NMDA antagonist and tolerance reduction to drugs, does this occur for Benzodiazepines

[pofacedhoe]

If someone takes ketamine while on benzo's will it lower their tolerance the way it does with opiates etc.?

I'm coming form a point of view of could it help a taper scenario

 

[Cotcha Yankinov]

My personal bet is that ketamine would ultimately not help with a benzo taper. I think you could find yourself more anxious, more stimulated, more predisposed to psychosis/paranoia in the midst of an already sleep deprived state and to boot would likely have a lower seizure threshold, particularly with ketamine.

Some studies have shown that benzos block some effects of ketamine. One might then infer that some of ketamine's effects may be amplified during benzo withdrawal.

CY

 

[asecin]

would ketamine help with alcohol withdrawal, or the very least, keep a person off alcohol long term? im not sure how the OP come up with the idea ketamine lowers opiate tolerance though...

 

[Cotcha Yankinov]

I think there was a paper or two suggesting ketamine may help with some aspects of alcohol withdrawal. Alcohol does have some NMDA antagonist effects.

I believe delirium tremens is largely due to NMDA receptor upregulation

 

[asecin]

alcohol doesnt have just some NMDA antagonistic effect, it has a lot of it from what i gather. but i havent found a single report of ketamine being helpful when it comes to alcohol quiting. maybe it hasnt been tested yet is all...

 

[Limpet_Chicken]

There seems also to be a proglutamatergic rebound effect after EtOH consumption does there not?

These days I scarcely drink, just a few beers is enough for me, on my meds, the reason being that after the sedative effects wear off, alcohol causes me to experience 'head shocks' and greater tendency towards more seizures and if one does happen then makes for the event itself to be harder to treat. Its just one more reason I don't like alcohol much. There distinctly seems to be a post-use excitatory phase. Compensatory effect against the NMDA antagonism?

 

[Cotcha Yankinov]

I think there was some investigation into AMPA antagonists for use in alcohol/benzo withdrawal that showed promise, as a lot of benzo/alcohol withdrawal is indeed glutamate rebound. AMPA receptors certainly contribute to NMDAr activation as well.

I'm not quite sure about the brain zaps/cranial nerve zaps, alcohol is active at 5-HT3 and 5-HT3 is expressed on cranial nerves though, maybe there is a connection?

 

[Limpet_Chicken]

Heh in my case actually I might be in a position to rule it out. I have plenty ondansetron. And obviously, plenty access to off the shelf or clean EtOH (seriously, I don't get how people can STAND drinking, beer, etc. fine, but when it comes to spirits, I need it to be down in one swallow, or its going to come back up again seconds later. Hell I HAVEN'T had any alcohol, and all I did then was THINK of the smell of EtOH or (not that I'd drink it) iPA, and I just gagged reflexively. Its awful, that stink.

I don't RECALL any difference with alcohol whilst taking ondansetron, and indeed probably have used it as a primer, in order to be able to get the filthy stuff down and keep it there (its just one of those things...I've probably got weird tastes. I could LIKE the smell of gone-off SOCl2, almost (but not quite) but if it comes to booze...if I can smell it, I don't very much want to drink it.

80% or so and a one-shot dose is about the only way my insides will tolerate it. How strong, out of curiosity IS the the 5HT3 agonism from EtOH, and again, out of curiosity, is this lacking in diethyl or diisopropyl ether? I don't get the nasty ass brain zap type stuff with either.

 

[Cotcha Yankinov]

I think the 5-HT3 agonism is mostly prevalent at higher levels of alcohol consumption (the vomit inducing levels), but I've heard of brain zaps with non-serotonergic substances once or twice here on BL... Still surprising to hear about it with something that isn't a serotonin releasing agent or reuptake inhibitor. I suppose it could be related to a temporary shortage of 5-HT signaling after NMDA antagonist mediated 5-HT release, combo'd with some GABA-A withdrawal mediated glutamate release and dehydration?

Headaches/migraines are largely cranial nerve mediated so I suppose that may not be helping, compared to a similar acting substance that doesn't have the dehydrating/headache inducing effects.