galantamine and DXM

[tantric]

my instinct is that messing with acetylcholine is BAD NEWS...but i'd like an expert's opinion on the potential interactions of this 'safe' acetylcholinesterase inhibitor and DXM...(the point being to remember more of high dose DXM trips)

 

[dopamimetic]

Don't do it. I can't say for sure, but even though DXM antagonizes some ACh receptors, it will lead to increased cholinergic activity - this is in fact one of the speculated reasons for long-term neurotoxicity in e.g. heavy ketamine users. So definitely not a good thing to try. Combination with an anticholinergic on the other side is safe (as long as you don't do stupid things because of too high dosing and delirium, that is).

Take care.
-dopa

 

[aced126]

May I ask what would be the reason of taking an anticholinergic along with DXM? Just neurotoxicity prevention?

 

[dopamimetic]

Some people like how the antihistamines (diphenhydramine is the most used) alter the trip. Haven't tried it personally, could easily become dangerous because of loosing contact with reality and such, but if one takes the right dose I'd expect a dream-like experience with e.g. realistic CEVs ... at least this is what I've extrapolated from reports.

 

[Memantine]

Cerebrocortical GABAergic neurons in the posterior cingulate and retrosplenial cortex get disinhibited in respons to NMDA blockade. And that in turn leads to an excessive release of acetylcholine leading to excitotoxicity.

NMDA antagonist neurotoxicity(NAN) is reduced by GABAergic agents, mAChr antagonists and alpha2-adrenergic agonists.

Galantamine on the other hand is expected to increase NAN.

 

[serotonin2A]

Cerebrocortical GABAergic neurons in the posterior cingulate and retrosplenial cortex get disinhibited in respons to NMDA blockade. And that in turn leads to an excessive release of acetylcholine leading to excitotoxicity.

NMDA antagonist neurotoxicity(NAN) is reduced by GABAergic agents, mAChr antagonists and alpha2-adrenergic agonists.

Galantamine on the other hand is expected to increase NAN.

Actually, the mechanism is slightly different. Blocking NMDA receptors reduces the activation of GABAergic interneurons, which disinhibits glutamatergic and cholinergic signalling. Disinhibiting GABA neurons woukd tend to block the toxicity. Ultimately I think the toxicity is primarily due to glutamate activating AMPA receptors because AMPA antagonists block the response.

 

[Memantine]

So reduced activation of GABAergic interneurons reduces the release of GABA onto GABA inhibitory receptors on glutamate and ACh releasing neurons resulting in an increased release of glutamate and ACh?

 

[serotonin2A]

^Yes, it has been known for some time that ketamine and PCP increase the release of glutamate and other transmitters through disinhibition. The particular neurons that degenerate are probably just unusually sensitive.

 

[Solipsis]

Does that also imply it's possible that via that way one may therapeutically prune those neurons if they are one of the causes of dysfunction or a disorder? The ethics of forms of chemical lobotomy are another matter of course... Or the price to pay for what sounds like chronic or permanent desensitization.

 

[tantric]

the point: someone asked if there was any way to remember more of high plateau DXM experiences. given how galantamine works with dream recall i considered it until i read how it works, then sought expert opinion. thanks, kudos, harm reduction all the way.

 

[dopamimetic]

Does that also imply it's possible that via that way one may therapeutically prune those neurons if they are one of the causes of dysfunction or a disorder? The ethics of forms of chemical lobotomy are another matter of course... Or the price to pay for what sounds like chronic or permanent desensitization.

That's a really interesting question indeed. If the acute effects of a dissociative are overly relieving, and chronic use of such one leads to a quasi-permanent state of the former, so this could really make sense ....... but there are all the papers about schizophrenia models based on ketamine and PCP. Then again, they use healthy rodents to try this on, and when I presume to have some weird opposite-of-schizo genetics, well ... no clue, but interesting.

An interesting thing is that tobacco, but not pure nicotine from e-cigarettes, gives a quite heavy boost to the effects of e.g. ketamine. But it's also short-lived, could be related to the harmala alkaloids in tobacco? Every time I've smoked a cigarette when on a low, sub-threshold dosage of a dissociative, after a few puffs I felt waves of pure euphoria, tingles all over and sometimes just had to smile without reason ... nice, but weird .. Have to say that I'm a light to non-smoker usually.

Edit: The problem I see here is that the long-term changes seem to at least partly related to loss of GABAergic neurons. This means more excitation and will probably make things worse in the sober state, the loss of inhibition will only feel good as long as the NMDAR's are blocked ... or am I wrong?

 

[Memantine]

I think it's not the loss of GABAergic neurons but rather the loss of glutamate/acetylcholine neurons.

Also i believe that there is some sort of NMDA/AMPA upregulation in response to chronic antagonism so yes you brain will probably be more "excitable" for some time.