications for opioid use disorder treatment.
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