Calcium channel blockers and NMDA drugs

[StMorningGlory]

I'm a heavy user of calcium channel blockers (Gabapentin 1600mg a day) and I tend to really enjoy dissociative drugs. I have heard references to it being a dangerous combo. I also found this:
https://www.ncbi.nlm.nih.gov/pubmed/1791974

In addition I have noticed since being on Gabapentin that NMDA drugs are subjectively different. Does anyone have more info?

 

[Solipsis]

I think I've been on both dissociatives like 3-MeO-PCP, K or MXE before and on pregabalin and found it alright but somehow I can't be specific about my experiences with comboing as I never paid much attention to it.

That link doesn't seem to suggest much of anything relevant, what are your references to the dangers?

 

[Help?!?!]

I found with pregabalin in the mix especially at higher doses, they potentiate each other nicely. Very enjoyable.

 

[StMorningGlory]

I had actually meant to post this link: https://www.ncbi.nlm.nih.gov/pubmed/10462185?access_num=10462185&link_type=MED&dopt=Abstract

It shows, although moderate, there in an increase in certain activity "VSCC blockers exerted only modest interactions with the behavioral effects of dizocilpine, and it is unlikely that VSCC blockers have remarkable potential as adjunct treatment aimed at correcting the negative side effects of NMDA receptor antagonists (e.g., dizocilpine)."

 

[Cotcha Yankinov]

The study appears to be checking for VSCC blocker's potential as an adjunct to NMDA antagonists to reverse some of the negative effects of NMDA antagonism. What they mean to say is that VSCC blockers didn't do a great job of reversing the effects, although you can see that VCSS blockade by some agents diminished locomotor response/sensitization to NMDA antagonism.

That being said, its important to note that Gabapentin is selective for a alpha2delta on the voltage gated calcium channel, this will result in wildly different subjective effects than a true calcium channel antagonist. Overall, gabapentin will still have the effect of decreasing glutamate and NMDA receptor activation, but to some degree its increase in GABA synthesis may counteract a small portion of NMDA antagonism.

 

[StMorningGlory]

Thank you for the response, that seems to answer that there shouldn't be any specific known dangers to combing the classes of drugs.

 

[Cotcha Yankinov]

Not acute dangers I believe, but Gabapentin is known to dumb people down and NMDA antagonists are known to have effects on cognition when used chronically.

 

[Solipsis]

That is quite true but IMO of a different order: NMDA antagonists screw with my ability to plan, orient, to think clearly and effectively about where the hell i am, what's going on etc - pretty messed up. Benzos like clonazepam blank me out, i just feel like a zombie - destroy my memory even worse than dissociatives probably.
Pregabalin does dumb me down over time but it's subtle or at least manageable even with daily use. Less synapses formed limits you I guess... Less sharp but function is still consistent and integrated.

But messing up your glutamatergic system etc, that actually impairs and desintegrates your functioning which feels much more worrisome.

 

[StMorningGlory]

Is there a way to reverse the dumbing down? Will just reduction of use or abstaining from them reverse it?

 

[Solipsis]

No, gabapentinoids block calcium channels and that's where thrombospondin also binds, which is involved in creation of new excitatory synapses. So it's not a side effect that can be separated from the main mechanism of action. But if you stop using the gabapentinoid there should be no reason why thrombospondin can't do it's job again as well as before.
The brain is a plastic thing, there isn't really something like reversing or going back to how it was before per se, it will always develop in a 'forward' direction - but I couldn't say if that means soon you'd be back at the same number of synaptic terminals per neuron from compensating and returning to homeostasis or how quickly... but it seems to me that it would happen to some extent, that the neurons that fire together wire together until at an appropriate gain. Besides, the therapeutic effect isn't persistent either.

It seems very likely that the same story holds for phenibut by the way.