17 replies to this topic

[Plasticperson]

Why does piracetam cause mania??? Some people get extremely manic from piracetam while others experience dullness. What is the mechanism behind this action?

[SuperjackDid_]

excite glutamate induce large amount release in dopamine .

but some said not enough choline

so we still need clearly explain behind mechanism of action.

[Dissolvedissolve]

We know piracetam is an NMDA modulator. So in certain individuals, especially those with low NMDA activity, this may cause a sufficient increase in glutamate signaling to create mania. In this vein, it should be noted that seizure drugs are often used to treat manic episodes, and they are primarily indirect glutamate antagonists (although this isn't saying much, since glutamate is the dominant excitatory neurotransmitter.

There's also evidence that piracetam potentiates NT release or activation (I can't remember which right now - it's on Pubmed.) This is why it potentiates stimulants. And so for someone who is for some sort of endogenous stimulation, this may be intensified.

These are only speculations. Feel free to add to or correct my statements.

[Adaptogen]

Is there a thread for a how to guide to stimulate this state? maybe we can find a way to harness the mania.

I see manic people on here all the time, writing 500 word+ essay posts about nothing...I don't know how much nootropic it takes to get there, but I have yet to reach it

Edited by Adaptogen, 04 February 2013 - 08:23 AM.

[LBGSHI]

We know piracetam is an NMDA modulator. So in certain individuals, especially those with low NMDA activity, this may cause a sufficient increase in glutamate signaling to create mania. In this vein, it should be noted that seizure drugs are often used to treat manic episodes, and they are primarily indirect glutamate antagonists (although this isn't saying much, since glutamate is the dominant excitatory neurotransmitter.

There's also evidence that piracetam potentiates NT release or activation (I can't remember which right now - it's on Pubmed.) This is why it potentiates stimulants. And so for someone who is for some sort of endogenous stimulation, this may be intensified.

These are only speculations. Feel free to add to or correct my statements.

A solid speculation; the theory is sound. It could also be placebo.

Is there a thread for a how to guide to stimulate this state? maybe we can find a way to harness the mania.

I see manic people on here all the time, writing 500 word+ essay posts about nothing...I don't know how much nootropic it takes to get there, but I have yet to reach it

I don't know why someone gave you -1 for this post, but I gave you +1 to cancel it out. It's a valid statement (we certainly do see people occasionally post fanciful stories with no real content on manic racetam trips), and a valid proposition (there might be a way to harness intentional mania for specific purpose...in fact, it's been discussed in other threads).

[Gorthaur]

Piracetam might also cause mania simply due to depletion of acetylcholine.

[LBGSHI]

Piracetam might also cause mania simply due to depletion of acetylcholine.

Is there any evidence for choline deficiency causing mania? You'd think this would be mentioned in relation to choline and acetylcholine inhibitors, but I haven't seen such a correlation.

[Gorthaur]

I can't find any hard evidence, just some older references here and there. My experiences with racetams and various forms of choline strongly suggest to me that mania requires low acetylcholine.

Central cholinergic factors may play a role in the ætiology of affective disorders. Specifically, a given affective state may represent a balance between central cholinergic and adrenergic neurotransmitter activity in those areas of the brain which regulate affect, with depression being a disease of cholinergic dominance and mania being the converse. Support for this hypothesis comes from animal experiments demonstrating antagonistic cholinergic and adrenergic central behavioural effects. Furthermore, reserpine, a drug which causes depression, has central cholinomimetic properties. Conversely, tricyclic antidepressants have central anticholinergic properties. In man, physostigmine and other centrally acting cholinomimetic agents which increase central acetylcholine levels counteract mania and may cause depression in some individuals. Considering manic-depressive disorders and related phenomena from the viewpoint of cholinergic-adrenergic balance, or conceptualising behaviour as having both adrenergic and cholinergic components, provides a framework for understanding the affective disorders.

http://www.thelancet...930218/abstract

Francis Mondimore postulated the biochemical theory that a lack of Norepinephrine causes a person to be depressed and that their level of Acetylcholine is very high. On the other side of the spectrum, when Norepinephrine is at a very high level, their state is a manic state and their level of Acetylcholine is very low. (See Illustration #1). The medication Lithium is used to treat both the depressed state and the manic state. It does not treat the level of neurotransmitters, but rather it treats the mechanism that determines how to release these neurotransmitters. (Mondimore 1990).

http://www.nyu.edu/c...rapy/manic.html

[chung_pao]

Is there a thread for a how to guide to stimulate this state? maybe we can find a way to harness the mania.

I see manic people on here all the time, writing 500 word+ essay posts about nothing...I don't know how much nootropic it takes to get there, but I have yet to reach it

I've been interested in this for a while and have tried different stacks and methods for the purpose of reaching "induced-mania".
What I've so far concluded is that a few specific things can contribute to reaching mania:

Increasing catecholamines. (using direct and indirect agonists like MAO-B inhibitors, modafinil, caffeine)
Decreasing acetylcholine or choline availability. (deprivation of any significant choline intake has contributed)
Increasing excitatory neurotransmission while decreasing inhibitory. (more potentiation of AMPA receptors, less agonism of GABA)
Low blood sugar also contributes to manic tendencies.

By far, I think potentiation of excitatory neurotransmission, decreasing acetylcholine and maximizing catecholamines (especially dopamine, if you want to make it pleasant) are the causative factors of this state.

Given the fact that piracetam makes the induction of mania easier, glutamate seems to play a big role.
Piracetam also increases choline uptake and its subsequent depletion, creating a "craving" for choline if this need is not met.

Of course, this is all anecdotal speculation.

Edited by chung_pao, 05 February 2013 - 01:32 AM.

[chung_pao]

I can't find any hard evidence, just some older references here and there. My experiences with racetams and various forms of choline strongly suggest to me that mania requires low acetylcholine.

...agents which increase central acetylcholine levels counteract mania and may cause depression...

...when Norepinephrine is at a very high level, their state is a manic state and their level of Acetylcholine is very low....

I agree with you on this.
I've definitely had manic tendencies in my past. These occurred during a time when my diet almost exclusively consisted of low fat dairy products, nuts, piracetam and coffee... (i.e. no significant sources of choline)

To describe mania from a first person perspective: Aggressive, extremely aroused, very motivated with no real reason to be so, jittery, anxious, unable to concentrate and block out distractions, asocial tendencies, compulsive and repetitive (ritualistic) tendencies. In one word: excited.

A definite characteristic is a worse memory. My learning was much worse during manic episodes, and I had to rehearse the same information a bunch of times before any of it stuck.
Nowadays, I always maintain decent choline levels, adjusted to meet my choline requirement (elevated during use of ampakines), and learning is much easier.

Btw: to reach a conclusion in this thread, why not just supplement with choline and observe the effects?
If you do, please update here.

Edited by chung_pao, 05 February 2013 - 01:58 AM.

[Absent]

There may be some chemical reason for it but I'll try to put it into laymen terms as I understand it and have personally experienced it.

Piracetam[with fishoil] Mania doesn't cause a person to be any more egotistical than they normally... it just gives them so much brain power which is often vented into egotistic rants and episodes. It's not the piracetam is causing them to be manic, it's basically just giving great power to their natural personality.

Truth is most people aren't very focused in their minds and it is really exaggerated and noticeable in manic episodes as their brain power is intensified. If their minds were more focused, that mania could be translated into hyper-intelligence, or into whatever they're focusing on. Though truth is most people aren't very focused as most people don't meditate, so as a result they're almost always partially involved with their ego, rather than being 100% focused on whatever the subject is. This can lead to very lengthy post, and very high mental energy levels where their lack of grounded focused is very noticeable.

[LBGSHI]

I can't find any hard evidence, just some older references here and there. My experiences with racetams and various forms of choline strongly suggest to me that mania requires low acetylcholine.

Central cholinergic factors may play a role in the ætiology of affective disorders. Specifically, a given affective state may represent a balance between central cholinergic and adrenergic neurotransmitter activity in those areas of the brain which regulate affect, with depression being a disease of cholinergic dominance and mania being the converse. Support for this hypothesis comes from animal experiments demonstrating antagonistic cholinergic and adrenergic central behavioural effects. Furthermore, reserpine, a drug which causes depression, has central cholinomimetic properties. Conversely, tricyclic antidepressants have central anticholinergic properties. In man, physostigmine and other centrally acting cholinomimetic agents which increase central acetylcholine levels counteract mania and may cause depression in some individuals. Considering manic-depressive disorders and related phenomena from the viewpoint of cholinergic-adrenergic balance, or conceptualising behaviour as having both adrenergic and cholinergic components, provides a framework for understanding the affective disorders.

http://www.thelancet...930218/abstract

Francis Mondimore postulated the biochemical theory that a lack of Norepinephrine causes a person to be depressed and that their level of Acetylcholine is very high. On the other side of the spectrum, when Norepinephrine is at a very high level, their state is a manic state and their level of Acetylcholine is very low. (See Illustration #1). The medication Lithium is used to treat both the depressed state and the manic state. It does not treat the level of neurotransmitters, but rather it treats the mechanism that determines how to release these neurotransmitters. (Mondimore 1990).

http://www.nyu.edu/c...rapy/manic.html

Cool; good stuff. Thanks for pointing those out.

There may be some chemical reason for it but I'll try to put it into laymen terms as I understand it and have personally experienced it.

Piracetam[with fishoil] Mania doesn't cause a person to be any more egotistical than they normally... it just gives them so much brain power which is often vented into egotistic rants and episodes. It's not the piracetam is causing them to be manic, it's basically just giving great power to their natural personality.

Truth is most people aren't very focused in their minds and it is really exaggerated and noticeable in manic episodes as their brain power is intensified. If their minds were more focused, that mania could be translated into hyper-intelligence, or into whatever they're focusing on. Though truth is most people aren't very focused as most people don't meditate, so as a result they're almost always partially involved with their ego, rather than being 100% focused on whatever the subject is. This can lead to very lengthy post, and very high mental energy levels where their lack of grounded focused is very noticeable.

I agree to an extent, but it's also obvious that most of the time people going manic on a racetam don't really make real sense in their posts. They sound flowery and artistic, as if to assume an air of eloquence and superiority, but they lack depth. You could describe this as lack of focus (which is probably true), but I think that's only one of the problems. I don't know if they're really more intelligent than before, so much as that they believe they are. Mania provides motivation and energy, but intelligence doesn't derive from mania (impressive accomplishments by manic people are due not only to their mania and subsequent drive and energy, but also due to inherent intelligence).

[Absent]

I agree to an extent, but it's also obvious that most of the time people going manic on a racetam don't really make real sense in their posts. They sound flowery and artistic, as if to assume an air of eloquence and superiority, but they lack depth. You could describe this as lack of focus (which is probably true), but I think that's only one of the problems. I don't know if they're really more intelligent than before, so much as that they believe they are. Mania provides motivation and energy, but intelligence doesn't derive from mania (impressive accomplishments by manic people are due not only to their mania and subsequent drive and energy, but also due to inherent intelligence).

Truth is most people aren't very focused in their minds and it is really exaggerated and noticeable in manic episodes as their brain power is intensified. If their minds were more focused, that mania could be translated into hyper-intelligence, or into whatever they're focusing on. Though truth is most people aren't very focused as most people don't meditate, so as a result they're almost always partially involved with their ego, rather than being 100% focused on whatever the subject is. This can lead to very lengthy post, and very high mental energy levels where their lack of grounded focused is very noticeable.

You're right. Mania doesn't translate into hyperintelligence. But anywhere there is great brain power lies the potential for hyperintelligence, if the focus is right. It could mean super learning potential, IF they apply it in that direction properly with enough focus.

[Plasticperson]

I can't find any hard evidence, just some older references here and there. My experiences with racetams and various forms of choline strongly suggest to me that mania requires low acetylcholine.

Central cholinergic factors may play a role in the ætiology of affective disorders. Specifically, a given affective state may represent a balance between central cholinergic and adrenergic neurotransmitter activity in those areas of the brain which regulate affect, with depression being a disease of cholinergic dominance and mania being the converse. Support for this hypothesis comes from animal experiments demonstrating antagonistic cholinergic and adrenergic central behavioural effects. Furthermore, reserpine, a drug which causes depression, has central cholinomimetic properties. Conversely, tricyclic antidepressants have central anticholinergic properties. In man, physostigmine and other centrally acting cholinomimetic agents which increase central acetylcholine levels counteract mania and may cause depression in some individuals. Considering manic-depressive disorders and related phenomena from the viewpoint of cholinergic-adrenergic balance, or conceptualising behaviour as having both adrenergic and cholinergic components, provides a framework for understanding the affective disorders.

http://www.thelancet...930218/abstract

Francis Mondimore postulated the biochemical theory that a lack of Norepinephrine causes a person to be depressed and that their level of Acetylcholine is very high. On the other side of the spectrum, when Norepinephrine is at a very high level, their state is a manic state and their level of Acetylcholine is very low. (See Illustration #1). The medication Lithium is used to treat both the depressed state and the manic state. It does not treat the level of neurotransmitters, but rather it treats the mechanism that determines how to release these neurotransmitters. (Mondimore 1990).

http://www.nyu.edu/c...rapy/manic.html

Your second quote makes complete sense to me. The days after I feel elated, white spots accumulate on the bottoms of my fingernails where the new nail growth starts. After researching the mechanism behind these white spots I have determined they are from an abundance of copper in my body and form during a toxic excess period. Coincidentally, "Dopamine beta-hydroxylase is a copper-containing enzyme that synthesizes norepinephrine from dopamine".I personally beleive that mania in certain instances is a manifesation of copper deposits dumping excess copper into the blood stream. The copper enter the blood streams forms excess Dopamine beta hydoxylase and, simultaneously, deposits onto the new nail growth.

There may be some chemical reason for it but I'll try to put it into laymen terms as I understand it and have personally experienced it.

Piracetam[with fishoil] Mania doesn't cause a person to be any more egotistical than they normally... it just gives them so much brain power which is often vented into egotistic rants and episodes. It's not the piracetam is causing them to be manic, it's basically just giving great power to their natural personality.

Truth is most people aren't very focused in their minds and it is really exaggerated and noticeable in manic episodes as their brain power is intensified. If their minds were more focused, that mania could be translated into hyper-intelligence, or into whatever they're focusing on. Though truth is most people aren't very focused as most people don't meditate, so as a result they're almost always partially involved with their ego, rather than being 100% focused on whatever the subject is. This can lead to very lengthy post, and very high mental energy levels where their lack of grounded focused is very noticeable.

My theory behind piracetams mania mechanism is quite different than that off the copper mechanism Acetylcholine and piracetam antagonize each other; essentially they have a see saw relationship in the brain. When one supplements piracetam with out a choline source, choline levels drop in the brain. When the choline levels drop in the brain the bodies inherent dopamine/choline seesaw relationship causes dopamine to surge. This surge in dopamine, caused by a drop in choline, induces mania.

Siro, i dont exactly know if i understand you correctly. Are you proposing that mania can help someone who has gifted intelligence/creativity who also exhibits low motivation and drive? By the means that this lowly motivated, intelligently gifted person can afford a deficit in intelligence/memory due to mania becasue they are so smart to begin with that a higher motivation combined with sub-genius level thinking (due to the mania memory/intelligence deficit) can generate someone capable of doing amazing things.

Edited by Plasticperson, 05 February 2013 - 02:46 PM.

[Absent]

My theory behind piracetams mania mechanism is quite different than that off the copper mechanism Acetylcholine and piracetam antagonize each other; essentially they have a see saw relationship in the brain. When one supplements piracetam with out a choline source, choline levels drop in the brain. When the choline levels drop in the brain the bodies inherent dopamine/choline seesaw relationship causes dopamine to surge. This surge in dopamine, caused by a drop in choline, induces mania.

Siro, i dont exactly know if i understand you correctly. Are you proposing that mania can help someone who has gifted intelligence/creativity who also exhibits low motivation and drive? By the means that this lowly motivated, intelligently gifted person can afford a deficit in intelligence/memory due to mania becasue they are so smart to begin with that a higher motivation combined with sub-genius level thinking (due to the mania memory/intelligence deficit) can generate someone capable of doing amazing things.

That's more or less one way to think about it. I try to think about it as if it were steroids for the mind(minus all the negative side effects of muscular steroids :p). If a skinny person takes a bunch of steroids, they may be hyped up, energized, and have more physical energy... but taking steroids alone will not turn them into a body builder. What it will do is given them the ability to gain muscle very very fast and efficiently. Piracetam can act in the same way. While it's unlikely to spontaneously make somebody a genius, it can allow for genius type traits to develop.

I am not just saying this out of theory. On some of my megadoses of Piracetam, in just a couple of days of randomly attempting, I was able to significantly enhance my visualization abilities, just my visualizing random crap throughout my day. The visualizations would be so powerful that they were borderline halucination. This didn't occur on it's own, but out of the mental intention and effort combined with the super-power of piracetam+fish oil mega dose.

This intense mental visualization is still with me today. It wasn't like some LSD induced halucinatory abilities. It was more like a learned skill. It is one of the few mental feats I have trained myself to do in very very short times with Piracetam Megadoses, though I don't like to brag about that sort of stuff. All I know is once you realize the powerful potential of something like this, you can do all sorts of amazing things.... but if you don't realize that powerful potential in a way that is applicable, then all you really have on your hands is a super-power stimulant-type combo. Intention is the key here. You can train your mind to do amazing things with or without a supercharged brain, but I find that Piracetam+Fishoil can speed up the process x100-1000 times in extraordinary ways. Had I never messed around with any mental thought tricks or thought experiments, I would have never learned this and probably not have taken anything tangible from the experiment.

This brings me to my final and somewhat related point that nobody has any excuse to be bored every. The mind can do some amazing goddamn things, that can make it more entertaining than anything on this planet.

[Galaxyshock]

This brings me to my final and somewhat related point that nobody has any excuse to be bored every. The mind can do some amazing goddamn things, that can make it more entertaining than anything on this planet.

Tell that to someone with severe anhedonia. They'll spit in your ignorant face.

Edited by Galaxyshock, 06 February 2013 - 09:34 AM.

[Plasticperson]

This brings me to my final and somewhat related point that nobody has any excuse to be bored every. The mind can do some amazing goddamn things, that can make it more entertaining than anything on this planet.

Tell that to someone with severe anhedonia. They'll spit in your ignorant face.

Yes but why they wouldn't experience any pleasure by doing so

[Adaptogen]

I have been taking alcar and the occasional dose of citrate as my choline sources. I think I will try dropping choline and see if this induces a more excitatory state. The other day I took 5 grams in the morning before class, and then two hours later took another 5 grams on an empty stomach. This led to a very euphoric and impulsive state. Walking around campus I honestly had the urge to climb into trees and grab random girls' hands.


So low levels of choline in the brain cause dopamine levels to rise? is there any downside to this? other than if you do not want mania or maybe a bit of brain fog...