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Characterizing post-mortem blood concentrations in methadone-related deaths
Guido Pelletti1,2, Valentina Giunchi3, Paolo Fais4,5
1Department of Medical and Surgical Sciences, Unit of Legal Medicine, University of Bologna, Via Irnerio 49, 40126, Bologna, Italy.
International Journal of Legal Medicine
|October 8, 2025
Summary
Methadone diversion is rising. This study analyzed methadone-related deaths, finding overlapping therapeutic and toxic blood concentrations, especially with multidrug use. Findings aid forensic interpretation of methadone toxicity.
Area of Science:
- Forensic Toxicology
- Pharmacology
- Public Health
Background:
- Methadone is crucial for opioid addiction therapy but faces increasing global diversion.
- Determining methadone's role in deaths is complex due to tolerance and polysubstance use.
- Forensic interpretation of post-mortem methadone levels requires understanding demographic and clinical factors.
Purpose of the Study:
- To identify demographic, clinical, and therapeutic characteristics of methadone-related deaths.
- To support forensic pathologists in interpreting post-mortem methadone concentrations.
- To analyze the relationship between methadone blood levels and cause of death.
Main Methods:
- Systematic literature review of methadone-related deaths with post-mortem toxicology.
- Integration of reviewed data with 240 individual cases from literature and Bologna's Institute of Forensic Medicine.
- Analysis of demographic data, blood methadone concentrations, and co-intoxicants.
Main Results:
- Median blood methadone concentrations were 300 ng/mL (children) and 503 ng/mL (adults), overlapping with therapeutic levels.
- Higher methadone blood concentrations were found in deaths solely due to methadone compared to multidrug intoxications (p < 0.001).
- Significant overlap exists between therapeutic and toxic methadone blood concentrations, emphasizing risks of polysubstance use.
Conclusions:
- Methadone-related deaths present complex toxicological profiles due to overlapping concentration ranges.
- The study highlights the increasing risk associated with multidrug intoxications involving methadone.
- This comprehensive case review provides a valuable resource for forensic interpretation of methadone toxicity.
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