Estimating the Daily Milligrams of Morphine Equivalent of Illicit Fentanyl Use in Los Angeles: Clinical and Epidemiological Implications.

Introduction: The market shift from heroin to illicitly-manufactured-fentanyl in North America led to surging opioid mortality. However, limited information exists about the doses of illicit fentanyl regularly consumed. We examined purity of fentanyl samples and estimate the typical daily oral milligrams of morphine equivalent (MME). Methods: Leveraging community-based drug checking data from Los Angeles, we ascertained the purity of 509 samples of fentanyl collected between September 2023 and January 2026 using liquid chromatography mass spectrometry. We assessed typical consumption quantity and routes of administration among 47 respondents who reported regularly using fentanyl. We estimate bioavailability and MME conversion factors from literature. To estimate daily MME, incorporating all parameter uncertainty, we used a bootstrapping approach with 1,000,000 draws, with sensitivity analyses to assess the impact of factors including the correlation between purity and quantity. Results: Among participants, the mean daily consumption of fentanyl was 1.07 grams (95% prediction interval: 0.03g-4.00g). Illicit fentanyl products had a mean fentanyl purity of 12.47% (0.23%-38.80%), and the mean estimated bioavailability based on routes of administration was 50.82% (30.64%-76.75%). The mean estimated IV fentanyl to PO morphine MME conversion factor was 1 to 183.15 (71.85 - 294.21). The mean estimated daily consumption in our sample was 8,887.55 MME (156.56 MME-41,761.3 MME). Conclusions: Under all plausible estimation scenarios, individuals consuming illicit fentanyl in Los Angeles on average use a quantity of MME several orders of magnitude higher than clinical guidelines or typical methadone doses. This likely contributes to high overdose mortality, high opioid tolerance, and more difficult methadone and buprenorphine induction.