In April 2023, Mexico’s federal government closed the country’s only methadone manufacturing plant following concerns about quality control. In Mexican-U.S. border cities, such as Tijuana, where the prevalence of opioid use disorder (OUD) is among the country’s highest, the city’s four methadone clinics are turning new clients away, and for existing clients are limiting doses or not dosing altogether. Although there are no accurate estimates of the number of persons with OUD in Mexico, there were ~1000 adults receiving methadone in Tijuana alone at the time of the plant closure. Few empirical studies have been conducted on the impact of methadone dispensing interruptions but these have focused almost entirely on methadone prescribers, rather than people with OUD and have only examined short-term effects. We propose to leverage our existing cohort infrastructure in Tijuana to meet these Aims: 1) To qualitatively explore the experiences of adults in Tijuana receiving methadone for the treatment of OUD following the closure of Mexico’s only methadone manufacturing plant. 2) To prospectively characterize the impact of the closure of Mexico’s only methadone manufacturing plant on rates of drug use relapse, overdose (OD), suicidality, anxiety, depression and mortality among adults with OUD in Tijuana. Specifically, we will compare PWUD who have had their methadone treatment interrupted vs. those who have not and those who have never or not recently received methadone treatment. 3) To estimate the number of ODs and deaths caused by the closure of Mexico’s only methadone manufacturing plant among PWUD in Tijuana over the first month and first year after the closure using dynamic modeling. We hypothesize that PWUD with methadone treatment interruptions will have higher rates of drug relapse, OD, depression, anxiety, suicidality and death. We will re-open recruitment in the parent study to enroll 200 PWUD in Tijuana who were recently receiving methadone treatment, and compare outcomes to the existing cohort (N=250 for a total of N=450). Participants will undergo quantitative interviews every 6 months over 18 months. A subset will be purposively sampled for prospective qualitative interviews. Dynamic modeling will be used to estimate the impact of treatment interruptions on rates of overdose and mortality, and micro- and macro-level interventions that may be undertaken to ameliorate the crisis. Findings will be used to inform policymakers at the municipal, state and federal level in Mexico, as well the US and international agencies.