NMDA Antagonist reverse withdraws and up regulate receptors

Does anyone else know about this.  There has been studies that using NMDA Aganostic if taking with dose can up regulate your gaba receptors and prevent tolerence which also lowers withdraw symptoms.  Drugs list Ketamine and Tramadol.  Dextromethorphan is also an NMDA Antagonist which is in OTC cough medicine.  NDMA antagonist prevent glutamate from flooding the system

Can you point to a research publication on this?

Don't know much about Ketamine but Tramadol is bad news, IMO. At a very low dose ceiling it decreases the seizure threshold - I wouldn't recommend it to anyone tapering or in early recovery. It also has a horrible W/D profile. DXM could be promising.

NMDA AND BENZODIAZEPINE TOLERANCE

NMDA antagonists have been shown to interfere with tolerance to benzodiazepines.

Pretreatment with either MK-801 or ketamine blocked tolerance to chlordiazepoxide-induced

motor impairment in rats tested on the tilt plane test, but this effect was dependent

on the dose ratio of the NMDA antagonist to that of the benzodiazepine (45). Thus, this

blockade was observed only when relatively low doses of chlordiazepoxide were used.

When a higher dose of this drug was used, MK-801 or ketamine failed to block chlordiazepoxide

tolerance. This study agrees with previous data demonstrating that NMDA antagonists

blocked cross-tolerance between chlordiazepoxide and ethanol in either direction

(53). The effect of NMDA antagonists on tolerance to benzodiazepines was also

observed in other studies. File and Fernandes (22), reported that pretreatment with

MK-801 blocked tolerance to the decrease in the number of head dips, and probably to the

decrease in ambulation produced by diazepam in rats tested in the hole-board apparatus.

The development of tolerance to the locomotor activity reduction induced by diazepam in

mice was prevented by treatment with the NMDA antagonist CPP [(3-((±)-2-carboxypiperazin-4-yl)propyl-1-phosphonic

acid)] (97).

CNS Drug Reviews, Vol. 5, No. 2, 1999

NMDA ANTAGONISTS AND TOLERANCE 169

As mentioned before, tolerance may have learned and unlearned components. Although

some studies have shown that NMDA antagonists preferentially block learned tolerance

to ethanol (56,99), NMDA antagonists were demonstrated to block both learned

and unlearned tolerance to chlordiazepoxide. Rats pretreated with MK-801 or ketamine

before chlordiazepoxide and returned to their cages exhibited reduced tolerance as compared

with control animals (45). These results would suggest that in addition to the impairment

of memory and learning, NMDA antagonists may also influence drug-receptor

interaction or effector mechanisms leading to the blockade of tolerance.

Additional evidence for the involvement of NMDA system in the tolerance to benzodiazepine

effects comes from a study on the protective effects of lorazepam against pentylenetetrazole

convulsions in mice. After 14 d of lorazepam administration complete tolerance

to its anticonvulsant effect developed. The concomitant administration of CPP and

lorazepam resulted in partial blockade of tolerance to the seizure protective effect of

benzodiazepines (61). Chronic administration of lorazepam caused a significant reduction

in in vivo binding of [3H]flumazenil in cerebellum, hippocampus and hypothalamus. This

reduction was not affected by the simultaneous treatment with CPP, suggesting that the behavioral

effect of the NMDA antagonist was not directly related to the downregulation of

benzodiazepine receptors (61).

Marin et al. (74) investigated the hippocampal synaptic plasticity during the development

of rapid benzodiazepine tolerance. At the third and fourth days of treatment with

diazepam, the tolerance to the reduction in locomotor activity of rats was developed. In

hippocampal slices obtained from these rats, increased synaptic plasticity, assessed by the

lower threshold needed to induce long term potentiation, was observed. The authors suggested

that these findings were in agreement with the hypothesis proposing that NMDA

receptors participate in learned tolerance (50).

NMDA AND BARBITURATE

I brought this up in another thread but it was suggested I open a new discussion for this topic.

 

I have recently been studying the use of NMDA antagonists for reversal of benzodiazepine withdrawal symptoms. This came up through some study and some personal experience with both tapered and cold turkey withdrawals.

 

The cold turkey experience I had was with alprazolam when I was living in India. I had been getting as many alprazolam tablets as I wanted from chemists without scripts so i developed a high tolerance over about 6 months. When the laws changed I couldn't access it anymore and had to go cold turkey. That was one of the most difficult and long withdrawals I have ever had.

 

The tapering experiences I've had were on nitrazepam and clonazepam (current). The nitrazepam taper went well to a certain point but I couldn't get below 5mg. By coincidence I had been prescribed tramadol at the same time. I started taking tramadol for an unrelated issue and forgot to take my nitrazepam and got NO withdrawal symptoms. I thought it was coincidence but after reading further I found that tramadol is a slight NMDA antagonist.

 

Although it is understood that NMDA antagonists can prevent glutamate from flooding the system, it is not mainstream practice to use NMDA antagonists to prevent or reduce withdrawal symptoms in benzo withdrawal.

 

It would be great to hear any opinions, experiences or research in this area.

 

I read on another benzo withdraw forum that a low dose of DXM will lower tolerence, lesson withdraws and stop glutimate from flooding the system .  30 to 60 mgs of DXM daily

Interesting stuff, but one needs to be careful tinkering with these chemicals and systems.

 

... from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805709/

 

Despite possessing a significant antidepressant potential, most of the NMDA receptor inhibitors given at pharmacologically active doses induce severe undesirable reactions because of which they cannot be used in the treatment of patients with mood disorders (Farlow 2004; Tricklebank et al. 1989; Willetts et al. 1990).

 

I also find myself wondering if those rats suffered withdrawal-like symptoms that were overlooked and/or if people who might try this approach would suffer even more than they currently do.  This could be an even stronger reaction than a c/t.  I'm not trying to simply throw fear/uncertainty into the thread, but I definitely don't want to see somebody go out and try something like this.

I would be very careful with this ... I read about it, but that was more about preventing tolerance ...

 

If it were a magic bullet, everyone would take it.

Tested it out.  Took 30mgs of dxm last night and woke up with out any sxs.  They should come back as the dxm wears off.  If they do i will take some while i am awake and see what happens

Ahhh... the Albert Hoffman approach.  Be careful, guinea pig.

Ahhh... the Albert Hoffman approach.  Be careful, guinea pig.

DXM has side effects of its own. I couldn't tolerate it when I was a turned into a guinea pig for a couple of days.  --V

following

 

This seems to be helping me.

I'm happy I found this thread.

 

I about a month ago I drank a decent bit of dxm syrup. It gave me a weird buzzy feeling. I did notice the next few days after drinking it were quite rough. I had a bad wave probably 2 or 3 days after taking it but it quickly went away.. and 3 days after that I had a horrific setback from opiates which I'm still in. I would be careful with any chemical you put in your body. You never know what might happen

This seems to be helping me.

 

Hey hope did a wave hit you a few days later like what happened to dinglemargoon?

*following*

 

and curious - i thought i read DHEA was thought to act similarly - can anyone comment?? 

Dxm seems to reduce anxiety for me at 10 months out this from trying store brand cold and flu tea with ingredients listed as dextromenthorphan, Phenylephrine and Acetaminophen. Gonna try delsym tommorow maybe at 40 mg twice daily

Dxm seems to reduce anxiety for me at 10 months out this from trying store brand cold and flu tea with ingredients listed as dextromenthorphan, Phenylephrine and Acetaminophen. Gonna try delsym tommorow maybe at 40 mg twice daily

 

Just an FYI..phenylephrine is akin to epinephrine/adrenaline but synthetic..not unlike ephedra either.  They are all similar - i.e.: it will keep most awake at night and could cause increased heart rate, blood pressure, etc.. So if you have any sympathetic nervous system issues - watch out for the ephedra/ephedrine/pseudaphed stuff

 

 

Dxm seems to reduce anxiety for me at 10 months out this from trying store brand cold and flu tea with ingredients listed as dextromenthorphan, Phenylephrine and Acetaminophen. Gonna try delsym tommorow maybe at 40 mg twice daily

 

Just an FYI..phenylephrine is akin to epinephrine/adrenaline but synthetic..not unlike ephedra either.  They are all similar - i.e.: it will keep most awake at night and could cause increased heart rate, blood pressure, etc.. So if you have any sympathetic nervous system issues - watch out for the ephedra/ephedrine/pseudaphed stuff

Thanks for the tip firefly

Dxm seems to reduce anxiety for me at 10 months out this from trying store brand cold and flu tea with ingredients listed as dextromenthorphan, Phenylephrine and Acetaminophen. Gonna try delsym tommorow maybe at 40 mg twice daily

 

Just an FYI..phenylephrine is akin to epinephrine/adrenaline but synthetic..not unlike ephedra either.  They are all similar - i.e.: it will keep most awake at night and could cause increased heart rate, blood pressure, etc.. So if you have any sympathetic nervous system issues - watch out for the ephedra/ephedrine/pseudaphed stuff

Thanks for the tip firefly

 

 

NP

 

Mind you - that all being said - they do put it in OTC cold meds because they do clear out the sinuses ...and some people CAN sleep on them..i don't know who..most people i know can't and the stuff wires me to no end...on a good day..forget a tapering-a-benzo day lol..

but thought i'd add that too

 

Dxm seems to reduce anxiety for me at 10 months out this from trying store brand cold and flu tea with ingredients listed as dextromenthorphan, Phenylephrine and Acetaminophen. Gonna try delsym tommorow maybe at 40 mg twice daily

 

Just an FYI..phenylephrine is akin to epinephrine/adrenaline but synthetic..not unlike ephedra either.  They are all similar - i.e.: it will keep most awake at night and could cause increased heart rate, blood pressure, etc.. So if you have any sympathetic nervous system issues - watch out for the ephedra/ephedrine/pseudaphed stuff

Thanks for the tip firefly

 

 

NP

 

Mind you - that all being said - they do put it in OTC cold meds because they do clear out the sinuses ...and some people CAN sleep on them..i don't know who..most people i know can't and the stuff wires me to no end...on a good day..forget a tapering-a-benzo day lol..

but thought i'd add that too

I actually have been getting some of the best sleep in weeks but that probably because of the dextromethorphanin there. I notice that this stuff makes me sweat like a beast tho.

Dxm seems to reduce anxiety for me at 10 months out this from trying store brand cold and flu tea with ingredients listed as dextromenthorphan, Phenylephrine and Acetaminophen. Gonna try delsym tommorow maybe at 40 mg twice daily

 

Just an FYI..phenylephrine is akin to epinephrine/adrenaline but synthetic..not unlike ephedra either.  They are all similar - i.e.: it will keep most awake at night and could cause increased heart rate, blood pressure, etc.. So if you have any sympathetic nervous system issues - watch out for the ephedra/ephedrine/pseudaphed stuff

Thanks for the tip firefly

 

 

NP

 

Mind you - that all being said - they do put it in OTC cold meds because they do clear out the sinuses ...and some people CAN sleep on them..i don't know who..most people i know can't and the stuff wires me to no end...on a good day..forget a tapering-a-benzo day lol..

but thought i'd add that too

I actually have been getting some of the best sleep in weeks but that probably because of the dextromethorphanin there. I notice that this stuff makes me sweat like a beast tho.

 

no doubt it's the dextromethorphanin...and i've no idea how the ephedra stuff affects one when it's mixed in with the other stuff...and the dose matters..so if you're sleeping well..good on ya!! more power to ya!! i'm jealous!! lol

hehe

Anyone know of a OTC preparation that is DMX only, or at least something without phenylephrine?

 

 

ETA:  Looks like there are a number of them.  In the US Robitussin and generic equivalents, typically store brands (CVS, Walgreens, Walmart (Equate), etc. etc.)

 

List of DMX only OTC medications:  https://drugs-forum.com/threads/dxm-products-database-dxm-only.107444/

 

I have no idea how current that list is.

 

 

Tested it out.  Took 30mgs of dxm last night and woke up with out any sxs.  They should come back as the dxm wears off.  If they do i will take some while i am awake and see what happens

did you try any more dxm after that ?

how did it turn out ?

 

so little is known about nmda antagonists and benzo withdrawal!

 

my experience with 10mg instant release dxm was as followed:

post ingestion time:

1-2hrs: feeling stressed and quite high at the same time

3-4hrs: feeling dysphoric (i attribute this due to it increase serotonin and lowering dopamine, i have a bit of a low dopamine problem)

5-6hrs+: went from very relaxed to quite relaxed.

24+ hours: still noticing reduced tolerance to my benzo after only that one time dxm dose.

 

i think i might want to use dxm around 18pm every day or every other day for up to 3 times the first few days only when i do a dosage reduction.

 

i seem incredibly sensitive to it so i want to be ultra careful.

i read reports on reddit about one guy doing quick tapers with agmatine+ 2x15mg extended release dxm daily longterm and he said it did wonders for preventing withdrawals.

 

dxm being a weaker nmda antagonist than say memantine, i'd think maybe careful use of dxm might not be that dangerous.

Tested it out.  Took 30mgs of dxm last night and woke up with out any sxs.  They should come back as the dxm wears off.  If they do i will take some while i am awake and see what happens

 

Is the DXM still working for you? Can you give us an update?