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Nitrous Oxide, DXM & Ketamine scientifically safe to take with DMT for rats...

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fathomlessness

fathomlessness

Rising Star
Serotonergic Agents That Activate 5HT2A Receptors Prevent NMDA Antagonist Neurotoxicity

- In the present study we present evidence that serotonergic agents possessing 5HT2A agonist activity prevent NMDA antagonist neurotoxicity in rat brain. Among the 5HT2A agonists examined and found to be neuroprotective are LSD and related hallucinogens.

Nitrous Oxide anesthesia induces increases in NMDA receptor protein expression in the aged rat brain

- N-methyl-D-aspartate (NMDA) receptors (critical in learning and memory) that display protein expression changes with age are modulated by inhalation anesthetics
 
I'm shocked that this isn't getting more attention here on the Nexus :shock:

I can't access the full text right now, but looking at this abstract, I have a couple of questions:

1) Where on Earth did this idea come from?
2) What exactly where the measures of brain damage used (histological studies, I imagine, looking for Olney's lesions?)
3) What exactly do they mean by this:
It is proposed that 5HT2A agonists may also prevent the psychotomimetic effects of NMDA antagonists.
Click to expand...

Taking LSD on top of ketamine or PCP is not going to balence out the psychotic aspects - if anything, you'll probably be tripping harder on that combination than on either one separately.

I do have a study knocking around somewhere that showed that unmedicated schizophrenic patients had abnormally high levels of 5-HT2A receptors, so exposure to something like LSD might (MIGHT) have antipsychotic activity after the experience is over, once all the 5-HT2ARs have been downregulated, but certainly not during the immediate experience...

Also, this quote makes me raise an eyebrow
evidence linking their hallucinogenic activity to agonist action at 5HT2C receptors, whereas antipsychotic activity would be attributable to agonist action at 5HT2A receptors.
Click to expand...

Again, I can't see the full text, so I don't know what evidence they are citing, but the connection between psychedelic effects and the 5-HT2AR seems pretty solid to me. Does anyone know of a study in which 5-HT2C knockout mice were given psychedelics? Did their heads twitch?

Blessings
~ND
 
Nathanial.Dread said:
Taking LSD on top of ketamine or PCP is not going to balence out the psychotic aspects - if anything, you'll probably be tripping harder on that combination than on either one separately.
Click to expand...

not necessarily. some of the sensory feedback from LSD may be attributed to glutamate, and PCP strongly antagonizes this.
I can speak directly from experience.. although it was weird, there wasn't any potentiation.
 
benzyme said:
Nathanial.Dread said:
Taking LSD on top of ketamine or PCP is not going to balence out the psychotic aspects - if anything, you'll probably be tripping harder on that combination than on either one separately.
Click to expand...

not necessarily. some of the sensory feedback from LSD may be attributed to glutamate, and PCP strongly antagonizes this.
I can speak directly from experience.. although it was weird, there wasn't any potentiation.
Click to expand...
Could you speak more about that combination? What effects do NMDAr antagonists have on classical psychedelics? Is it less visual? Less profound? Less...?

Blessings
~ND
 
less emotional, i suppose. the visuals were not as vivid, though they were sharp and flowing with the characteristic 8mm film quality inherent with pcp experiences, rotating field of view. auditory was dull, mostly the high-pitch buzz of pcp. time didn't register, as you could imagine
the experience was not unlike an aya experience i once had, 15g chacruna, 90g caapi,

in conclusion, the LSPCP experience wasn't necessarily more intense, it was more of a combination of effects, with some turned down a notch (emotional, auditory/visual quality)
 
benzyme said:
less emotional, i suppose. the visuals were not as vivid, though they were sharp and flowing with the characteristic 8mm film quality inherent with pcp experiences, rotating field of view. auditory was dull, mostly the high-pitch buzz of pcp. time didn't register, as you could imagine
the experience was not unlike an aya experience i once had, 15g chacruna, 90g caapi,
Click to expand...
Hmm. Sounds like like the PCP is modulating the effect of the psychedelic a little bit, instead of vice versa. Emotional bluntness sounds about right.

Blessings
~ND
 
In my days of heavy NMDA antagonist abuse (pretty much just DXM, MXE, and ketamine where I could find it), I found that combining those drugs with tryptamines was as the kids say, the bomb. So, I guess maybe if I ever use dissociatives again, I will feel safer if I eat some mushroooms as well... beware of the interaction between NMDA antagonists and MAOIs though.
 
slewb said:
beware of the interaction between NMDA antagonists and MAOIs though.
Click to expand...

Aren't they completely unrelated neuronal systems?

Examples of monoamine transmitters are:
1) Catecholamines:
- Dopamine (DA)
- Norepinephrine (NE) aka Noradrenaline, (NA)
- Epinephrine (Epi) (adrenaline)

2) Melatonin

3) Histamine

4) Serotonin (5-HT)

5) Thyronamines, a group of compounds derived from thyroid hormones (still fairly new group this is)

6) Trace amines:
- β-Phenylethylamine (PEA, β-PEA)
- Tyramine
- Tryptamine


NMDA uses glutamate? So any increase in glutamate from MAOI is reduced by NMDA antagonism.

www.ncbi.nlm.nih.gov

Indantadol, a novel NMDA antagonist and nonselective MAO inhibitor for the potential treatment of neuropathic pain - PubMed

Indantadol is an oral and nonselective monoamine oxidase inhibitor and NMDA antagonist that is being developed by Vernalis plc, under license from Chiesi Farmaceutici SpA, for the potential treatment of neuropathic pain. In preclinical studies, indantadol exhibited neuroprotective effects after...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
 
MERGED

I seem to hear a lot of people say it "puts bubbles in your brain" "kills brain cellz" but with the evidence of what is going on with rats I would personally be inclined to think it isn't harmful at all on serotonergics like DMT.

Do you subjectively feel that this is a safe and wise combination for altering the nature or intensity of dimethyltryptamine?
 
In regards to MAOIs and NMDA antagonists, a good many NMDA antagonists are not highly selective and act as SERT & NET inhibitors, so they're serotonin/norepinephrine reuptake inhibitors. Which is not a good idea to take with a MAOI because it greatly increases the amount of neurotransmitters floating around your synaptic cleft.

Bottles of DXM cough syrup always warn not to take with MAOIs, and according to this paper, MXE, PCP, 3-MeO & 4-MeO-PCP shouldn't be any good either. Ketamine seems to be different in this regard, so I don't know what to say about it.
 
I got my hands on the full text paper, and while it's interesting, the first thing that jumped out at me is that they appeared to be looking at Olney's lesions in rats, and while psychedelics did limit the development of lesions, humans don't seem to get those, as far as we know, so generalizing this to our brains may be premature.

Blessings
~ND
 
Ketamine and nitrous are the only dissios thatbdoesnt feel like poison imo.
Ive tried most of them including the pcp analogues.

Im not sure if its the binding profile or the longer duration that cause this.
But i can be high on ketamine for a whole day then go training hard the next day as long as i mind hydration.
But with all the other ones i will feel like crap for a few days after.
 
kerelsk said:
In regards to MAOIs and NMDA antagonists, a good many NMDA antagonists are not highly selective and act as SERT & NET inhibitors, so they're serotonin/norepinephrine reuptake inhibitors. Which is not a good idea to take with a MAOI because it greatly increases the amount of neurotransmitters floating around your synaptic cleft.

Bottles of DXM cough syrup always warn not to take with MAOIs, and according to this paper, MXE, PCP, 3-MeO & 4-MeO-PCP shouldn't be any good either. Ketamine seems to be different in this regard, so I don't know what to say about it.
Click to expand...

So Ketamine & Nitrous Oxide is safe then? How intense is this neurotransmitter increase though? Are we talking serotonin syndrome or just sleep difficulties? Also those MAOI warnings are for standard MAOI not RIMA.
 
Nathanial.Dread said:
so generalizing this to our brains may be premature.
Click to expand...

Is that just because of the olney's lesions or is there some other reason you think it is premature to infer the brain activity is similar in comparison?
 
Olney's lesions were never found in humans, and, as Benzyme suggests, it's hardly a well-supported fact (and may be completely discredited). Consequently, looking at a paper that uses Olney's lesions as a measure of brain damage, or as a metric of how neuroprotective something may be, I'm hesitant to draw any strong conclusions.

Also, this paper only appears to have been cited 3 times, and there's been, to my knowledge, no attempt to replicate these findings, and from that fact alone I'm skeptical. One study making a very bold claim isn't 'proof' by any stretch of the imagination.

Blessings
~ND
 
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