Marijauna and DXM is a frequently used combination, albeit one which has
seen little research. Competitive NMDA blockade enhances marijuana
catalepsy (210), and conceivably noncompetitive blockade would as well.
Dizocilpine, a dissociative used in research, decreases the analgesic
effects of marijuana (214), and causes downregulation of anandamide
receptors (THC receptors) (218).
Dissociatives may block the depletion of 5HT (serotonin) caused by MDMA
(ecstasy) (241). However, there is also the potential for hypertensive
problems, so I wouldn’t advise this combination. Methamphetamine produces
vacuolation of neuron terminals due to a collapsed vesicular proton
gradient (181) (translated into English, this means that speed damages
brain cells by breaking open the little bubbles of neurotransmitters inside
the cells). However, dizocilpine (and presumably other dissociatives) may
prevent this (219). It also seems to block methamphetamine induced 5HT
depletion (241).
Antidepressants and dissociatives seem to interact as well, not necessarily
in a good way. Both desipramine and dissociatives increase prefrontal lobe
dopamine activity; the combination is highly synergistic (277). Even worse,
dissociatives may actually reverse the antidepressant effect (229).
Dizocilpine reduces 5HT2 receptor density (212), and increases 5HT binding
in the hippocampus and striatum (252). On the other hand, one paper found
that dizocilpine helped antidepressants in some tests (245,250).
Finally, dissociatives block tolerance to many drugs, including alcohol
(232), cocaine (247), nicotine (249), and morphine (248).
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