NMDA antagonists for tolerance, a collection of the evidence and anecdotal reports

[thikal]

Heh, you guys are seriously making me drool in anticipation of trying Memantine....and that's not just the Theanine hypersalivation!

It wasn't the adaptation phase end when I write this, I was wrong^^ Today I'm still a little bit weird/stupid/feel little drunk. Piracetam at 1g fix nothing to this (and I don't want to eat 10g of this nasty stuff god not!). I will try GBL again tonight, hope more euphoria than the other time! Will mix it with some squeegee (Is it the write word?), I'm exited. Did you ever vomit chese fondue? Not? Lot of fun hehe, it's like a rope when you throw it.

 

[Wizzle]

Maybe act a little confused, in combination with the drooling you might be able to score some memantine from your own physician

 

[MeDieViL]

Guys, we also shouldnt forget that amisulpiride upregulate GHB receptors (combined with agonism) this may be perhaps an essential addition for those focussing on vitamine G.

 

[MeDieViL]

Today upped my memantine dose to 40mg and also added acamprosate to my regime, might take a break of DXM, to see how much extra benefits it would provide.

One time for sure, memantine is working amazing allready for stim tolerance, effects ive never manged to pull of with DXM or acamprosate on their own, i do think they cna be good augmenters, nonetheless DXM on its own can work perfectly fine for other individual.

 

[MeDieViL]

By accident i took 60mg DXM this morning after wich i combined it with 120mg 5APB, didnt notice any effects of serotonine syndrome (wich may be caused by memantine, wich has a protective role) still there appeared to be synergy and in general ppl dont report the same blunting response as adding dear prozac to our happyness pill, well maybe thats another indication that DXM might be a serotonine releasing agent, definatly take this post not serieusly of me tough as it without doubt can end DEADLY, but if like to hear some other opinions on this subject.

 

[chaos_destroy]

^I imagine at those sort of low doses of DXM that risk of serotonin syndrome would be quite low anyway right?

 

[MeDieViL]

There should still be plenty of mdma supression occuring, anyone knows any more reports about this combo, mostly ive read that dxm potentiates mdma by those few that combined them.

 

[MeDieViL]

I gotta say that memantine works FAR better then DXM or acamprosate, noticing some major benefits with dxm or acamprosate on their own never really gave me, i do think those 2 can be perfect augmentors to make mem more effective.

Il elaborate more later.

 

[MeDieViL]

^I imagine at those sort of low doses of DXM that risk of serotonin syndrome would be quite low anyway right?

Speaking of that, i think i remember reading that memantine can supress serotonine syndrome in a rodent study's, not sure wheter that doses were very relevant for us tough, need to dig those up again, after wich well start our next quest, figuring out what memantine doesnt help with haha.

 

[MeDieViL]

Levorphanol
From Wikipedia, the free encyclopedia
Levorphanol

Systematic (IUPAC) name
17-methylmorphinan-3-ol
Identifiers
CAS number 77-07-6
ATC code None
PubChem CID 5359272
DrugBank APRD00764
ChemSpider 16736212
UNII 27618J1N2X
KEGG D08123
ChEMBL CHEMBL651
Chemical data
Formula C17H23NO
Mol. mass 257.371 g/mol
SMILES eMolecules & PubChem
InChI[show]
Pharmacokinetic data
Bioavailability 70% (oral); 100% (IV)
Protein binding 40%
Metabolism Hepatic
Half-life 11-16 hours
Therapeutic considerations
Pregnancy cat. C
Legal status Controlled (S8) (AU) Schedule I (CA) Schedule II (US) Class A (UK)
Dependence liability High
Routes oral, intravenous, subcutaneous, intramuscular
(what is this?) (verify)
Levorphanol (Levo-Dromoran) is an opioid medication used to treat severe pain. It is the laevorotary stereoisomer of the synthetic morphinan (Dromoran) and a pure opioid agonist, first described in Germany in 1948 as an orally active morphine-like analgesic. Morphinan is the parent drug and prototype of a large series of opioid and/or NMDA antagonists and opioid agonists used in medicine including nalbuphine, butorphanol, dextromethorphan, and others.
Levorphanol labeled with tritium was used in the research which led to the discovery of opioid receptors in the human nervous system, including the first study published in 1971.[1]
Levorphanol has the same properties as morphine with respect to the potential for habituation, tolerance, physical dependence and withdrawal syndrome. It is 4 to 8 times as potent as morphine and has a longer half-life. Approximately 30 mg of oral morphine is roughly equianalgesic to 4 mg of oral levorphanol.[2] The laevo isomer is the source of the narcotic properties of the racemic drug Dromoran, but the dextro isomers are also useful in medicine: in addition to acting on sigma receptors, the O-methyl derivative of its dextrorotary isomer, dextromethorphan, is a common NMDA receptor antagonist and pro-drug to dextrorphan.[3] Oral doses of levorphanol come in 2 mg and 4 mg strengths or subcutaneous injection every 6 to 8 hours.
Levorphanol has affinity to μ, κ, and δ opioid receptors, but lacks complete cross-tolerance with morphine. The duration of action is generally long compared to other comparable analgesics, and varies from 4 hours to as much as 15 hours. For this reason levorphanol is useful in palliation of chronic pain and similar conditions. Levorphanol has an oral to parenteral effectiveness ratio of 2:1, one of the most favourable of the strong narcotics. Its NMDA actions, similar to those of the phenylheptylamine open-chain narcotics such as methadone and ketobemidone, make levorphanol useful for types of pain that other analgesics may not be as effective against; levorphanol's sigma receptor, SNRI properties make it even more useful particularly for neuropathic pain.[4]

The best thing i can come up with right now dextromethorphan is pretty closely related to levorphanol.

Dextromethorphan is the dextrorotatory enantiomer of the methyl ether of levorphanol, an opioid analgesic.

And what do we know of opiates? They are serotonine releasers in several brainarea's, so in my opinion, it might be quite possible DXM is a releasing agent.

However ive just posted some really lose connections, and my knowlmedge is pretty limited on this, so definatly cant make a conclusion for sure, just hoping this would sparkle a interesting discussion.

Bull Exp Biol Med. 2007 Aug;144(2):210-3.
Self-administration of morphine by rats causes monoamine release in the anterior cingulate cortex.
Sudakov SK, Rusakova IV, Trigub MM, Kudrin VS, Klodt PM.
Source
National Research Center of Narcology, Federal Agency for Health Care and Social Development. [email protected]
Abstract
Monoamine content in the microdialysate from the anterior cingulate cortex was measured in rats after injections and self-administration of morphine. Forced intraperitoneal injection of morphine did not lead to appreciable changes in the monoamine levels in the dialysate. Self-administration significantly increased monoamine levels in the extracellular space of the anterior cingulate cortex. Changes in catecholamine levels in the extracellular space of the anterior cingulate cortex correlated with the intensity of self-administration. The more morphine the animals injected to themselves, the greater was the increment in dopamine and norepinephrine levels. It seems that the increase of serotonin content in the anterior cingulate cortex did not depend on blood morphine concentration, but just reflected the fact of narcotic self-administration. The release of serotonin from nerve endings in the anterior cingulate cortex gradually increased at the beginning of the session, after which serotonin concentration started to decrease. The results indicate that monoamines are released from nerve endings in the anterior cingulate cortex only in response to self-administration of morphine. Catecholamines were released after each self-administration of the narcotic, while serotonin release seemed to be associated with the general status of the animal realizing this behavior.

Synapse. 2005 Apr;56(1):29-38.
Dopamine and serotonin release in dorsal striatum and nucleus accumbens is differentially modulated by morphine in DBA/2J and C57BL/6J mice.
Fadda P, Scherma M, Fresu A, Collu M, Fratta W.
Source
Department of Neuroscience and Centre of Excellence Neurobiology of Dependence, Cittadella Universitaria, S.S. 554, 09042 Monserrato, University of Cagliari, Italy. [email protected]
Abstract
Numerous studies have demonstrated that genetic factors significantly influence opioid ability to induce behavioral modification in mice. This differential sensitivity has been extensively studied, particularly in the DBA/2J and C57BL/6J strains. In the present study, using the "in vivo" microdialysis technique in these strains, we investigated the effect of morphine administration on the extracellular levels of dopamine (DA), serotonin (5-HT), and their metabolites in the nucleus accumbens and dorsal striatum--areas thought to be involved in morphine-induced locomotor hyperactivity. In the nucleus accumbens, morphine (20 mg/kg) significantly increased extracellular levels of DA in both strains. However, in dorsal striatum the morphine-induced increase of extracellular DA was lower in DBA/2J mice than in C57BL/6J. Moreover, morphine significantly stimulated 5-HT and 5-hydroxyindolacetic acid (5-HIAA) release both in nucleus accumbens and dorsal striatum of C57BL/6J mice, whereas it decreased 5-HT release without modifying 5-HIAA levels in DBA/2J mice. These results suggest that the different behavioral and biochemical responses to acute morphine described in these two strains could be mediated by different sensitivity of both the dopaminergic and the serotonergic systems.

 

[MeDieViL]

Oh yeah, this was the study i was referring too.

Pharmacopsychiatry. 2004 Mar;37(2):57-62.
Memantine, an NMDA antagonist, prevents the development of hyperthermia in an animal model for serotonin syndrome.
Nisijima K, Shioda K, Yoshino T, Takano K, Kato S.
Source
Department of Psychiatry, Jichi Medical School, Kawachi-Gun, Tochigi-Ken, 329-0498, Japan. [email protected]
Abstract
BACKGROUND:
Serotonin (5-HT) syndrome is the most serious side effect of antidepressants. Although several drugs have been used for the treatment of 5-HT syndrome, a universal pharmacotherapy has not been established. NMDA receptor antagonists have been reported to have neuroprotective effects. In the present study, the efficacy of NMDA antagonists, including memantine and MK-801, and potent 5-HT (2A) antagonists, including risperidone and ketanserin, was evaluated in a 5-HT syndrome animal model.

METHODS:
5-Hydroxy-l-tryptophan (100 mg/kg) and clorgyline (2 mg/kg) were administered intraperitoneally in rats to induce 5-HT syndrome. The rectal temperature of the rats was measured, and the noradrenaline (NA) and 5-HT levels in the anterior hypothalamus were measured using a microdialysis technique.

RESULTS:
In the group pretreated with saline, the rectal temperature increased to more than 40 degrees C, and all of the animals died within 90 min of the drug's administration. The NA and 5-HT levels in the anterior hypothalamus increased to about 15- and 1100-fold of the pre-administration levels, respectively. Pretreatment with risperidone (0.5 mg/kg) and ketanserin (5 mg/kg) prevented the development of hyperthermia and the increase in the NA level. Memantine (10 mg/kg) and MK-801 (0.5 mg/kg) also prevented the development of hyperthermia and the increase in the NA level. These results suggest that NMDA antagonists, as well as potent 5-HT (2A) antagonists, may be effective drugs for the treatment of 5-HT syndrome.

CONCLUSIONS:
Since memantine is clinically well tolerated, this drug is a particularly promising therapeutic drug for 5-HT syndrome treatment.

 

[thikal]

Guys, we also shouldnt forget that amisulpiride upregulate GHB receptors (combined with agonism) this may be perhaps an essential addition for those focussing on vitamine G.

Really interesting but Amisulpiride as to much side effects on his one for me to add to my decrease tolance stack. Don't want to become a fatty impotent zombi just for more euphoria when I take some G! 8( Anyways, I'm on 40mg memantine during 3-4 days ago and at this dose it lessen greatly sides effects of GBL in me. I'm not any more in a shitty mood 2h after some G. Maybe euphoria will come back later.

 

[MeDieViL]

For me the biggest issue of G is that it gives me horrible brainzaps or even absence seizures (harmless seizures, but yeah the last thing you want), i went to 40mg of memantine yesterday, went back home dont have any g here atm but will try it soon.

Thats definatly a good sign, looks like we may be on the right track, just hope i can get rhid of those brainzaps and seizures as now i can only take G with etizolam or other benzo's, wich damen convulsant activity (brainzaps are basicly realy mild seizure activity, same as when you get them after mdma, serotonine receptors play a role in regulating seizure activity.

Ive added 333mg acamprosate to my regime 3 times a day, definatly notice a synergy with memantine, atleast with stims added, gives it an anxiolytic feel and feels like it perfectly synergizes with mem.

 

[Limpet_Chicken]

Acamprosate is not a typical NMDA antagonist. It is an antagonist at the polyamine binding site of the NMDAr, not the phencyclidine binding site, glycine site, glutamate (competitive) binding site or the binding site of channel blockers.

 

[thikal]

So I had the first methylone experience on memantine two days ago.

Substances I took before the experience:
- 40mg memantine / day
- piracetam
- choline
- a multivitamin tab
- some fish oil
- a huge glass of sprem
- magnesium citrate
(Spot the odd one out)

I didn't took an empathogen for 2 months before the experience, took like 200mg of MDPPP a week before. On the morning before methylone, I eat (10mg) and smoke (like 5mg but I don't know to chase the dragon well, there was waste) of AMT with little results. Two glass of wiskey killed all the AMT effect but it can be a facter anyways.

T0= 100mg methylone (at midnight)
T+45min = 100mg methylone
T+1h45 = 50mg methylone
T + 2h45 = 20md 2C-D

Before the 2C-D, I had real great time because of the quality of methylone (didn't have methylone of this quality for like one year on a half, but think memantine is a huge facter here). When I took this 2C-D, whow I instantly loose all track of the time and took a HUGGGGGE rolling right on my fucking face. I told my frend to get ready to phone help because I thought I was overdosing severly. Now I think my vital signs weren't frightening, no scaringly fast heartbreath (maybe a little bit but it's normal on this compounds), no fucking fever, no setoninergic syndrome, no headache, but my muscle were frightening stretch to death. Just a crasy powerfull euphoria whis all my surrounding melt down slowly like wax whis strange colors. I thing I just had a stupid panic attac. But yes it was more powerfull euphoria that my first time on methylone (when I add 2C-D).

I took 2 or 3 benzos to ease my muscles and all was okay (one half of nocran put me to sleep for 12 hours normaly hehehe). The comedown? Just fucking tired, I slep a lot this two last day. Feeling baseligne two days later. I think 2C-D can be extremly powerfull to kill the craving at the end of a stim session, in a FUCKING nice way.

To speak about memantine, I think I had the clear great euphoria (before I took 2C-D) and the little to no crash thanks to memantine. Want to do this mix again, without the AMT in the morning and with 10mg 2C-D instead of 20 The final word: Holly shit I crave more hehe.

EDIT: has memantine an action with seizure? Because I really felt on the comeup like I might have a fucking seizure... More fear that harm anyways, blissfull experience if I hadden think i'm going to die lol.

 

[thikal]

Hoo medieval I have to add this: memantine didn't give me again GBL euphoria, but she (the memantine, I don't know if I have to use "she" or "it") had take down my physical tolerance to the level I started. 3 years ago, I had to take 1,5mL to feel the effects, I climbed until 2,8mL. Right now, I just took 1,6mL anf feel like it's too much (but haven't got real euphoria). I drink 2 beer and I'm drunk too, it's funny.

 

[MeDieViL]

Well perhaps in a few days the euphoria will come, or might you be up for a 60mg experiment? Its definatly working on GBL so returning the euphoria should be possible.

 

[thikal]

Well perhaps in a few days the euphoria will come, or might you be up for a 60mg experiment? Its definatly working on GBL so returning the euphoria should be possible.

Yes I didn't have any side effect at 40mg so i will put my dosage to 60mg. But my suplies will end really soon I'm afraid and I have no money to order more right now. Holly shit, I have to find a job^^ I think I have to be on memantine all the summer.

Returning the euphoria should be possible yes, but if not, it's not really terrible. I think I drank more than 2L of this nasty stuff[EDIT: I mean I drank lot of GBL these last 3 years, in very truth I don't remember very well because GBL messed up my memory]. The results on the comedown with methylone and memantine are really interested by itself.

 

[InsatiablePeace]

I found chain smoking to enhance the euphoria of GBL... each and every time. GBL by itself is just sedative to me now. Cigs go hand in hand with it (similar to alcohol in fact).

Not healthy, but just an observation.

 

[MeDieViL]

I think I drank more than 2L of this nasty stuff. The results on the comedown with methylone and memantine are really interested by itself.

?

Cant really tolerate cigs, so drinking some nicotine tea ive just brewed lol:
http://www.erowid.org/experiences/exp.php?ID=63157

No stims atm so well see wheter it brings some extra euphoria to g like for the above guy, i may need the maoi's in the tobacco smoke tough, wish i had some curcumin now wich would substitute for that.