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It’s the result of interacting biological systems—energy metabolism, oxidative stress, immune signaling, and structural integrity—changing over time

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CYP2D6, CYP3A4 and CYP2B6 catalyze the metabolism of tramadol (Miotto et al., 2017) with the productions of O -desmethyltramadol (metabolite M1) via the O -demethylation reaction catalyzed by CYP2D6 and N -desmethyltramadol (M2) catalyzed by CYP2B6 and CYP3A4 ( Figure 3A )