25 replies to this topic

[Comblop]

Over the past ~3 years, I've had periods of heavy abuse of NMDA antagonists (a habit that I've mostly kicked) and alcohol (still drink heavily to this day). I'm sure the alcohol has been causing some lasting deficit on its own, but my main concern is the NMDA antagonists (mainly Dextromethorphan, and a small amount of Methoxetamine). Ever since a massive ~6 month binge on DXM when I turned 18, in which I probably spent over ~$1500, things haven't quite been the same. It's as though my brain was dipped into a deep-frier and has never quite recovered.

My short term memory has faltered to an extraordinarily degree eg results from Cambrige Brain Sciences for Short-Term Memory: http://i.imgur.com/ux2bxTX.png), I find myself slow to learn new things like fine motor tasks, and I no longer enjoy many things I used to unless I have been drinking (anhedonia). I'm hoping there's something I can do (in addition to abstinance) to reverse the damage I believe I've caused.

I have no real income because I am unable to find a job, mainly due to Anhedonia/Depression/Anxiety, but I'm still interested to potential solutions to this issue for when I do have an income to spend. Any suggestions for these specific problems would be very much appreciated.

[Flex]

Coluracetam seems to reverse some Nmda-blocker related problems.

But its uptillnow still a research chemical( as far as i know)

So it would be maybe risky to use this.

In general following things do regenerate the brain to some extend:

Ashwaghanda( be carefull about the dosage its an anticoagulant)

Lions mane( if you choose an extract, it must contain a water extract as well)

And some other( i will post them in a few days)

[OpaqueMind]

First of all if you're serious about this you need to stop taking both of these substances. Depending on how heavily you drink alcohol, you may need to wean yourself off of it, as it is physically addictive and can cause seizures if the use is seriously heavy and stopped immediately. I don't know how much you have to be drinking for that to be a problem, maybe you could google it. Either way, you need to stop both of these as fast as possible. The brain is an incredibly adaptive organ, and it has adapted to deal with the aberrant chemical conditions that have been created for it in this continual flood of foreign chemicals. The only problem is that these adaptations evidently don't support higher cognitive functions, they simply support the survival of your brain. Don't get me wrong, that's a good thing, but if you want your brain to go beyond mere survival mode and into effective thinking mode the first step is to stop taking those things which force it into survival mode.

I understand that it is really hard to do this, especially if a habit is consistent. However, there are ways to soften to fall. It's gonna feel shite adapting to your non-chemically flooded brain, but it is a necessary hurdle in the road to recovery, even surpassing your currently degraded state. I know, I escaped similar patterns myself just a few years ago, and have rebuilt myself into something resembling coherency. It seems impossible from within the chaos; the mind cannot fathom what lies utterly beyond itself. If you are willing to stop all intake of these harmful substances then I am willing to describe to you the next steps in your evolution. If not, then I cannot help you. The foundations must first be laid before any stable structure can be built.

[Olon]

My personal theory is that messing with glutamate receptors (I include the racetams here) not only causes neurotoxicity, but also a permanent dysregulation of glutamate-receptor regulating signaling cascades. Still waiting for someone in such a situation who tries CAMKII activators like nobiletin/Sytrinol or tianeptine.

[lammas2]

I would say piracetam has given me some relief after using DXM recreationally. This may sound old, but daily exercise is also a must.

[Flex]

Edit

My personal theory is that messing with glutamate receptors (I include the racetams here) not only causes neurotoxicity, but also a permanent dysregulation of glutamate-receptor regulating signaling cascades. Still waiting for someone in such a situation who tries CAMKII activators like nobiletin/Sytrinol or tianeptine.

Nefiracetam does also CamkII activation (region specific)
http://www.ncbi.nlm....pubmed/19233146

..Nefiracetam treatment (1 mg/kg/day) significantly elevated CaMKII but not ERK activities in the amygdala, prefrontal cortex and hippocampal CA1 regions. In addition, we found an elevation of cAMP response element-binding protein (CREB) phosphorylation in the amygdala and prefrontal cortex but not in the hippocampal CA1 region. Increased CREB phosphorylation was associated with activation of CaMKI and CaMKIV as well as CaMKII in these regions. Taken together, in addition to CaMKII, CaMKI and CaMKIV activation mediated by nefiracetam treatment might mediate CREB phosphorylation following chronic nefiracetam treatment, thereby eliciting an anti-depressive and cognition-enhancing effect on OBX mice...

Olon what are Your opinions on this case ?
http://www.longecity...ceutical-means/

Could Cerebrolysin ( or anything else) reverse some damages on Amphetamine related damage ?

Edited by Flex, 07 December 2013 - 08:47 PM.

[Olon]

That nefiracetam also stimulates AMPA receptors indirectly by CAMKII activation should make it less dangerous as far as permanent dysregulation is concerned, but on should be more careful with the dose than with other racetams. Here is a paper about the effects of repeated application of PCP (alias angel dust) in mice that indeed says CAMKII is involved and that glycine (so also sarcosine) is effective. http://www.ncbi.nlm....pubmed/17344353 I would try to get up CAMKII activation first, however. Concerning former genius' problem of cognitive decline after NMDA plus amphetamines the partial response to modafinil and selegiline points towards a permanent reduction of dopamine release, that can be due to death of dopaminergic neurons (monoaminergic metabolism is not healthy for cells). Stimulation of D1 receptors in the prefrontal cortex inhibits potassium channels, from which I think it' responsible for its pro-cognitive effect. 4-AP (alias 4-aminopyridine) inhibits A-type channels, is approved for improvement of motor skills in MS, and is easily available as a chemical. One should know that it's really pure, however, and not exaggerate with the dose because of its pro-convulsive effect. Globally messing with GIRK channels could be done with barium ions, but is dangerous becaue of thermoregulation issues. D1 agonist would the the most convenient way, I don't know whether a D1 agonist is available, however.

[Ark]

If possible you should see a real MD.

[Olon]

Never worked in psychiatry, but I am a real MD and I can tell you the damages of chronic NMDA receptor antagonist abuse are not topic of standard psychiatry textbooks. Standard therapy for the damages of MDMA abuse is modafinil.

Edited by Olon, 08 December 2013 - 12:12 PM.

[Flex]

@ Olon

Thx

[Comblop]

First of all if you're serious about this you need to stop taking both of these substances. Depending on how heavily you drink alcohol, you may need to wean yourself off of it, as it is physically addictive and can cause seizures if the use is seriously heavy and stopped immediately. I don't know how much you have to be drinking for that to be a problem, maybe you could google it. Either way, you need to stop both of these as fast as possible.

I've had minor withdrawal symptoms from alcohol (rebound insomnia/anxiety) but it's not severe enough to be lifethreatening. I haven't used NMDA antagonists for 6+ months, so that's mostly done with, although I still get wicked cravings that are sometimes infinitely more intense than my alcohol cravings. Alcohol will be a lot harder because it's cheaper and there's less of an obvious damage being done, so there's less motivation to quit. Plus, I'm pretty sure I experience PAWS (Post-Acute Withdrawal Syndrome) if I try to stay off the alcohol for extended periods of time. All excuses, I know, but like you said it's a pretty hard thing to do.

If possible you should see a real MD.

I'm already seeing a family doctor for other things and recently had a complete physical done, but I don't think there's any point in telling them about the NMDA antagonist abuse, since I'm highly skeptical that your average family doctor would know much of anything about that. I will be mentioning the alcohol abuse in order to explore pharmaceutical options for quitting, though.


To the rest, thanks for the suggestions, I'll look into them. More suggestions is definitely welcome. I hear a lot of people reccomend racetams for long-term DXM abuse, but I'm curious as to which one might have the most hypothetical benefit in that specific scenario.

[Flex]

That nefiracetam also stimulates AMPA receptors indirectly by CAMKII activation should make it less dangerous as far as permanent dysregulation is concerned, but on should be more careful with the dose than with other racetams. Here is a paper about the effects of repeated application of PCP (alias angel dust) in mice that indeed says CAMKII is involved and that glycine (so also sarcosine) is effective. http://www.ncbi.nlm....pubmed/17344353 I would try to get up CAMKII activation first, however. Concerning former genius' problem of cognitive decline after NMDA plus amphetamines the partial response to modafinil and selegiline points towards a permanent reduction of dopamine release, that can be due to death of dopaminergic neurons (monoaminergic metabolism is not healthy for cells). Stimulation of D1 receptors in the prefrontal cortex inhibits potassium channels, from which I think it' responsible for its pro-cognitive effect. 4-AP (alias 4-aminopyridine) inhibits A-type channels, is approved for improvement of motor skills in MS, and is easily available as a chemical. One should know that it's really pure, however, and not exaggerate with the dose because of its pro-convulsive effect. Globally messing with GIRK channels could be done with barium ions, but is dangerous becaue of thermoregulation issues. D1 agonist would the the most convenient way, I don't know whether a D1 agonist is available, however.

To find a pure D1 agonist is surely dificult from e.g. plant extracts and so.

But Antiparkinsonian agent could be a option, furthermore L-Dopa( from mucuna pruriens) does bind more at the D1 than to the others.

[Olon]

Remark about nefiracetam: In a currently running thread someone reports about tolerance even with this substance. http://www.longecity...iracetam-trial/

[platypus]

Alcohol-abuse causes depression in itself, so staying off the booze would probably be the best 1st move, if possible.

[Ark]

Consider adding coconut oil supplement to your regime to increase energy.

[Sciencyst]

Sarcosine, a GlyT1 inhibitor. It is especially useful for NMDAR hypofunction. It inhibits the the GlyT1 glycine transporter, thereby increasing the amount of glycine (a co-agonist for NMDAR receptor activation). It increases NMDA signalling and it seems to reverse NMDA dysregulation. You see, NMDA antagonists dramatically screw up LTP, and I believe sarcosine can repair the damage, but has no added benefit for an already healthy brain.


Rescue of hippocampal LTP and learning deficits in a rat model of psychosis by inhibition of glycine transporter-1 (GlyT1)
http://onlinelibrary...08.06433.x/full
Systemic application of the GlyT1-inhibitor N[3-(4’-flurophenyl)-3-(4’-phenylphenoxy) propyl]sarcosine (NFPS) rescued LTP but had no effect on LTD in MK801-treated animals. Application of the antagonist to vehicle-treated controls resulted in a disruption of LTP but not LTD. NFPS significantly ameliorated reference memory deficits in a radial maze that occurred following MK801 treatment. NFPS-treated controls performed less well, however, than vehicle-injected controls

Sarcosine blocks effects of ketamine:
http://www.sciencedi...304394009015493

Interactions between the glycine transporter 1(GlyT1) inhibitor SSR504734 and psychoactive drugs in mouse motor behaviour
http://www.sciencedi...924977X09000649
Here, we evaluated the effects of SSR504734 in response to three psychomimetic drugs: phencyclidine, amphetamine, and apomorphine in male C57BL/6 mice. SSR504734 attenuated phencyclidine-induced (5 mg/kg, i.p.) hyperlocomotion, but potentiated the motor stimulant and motor depressant effects of amphetamine (2.5 mg/kg, i.p.) and apomorphine (0.75 mg/kg, s.c.), respectively. Hence, SSR504734 not only confers resistance to NMDAR blockade, but also enhances the locomotor response to dopaminergic stimulation.


Reversal of phencyclidine-induced dopaminergic dysregulation by N-methyl-D-aspartate receptor/glycine-site agonists..
Treatment with either high-dose glycine or NFPS (N[3-(4"-fluorophenyl)-3-(4"-phenylphenoxy)propyl]sarcosine, GlyT1 inhibitor based on sarcosine) along with PCP prevented PCP effects.
http://europepmc.org...fXprjjmQ5nKs8.4


d-Serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats
http://www.sciencedi...166432807003920

[socialpiranha]

All of your symptoms can be explained by hippocampal atrophy. Anything that increases bdnf in the hippocampus would help to reverse this.

[Comblop]

Just a small update (unfortunately I kind of forgot I even made a thread here until recently....damn memory); saw a doctor again and I was diagnosed with both Hypothyroidism and severe Vitamin D deficiency. I hope that treating these things may help some of the problems outlined in the OP.

Thanks for all the suggestions, I'm definitely going to save this thread for future reference when I have the money to afford some of the possibilities mentioned here

[OpaqueMind]

Sarcosine, a GlyT1 inhibitor. It is especially useful for NMDAR hypofunction. It inhibits the the GlyT1 glycine transporter, thereby increasing the amount of glycine (a co-agonist for NMDAR receptor activation). It increases NMDA signalling and it seems to reverse NMDA dysregulation. You see, NMDA antagonists dramatically screw up LTP, and I believe sarcosine can repair the damage, but has no added benefit for an already healthy brain.

This is very interesting. I've taken a fair amount of ketamine and methoxetamine in my time and definitely feel like my memory has taken some damage. What made you come to this conclusion? Have you experienced this yourself, or seen it work in other people? Need the dosing of sarcosine be continual or is it simply enough until the symptoms abate?

[pedr0vsky]

If you abused alcohol you definitely have to try Sulbutiamine: http://en.wikipedia....ki/Sulbutiamine

For the brain damage my advice is racetams, any of them...

Edited by pedr0vsky, 10 February 2014 - 07:35 PM.

[Strelok]

All of your symptoms can be explained by hippocampal atrophy. Anything that increases bdnf in the hippocampus would help to reverse this.

So what are the best ways to accomplish this?

[socialpiranha]

I'm not totally sure of the best way, but ssri's accomplish it over time, celecoxib works faster apparently. Also a few flavonoids and some other drugs i can't recall right now. Basically what happens is the glucocorticoid receptor becomes desensitized to glucocorticoids due to overstimulation and basic upkeep in the hippocampus is downregulated.

[Strelok]

I'm not totally sure of the best way, but ssri's accomplish it over time, celecoxib works faster apparently. Also a few flavonoids and some other drugs i can't recall right now. Basically what happens is the glucocorticoid receptor becomes desensitized to glucocorticoids due to overstimulation and basic upkeep in the hippocampus is downregulated.

If you come across them, I'd definitely be interested to know which flavonoids can accomplish this. I'm not interested in taking any pharmaceuticals at the moment.

[socialpiranha]

mainly 7,8 dihydroxyflavone we have a group buy for it on the go unfortunately it is closed now for new members but If everything goes well i'm sure there will be another buy soon.

[Sciencyst]

Sarcosine, a GlyT1 inhibitor. It is especially useful for NMDAR hypofunction. It inhibits the the GlyT1 glycine transporter, thereby increasing the amount of glycine (a co-agonist for NMDAR receptor activation). It increases NMDA signalling and it seems to reverse NMDA dysregulation. You see, NMDA antagonists dramatically screw up LTP, and I believe sarcosine can repair the damage, but has no added benefit for an already healthy brain.

This is very interesting. I've taken a fair amount of ketamine and methoxetamine in my time and definitely feel like my memory has taken some damage. What made you come to this conclusion? Have you experienced this yourself, or seen it work in other people? Need the dosing of sarcosine be continual or is it simply enough until the symptoms abate?

I extrapolated it from the literature. It repaired my mxe/dxm induced damage. Current studies all say it begins to have beneficial effects in schizophrenia at the 4-6 weeks mark. I took it daily for about a month, and it seems to have helped in the long term for myself. I cannot say if this is true for everyone, and the risks of taking it for very extended periods of time are unknown. For example, d-cycloserine is an NMDA co-agonist, but chronic administration supposedly causes the receptor to react to it as if it were an NMDA antagonist, and it can therefore cause psychosis if used for too long. I don't think this would be the case with sarcosine because it's not an agonist at NMDA, rather it blocks the synaptic clearance of NMDA and serine, thereby increasing the amount of NMDA co-agonists present. Still, caution is advised. I might just take it daily for 6 weeks, and then have a 2 week washout period before beginning again. Sarcosine seems very safe and nontoxic, yet I would wait for studies to prove it before taking it for years (yes, years) at a time without washout periods. I'd estimate that taking it for time periods shorter than a year would be extremely well tolerated, though.

Sarcosine needs time to work, except for in the case of neural rescue during NMDA antagonist intoxication, where its benefits seem to be instantaneous.

So in closing... sarcosine is awesome and seems to restore brain functionality in those with disturbed glutamate systems, and I believe it might be the best option for victims of dissociative use who are trying to get back to normal, however, I'd really like to see more studies being done on it.

Edited by katuskoti, 15 February 2014 - 06:18 AM.

[hathor]

interesting...i've used a lot of ketamine, mxe, dxm, and nitrous oxide over the past 12 years or so. i always attributed the schizo stuff to psychedelics and stimulants though rather than nmda. in 2011 i was taking as much as 650mg of 4-fa a day at one point, as much as an ounce of piracetam in a day. in 2010 i thought daily LSD use was a good idea which i did for about a month before completely losing grip on reality. in 2012 i was on risperdal and in 2013 i was on adderall. now in 2014 i'm on zyprexa and oxiracetam. i mostly think that my congitive issues are related to massive overdoses of various rx, nootropic, and rec drugs, there are three times in particular where i OD'd on a bunch of that stuff in combo, in 2010 and 2011 and for the past two years i've been trying to recover my brain to get it back to functional again.