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Repairing cognition after vyvanse+piracetam excitotoxicity..


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#1 Getting High On Life

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Posted 05 July 2010 - 01:25 PM


Hey guys... I will cut right to the chase... this is really depressing and I would definitely appreciate some help.... Right now I am about 9 months post.


Incidents
1. Vyvanse + Piracetam + low dose dep+ Nicotine ... multiple times. The Piracetam was 3 to 4 g, vyvanse was a borderline euphoric dose. This resulted in possibly week long periods of 180 systolic plus blood pressures, rebound depression from the vyvanse and subsequently multiple dosings in one day.... but i did get increased productivity!... also the piracetam was only run for a couple of days. This was before obviously I had understood the nmda issue with piracetam and vyvanse
2. DXM 60 mg + vyvanse + low dose dep + Nicotine I had borderline serotonin syndrome and a adrenergic storm incidient once or twice... complete with the slight muscle twiching and high bps. ... I tried to use DXM as nmda antagonist before I got mematine. I did corroted sinus massage and valvasla maneuver to bring my BP down. It eventually got to the point where I could not feel the vyvanse working at all If I did not take the nicotine gum..(1-4 mg)... It felt like my dopamine was "locked up" and nicotine had the key.
3.Nicotine + Vyvanse + L-tyrosine.
4. Dep+ L-Tyrosine.

Probably combinations of all of the above too.. I can't really remember.

Symptoms

1. Obviously depression... but this has subsided.
2. Very Impared verbal recall. (For Sure)
3. Sluggish cognitive tempo (although I have always had this... but I think it got worse).
4. Anhedonia? ( again not sure if it has been this bad)
5. I can intuit a concept in my right brain but my left brain has a hard time describing and explaining it.
6. Impaired overall memory.
7. Poor spelling/writing.

What I am doing so far

1. Exercise
2. Cod Liver Oil
3. Ashwaganda
4. General thyroid support, adaptogens and 67 mcg bid of sustained release T3.
5. Lions mane bid.
6. Curcumin in the morning with a meal.
7. Was taking vinopectine... but stopped upon reading it's adverse effects in a recent thread.
8. Dual-n-Back (stopped for a month due to travel.

All for only about a month or two.... I cannot tell and major difference so far but I am keeping optimistic (sometimes)... I honestly Just feel stupid right now.... and like my brain is locked in a bubble and can't communicate.

Types of damage I suspect

1. Well the piracetam and dopaminergic stimulation probably sent my nmda receptors insane and killed off half of them.
2. Bye bye serotonin system.
3. oxidative stress
4. reduced dopamine??


I realize there have been other similar threads but I feel that this is enough of a departure from the usual MDMA issues.

The possible solutions I can think of include just generally taking NGF and growth stimulating nootropics along with exercise and trying to funnel that into some good remodeling with brain workouts. Anything else I am missing? Anything specific the the nmda damage? What about taking mematine to hopefully up regulate the receptors ones I have left or piracetam to do the same... or should I not mess with them and leave them be. Maybe see a neurologist and get scanned for excitoxic lesions?

Thanks!
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#2 aLurker

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Posted 05 July 2010 - 01:49 PM

Thank you for posting. It serves as a warning for others experimenting with this stuff such as myself. From what I've read on the forums people especially seem to have had really bad experiences with DXM and bad combinations involving Deprenyl (Deprenyl + basically anything which involves dopamine/MAOIs/stims/pandas/whatever).

You're already doing most of the stuff I'd recommend. More mental exercise in the form of meditation, learning new things and new experiences; that's always recommended.

And since this is a nootropics forum I'll also recommend MOAR noots: ALCAR should help since it acts as a neurotrophic factor which should potentate the effects of the others stuff. Do a search about it.

I just got my package of ALCAR an hour ago so I can't personally recommend it yet but I ordered it since it seems safe enough and others can't seem to stop praising it, so yeah... peer pressure, all the cool kids are doing it.

Edited by aLurker, 05 July 2010 - 01:53 PM.


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#3 kassem23

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Posted 05 July 2010 - 02:08 PM

I also vouch for ALCAR on this one. You could try Lion's Mane as well.

#4 aLurker

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Posted 05 July 2010 - 02:23 PM

Since you mentioned thyroid stuff and I have experience with this:
I had some bad thyroid values and hypothyroid symptoms last year and got the lab results up to normal again by doing the following:
Less fluoride and more iodine!!! By doing this I could feel a difference within days. Only use mouthwash without fluoride/chloride (baking soda, peppermint oil and salt for instance) and use less fluoridated toothpaste/water. Supplement iodine. Maca root might help you here too.

It was probably my excessive use of fluoridated mouthwash which was the villain in my own case though.

The reason we use fluoride is because it kills harmful bacteria in your mouth but excessive use also kills your thyroid and counteracts the iodine it needs, do your own research about this.

Edited by aLurker, 05 July 2010 - 02:30 PM.


#5 Mindweaver

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Posted 05 July 2010 - 02:27 PM

Ashwa/Lion's Mane before bed.. ALCAR/Piracetam/Alpha GPC during the day has been my regime. ALCAR is highly recommended, and you've already got LM/Ashwagandha so you're on the right track.

#6 aLurker

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Posted 05 July 2010 - 02:38 PM

Another thing, you might already know this but black pepper (piperine) helps the absorption of turmeric/curcumin so be sure to add that to your meal.

#7 Getting High On Life

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Posted 05 July 2010 - 02:39 PM

Good to know I am on the right track, and that hopefully others will learn from this.


Ashwa/Lion's Mane before bed.. ALCAR/Piracetam/Alpha GPC during the day has been my regime. ALCAR is highly recommended, and you've already got LM/Ashwagandha so you're on the right track.



Is piracetam going to be a good idea even with my prior nmda issues? Maybe I should just leave that system alone?


I'll try the floride thing thanks.

#8 adamh

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Posted 05 July 2010 - 04:00 PM

Piracetam can only help. It was that other junk which hurt you, imo. Try about 1 gm per day. You don't need a ton of it.
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#9 chrono

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Posted 05 July 2010 - 05:03 PM

Sounds like you're doing a lot of great things already. I might add magnesium (glycinate, malate or taurate) for general brain support, and maybe a good multi. An antioxidant like green tea extract may also help, and EGCG has some neuroregenerative properties as well.

I'll third or fourth the recommendation for ALCAR. It increases sensitivity to NGF, and induces its release. It may also enhance your mental clarity.

I obviously can't say for sure, but I think you may be taking the possible NMDA excitotoxicity issue more seriously than you need to. I took these together many times before I read that thread, and never noticed any detriment. Higher dosages may have compounded effects, but I really doubt that taking piracetam with AMP twice has screwed up your NMDA system as much as you seem to think.

2. DXM 60 mg + vyvanse + low dose dep + Nicotine I had borderline serotonin syndrome and a adrenergic storm incidient once or twice... complete with the slight muscle twiching and high bps.

2. Bye bye serotonin system.

I may be missing something really obvious, but I don't see anything here with the potential to cause serotonin syndrome, or damage your serotonin system. Deprenyl + amphetamine is a bad combination because it induces dopamine release, and DPR's MAOI effect inhibits its breakdown. Can lead very easily to hypertensive crisis, even at much lower than therapeutic dosages of AMP. I assume that's why your blood pressure was so high in both of your examples.

I guess DXM may have caused some kind of damage, but 60mg is essentially a dose used for cough suppression. All the reports I've read of cognitive dysfunction have involved much higher dosages.

I guess I'm saying to keep doing what you're doing, but that your diagnosis may be wrong. It may be that the difficulties you're experiencing are entirely from recreational doses of amphetamine, amplified by an MAOI to dangerously high levels.

I don't think that piracetam has much potential to "heal" anything that may be wrong, but it may help to ameliorate your mental difficulties and improve your cognition generally while you're taking it. I suggest that it particularly has a synergy with ALCAR.

Edited by chrono, 06 July 2010 - 03:19 PM.


#10 golden1

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Posted 05 July 2010 - 05:45 PM

I don't think I've ever seen piracetam associated with neurotoxicity in a real study.. only neuroprotective effects..

I really doubt that piracetam contributed to the damage.. I've taken it with mdma, lsd, vyvanse, alphamethyltryptamine, and tons of other drugs and never experienced anything that would point to neurotoxicity. I live just as good of a life if not better.

Do you have anything showing that piracetam would contribute to glutamate neurotoxicity when combined with amphetamine? I know it's been stated before on these forums, but all other studies show neuroprotective effects(although none tested in combination with amphetamine) and I have used piracetam enough to kind of guess that there is no way it induced neurotoxicity especially to the extent that you mention.

I think the culprit is more likely to have to do with 2, 3, and 4.

I do want to say, just hang in there. Fish oil, b vitamins, maybe even piracetam or aniracetam, and a healthy diet with sleep will help over time. If I were you I would definately try aniracetam, only because it has a way of making my brain feel like it is healing itself to perfection.

Edited by golden1, 05 July 2010 - 06:07 PM.


#11 dilenja

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Posted 05 July 2010 - 05:48 PM

I've not yet seen evidence sufficient enough to corroborate a statement such as 'piracetam can only help'... Piracetam is shown to increase NMDA activity through calcium influx, but I have yet to see research which establishes an upper threshold or ceiling for this activity. Perhaps it could help, but it could also hurt...

OP,

- In lieu of Cod Liver oil perhaps you might consider trying high DHA omega 3s, 1 to 4g per day.
- Uridine supplements should also be beneficial when combined with DHA for promoting neurogenesis. It is through Uridine, that the cytdine component of Citicoline is believed to be able to restore membrane fluidity. Triacetyluridine, in particular may be an effective choice, and is found OTC made by a company called Cardiovascular Research. Magnesium, and Calcium Orotate are also likely to be good adjunct sources of Uridine (through synthesis).
- Sigma 1 agonists, such as Fluvoxamine (Luvox), Donepezil, Memantine, and certain Antipsychotics have been shown to protect cells against glutamate or NMDA mediated neurotoxicity. Fluvoxamine is shown to be beneficial for improving cognitive impairments associated with comorbid stress, psychosis, depression, OCD, and anxiety (if these happen to be present).
- Yes, memantine indeed could be effective and worthy of consideration. There is a plethora of ancedotal research available with respect to this
- Galantamine in doses of .05 to .1 mg/kg has been shown to exert effect primarily upon Alpha 7 Nicotinic receptors (rather than as a Cholinesterace inhibitor), and could be something to consider in lieu of Nicotine and also to 'resensitize' Alpha 7 receptors.
- Good to see you dropped Vinpocetine..
- Perhaps consider a good multivitamin, or at least a top notch B complex. Recommend AOR's B complex if you opt for the latter.
- Have you had your thyroid levels checked? If not, you should do so. Normal range for TSH is .5 to 4.5. If TSH comes back between 1.5 and 4.5 you should also ask for a TSR test. A difference of >15 on the TSR test indicates likely hypothyroidism.
- Be certain to include a good mix of Intense cardiovascular activity and also weight training with high weight and low reps in your excercise regimen.
- Be happy, and make this a priority... this IMO is as important as any other advice you will find in facilitating neurogenesis, as otherwise stress and depression will create an environment which is not conducive to brain repair. If you are having difficulty here, you will really have to take the bull by the horns yourself.

Piracetam can only help. It was that other junk which hurt you, imo. Try about 1 gm per day. You don't need a ton of it.



#12 Animal

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Posted 06 July 2010 - 02:55 PM

Haha, 'Getting High On Life', what an ironic user name considering your reckless abuse of those substances to get some sort of buzz. Still, we've all been ignorant and immature at some point in our lives, and it's important that you have recognised that and taken responsibility for your actions. I have massively abused mescaline combined with certain potent research chemicals (of which I have almost unlimited access to) in the past which is probably worse for your neurological health then what you have done. But now I am essentially fully recovered, if not superior in functionality to my pre-abuse self, through making a certain concerted effort to heal myself through any means necessary. So I'm optimistic you can make a full recovery too. Over what time period were you abusing these substances?

I would recommend going the pharmaceutical route, rather then the holistic one since I doubt you'll get a satisfying response otherwise. Personally I would recommend Tianeptine/Stablon, as not only does it increase NGF activity, it also helps regenerate serontonergic sensitivity while having a mild dopaminergic effect, both of which will have a positive effect on mood. It's easy to get hold of, most online pharmacies sell it. The only inconvenience is that is has to be taken at regular intervals 3 times a day. But that is a small price to pay for the improvement I'm sure you'll experience. Please just trial it for two weeks and if you don't feel it is helping then ditch it. It has an almost non-existent side-effect profile and no associated withdrawal syndrome so the only thing your are risking is the money you spend on it.

Oh an if you intend to take Memantine then don't begin taking them at the same time, because you need to identify the individual effects, and the dual adjustment period would be rather unpleasant. I do recommend Memantine as well, but definitely Tianeptine first since it should hopefully eliminate any frustration associated with your impatience to be well again.

Edited by Animal, 06 July 2010 - 02:58 PM.


#13 Getting High On Life

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Posted 06 July 2010 - 04:41 PM

Haha, 'Getting High On Life', what an ironic user name considering your reckless abuse of those substances to get some sort of buzz. Still, we've all been ignorant and immature at some point in our lives, and it's important that you have recognised that and taken responsibility for your actions...




Animal - Haha yea thanks. I guess I I didn't make it obvious but just so you and everyone knows... this was not a recreational escapade, I have CFS, SAD, ADD-I and dysrithmia and I was merely trying to get through my last semester of my junior year without failing out as well while at the same time treating my depression (the prescribed vyvanse treated both but quickly wore off necessitating all the support drugs and a quest for MOAR DOPAMINES)... although this was reckless as well.

Anyway, This one and off for about 2 months with some breaks when I did not need cognitive performance for school or extracurricular activities.


I will give that a shot... do you know if I can stack it with herbs specifically alcar, ash and other NGF enhancers? What about curcumin?... this is of course adding them in after I isolate the effects of the stablon. Also I am considering Pentoxifylline to increase cerebral blood flow for both my new and pre existing issues as per this thread : http://www.mindandmu...wtopic=42450... what do you think about a Tianeptine, mematine, pentoxfylline trifecta? Too many drugs again?


golden1-

Nope, just from what i have read on this forum and it does kinda make sense ( not that that really means anything).

Anyway I REALLY REALLY appreciate all the input and I am in the process of synthesizing everything together in one large plan.

Chrono-

Yea maybe I am overreacting but I was referring to the DXM... I probably tossed in some tyrosine for good measure.




All-

Again I really really really appreciate all your input(s) and I am working to come up with one big meta plan for my recovery which I will post... You guys have given me alot more hope than I had before.

-Me

Edited by Getting High On Life, 06 July 2010 - 04:46 PM.


#14 Animal

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Posted 06 July 2010 - 05:03 PM

what do you think about a Tianeptine, mematine, pentoxfylline trifecta? Too many drugs again?


I think that should be perfectly fine, the mechanism of action of each is wildly different so there should be no negative side-effects from such a combination. Of course you will need to introduce each individually, so as to not confuse any positive or negative. Personally I believe the Tianeptine and Memantine to be the most important pharmaceuticals since they each address multiple issues that you have mentioned.

What do you consider the most imperative symptom to treat? As this will help you decide which of the two to take first. Both Tianeptine and Memantine are long term drugs that present increased effectiveness with time, and require a minimum of 2 weeks for noticeable effects to occur.

If you are having mood disturbances, then I would definitely recommend you begin with the Tianeptine. :cool:

#15 Getting High On Life

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Posted 06 July 2010 - 05:14 PM

what do you think about a Tianeptine, mematine, pentoxfylline trifecta? Too many drugs again?


What do you consider the most imperative symptom to treat?


Verbal recall, writing and memory issues... However I also work in a slightly fast paced job so speeding up my reaction time and cognitive clock speed might be just as important... I am concerned the memantine might hurt this? ... the DXM helped so memantine might also after the initial break in period... but I am trying to delineate the difference between lack of a reaction from simply being slow vs lack of a reaction because I am in my head thinking space cadet style.... but there I go over analyzing again maybe I should just do it right?

#16 outsider

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Posted 09 July 2010 - 08:25 AM

And you could add Celastrus paniculatus, one of the best ayurveda memory herb. It protects by modulating the glutamate receptors and by antioxidant activity.


Celastrus paniculatus seed water soluble extracts protect against glutamate
toxicity in neuronal cultures from rat forebrain.

Godkar PB, Gordon RK, Ravindran A, Doctor BP.

Division of Biochemistry, Department of Biochemical Pharmacology, Walter Reed
Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD
20910/​7500, USA. Richard.Gordon@na.amedd.army.mil

Aqueous extracts of Celastrus paniculatus (CP) seed have been reported to
improve learning and memory in rats. In addition, these extracts were shown to
have antioxidant properties, augmented endogenous antioxidant enzymes, and
decreased lipid peroxidation in rat brain. However, water soluble extracts of CP
seed (CP/​WSE) have not been evaluated for their neuroprotective effects. In the
study reported here, we used enriched forebrain primary neuronal cell (FBNC)
cultures to study the neuroprotective effects of three CP/​WSE extracts (a room
temperature, WF; a hot water, HF; and an acid, AF) on glutamate/​induced
toxicity. FBNC were pre/​treated with the CP/​WSE and then with glutamate to
evaluate the protection afforded against excitatory amino acid/​induced toxicity.
The criteria for neuroprotection were based on the effects of CP/​WSE on a
mitochondrial function test following glutamate/​induced neurotoxicity.
Pre/​treatment of neuronal cells with CP/​WSE significantly attenuated
glutamate/​induced neuronal death. To understand the molecular mechanism of
action of CP/​WSE, we conducted electrophysiological studies using patch/​clamp
techniques on N/​methyl/​D/​aspartate (NMDA)/​activated whole/​cell currents in FBNC.
WSE significantly and reversibly inhibited whole/​cell currents activated by
NMDA. The results suggest that CP/​WSE protected neuronal cells against
glutamate/​induced toxicity by modulating glutamate receptor function.

Publication Types:
Research Support, Non/​U.S. Gov't
Research Support, U.S. Gov't, Non/​P.H.S.

PMID: 15234755 [PubMed /​ indexed for MEDLINE]

Edited by outsider, 09 July 2010 - 08:30 AM.


#17 brain

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Posted 11 July 2010 - 02:20 AM

I used the adderall/piracetam combination again about 10 days ago, three days in a low. I stuck to fairly low doses, 10 - 20 mg/day. I was on deprenyl but I've found that I can't notice it being potentiated very much, much unlike what it does to ritain. There is actually a study showing that it blunts the effect in rats. I again felt overstimulated and the combination felt very 'dirty', but it wasn't anything too bad so I continued for two more days, figuring that if I was causing much excitotoxic damage I'd probably feel extremely overstimulated. Part of why I tried it again was because I became near convinced that the last time I used the combination the effect was actually caused by mixing green tea with the deprenyl/adderall (it potentiates it a lot, surprisingly)

Result is that I think I killed some cells, certain memory/executive functions aren't working as well. My memory as a whole doesn't seem worse, and my cognitive function as a whole seems about the same, but a certain type of short term memory is noticeably fried. I'll walk into a room and forget why I'm there, or open a new browser tab and forget why I opened it, even if it's only a brief thought that separates the two events. I used to be like this years ago but It hasn't been a problem for a while. Then some other stuff, like impaired divided attention. It seems pretty obvious what's happened and I can't think of another explanation, other than maybe weird sleep schedules, but I usually have those.

I guess maybe I'll have to add some ALCAR to my stack. I feel fairly confident that these functions will come back with time, and don't find them very impairing, more just worrying, because the dysfunction seems scattered enough that I really have to wonder what else it took out.

#18 bobman

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Posted 11 July 2010 - 06:51 AM

what do you think about a Tianeptine, mematine, pentoxfylline trifecta? Too many drugs again?


What do you consider the most imperative symptom to treat?


Verbal recall, writing and memory issues... However I also work in a slightly fast paced job so speeding up my reaction time and cognitive clock speed might be just as important... I am concerned the memantine might hurt this? ... the DXM helped so memantine might also after the initial break in period... but I am trying to delineate the difference between lack of a reaction from simply being slow vs lack of a reaction because I am in my head thinking space cadet style.... but there I go over analyzing again maybe I should just do it right?


I can't imagine that memantine is a sure thing as far as cognition is concerned. From what I recall memantine is a pre-synaptic calcium release inhibitor. When speaking just about neuronal signalling, unless you have some gross excess in calcium-glutamate excitatory cascades, memantine would not benefit you, and most likely would have a negative impact on excitatory ltp and therefore learning & integration. In addition, there is new research suggesting that astrocytes play a major role in cognition. The postulate is that they directly contribute to the brain's processing capacity, in potentially far greater magnitude than neurons do (though everything is speculation at this point, based on research showing information processing independent of neurons, via calcium waves). The researcher that was quoted in the article I'm referencing, suggests that astrocytes play a major role in creative association.

#19 Getting High On Life

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Posted 15 July 2010 - 10:38 PM

I really want to restart piracetam... anyone know if its safe to take now after possibly screwing around with my nmda gluatamate system??????

So I'm ordering some fungi perfecti lions mane as per the lions mane thread along with ash and there is evidence that ginseng increases brain glucose utilization which is an issue potentially implicated in my ADD-I/SCT.

I'm also looking into undermethylation....

#20 Magister TH

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Posted 14 October 2010 - 06:08 PM

I recommend that you wash out everything else than the cod liver oil and other essential building materials and try to live healthy (working, exercising, eating and sleeping with a precise, balanced timetable). The washout should be done gradually to avoid any rebound effects etc.
This would normalize your medicalized brain functioning from the chronic unnatural state in which it has been.

After 3-6 months you could start to take uridine something like < 10 grams/day divided into 3 equal dosages (before meals) for a period of time. Try something like 1 month on, then 1 month off with gradual wash out periods. Uridine turns into UMP which in turn is needed in RNA synthesis. By taking uridine with omega-3 oils you could start to enhance the normalized brain physiology and give it a chance to repair itself.
See http://en.wikipedia....al_Intelligence

Take care.

#21 Ark

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Posted 15 October 2010 - 08:59 AM

I'm going to go out on a limb and say your problems are coming from DXM so I'd quit that at least if I were you.
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#22 brain

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Posted 15 October 2010 - 01:39 PM

I'm going to go out on a limb and say your problems are coming from DXM so I'd quit that at least if I were you.



I had severe problem from the piracetam + adderall. Noticeable memory loss and impaired attention for months afterward. To the OP: I recovered after a couple of months by using piracetam + alpha-GPC + ALCAR + fish oil. I also used Dual-N-Back, for what that's worth.

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#23 Ark

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Posted 16 October 2010 - 07:03 AM

I took both together at much higher dosage and nothing negative, can you at least offer some sort of study to support your argument. Usually people get addicted to DXM and want to stay on it,(even though its nasty cognitive effects become noticeable in day to day life) also its common to branch problems off in hopes to continue the drug abuse, Like I said quit the DXM.




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