To some degree drug tolerance and addiction is suspected to be dependent on
long-term potentiation. NMDA receptors are
important in long-term potentiation, so some have suggested that PCP site antagonists may weaken LTP and thereby lower tolerance, and in a similar way break the "vicious cycle" of depression. This is all really beyond the scope of my understanding, so have a link:
http://www.bluelight.ru/vb/threads/467887-NMDA-antagonists-and-synaptic-plasticity
Related is the effect of NMDA antagonists in treating phantom limb pain and similar extra-sensory perceptual disorders. In short it seems like methoxetamine is actually able to make the brain forget its old limb. But let's make this all more general:
We've learned -- from treating depression to reducing tolerance to strange week-long afterglows of powerful dissociative experiences -- that PCP site antagonists have "lingering effects" that persist for up to several weeks after the drug has been cleared from the system.
The apparent tolerance reduction appears to be part of the lingering effects, especially since it dissipates after the dissociative is discontinued.
I'd be very very cautious about trying to use this for hedonistic ends for any long period of time. The bottom line is that we really don't know what's going on. I'm usually suspicious of "tolerance-lowering" efforts regardless of method: the goal seems to be to reinforce reckless behavior.
Incidentally, the fashionable term has gone from "non-competitive antagonist" to "uncompetitive antagonist" to "uncompetitive pore-blocker" and the receptor is either the NMDA glutamate receptor or the NMDA glutamate/glycine-linked ion channel, and, frankly, this is all a bit annoying, so I say PCP site antagonist, which is short and obvious.