Dextrorphan is a metabolite of DXM (i.e., the body converts DXM to
dextrorphan). The conversion from DXM to DXO occurs via removal of the methyl group at position 6, a process called “O demethylation”. DXO is very similar chemically to DXM, and reacts with the same receptors in the body, but with a very different spectrum. Whereas DXM is strongest at the PCP2 and sigma receptors, DXO primarily targets the NMDA receptor (see Section 10).

The practical upshot is that the dissociative and intoxicating or “stoning” effects are stronger with DXO, whereas the stimulation, cognitive alterations, delusions, and psychotomimetic (literally, “psychosis-like”) effects are stronger with DXM. Most DXM users find some balance between the two to be the most pleasurable. Too much sigma activity is usually regarded as dysphoric (strongly unpleasant) and disturbing, and if prolonged, may be dangerous (101,135).

Fortunately, you don’t have to worry about converting DXM to DXO; the body does it for you via an enzyme called P450-2D6 or CYP2D6 (also called debrisoquine 4-hydroxylase). However, between 5 to 10% of the Caucasian population lacks this enzyme (12-15), and in the rest of us it can vary.  Many drugs can temporarily block P450-2D6 from working (10-11) and thus alter the balance between DXM and DXO. For a list of these drugs, see
Section 15.1.

One of DXM’s metabolites, 3-methoxymorphinan, can itself block P450-2D6.  As a consequence, taking a second dose some time after the first dose of DXM will probably increase the ratio of DXM to DXO in the bloodstream. Taking the dose all at once, on the other hand, will probably increase the relative amount of DXO. Generally, then, the quicker the dosing, the more DXO and less DXM, and the more NMDA blockade (like ketamine) and the less sigma and PCP2 activity. Subcutaneous injection leads to very little conversion from DXM to DXO.

When discussing effects, this text usually uses “DXM” to refer to both
dextromethorphan and its metabolite, DXO. A few people have used DXO specifically; one indicated that it did in fact have fewer cognitive
effects than DXM.

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