Methadone plus a synthetic cannabinoid worsens cardiac repolarisation, hinting at a hidden overdose risk
- Mortality records of deaths involving synthetic cannabinoids flagged methadone as the co-detected medication most associated with QT risk, and fatal methadone levels looked lower in these mixed cases.
- In isolated guinea pig hearts, methadone alone lengthened the QTc interval, the cannabinoid 5F-ADB alone did not, yet together the effect grew.
- Modelling and patch-clamp work showed 5F-ADB blocks hERG only weakly, so the interaction likely involves more than direct channel inhibition.
💡 Points Based on the abstract
This probably is not a channel-block story: 5F-ADB barely touches hERG yet still amplifies methadone's QTc effect. A pharmacokinetic check comes first, namely whether the cannabinoid inhibits CYP-mediated methadone clearance and raises free exposure. Post-mortem levels are also prone to redistribution, so the lower fatal concentrations need a matched methadone-only control before anyone leans on them.