Why does DXM Affect Different People So Differently?
Several reasons. First off, there is a liver enzyme known as cytochrome P450-2D6 (also CYP2D6, or debrisoquine 4-hydroxylase), which metabolizes DXM. Some people lack this enzyme, and of those who have it, subtle genetic variations can result in different activity (10-18). Thus, while one person may metabolize DXM quickly, another may not (there are other pathways which are much slower). Certain drugs – such as fluoxetine (ProzacTM) can inhibit this enzyme (39). A partial list of P450-2D6 inhibiting drugs is given in Section 15.1. Second, some of the effects of DXM are due to the DXM itself, and some are due to its metabolite dextrorphan (DXO), which is more similar to PCP and ketamine in its neuroreceptor activity (43). Some individuals may metabolize high doses of dextromethorphan to dextrorphan more quickly than others. Incidentally, my opinion – based on anecdotal evidence of recreational DXM use while on fluoxetine – is that both DXM and dextorphan are responsible for the psychoac
