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Author: Subject: Natural equivalents of an antidepressant nmda antagonist
symboom
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biggrin.gif posted on 19-5-2020 at 16:05
Natural equivalents of an antidepressant nmda antagonist


So after doing a lot of research for antidepressants that I could help myself in I stumbled across dextromorphan (dxm).
The company Axome is trying a two-in-one pill of DXM and the common antidepressant bupropion for a new medicine called AXS-05 it consists of a proprietary formulation and dose of bupropion and dextromethorphan , or DM, ... defined as having TRD if they have failed two or more antidepressant therapies.

what's fascinating about this is the detachment from ones body. I got the idea that it could work when I realize my body can do the same thing such as the response of the fight, flight or freeze response natural of the body to deal with stressors. particularly the freeze response. I know it is not advisable to self experiment but in this case it was based on lots of research.
Along with deciding slowly what the theraputic index is for me. Making sure not to pass the point of intoxication so moderation is key in this regard.

Quote from Wikipedia
It has multiple mechanisms of action, including actions as a nonselective serotonin reuptake inhibitor and a sigma-1 receptor agonist. DXM and its major metabolite, dextrorphan, also block glutamate receptors at high doses, which produces effects similar to, yet distinct from, the dissociative states created by other dissociative anesthetics such as ketamine, nitrous oxide, and phencyclidine.


Here are promising canadates for a natural alturnative to dxm
These herbs effect glutamate and are nmda antagonists

Nmda antagonist of nature

Psychotria colorata

Psychotria lyciiflora

Calycodendron milnei

Tabernaemontana divaricata

Acourous calamus

Hodgkinsonia frutescens

Cats claw

Sophora flavescens

Corydalis yanhusuo

Glaucium flavum

Croton lechleri

Stephania rotunda

pukatea

Phellodendron amurense

Galbulimima belgraveana

Zizyphus jujuba

Cyperus articulatus

Bacopa monnieri

Searsia pyroides

This list originates from my post
http://www.sciencemadness.org/talk/viewthread.php?tid=81743#...

In that post it shows what chemicals are in each herb
Including those responsible for it's phychoactive effects

https://www.globenewswire.com/news-release/2019/01/07/168105...

Thank you in advance

[Edited on 20-5-2020 by symboom]

[Edited on 20-5-2020 by symboom]




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Classifying herbs based on neuroreceptor activation http://www.sciencemadness.org/talk/viewthread.php?tid=81743
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[*] posted on 19-5-2020 at 16:15


Robotripping as an antidepressant does not sound very good. I've never done dxm recreationally, nor do I ever plan to, but I can tell you first-hand; disassociating your life away really isn't a cure.

That being said, there's about as much good science behind DXM working as an antidepressant as there is science promoting SSRI's...

I've read stories about dude's getting brain damage from robotripping. Be careful.
Psychotropic drugs are really, really, REALLY complicated.




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[*] posted on 19-5-2020 at 16:24


Very true that's why it's only used as a tool I would use it for two days along with kava to relax the sign effects. This medication combo helped cure my severe depression of 10 years so I am excited that it worked. Following the theraputic index is very important in this regard. It will be of no use if it is passed and one become too intoxicated to even talk through therapy.

DXM is also effective in pseudobulbar affect
The crying or laughing may start as a response to a situation, such as a sad movie, but the feelings are more intense and last longer than expected. They're difficult or impossible to stop
Which if you can't express your feeling in therapy it's would be harder to get through so this tool is quiet useful but I bet nature has a ever better compounds with less sign effects.

I pretty much copied what the research says from axome. So I'm really glad they done that research along with already taking Bupropion i realize I'll give it a shot and used it to help me in talk therapy medication only gets you there 50 percent of the way talk therapy is the rest of it. It must be thought as a tool not for fun the way it is abused as this would make it ineffective.

I'm just putting prices of a puzzle together research that have already been made. Not very much is known about those nmda antagonist containing herbs.

[Edited on 20-5-2020 by symboom]
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[*] posted on 19-5-2020 at 17:09


I suspect that the new drug has DXM in it in virtual microdoses.
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[*] posted on 19-5-2020 at 17:25


NMDA antagonists aren't my thing, and I don't know if there is anything natural that would have an effect like the synthetic substances useful to treat depression.

I just wanted to remind you that nature has very effective antidepressants, just acting via 5HT in that case.
Thinking of psilocybe mushrooms, which are taken in microdoses daily for a few weeks or even up to a few months.
I tried that and it was massively helpful with an apparent effect, it did take a few days but then it improved each day a bit more over 2-3 weeks, and remained there a few months even after their use was stopped.
It is not want you look for of course, but it does work and it is natural.
You need to take a dose daily though, unlike these NMDA antagonists which probably act very long after a single dosage, at least that is what I read.
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[*] posted on 19-5-2020 at 17:37


I do understand that but the stigma of phychadelics makes it more harder to access those tools.
It's just one tool out of many everyone has a different defence mechanism which could hinder a patients progress in therapy.
Along with the so called bad trips that can happen with phychadelics even in a controlled environment can be damaging to the phyche especially if the person is hesatant to let go.


DXM is taken with Bupropion to prolong it's effect I think it also help by putting the person in a talkative positive state also called pressured speech. That I think Is very helpful side effect of the antidepressant stimulant to help a person in talk therapy.


Exactly
It is not want you look for of course, but it does work and it is
natural.
Everyone is different and different things will work for different people that may be due to a persons unique defence mechanism.

[Edited on 20-5-2020 by symboom]
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[*] posted on 20-5-2020 at 05:28


I have never seen any antidepressant based on NMDA receptors yet. Current antidepressants increase serotonin (SSRI, SARI, NaSSA), dopamine (NDRI), noradrenaline neurotransmission (NaSSA, NDRI). Also agomelatine is atypical antidepressant which normalizes circadian rhythm (like endogenous melatonin) which is impaired by depressive disorder. I'm also familiar with electroconvulsive therapy which we do not yet exactly know in details how does it work, but at the end it causes neuroregeneration - the same process as caused finally by antidepressants, by psychotherapy. Bupropion you mentioned is NDRI, it increases noradrenaline and dopamine neurotransmission by their reuptake inhibition.
The only effect of NMDA known to me used in medicine are antagonists of NMDA - ketamine, phencyclidine etc used in anaesthesia and memantine which slows down apoptosis of neurons as a treatment of dementia.
There are already supporting medicals based on EPA/DHA increasing the effect of major antidepressants, by my opinion eating sea food and sea fish is a supply rich enough for EPA/DHA better than pills (they seem to help to neuroregeneration).




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[*] posted on 20-5-2020 at 07:41


I don't know if DXM is good for this purpose, but what I'm interested in is ketamine microdosing. I have read, I don't remember where though, that ketamine when microdosed for short amount of time, let's say one week drastically improves one's mood and that it is effective in profound depression treatment, when normal medicines (SSRI's IMAO's) don't work.

I have some video on YT, it may seem little trivial, but certainly it does explain something:
https://www.youtube.com/watch?v=GnL4p-35Grg

What I remember is that NMDA receptor regulates the whole neuronal activity and when it is overactive, oxidative processes go faster in brain and it is unhealthy. But antagonisation of NMDA receptor decreases neuronal activity and after it ceases out, brain strives for balance and makes new neuronal pathways. I'm not sure if that is exactly, but maybe someone can tell me.

[Edited on 20-5-2020 by mackolol]
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[*] posted on 20-5-2020 at 08:56


I wasn't sure either until I saw a link for axome in which they use dextromorphan.
https://axsome.com/axs-pipeline/about-axs-05/

I think ketamine and dxm are similar in that they affect nmda receptors one of course stronger than the other as both are nmda antagonists.from personal experience I understand why it would be effective in helping you detach from your body a little for a patients therapy. I feel like it mimics the body's own ability to do so on it own. But it give the person more control of when it is appropriate to do so. I believe that's what neuro receptor is responsible when it happens in depersonalization/derealization. It the natural body response it turns off and on and is not consistent. I feel like it stresses the brain and activates it even when your not in danger as a natural defence mechanism. I believe it takes a lot of the brains internal resources in order to sustain that state.
So I am interested in understanding the nmda receptors better.

Maintaining the brains natural defence and coping mechanisms comes at a cost of the executive functioning part of the brain in order for the brain to compensate in maintaining enough energy to power everything. Which would explain why phychosis could eventually occur in people with severe depression.

Excerpt from website

AXS-05 is a novel, oral, investigational NMDA receptor antagonist with multimodal activity under development for the treatment of CNS disorders. AXS-05 consists of a proprietary formulation and dose of bupropion and dextromethorphan, or DM, and utilizes our metabolic inhibition technology. The DM component of AXS-05 is a non-competitive N-methyl-D-aspartate, or NMDA, receptor antagonist, also known as a glutamate receptor modulator. The DM component of AXS-05 is also a sigma-1 receptor agonist, nicotinic acetylcholine receptor antagonist, and inhibitor of the serotonin and norepinephrine transporters. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan, and is a norepinephrine and dopamine reuptake inhibitor, and a nicotinic acetylcholine receptor antagonist. AXS-05 is an investigational drug not yet approved by the FDA.

Besides ketamine it seems like dxm is another nmda bassed antidepressant although not as strong comparatively.
It's quite fascinating that there are multiple path ways for treatment serotonin nmda even some specific opioids although that would be more dangerous to use.

This is just my theory I have been wanting to find articles on this phenomenon to see if it confirms my theories but those damn pay walls.

[Edited on 20-5-2020 by symboom]
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[*] posted on 20-5-2020 at 10:07
DXM


DXM is a big nothing-burger unless one enjoys
doing the roboshuffle.

My take on DXM is it creates more hassles than it solves.:o




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[*] posted on 20-5-2020 at 11:22


I understand your point it might help some though of course not to the extent of intoxication such as cognitive and memory impairment and without causing hallucinations so you are right about that if your doing the roboshuffle you probably past the theraputic index levels which are much more narrow than serotonin based treatments. DXM would only be a hindrance in higher doses. I can see why serotonin is the preferred method of treatment I think it's theraputic index I much larger than a nmda antagonist but nmda antagonist antidepressants do show promise in treatment resistant depression. Which is the toughest thing for many clinicans to figure out what will work having the person eventually try multiple ineffective treatments.
Money is being spent on research in this there must be some potential in focusing on a different neuro receptor than serotonin.
Also there may be better natural nmda antagonists that arnt as intoxicating at higher doses and have a much wider theraputic index along with being safer phychologically by not putting a person under stress which can happen with phychadelics.

[Edited on 20-5-2020 by symboom]

[Edited on 20-5-2020 by symboom]

[Edited on 20-5-2020 by symboom]

[Edited on 21-5-2020 by symboom]
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