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Could I have done damage? (Citicoline + Adderall during school) (Piracetam + L-Theanine this summer)

citicoline adderall l-theanine piracetam damage

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#1 Axmann8

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Posted 16 August 2014 - 01:06 AM


I am a 22-year-old nursing student. I have never smoked, drank alcohol, nor abused any legal (or illegal) substance. My grandma has Alzheimer's disease and I became deeply interested in the nootropic community as a result of stumbling across research on piracetam as a cognitive enhancer.

Last semester during school, I had been taking ~250-500 mg CDP-Choline and ~30 mg Adderall (two 15mg XRs a day) daily. The only other "drug" I was using was caffeine (in the form of a lot of coffee). The Adderall was prescribed to me and, in general, has improved my life significantly. I went from doing literally nothing to getting into a pretty competitive BSN nursing program.

Near the end of last semester, I had a breakup that was rough on me (mostly because of my low self-esteem in the looks department) and began to use fairly good doses of L-theanine to try to mellow out my anxiety. Over the summer, I quit taking Adderall because I was getting some slight paranoia (probably as a result of my poor sleep combined with the Adderall every day), and I was also having weird blood pressure changes (for example, crouching real fast at the store or whatnot to look at a lower shelf would cause some weird, almost-lightheaded feelings. I also began to have strange, "air trapped in chest"-type feelings. I went to the ER for tachycardia one night; they ran tests and didn't find anything abnormal. On my own research, I figured I had depleted my magnesium causing muscle spasms and began to take a high-quality magnesium supplement, and those symptoms eventually went away. I decided I would stop the Adderall over the summer and that it would be good to let my body relax and rest.

 

Most of the summer went by completely fine, however, maybe about a month or so ago I'd decided to start trying piracetam again (by itself, not with the Adderall). I wasn't taking megadoses, just around 2.4 g or so, and only for a period of about 1 week or so, since I didn't like the vivid dreams. I was still using l-theanine at the time.

Right after I stopped taking piracetam that time (even though I'd taken it before and stopped with no issue) (I was still using good doses of L-theanine at the time), I started having these awful mood swings (highly uncharacteristic for me) and anxiety attacks. I also noticed that I felt very down and everything seemed very foggy (it feels like my vision has declined as well). Nothing just has the vibrance and emotional depth that it did last semester with citicoline + Adderall. I was sharp as a razor, felt motivated and driven, social, and my mood was always stable and happy.

Is there a possibility I've done any permanent damage as a result of citicoline, adderall, or l-theanine use? This all started around when I began piracetam again, but the doses were just so low that I struggle to indict piracetam as a cause.



#2 zompy

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Posted 16 August 2014 - 04:10 AM

I think it might have something to do with your Adderal use as all other drugs have been proven a lot safer then an amfetamine like drug.

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#3 Axmann8

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Posted 16 August 2014 - 05:01 AM

I think it might have something to do with your Adderal use as all other drugs have been proven a lot safer then an amfetamine like drug.

 

We're often very quick to indict amphetamine because of its incredibly powerful mechanism of action and abuse potential (among other things).

That said, there are people who have taken high doses of Adderall their entire life and are doing just fine. Generally speaking, when used at low to moderate doses, the potential for long-term damage there is slim, and in the event any damage actually is done, the human brain is quite vigilant in repairing it with time. Even those who have suffered strokes leading to massive neural injury are capable of restoring lost function.

Research on citicoline is still early, and the mechanism of the racetam class is not yet fully understood, either. Either all of this is due to depression, some unknown mechanism throwing my neurotransmitter balance off, or some other cause entirely.

Whatever the cause may be, I'm committed to fixing it.


Edited by Axmann8, 16 August 2014 - 05:03 AM.


#4 barbelith42

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Posted 21 August 2014 - 11:14 AM

This is the composite knowledge of almost a decade of my experiences on, off, and around being prescribed this powerful tool. Like any, it must be used with respect. You're putting part of your body into overdrive and must respect that -- and, in so doing, yourself. The synergistic effects will be cumulative and permanent in a positive way.

 

1. You'll be fine. Really. Remember that.

2. Sleep. No kidding. Just because you feel like you can stay up doesn't mean your body is in any way more receptive to it than before you took the medication. It's tricky that way. Which leads to

3. Eat. You need balanced, consistent nutrition including all vitamins, branched chain amino acids, and low glycemic index carbohydrates balanced with a good macronutrient balance with good freshly-cooked protein and the gamut of healthy fats. If you have genetic issues metabolizing, e.g. MTHFR/MTRR mutations & folic acid (23andme cleared that up for me), take care of them ASAP.

4. Exercise. If you don't use it, you'll lose it. Remember, stimulants induce catabolism (metabolizing proteins -- as in your muscles -- and fats -- including in your brain) in cases of caloric deficit, and potent stimulants won't stop as per usual. This will also dramatically re-balance everything in your physical and neurochemical profile, provided you get enough nutrients and sleep. Seriously, dopamine, serotonin, endorphins (endogenous opiod-like painkillers & happy fun time chemicals), et.c. go up -- permanently -- and cortisol goes down.

5. Meditation. It actually works.

6. Yoga/nature/sex/travelling/friends -- whatever centers you and brings you back to that happy place. Part of the composite issue is that by worrying about a stimulant's side-effects obsessively while on stimulants (or even not) you are wiring your cells to fire together in the Hebbian fashion to continue a negative feedback loop of psychological, and thus physiological, stress and unhappiness. This, again, increases your cortisol levels.

 

That brings me to cortisol management. Initially, cortisol is part of the effect of the chemical working as intended, as it is elevated in response to exercise, stress, and as a metabolic by-product of dopamine and norepinephrine -- which are significantly and continuously elevated on stimulants -- degrading along their metabolic pathway into adrenaline, which includes multiple steps that increase cortisol. This is part of what stimulants do. In the short-term, this can increase monoamine concentrations (as well as increase the level of hormones like testosterone). However, chronically elevated cortisol is highly correlated with significant stress, and essentially begins a regulatory feedback control mechanism using hormones to regulate neurotransmitters. A little bit of cortisol is excellent for getting you up and going from sleep in the morning, but it needs to decrease at troughs in your circadian rhythm or you will have problems. Some of these include: suppression of endogenous testosterone and growth hormone, reduction of slow-wave (deep, muscle-repairing, hormone- & neurotransmitter-rebalancing) as well as NREM (dreaming, memory consolidation, various neural hedge-trimming) sleep, and a slow increase in calcium channel (and others that I cannot accurately recall at the moment, but I suspect potassium channel and possibly sodium channel) firing rate along with your aforementioned magnesium-mediated signalling increase. Over time, as those become imbalanced, you can also potentially experience a glutamate/GABA imbalance similar to the withdrawal from GABAergics like alcohol & benzodiazepenes.

 

All of this can make your body feel somewhere between an induced anxiety disorder and, well, chronic fatigue syndrome. Luckily, the withdrawal from amphetamines makes you feel tired because it's repairing overworked mitochondria and slowly up-regulating downregulated dopamine receptors as well as possibly similar effects upon endorphins. The adrenaline-like effects from excess norepi/epi would continue unabated, and the undiscriminating alpha 1,2 & beta 1,2 adrenergic stimulation eventually gets tiresome to even the most indefatigable smooth muscle, hence jaw clenching and chest pains from, mostly, really tight muscles and constricted blood vessels.

 

Pharmaceutically, you can try to counteract this physiologically with adrenergic blockers: beta blockers like propranolol -- which also works off-label for anxiety, but is totally unselective -- or alpha 2 agonists like guanfacine (originally prescribed as an adjunctive medication for stimulants, but I believe was shown to be somehow unsafe) or clonidine (also used for sleep and easing withdrawals). There are other medications like this, but these are all heart medications, so beware -- consult with your medical profession, and have them consult with pharm/psych/neuro/cardio et.c. specialists as well to be extra sure. Adding anything can complicate the variables, and these can have paradoxical rebound that could exacerbate your situation. The other alternatives like benzodiazepenes and SSRI's have some significant health issues with addiction and withdrawal/post-acute withdrawal syndromes that may or may not ever recede, depending on whom you ask. I would advise not going down that road unless you have exhausted every other imaginable option for that reason. Don't turn a resolvable temporary psychologically-mediated issue into a longer-term physiological issue.

 

All of these things are mostly insignificant and unnoticeable until you run yourself down, and you do that by being stressed, not eating right, and not working out while not sleeping enough.

 

Also, check your dosage -- maybe the XR 30mg is too much for you. I know adults (both >6' & >=200lb) who have been taking Adderall since they were in elementary school who didn't like taking Adderall XR 30mg because it was, quote, "too much": http://pi.shireconte...lXR_USA_ENG.PDF -- see page 6 for ng/mL plasma concentrations across T(hr). Also note how important food consumption is in the text directly below that graph: the effective time increased from 5.2hrs fasted to 7.7hrs after a high-fat meal. I like steak, eggs, and potatos; but that may be overkill on your HDL/LDL lipid frag panel. To be fair, I also know a ~5'10" & ~160lb guy who was prescribed XR 30mg b.i.d (twice a day).

 

If you like the effectiveness of dosage but experience these peripheral side effects, consider large vitamin C doses a few hours before you wind down for the day so you can help excrete the amphetamines at a significantly faster rate -- there's a reason they tell you not to drink fruit juices when you take it, but that can help at the end of your day.

 

Stack to improve symptoms on or off medication:

Day:

- a simple multivitamin every day helped immeasurably. Don't forget! And try to take it in the evening as per the above vitamin C issue which I'll mention in a moment. (I'm using NOW Adam, which surprisingly has a solid quantity of high-bioavailability forms of vitamins & minerals -- very important) 

- Fish oil (high DHA 400+ as per the inspirational MrHappy) seems to help, especially with

- Uridine, which MrHappy cued me to. It had subtle but noticeable effect over time -- simply more positives and less negatives from the medication. 100-200mg daily, or twice daily -- I'm new here, go with his recommendations.
- CDP-Choline taken sparingly -- every few days (a post I read after I stopped my daily regimen stated that it and its metabolites can last for days, no citation there), but when I take it regularly at ~100-250mg it doesn't seem to cause any drowsiness or headaches, but rather calmly energizes me. If I take it every day, i.e. to stave off potential head pressure sensations from Noopept, I'll have ~150mg 1x or 2x a day.

- ALCAR -- I don't like too much, maybe 200-400mg. I feel like it can overload me. Anytime I feel "overload" I expect negative repercussions as my body balances itself back out.

- Noopept (with piracetam, but only for the verbal fluency increase) -- I wasn't a huge fan of piracetam 400-800mg, even 2-3 times a day with or without CDP-choline, if simply because I didn't notice much effect besides a slight overfocus (although the verbal fluency increase was cool, but I don't usually have a problem with that). Then I added Noopept, which seems to work almost as well on its own. Well, it works, and may be too potent -- sometimes I feel like a zombie computing machine, particularly combined with low dose Adderall. Less is more: 5-10mg, maybe 2x (or even 3x? seems to begin to wear off between hour 3-5 similar to instant release Adderall). At the end of the day I seem to sleep a bit harder, especially if I only took it in the morning. I've even had some vivid, occasionally lucid dreams. I like to take it 3-5 days a week as I don't like my state of mind to be modified every single day of the week.

 

At the end of the day:

- Vitamin C -- particularly C, and in higher (I'm still playing with specifics) dosages in order to increase the rate of renal excretion of amphetamine & its metabolites. If taken earlier it will "dull" the effects, which is good if you haven't reached max plasma concentration yet and suspect overstimulation when you do arrive. If you are already overstimulated, you may have a minor sensation of sedation as you relax and reach equilibrium. May make medication ineffective, though.

- Magnesium Glycinate -- It does calm you down and acts as a mild muscle relaxant. I just happen to like glycinate, and maybe 150mg-300mg (for about 20-40mg elemental magnesium -- compare to 500mg Mg oxide that contains 12mg elemental magnesium) a few hours before bed. to be sure to check ozone's post (http://www.longecity...agnesium-types/) and order a high bioavailability kind. I like this one because mag cit is used as a laxative and this is the next best thing. Check into the threo- form, but I haven't tried it and have heard conflicting reports (and it's expensive.)

- L-Theanine -- it seems that most people love it and a few hate it, but in smaller doses (50mg) it helps to take the edge off any time of the day. Sometimes I'll have 100-200mg before bed to really drop me, but it seems that there is increased sedation from magnesium and/or any other somnolence-promoting agent like melatonin (which I unfortunately metabolize slowly and/or abnormally, thanks insomnia -- which you can thank for this post) or Ambien (which I, unfortunately, take more than I likely should and am attempting to slowly titrate off of and replace)-- something, possibly via the supposed enhancement of GABA effectiveness or serotonin acting at its inhibitory receptors -- if I have:

 

Special synergy note:

- Caffeine -- I rarely have coffee with any regularity anymore unless I'm in finals or taking a break from Adderall. If I do, the AM. but be aware that caffeine will exert a synergistic effect with amphetamines that may significantly wear you out. It definitely increases the rate that you will metabolize and/or simply excrete amphetamines causing the Tmax of the above curve to be shorter. 

 

Experimental potentially-crazy or simply too-new-to-be-widespread "nootropics":

- Selank -- On its own, the first time I used it I felt noticeably calm, yet awake. Apparently acts to prevent enkephalins from degrading, which are the delta-opiod receptor endogenous opioid peptide similar to endorphins' action at mu-opioid receptors. It seems to -- if only via its generally calming qualities, but I suspect chemically -- reduce chronically elevated cortisol levels. Too much may make you not want to do anything. I found about 25-50mcg (vs. the 250-500mcg recommended to me) subcutaneously would take the overly-driven "hard" edge that early-morning Adderall can bring, particularly without enough sleep and/or with caffeine, without reducing the cognitive effects. I suspect a synergy between the secondary endorphin-activating effects of amphetamine at, if I recall correctly, sigma opioid receptors. I believe caffeine also has some sort of similar effect on endorphins.

- P21 -- A surprisingly useful tool recently added to my toolbox. Added an incredible ease of fluid thinking, if simply through accessible energy and capacity to manage attention and thus increased working memory. 125-250mcg provided ever-so-slight energy and noticeable awareness and lucidity for 3-6 hours on its own and with Adderall. 500-750mcg was fine without Adderall. More than that increased the effects but resulted in the slightest urge to take a nap after more of the positive effects above. At 1.5mg the effects seemed to result in diminishing returns in positive effects with a more pronounced sense of wanting to take a pleasant nap. Induced remarkably vivid memories of dreams the night before, and in particular involved becoming lucid, turning a neutral dream into positive, controlled one, and then waking myself up consciously feeling warm, calm energy. It seemed to be easier to store and retrieve complex information (bio, chem, calc). I've only tried it for 5 days and am taking a short break, as that is the protocol for Cerebrolysin, of which it is apparently a highly-active component peptide.

 

Next I intend to try Semax.

 

N.B.: I really reacted specifcally well to metabolically-active vitamin B complex (P5P for B6, methylcobalamin for B12) as well as pre-methylated folate due to the above MTHFR/MTRR issue that I recognized upon running my 23andme results at nutrahacker.com & geneticgenie.com (the former has actual recommendations along with the latter's list of methylation-related genes). Not to plug brands, but Thorne Research Methyl Guard surprised me and replaced all of my activated B and folate supplements in one for cheaper. A good high-bioavailability multivitamin with metabolically active B (e.g., P5P & methylcobalamin) lets you skip the Methyl Guard unless you want 5-methyltetrahydofolate to bypass methylation of folic acid for some reason. I really like this whole nutrigenetics angle and have been getting into it in the last few months with noticeable effects. Consider it if you want to do more research on yourself that has some (at least somewhat) scientifically-backed reasoning custom tailored to you.


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#5 Esoparagon

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Posted 21 August 2014 - 04:53 PM

L-theanine - an amino acid supplement, increases GABA. Probably not going to damage you, might downregulate some receptors.

CDP choline - choline and uridine supplement. Increase phosphodylcholine synthesis. Not going to damage you.

Piracetam - literally the safest nootropic with decades of track records, can't overdose, people take 10g a day, it's like candy.

Adderal - regulated, amphetamine, potent prescription medication.

 

One of these things is not like the others. One of these things just doesn't belong.



#6 Flex

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Posted 22 August 2014 - 08:45 PM

My theory would be that the combination of Adderal (or adderal alone) has damaged Your health

and that Piracetam afterwards, was the cherry-top of that allready damaged connection (sry for the expression)

 

Some people have here on longecity reported that they have either enduring positive effects or enduring negative effects through Piracetam.

http://www.longecity...ic/#entry549966

But I cant find anything in ncbi.

 

Anyway, I´ve learned that the Striatum is capable to restore lost neurons and Astrocytes through the subventricular zone.

This could at least partly contribute for the mood and motivation.

 

Besides that I would stop takin any -racetam and look for Bdnf (sport), Gdnf & etc. enhancing stuff and chinese herbs like: chinese foxglove / rehmannia glutinosa

( even 5 -10 drops of a 5:1 tincture thinns my blood, so be careful. the cause for this is ADP inhibition !? similair to plavix)

 

You can find more infos in my thread:

http://www.longecity...esting-effects/

 

 


Edited by Flex, 22 August 2014 - 08:46 PM.


#7 mindpatch

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Posted 23 August 2014 - 07:06 PM

This is the composite knowledge of almost a decade of my experiences on, off, and around being prescribed this powerful tool. Like any, it must be used with respect. You're putting part of your body into overdrive and must respect that -- and, in so doing, yourself. The synergistic effects will be cumulative and permanent in a positive way.

 

1. You'll be fine. Really. Remember that.

2. Sleep. No kidding. Just because you feel like you can stay up doesn't mean your body is in any way more receptive to it than before you took the medication. It's tricky that way. Which leads to

3. Eat. You need balanced, consistent nutrition including all vitamins, branched chain amino acids, and low glycemic index carbohydrates balanced with a good macronutrient balance with good freshly-cooked protein and the gamut of healthy fats. If you have genetic issues metabolizing, e.g. MTHFR/MTRR mutations & folic acid (23andme cleared that up for me), take care of them ASAP.

4. Exercise. If you don't use it, you'll lose it. Remember, stimulants induce catabolism (metabolizing proteins -- as in your muscles -- and fats -- including in your brain) in cases of caloric deficit, and potent stimulants won't stop as per usual. This will also dramatically re-balance everything in your physical and neurochemical profile, provided you get enough nutrients and sleep. Seriously, dopamine, serotonin, endorphins (endogenous opiod-like painkillers & happy fun time chemicals), et.c. go up -- permanently -- and cortisol goes down.

5. Meditation. It actually works.

6. Yoga/nature/sex/travelling/friends -- whatever centers you and brings you back to that happy place. Part of the composite issue is that by worrying about a stimulant's side-effects obsessively while on stimulants (or even not) you are wiring your cells to fire together in the Hebbian fashion to continue a negative feedback loop of psychological, and thus physiological, stress and unhappiness. This, again, increases your cortisol levels.

 

That brings me to cortisol management. Initially, cortisol is part of the effect of the chemical working as intended, as it is elevated in response to exercise, stress, and as a metabolic by-product of dopamine and norepinephrine -- which are significantly and continuously elevated on stimulants -- degrading along their metabolic pathway into adrenaline, which includes multiple steps that increase cortisol. This is part of what stimulants do. In the short-term, this can increase monoamine concentrations (as well as increase the level of hormones like testosterone). However, chronically elevated cortisol is highly correlated with significant stress, and essentially begins a regulatory feedback control mechanism using hormones to regulate neurotransmitters. A little bit of cortisol is excellent for getting you up and going from sleep in the morning, but it needs to decrease at troughs in your circadian rhythm or you will have problems. Some of these include: suppression of endogenous testosterone and growth hormone, reduction of slow-wave (deep, muscle-repairing, hormone- & neurotransmitter-rebalancing) as well as NREM (dreaming, memory consolidation, various neural hedge-trimming) sleep, and a slow increase in calcium channel (and others that I cannot accurately recall at the moment, but I suspect potassium channel and possibly sodium channel) firing rate along with your aforementioned magnesium-mediated signalling increase. Over time, as those become imbalanced, you can also potentially experience a glutamate/GABA imbalance similar to the withdrawal from GABAergics like alcohol & benzodiazepenes.

 

All of this can make your body feel somewhere between an induced anxiety disorder and, well, chronic fatigue syndrome. Luckily, the withdrawal from amphetamines makes you feel tired because it's repairing overworked mitochondria and slowly up-regulating downregulated dopamine receptors as well as possibly similar effects upon endorphins. The adrenaline-like effects from excess norepi/epi would continue unabated, and the undiscriminating alpha 1,2 & beta 1,2 adrenergic stimulation eventually gets tiresome to even the most indefatigable smooth muscle, hence jaw clenching and chest pains from, mostly, really tight muscles and constricted blood vessels.

 

Pharmaceutically, you can try to counteract this physiologically with adrenergic blockers: beta blockers like propranolol -- which also works off-label for anxiety, but is totally unselective -- or alpha 2 agonists like guanfacine (originally prescribed as an adjunctive medication for stimulants, but I believe was shown to be somehow unsafe) or clonidine (also used for sleep and easing withdrawals). There are other medications like this, but these are all heart medications, so beware -- consult with your medical profession, and have them consult with pharm/psych/neuro/cardio et.c. specialists as well to be extra sure. Adding anything can complicate the variables, and these can have paradoxical rebound that could exacerbate your situation. The other alternatives like benzodiazepenes and SSRI's have some significant health issues with addiction and withdrawal/post-acute withdrawal syndromes that may or may not ever recede, depending on whom you ask. I would advise not going down that road unless you have exhausted every other imaginable option for that reason. Don't turn a resolvable temporary psychologically-mediated issue into a longer-term physiological issue.

 

All of these things are mostly insignificant and unnoticeable until you run yourself down, and you do that by being stressed, not eating right, and not working out while not sleeping enough.

 

Also, check your dosage -- maybe the XR 30mg is too much for you. I know adults (both >6' & >=200lb) who have been taking Adderall since they were in elementary school who didn't like taking Adderall XR 30mg because it was, quote, "too much": http://pi.shireconte...lXR_USA_ENG.PDF -- see page 6 for ng/mL plasma concentrations across T(hr). Also note how important food consumption is in the text directly below that graph: the effective time increased from 5.2hrs fasted to 7.7hrs after a high-fat meal. I like steak, eggs, and potatos; but that may be overkill on your HDL/LDL lipid frag panel. To be fair, I also know a ~5'10" & ~160lb guy who was prescribed XR 30mg b.i.d (twice a day).

 

If you like the effectiveness of dosage but experience these peripheral side effects, consider large vitamin C doses a few hours before you wind down for the day so you can help excrete the amphetamines at a significantly faster rate -- there's a reason they tell you not to drink fruit juices when you take it, but that can help at the end of your day.

 

Stack to improve symptoms on or off medication:

Day:

- a simple multivitamin every day helped immeasurably. Don't forget! And try to take it in the evening as per the above vitamin C issue which I'll mention in a moment. (I'm using NOW Adam, which surprisingly has a solid quantity of high-bioavailability forms of vitamins & minerals -- very important) 

- Fish oil (high DHA 400+ as per the inspirational MrHappy) seems to help, especially with

- Uridine, which MrHappy cued me to. It had subtle but noticeable effect over time -- simply more positives and less negatives from the medication. 100-200mg daily, or twice daily -- I'm new here, go with his recommendations.
- CDP-Choline taken sparingly -- every few days (a post I read after I stopped my daily regimen stated that it and its metabolites can last for days, no citation there), but when I take it regularly at ~100-250mg it doesn't seem to cause any drowsiness or headaches, but rather calmly energizes me. If I take it every day, i.e. to stave off potential head pressure sensations from Noopept, I'll have ~150mg 1x or 2x a day.

- ALCAR -- I don't like too much, maybe 200-400mg. I feel like it can overload me. Anytime I feel "overload" I expect negative repercussions as my body balances itself back out.

- Noopept (with piracetam, but only for the verbal fluency increase) -- I wasn't a huge fan of piracetam 400-800mg, even 2-3 times a day with or without CDP-choline, if simply because I didn't notice much effect besides a slight overfocus (although the verbal fluency increase was cool, but I don't usually have a problem with that). Then I added Noopept, which seems to work almost as well on its own. Well, it works, and may be too potent -- sometimes I feel like a zombie computing machine, particularly combined with low dose Adderall. Less is more: 5-10mg, maybe 2x (or even 3x? seems to begin to wear off between hour 3-5 similar to instant release Adderall). At the end of the day I seem to sleep a bit harder, especially if I only took it in the morning. I've even had some vivid, occasionally lucid dreams. I like to take it 3-5 days a week as I don't like my state of mind to be modified every single day of the week.

 

At the end of the day:

- Vitamin C -- particularly C, and in higher (I'm still playing with specifics) dosages in order to increase the rate of renal excretion of amphetamine & its metabolites. If taken earlier it will "dull" the effects, which is good if you haven't reached max plasma concentration yet and suspect overstimulation when you do arrive. If you are already overstimulated, you may have a minor sensation of sedation as you relax and reach equilibrium. May make medication ineffective, though.

- Magnesium Glycinate -- It does calm you down and acts as a mild muscle relaxant. I just happen to like glycinate, and maybe 150mg-300mg (for about 20-40mg elemental magnesium -- compare to 500mg Mg oxide that contains 12mg elemental magnesium) a few hours before bed. to be sure to check ozone's post (http://www.longecity...agnesium-types/) and order a high bioavailability kind. I like this one because mag cit is used as a laxative and this is the next best thing. Check into the threo- form, but I haven't tried it and have heard conflicting reports (and it's expensive.)

- L-Theanine -- it seems that most people love it and a few hate it, but in smaller doses (50mg) it helps to take the edge off any time of the day. Sometimes I'll have 100-200mg before bed to really drop me, but it seems that there is increased sedation from magnesium and/or any other somnolence-promoting agent like melatonin (which I unfortunately metabolize slowly and/or abnormally, thanks insomnia -- which you can thank for this post) or Ambien (which I, unfortunately, take more than I likely should and am attempting to slowly titrate off of and replace)-- something, possibly via the supposed enhancement of GABA effectiveness or serotonin acting at its inhibitory receptors -- if I have:

 

Special synergy note:

- Caffeine -- I rarely have coffee with any regularity anymore unless I'm in finals or taking a break from Adderall. If I do, the AM. but be aware that caffeine will exert a synergistic effect with amphetamines that may significantly wear you out. It definitely increases the rate that you will metabolize and/or simply excrete amphetamines causing the Tmax of the above curve to be shorter. 

 

Experimental potentially-crazy or simply too-new-to-be-widespread "nootropics":

- Selank -- On its own, the first time I used it I felt noticeably calm, yet awake. Apparently acts to prevent enkephalins from degrading, which are the delta-opiod receptor endogenous opioid peptide similar to endorphins' action at mu-opioid receptors. It seems to -- if only via its generally calming qualities, but I suspect chemically -- reduce chronically elevated cortisol levels. Too much may make you not want to do anything. I found about 25-50mcg (vs. the 250-500mcg recommended to me) subcutaneously would take the overly-driven "hard" edge that early-morning Adderall can bring, particularly without enough sleep and/or with caffeine, without reducing the cognitive effects. I suspect a synergy between the secondary endorphin-activating effects of amphetamine at, if I recall correctly, sigma opioid receptors. I believe caffeine also has some sort of similar effect on endorphins.

- P21 -- A surprisingly useful tool recently added to my toolbox. Added an incredible ease of fluid thinking, if simply through accessible energy and capacity to manage attention and thus increased working memory. 125-250mcg provided ever-so-slight energy and noticeable awareness and lucidity for 3-6 hours on its own and with Adderall. 500-750mcg was fine without Adderall. More than that increased the effects but resulted in the slightest urge to take a nap after more of the positive effects above. At 1.5mg the effects seemed to result in diminishing returns in positive effects with a more pronounced sense of wanting to take a pleasant nap. Induced remarkably vivid memories of dreams the night before, and in particular involved becoming lucid, turning a neutral dream into positive, controlled one, and then waking myself up consciously feeling warm, calm energy. It seemed to be easier to store and retrieve complex information (bio, chem, calc). I've only tried it for 5 days and am taking a short break, as that is the protocol for Cerebrolysin, of which it is apparently a highly-active component peptide.

 

Next I intend to try Semax.

 

N.B.: I really reacted specifcally well to metabolically-active vitamin B complex (P5P for B6, methylcobalamin for B12) as well as pre-methylated folate due to the above MTHFR/MTRR issue that I recognized upon running my 23andme results at nutrahacker.com & geneticgenie.com (the former has actual recommendations along with the latter's list of methylation-related genes). Not to plug brands, but Thorne Research Methyl Guard surprised me and replaced all of my activated B and folate supplements in one for cheaper. A good high-bioavailability multivitamin with metabolically active B (e.g., P5P & methylcobalamin) lets you skip the Methyl Guard unless you want 5-methyltetrahydofolate to bypass methylation of folic acid for some reason. I really like this whole nutrigenetics angle and have been getting into it in the last few months with noticeable effects. Consider it if you want to do more research on yourself that has some (at least somewhat) scientifically-backed reasoning custom tailored to you.

A post worthy of a bookmark.  Nice job!



#8 barbelith42

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Posted 24 August 2014 - 01:11 AM

Thanks mindpatch!

 

I actually had a huge page-long edit of this post involving research, citations, and further discussion about MGluR hyperactivity potential mediated by *racetam overuse with stimulants as well as NGF/BDNF as per Flex but apparently you can only edit within a certain time window and it was lost when I hit submit, but I'll try to recap here and let you guys hit pubmed and google scholar if you want the exact details. The important ones involved amphetamine-related learned fear/helplessness and subsequent increased cortisol and how BDNF/NGF and P21 were capable of reversing -- and even improving -- exactly the same functions in limited in vitro testing for brain function and in vivo testing using mice.

 

RE: Flex: -- first off, I've read a lot of your posts, and much respect to your for your knowledge and work that you contribute, glad to have you in the conversation! -- due to the *racetam's ability to increase glutamatergic signalling it is possible that the combination caused some kind of excitotoxicity, although personally I feel this is highly unlikely from my objective research and subjective experimentation and *racetam protocols, but everyone is different. It is much more likely that temporary down-regulation occured, particularly in light of the combination of neural firing rate increasing substances. Your GABA/glutamate balance is a fundamental aspect of the ability of the nervous system to transmit electrical impulses from cell to cell and this works essentially the same way as it does with any orgasm possessing a nervous system. It is very difficult to permanently damage. However, the ability to rapid adjust to environmental stimuli (particularly increased activity that can cause excitotoxicity) has been a positive adaptation for, well millions of years; as such, it's a very easy thing to do. This is similar to the "why do I feel so good the day after drinking" glutamate rebound effect after dousing your (C/P)NS in GABA positive allosteric modulating ethanol and its by-products. This system shifts rapidly to react, but slowly up- and down-regulates to protect.

 

Give it some time along with the right diet, exercise, and mental and emotional processes to produce the perfect environment to be restored -- now that you know this can happen, you can actually work to make this potentially function better than before. NGF and BDNF stimulating agents will provide a great supplemental support for this, hence my fondness for Noopept and P21 along with Selank, magnesium, theanine, and vitamin c to produce an environment where cortisol is allowed to drop to its natural troughs along the circadian rhythm and allow sleep to be as fully restorative as it should be, or more.

 

The ability for progenitor cells -- adult stem cells, not pluripotent as in pre-natal ones but selectively able to become one of a set of functions -- in the hippocampus and subventricular zone (SVZ) is highly documented, however the ability of this to migrate and how far is disputed in humans. Other animals like mice are gifted with neuroblasts that migrate from these regions around the brain and are thus able to regrow dendrites, glia, et.c. in other places. Recent research indicates limited ability to migrate within localized regions, e.g. the cortex for learning motor functions and the areas ennervated by the SVZ, which are luckily quite a few and those implicated in ADHD and the whole dopaminergic meso-limbic-cortical system (nucleus accumbens, prefrontal cortex, potentially the caudate/caudal brain stem & amygdala where they are connected to the hippocampus) as well as the nigrostriatal system (striatum, et.c.). Providing and environment where there are increased quantities of NGF/BDNF and the proper stimulation via exercise, meditation, and learning (VERY IMPORTANT for starting the process of even beginning to use those growth factors -- this is an ACTIVE process, just like muscular hypertrophy, so use it or lose it!) and allowing enough REM sleep to trim unused and unwanted connections being formed, particularly in the hippocampus where you can have all kinds of strange state-based memories form and induce cortisol release related to past memories of exposure to stimulants (which is also why cortisol management is so important) and induce anxiety/PTSD-like symptoms.


Edited by barbelith42, 24 August 2014 - 01:31 AM.


#9 Izan

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Posted 24 August 2014 - 02:56 PM

berbelith42, did p21 give you also physical energy and motivation ''to get things done''? 



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#10 barbelith42

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Posted 25 August 2014 - 12:29 AM

Yes, definitely.

It's very subtle compared to the driving nature of other stimulants like caffeine, modafinil, or amphetamine -- all of which have pretty significant negative side effects -- but absolutely noticeable. It's exactly what I was hoping to find.

Today, for example, I had a hard time getting my head in the game to prep for work, classes, and labs this week even after taking a recovery day yesterday and getting a good night's sleep. I also am probably in mild caffeine withdrawals from Tu-F use. I had 1.5mg of P21 an hour ago and at some point in the last half hour I just started to organize my schedule, prep my labs, finish my homework, and respond to posts without any extrinsic motivating factor like feeling anxious about deadlines -- rather, it seems simply a better choice to do it now, catch the sunday night TV that I follow, and go to sleep sooner sooner so that I'm good to go Monday AM.

I'd like to point out that Ceretropic's Jason (aka guacamolium on reddit nootropics) said that he now prefers P21 to Semax, the supposedly more stimulantory of the Russian peptides that they have, (as compared to the non-sedating antioxylytic Selank, which I also highly approve of) which I will compare myself when they restock ther 120mg vials. I'm trying to run P21 as per the Cerebrolysin protocol of 5d/wk for 4-6wk first before advising further regarding its continued usefulness, but if it's anything likw Cerebrolysin it should continue to be effective and even provide long-term benefits. The only side effect I've noticed is that when I sleep, I dream more. I also can get a mild sensation of being able, but not requiring, a nap after 3-5hr, but that is likely related to circadian rhythm fluctuations. When I do take a nap at that time, I feel that it's much easier to wake up in 30-180m fully refreshed and with a crystal clear recollection of material studied during that time. Noopept synergizes especially well with it as their effective durations seem to overlap and their benefits counterbalance the other's side effects, such as overfocus, asociality, flat affect from Noopept and unfocused interest when on P21 -- but I'm seriously ADHD, so the simple fact that I'm here posting all these data without being caffeinated or required to is very telling and exciting for me personally. They both individually give me a bit of tiredness in a different way: Noopept seems to have a level of fatigue at the end of its effective duration, gives vivid dreams, and makes me feel like I NEED more sleep; whereas P21 gives me -- a chronic insomniac -- the ability to drift into a rereshing sleep (even a short nap that doesn't interfere with my night's sleep!) but leaves me feeling less psychologically fatigued all day.

On Adderall off days I get work done with the help of a multvitamin, uridine (200mg), fish oil, and CDP choline (100mg) followed by these separate or together: 10mg of Noopept 1-3x and 500-1,500mcg P21 1-3x, usually every 4hr or so. I find one dose of P21 can help the whole day more than Noopept at one dose.

If any peripheral overstimulation, anxiety, or anhedonia occurs from stimulants or racetams (particularly Noopept), I find Selank OR L-Theanine to be highly effective at 125-250mcg and 25-100mg respectively. Combos of the two can be a bit intense, probably due to amplified GABA effectiveness or some kind of L-Theanine mild serotonergic activity. I find it hard to get motivated after both without stimulant assistance, even with P21 -- but the 3 together can make a recovery/rest day incredibly effective. Selank also amplifies runner's high likely via endorphins and can go great with a workout -- combine with D-Phenylalanine's endorphin-boosting effects at 250-500mg+ for an almost overwhelming post-workout high.

What I can recommend to anyone using this -- or any other motivating neurotrophic agent -- is this: use this capacity wisely to improve your higher learning and reasoning functions, improve your workouts and motor coordination, improve your reading list, and improve your habits. Build a new routine that is more effective, and you can truly improve yourself in the process.

See my latest post in the Cerebrolysin thread and CNTF based peptide P21 thread for other details.


Edited by barbelith42, 25 August 2014 - 12:40 AM.






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