The data above showing the ceiling effect of mitragynine in respiratory depression together with previous reports suggesting the need of metabolic conversion of mitragynine to 7‐OH mitragynine by CYP3A to induce anti‐nociception (Kruegel et al., 2019) led us to hypothesise that such metabolic conversion is also required to mediate the respiratory effects of mitragynine and underlies the built‐in ceiling for the effects of this compound. Here, CYP3A4 is linked to Respiratory insufficiency due to muscle weakness.