Naloxone reverses a DXM trip

[IndustrialStrength]

^ While your making that note is it possible to fix the entry in the BL wiki regarding Mirtazapine & Hallucinogens?

I apologize if this was answered & I'm missing it as I'm really out of it do to dual w/d's & due to misinformation.
I was taking Phenibut thinking it would help with Klonopin withdrawals mostly the seizure problem as I have a history & have had some already in this taper (not by choice) so after 4 days I discontinued it today.
As a result as I stated I am out of it to put it mildly, but does Mirtazapine interact with Ketamine?

If so that should also be changed in the BL Wiki as in the BL Wiki it states

Ketamine

The effects of this drug should not be altered by mirtazapine and the combination is not known to be dangerous.

Thanks for answering what may be a stupid question or may already be answered. BTW in the wiki it already states that dxm & mirtazapine are contraindicated. I'm not sure if it was that way already or if you already fixed it.

Though if you fixed it the section on Hallucinogens also needs fixing as that still states

Hallucinogens

Hallucinogens seem to be MUCH stronger in combination with mirtazapine, so please be VERY CAREFUL! A dangerous interaction with shrooms has been observed in one person taking mirtazapine. Please avoid hallucinogens while taking mirtazapine or dose very carefully.

Don't mean to be repetitive but I'm of the opinion that the BL Wiki should be as accurate as possible especially on something that would be so often looked at as Anti-Depressants and Recreational Drugs even with the disclaimer.
Thanks for your time & I apologize if my post contains a question that was already answered that I am just misunderstanding or missing due to my current mental state.

I can always delete these posts after the relevant BL Wiki sections are fixed so as not to clutter the thread.

 

[serotonin2A]

DXM has no 5-ht2a affinity, so who cares?

Did you even read the posts I was responding to? It was mentioned earlier in the thread that buprenorphine can block the effects of LSD. My post is relevant to that topic. Adder posted a hypothesis regarding interactions between kappa receptors and 5-HT2A, and I was specifically responding to that. So I don't see why it is necessary to disregard my post in such a flippant manner. Although you may not care about the topic, others apparently care enough about it to discuss it in this thread.

Is it the policy of moderators of this board to discourage responses to other posts? Because that's what it seems like you are saying. Either that or you didn't read all of the posts in the thread.

 

[anubis23]

Ctrl+F "The value of naloxone use in dextromethorphan toxicity" here: http://www.dextroverse.org/Archives/Massive_DXM_Ingestion_and_Abuse.pdf
I would suggest from personal experience that either glycine, noopept, or even piracetam and related substances would be safer and more reliable alternatives. Sometimes even after a week of ceasing noopept use, I can't feel the full effects from DXM.
Buprenorphine and DXM use can result in a high risk of overdose, so take caution and avoid that mixture.

There is some research concerning a naloxone-sensitive sigma receptor, and a naloxone-inaccessible sigma receptor, that may play a part in this partial reversal of Dextromethorphan. Part of its hallucinogenic activity may be explained by the sigma activity, and there is a study concerning DMT as one candidate for being its endogenous neurotransmitter but this is speculation on my part.

The binding affinities for DXM to the Mu, Kappa and Delta receptors are quite low, but no doubt do play a role in its effect.

 

[adder]

I would suggest from personal experience that either glycine, noopept, or even piracetam and related substances would be safer and more reliable alternatives. Sometimes even after a week of ceasing noopept use, I can't feel the full effects from DXM.
Buprenorphine and DXM use can result in a high risk of overdose, so take caution and avoid that mixture.

Isn't neurotoxicity of NMDA antagonists a result of rebound hyperactivity of NMDA receptors (excitotoxicity)? I know piracetam on its own is considered very safe but it can actually cause some side effects in combination with various drugs. On one occasion I experienced a temporary peripheral vision loss after combining piracetam with caffeine. More recently I tried using piracetam a few days after taking DXM (half a year or more after quitting benzodiazepines). I noticed that my withdrawal symptoms worsened a few days after a DXM dose (which I attribute to rebound NMDA hyperactivity, it seems plausible, but who knows) and then my anxiety and depression worsened even more after taking piracetam (again addition to NMDA channels hyperactivity?). Benzodiazepine withdrawal is mostly due to overactive glutamate system and underactive GABA system, although I haven't seen any concrete research on this, withdrawal symptoms seem to fit.

As a side note, I've been recently prescribed 800mg of piracetam a day by a neurologist. This time I'm experiencing no side effects at all so far (even though my daily caffeine intake is ~200mg). Anyway, I'm wondering what effects it could have on top of an NMDA antagonist.

 

[anubis23]

You are correct NAN is largely influenced by rebound hyperactivity of NMDA. Piracetam will definitely increase the effect of stimulants and I have noticed more unpleasant effects from caffeine as well. You are also correct to suspect DXM as worsening the effect of benzodiazepine withdrawal, as an NMDA antagonist would most likely result in interruption of normal glutamate decarboxylase activity, ( the precursor to GABA production.) I suspect since piracetam is a very very weak positive allosteric modulator of NMDA through other channels and the racetams seem to favor activity on other methods that eating a bowl of MSG laden ramen would be more reason for concern than piracetam after DXM. I feel definitely less " hung over " after nootropics after DXM, but the acetylcholine activity of both drugs may yet also play a role. Piracetam has a mild anti myoclonus effect but leviracetam has more research in the world of anti seizure activity.

Piracetam does not significantly act on or modulate the other two glutamate receptor subtypes, NMDA and Kainate receptors,[17][3] although 500mg/kg to aged mice for 2 weeks may increase the amount of NMDA receptors expressed.

http://examine.com/supplements/Piracetam/#summary3-4

However, I would like to say that not every nootropic is created equal, and would definitely avoid attempting stuff in the -INIFRAM after NMDA antagonists as they do not have as much research especially with concurrent substance use.

 

[ebola?]

While you're making that note is it possible to fix the entry in the BL wiki regarding Mirtazapine & Hallucinogens?

That FAQ was written well over a decade ago, so a lot of its references aren't exactly cutting edge (and "some dude had a bad time" isn't a very reliable reference ). But you're right in that it could use an overhaul.

Mirtazapine is a potent alpha-2 adrenoreceptor antagonist. These are known to enhance the formation of Olney's lesions in rats dosed with NMDA antagonists (eep!!) so it's possible that this also enhances the primary effects of dissociatives

Well shit. Here's hoping that relegating use of mirtazapine to 7.5-15 mg for sleep (presumably where anti-histaminergic activity overshadows a2 adrenergic antagonism) and sporadic access to dissociatives left my brain relatively unscathed.

ebola

 

[sekio]

Olney's lesions in rats dosed with NMDA antagonists

two questions: is this seen in primates, and what ROA are we talking? I thought olney's lesions were a non-primate thing.

Arguably a lot of other drugs like yohimbine and the kratom alkaloids are a2a antagonists too. In fact as I recall kratom has a few mild NMDA antagonists in it. I guess I'm not going to be infusing any rat brains with kratom tea any time soon. Not any rats I want to keep, anyway.

 

[anubis23]

two questions: is this seen in primates, and what ROA are we talking? I thought olney's lesions were a non-primate thing.

Arguably a lot of other drugs like yohimbine and the kratom alkaloids are a2a antagonists too. In fact as I recall kratom has a few mild NMDA antagonists in it. I guess I'm not going to be infusing any rat brains with kratom tea any time soon. Not any rats I want to keep, anyway.

With kratom there is so many conflicting alkaloids it is really hard to tell the sum effect as most studies are of the isolated alkaloids.
But as far as I know there are no conflicting substances towards the NMDA antagonists in it (most notably rhynchophylline comes to mind.)

On the other hand, the alpha 2-adrenoceptor antagonists yohimbine (0.5 mg/kg, IP), and idazoxan (0.2 mg/kg, IP), significantly attenuated the suppressant effect of mitragynine.

http://www.ncbi.nlm.nih.gov/pubmed/9164589



About DXM:
http://www.sciencedirect.com/science/article/pii/1382668996000166
I.P. injection^

http://www.ncbi.nlm.nih.gov/pubmed/17573115


Here is a collection of primate studies for you:

http://toxsci.oxfordjournals.org/content/98/1/145.abstract
http://omicsonline.org/nonhuman-primate-models-and-developmental-neuronal-toxicity-2157-7609.1000e113.php?aid=10313
Pretty messed up methodology.^

 

[atara]

Did you even read the posts I was responding to?

I thought adder was discussing DXM, but he was actually responding to the post just before his. My quip was directed at both of you; my mistake.

Straw poll on splitting this thread? It's all over the place, and six years old to boot.

You are correct NAN is largely influenced by rebound hyperactivity of NMDA.

It... er, doesn't seem to be. For one thing it's prevented by anticholinergics which don't prevent the neurotoxicity of NMDA itself; additionally it seems to involve heat shock protein, whereas NMDA excitotoxicity is caused by Ca²⁺ influx. This article states that NMDA antagonism causes over-compensating ACh release leading to muscarinic neurotoxicity which isn't quite the same thing.

Well shit. Here's hoping that relegating use of mirtazapine to 7.5-15 mg for sleep (presumably where anti-histaminergic activity overshadows a2 adrenergic antagonism) and sporadic access to dissociatives left my brain relatively unscathed.

Unless you took them at the same time I think a real problem is unlikely.

But my memory was backwards. Alpha-2 agonists are known to reduce neurotoxicity; muscarinic antagonists reduce neurotoxicity, muscarinic agonists (see above paper) increase neurotoxicity. Alpha-2 antagonists probably increase neurotoxicity but nobody has tried to make the rats' nerve cells even more dead. In addition alpha-2 receptor activation decreases ACh release which is probably the mechanism of neuroprotection, so there's a molecular basis for antagonism increasing ACh release and doing bad things -- but it hasn't been tested and I shouldn't have said that.

two questions: is this seen in primates, and what ROA are we talking? I thought olney's lesions were a non-primate thing.

The only evidence to my knowledge of NAN in primates is that one recent study of heavy ketamine users. However muscarinic agonism can totally be toxic in primates so you probably don't want to push your luck.

Arguably a lot of other drugs like yohimbine and the kratom alkaloids are a2a antagonists too

25C-NBOMe is a mu-opioid agonist, but do any of these effects happen at clinically relevant concentrations?

 

[anubis23]

Ah, interesting thank you for the clarification and elucidation into the downstream pathways of that.

 

[mandeegibs]

Hi, im new. I signed up because i was looking for this info all day about dxm and sub.
Now i dont take subs normally. I just have some pieces to help me not go in withdrawal til i get my next check.
So yesterday i only had maybe 3mg worth of sub divided in 3 different times (like 1 mg at 8am, 1 at 11, 1 at 2) and i scored some H around 7. I got 2 tickets, and didnt feel it.
Which i know they say u cant with sub. But i have taken small amounts of sub before and was still successful getting high later that day. I think the dope was bunk, but thats a whole different story.
So anyways, i had wasted all my money, and wanted to get more than what u get out of this small amount of sub then normal. So i started looking at the dxm factor. Couldnt find much so decided id just test it.
I wanted to go the robo gel pills, but all the stores near me were out so i settled for the robo cough syrup. Drank the whole bottle. About an hour late puked (as i normally do with dxm) and then shot up a small piece of sub.
I was feeling great!! Like it couldve been more of a dxm high, but it was better than the previous night. So im chilling for a few hours. And then i think "i wonder what will happen if i take a littlw more sub" so i did and let me tell you. I feel like ive just done 3 bags. Or taken a whole 80 oxy. I feel great.
Not saying this happens all the time. Just telling my experience. Im happy with my choice tonight!

 

[aced126]

What's the point of putting the naloxone in the tablet then? Isn't it to dissuade IV admin because naloxone has higher affinity for mu?

 

[serotonin2A]

What's the point of putting the naloxone in the tablet then? Isn't it to dissuade IV admin because naloxone has higher affinity for mu?

Naloxone actually has lower affinity. In this case what might matter the most is the association rate, since both drugs are being administered at the same time. Conceivably, naloxone may have a faster association rate -- the high affinity of buprenorphine is mainly because it has an extremely long dissociation rate.

 

[neversickanymore]

I have been having trouble finding a study I remember reading over ten years ago.

In part of it they administered nalaxone to heavy canibus users and were pretty surprised to see them go into severe acute withdrawls akin to acute opiate withdrawls.

 

[serotonin2A]

I have been having trouble finding a study I remember reading over ten years ago.

In part of it they administered nalaxone to heavy canibus users and were pretty surprised to see them go into severe acute withdrawls akin to acute opiate withdrawls.

The same thing happens in rats:

http://link.springer.com/article/10.1007/BF00497855

It's not entirely clear why these interactions occur. Naloxone is an inverse agonist and one thing that may be going on is that the cannabinoid withdrawal syndrome is normally be suppressed by MOR constitutive activity.

 

[dopamimetic]

Naloxone put me into hellish withdrawal even whilst being 'sober' (taking memantine/clonidine daily and methylphenidate near daily, low to normal doses). Foolishly crushed a tilidine/naloxone pill thinking that I am not opioid dependent and not doing IV either so I would feel the tilidine or not.. but instead I experienced every single pain and fear I could ever think of ... crying out of no reason, urgent feelings of doom and total emptiness - up to today I am not sure why I react this way to naloxone (happened to think to be in need of naloxone recently, so I can confirm this is repeatable and independent upon having active opioids in my brain or not).

I do not want to experience anything remote like this ever again and do not wish this to anyone.

Paradoxically I have had prolonged opioid use (AH-7921 and butyr-fent) twice, always combined with the memantine/clonidine, and got away with minimal discomfort...

So, once again, I happen to have a really weird nervous system.

 

[DeathIndustrial88]

Mirtazapine is a potent alpha-2 adrenoreceptor antagonist. These are known to enhance the formation of Olney's lesions in rats dosed with NMDA antagonists (eep!!) so it's possible that this also enhances the primary effects of dissociatives. However this combination is sort of obviously a bad idea, because even though we're still not sure if Olney's lesions form in humans it isn't wise to push your luck.

Also, I should probably make a note somewhere that this combination is contraindicated.
[/QUOTE]

Shit. Does that mean all those nights for a few years that I used Remeron at the tale end of dxm trip to go to bed could have been damaging myself even further? I guess it didn't help that I also used meth a bunch of time ontop of high dxm dose trips. I developed myclonic jerks about 4 years ago after doing this for a few years. Those myoclonic jerks are still present to this day, even after ceasing any dxm tripping.