Brain Function Boosters 3.0

Nutrition
22

[quote]Alpha F wrote:

[quote]buffd_samurai wrote:

I, unfortunately, do not tolerate aniracetam very well. Seriously speaking, it puts me in a SERIOUSLY bad mood. It basically turns me into a “bad drunk”, i.e. someone who is overly aggressive and “throws their weight around” when under its “influence”. Why this is, I don’t know. But it looks like fat soluable racetams are definitely not for me.

Anyone else like this? [/quote] Yes.[quote]
Anyone had a reasonable rationale mechanism that might explain such strange reactions for me?[/quote]
You could be dopamine dominant in your genetic brain make up.
By taking a substance that might enhance dopamine levels in you pre frontal cortex you tip over an already high dopamine level. Two of the functions implicated on the pre frontal cortex are: personality expression and moderation of correct social behavior. If you are, by default, high dopamine, low serotonin and low norepinepherine, enhancing dopamine and serotonin might explain the neurological effect on your mood and behavioural changes.

"Aniracetam enhances cortical dopamine and serotonin release via cholinergic and glutamatergic mechanisms in SHRSP

Shirane M, Nakamura K.

CNS Supporting Laboratory,
Nippon Roche Research Center,
200 Kajiwara, 247-8530, Kamakura, Japan
Brain Res 2001 Oct 19;916(1-2):211-21

Abstract

Aniracetam, a cognition enhancer, has been recently found to preferentially increase extracellular levels of dopamine (DA) and serotonin (5-HT) in the prefrontal cortex (PFC), basolateral amygdala and dorsal hippocampus of the mesocorticolimbic system in stroke-prone spontaneously hypertensive rats. In the present study, we aimed to identify actually active substances among aniracetam and its major metabolites and to clarify the mode of action in DA and 5-HT release in the PFC. Local perfusion of mecamylamine, a nicotinic acetylcholine (nACh) and N-methyl-D-aspartate (NMDA) receptor antagonist, into the ventral tegmental area (VTA) and dorsal raphe nucleus (DRN) completely blocked DA and 5-HT release, respectively, in the PFC elicited by orally administered aniracetam. The effects of aniracetam were mimicked by local perfusion of N-anisoyl–aminobutyric acid (N-anisoyl-GABA), one of the major metabolites of aniracetam, into the VTA and DRN. The cortical DA release induced by N-anisoyl-GABA applied to the VTA was also completely abolished by co-perfusion of mecamylamine. Additionally, when p-anisic acid, another metabolite of aniracetam, and N-anisoyl-GABA were locally perfused into the PFC, they induced DA and 5-HT release in the same region, respectively. These results indicate that aniracetam enhances DA and 5-HT release by mainly mediating the action of N-anisoyl-GABA that targets not only somatodendritic nACh and NMDA receptors but also presynaptic nACh receptors."

[/quote]

What a wonderful rationale…thankyou so much for posting this!

Any information on whether other racetams could act in this manner? I am specifically interested in piracetam. My fear is that I won’t be able to use any of them as I’ve read pira and ani have almost the same effects just that ani seems to be more powerful on a per unit dosage.

In the end though, the only way to really know is to try it as I plan to and report back here. I’m still going to continue my experiment with ani + DMAE to see if that possibly improves things…however the mechanism above would indicate things could get worse. I gotta try it though.

24

[quote]buffd_samurai wrote:
What a wonderful rationale…thankyou so much for posting this!

Any information on whether other racetams could act in this manner? I am specifically interested in piracetam. [/quote]

You are welcome.
I have an interest in neurology as a hobby and it is only from that position that I speak.
I have read papers indicating piracetam has adverse side effects; increased aggression, agitation and irritability and sexual arousal.
My observation is that whilst a substance may not increase dopamine levels it can enhance it by inhibiting the enzyme that breaks down dopamine.
I also invite you to think about piracetam’s role in the catecholamine system.
As suggested with antipshycotic drugs, piracetam might accelerate brain catecholamine turnover by blocking its receptors.

Other research papers suggest Piracetam increases the brain’s turnover of Adenosine Triphosphate (ATP) within the Cerebral Cortex which is associated with increased Energy production within the brain ( think of the effects of enhanced protein synthesis and energy output in a brain wired this way: high dopamine, low serotonin, low norepinephrine ).

Also consider that where nootropics are being compared to MAOI such as Prozac, the rise in dopamine levels may not be significant. However, in a brain which is high in dopamine, low in serotonin and low in norepinephrine, this insignificant enhancement becomes significant enough to cause adverse effects. Coincidently, Prozac was notorious for causing aggressive and violent behavior in certain individuals in spite of being labelled “The Happy Pill” ( I read three books on it in the 90’s ). These individuals literally ‘lost their minds’ and acted on their base impulses without inhibition.

Another paper also suggested piracetam also increased prolactin concentrations in serum. I don’t know what that would mean for you - if you are not on steroids that may be significant and add to your adverse effect in ways only you can discern as you must consider your individual endocrine and neurological make up.

Yohimbe Bark, as piracetam, is also suggested as a dopamine re uptake inhibitor. Interestingly enough I cannot tolerate yohimbine very well. HOT-ROX is overkill for me and Spike pill with yohimbine only when my progesterone levels are high ( luteal fase ).
I need to be severely sleep deprived not to become volcanic on HOT-ROX. Seriously.

Interesting you mentioned Spike, because Caffeine-Free Spike was the best for brain alertness for me. When sleep deprived a pill of Caffeine-Free Spike and a can of Spike Shooter was perfect. I once took this concoction rested and my brain did not stop for 48 continuous hours, no sleep at all and relentless.
Real shame I cannot find Caffeine-Free Spike any more.

25

[quote]bushidobadboy wrote:

[quote]buffd_samurai wrote:

[quote]Alpha F wrote:

[quote]buffd_samurai wrote:

I, unfortunately, do not tolerate aniracetam very well. Seriously speaking, it puts me in a SERIOUSLY bad mood. It basically turns me into a “bad drunk”, i.e. someone who is overly aggressive and “throws their weight around” when under its “influence”. Why this is, I don’t know. But it looks like fat soluable racetams are definitely not for me.

Anyone else like this? [/quote] Yes.[quote]
Anyone had a reasonable rationale mechanism that might explain such strange reactions for me?[/quote]
You could be dopamine dominant in your genetic brain make up.
By taking a substance that might enhance dopamine levels in you pre frontal cortex you tip over an already high dopamine level. Two of the functions implicated on the pre frontal cortex are: personality expression and moderation of correct social behavior. If you are, by default, high dopamine, low serotonin and low norepinepherine, enhancing dopamine and serotonin might explain the neurological effect on your mood and behavioural changes.

"Aniracetam enhances cortical dopamine and serotonin release via cholinergic and glutamatergic mechanisms in SHRSP

Shirane M, Nakamura K.

CNS Supporting Laboratory,
Nippon Roche Research Center,
200 Kajiwara, 247-8530, Kamakura, Japan
Brain Res 2001 Oct 19;916(1-2):211-21

Abstract

Aniracetam, a cognition enhancer, has been recently found to preferentially increase extracellular levels of dopamine (DA) and serotonin (5-HT) in the prefrontal cortex (PFC), basolateral amygdala and dorsal hippocampus of the mesocorticolimbic system in stroke-prone spontaneously hypertensive rats. In the present study, we aimed to identify actually active substances among aniracetam and its major metabolites and to clarify the mode of action in DA and 5-HT release in the PFC. Local perfusion of mecamylamine, a nicotinic acetylcholine (nACh) and N-methyl-D-aspartate (NMDA) receptor antagonist, into the ventral tegmental area (VTA) and dorsal raphe nucleus (DRN) completely blocked DA and 5-HT release, respectively, in the PFC elicited by orally administered aniracetam. The effects of aniracetam were mimicked by local perfusion of N-anisoyl–aminobutyric acid (N-anisoyl-GABA), one of the major metabolites of aniracetam, into the VTA and DRN. The cortical DA release induced by N-anisoyl-GABA applied to the VTA was also completely abolished by co-perfusion of mecamylamine. Additionally, when p-anisic acid, another metabolite of aniracetam, and N-anisoyl-GABA were locally perfused into the PFC, they induced DA and 5-HT release in the same region, respectively. These results indicate that aniracetam enhances DA and 5-HT release by mainly mediating the action of N-anisoyl-GABA that targets not only somatodendritic nACh and NMDA receptors but also presynaptic nACh receptors."

[/quote]

What a wonderful rationale…thankyou so much for posting this!

Any information on whether other racetams could act in this manner? I am specifically interested in piracetam. My fear is that I won’t be able to use any of them as I’ve read pira and ani have almost the same effects just that ani seems to be more powerful on a per unit dosage.

In the end though, the only way to really know is to try it as I plan to and report back here. I’m still going to continue my experiment with ani + DMAE to see if that possibly improves things…however the mechanism above would indicate things could get worse. I gotta try it though. [/quote]

Well it is ani that is noted for its anxiolytic effects. Nothing I have read on pira, mentions this.

I would suggest you try bacopa, for a different type of anxiolytic effect.

BBB[/quote]

Thankyou for the suggestion my good friend. I will indeed get some for further experimentation. Currently, I have some L-Theanine that I wanted to try later on…and I did read your earlier posts where you suggested the use of Bacopa.

26

[quote]Alpha F wrote:

[quote]buffd_samurai wrote:
What a wonderful rationale…thankyou so much for posting this!

Any information on whether other racetams could act in this manner? I am specifically interested in piracetam. [/quote]

You are welcome.
I have an interest in neurology as a hobby and it is only from that position that I speak.
I have read papers indicating piracetam has adverse side effects; increased aggression, agitation and irritability and sexual arousal.
My observation is that whilst a substance may not increase dopamine levels it can enhance it by inhibiting the enzyme that breaks down dopamine.
I also invite you to think about piracetam’s role in the catecholamine system.
As suggested with antipshycotic drugs, piracetam might accelerate brain catecholamine turnover by blocking its receptors.

Other research papers suggest Piracetam increases the brain’s turnover of Adenosine Triphosphate (ATP) within the Cerebral Cortex which is associated with increased Energy production within the brain ( think of the effects of enhanced protein synthesis and energy output in a brain wired this way: high dopamine, low serotonin, low norepinephrine ).

Also consider that where nootropics are being compared to MAOI such as Prozac, the rise in dopamine levels may not be significant. However, in a brain which is high in dopamine, low in serotonin and low in norepinephrine, this insignificant enhancement becomes significant enough to cause adverse effects. Coincidently, Prozac was notorious for causing aggressive and violent behavior in certain individuals in spite of being labelled “The Happy Pill” ( I read three books on it in the 90’s ). These individuals literally ‘lost their minds’ and acted on their base impulses without inhibition.

Another paper also suggested piracetam also increased prolactin concentrations in serum. I don’t know what that would mean for you - if you are not on steroids that may be significant and add to your adverse effect in ways only you can discern as you must consider your individual endocrine and neurological make up.

Yohimbe Bark, as piracetam, is also suggested as a dopamine re uptake inhibitor. Interestingly enough I cannot tolerate yohimbine very well. HOT-ROX is overkill for me and Spike pill with yohimbine only when my progesterone levels are high ( luteal fase ).
I need to be severely sleep deprived not to become volcanic on HOT-ROX. Seriously.

Interesting you mentioned Spike, because Caffeine-Free Spike was the best for brain alertness for me. When sleep deprived a pill of Caffeine-Free Spike and a can of Spike Shooter was perfect. I once took this concoction rested and my brain did not stop for 48 continuous hours, no sleep at all and relentless.
Real shame I cannot find Caffeine-Free Spike any more.

[/quote]

I too very much miss Caffeine-Free Spike. That product provided me with alot of versatility in trying different combo of things.

With regards to Yohimbine as found in HOT-ROX, I have actually had good experience with that…so my situation becomes a bit more confusing if I really am dopamine dominant. As a matter of fact, my favorite brain stack (before delving into some of these nootropics) was basically HOT-ROX Extreme + Caffeine-Free Spike. That was it. And that was actually pretty great!

I haven’t touched the normal formula Spike yet…the one with Yohimbine AND what seems to be quite a bit of caffeine. I am especially wary of caffeine as too much just sends me over the jitter edge…and I really hate that feeling. Now with this wonderful thread and Bushy’s excellent revelations, I have just learned about the relationship between cortisol and caffeine.

Thankyou again for even more information on Piracetam. It is still something I plan on experimenting with…I haven’t given up on the racetams yet…just maybe Aniracetam.

27

[quote]bushidobadboy wrote:

Ah yes! I didn’t think about the increased ATP synthesis in neurones from the use of vinpo. Now whilst that is not a directly linked effect on muscle insulin sensitivity, it is, I suppose a good way to reduce blood glucose levels.

This has opened up a new train of thought for me, cheers!

BBB
[/quote]

Well I think I was referring mostly to how piracetam and vinpocetine are supposed to enhance cerebral blood flow, which should permit more glucose to go there. Downstream effects from this might be a bit different for me (as a type 1 diabetic) from the normal person, especially as it pertains to the insulin or other glucose-relevant systems in the CNS, but predicting those is a dicey subject for me right now.

However an interesting consideration lies in the fact that cognitive disorders like AD and PD and diabetes (type 2) are associated with decreased cerebral blood flow as well as loss of insulin function (from decreased receptor expression and insulin resistance) in the brain.

So it may not be out of reach to begin considering the possibility that these two factors are highly intertwined as cognitive dysfunction progresses in aging people. Or re-stated, that lessened glucose entry into the brain can influence grander scale losses in hormone function, including the extremely important brain-insulin system, but also extending into other dysfunctions that result in formation of entities such as amyloid plaques and Lewy bodies.

Just a few more things to think about as we keep popping these noots well into “old age.” :stuck_out_tongue_winking_eye:

28

[quote]buffd_samurai wrote:

I too very much miss Caffeine-Free Spike. That product provided me with alot of versatility in trying different combo of things.

With regards to Yohimbine as found in HOT-ROX, I have actually had good experience with that…so my situation becomes a bit more confusing if I really am dopamine dominant. [/quote]
No necessarily. I may have higher levels of dopamine than you, or perhaps a lower norepinephrine ( I don’t get anxious. I get angry )…or perhaps it is to do with that fact I fall into a different gender group and being female ‘less is more’. Two pills of HOT-ROX is my maximum comfortable dose when under duress.

What I am trying to say and the reason I responded to your initial post is that there are other factors to dial in and it is not as simple as boxing people into gender groups, age groups, level health groups, or even neurotransmitter groups. You are unique and highly complex flowing inside a simple single unit.[quote]
As a matter of fact, my favorite brain stack (before delving into some of these nootropics) was basically HOT-ROX Extreme + Caffeine-Free Spike. That was it. And that was actually pretty great![/quote] Yes, I think I remember you from the old threads.

Vitamin B6 and Vitamin C are also in the dopamine re uptake inhibitors list. If you responded so well to HOT-ROX and Spike Caffeine free you may only need a simple stack of these with little or no caffeine, or just yohimbine.

Good luck.

30

Got your e-mail BBB, thanks a lot.

I found one of those generic “focus” products in the cabinet at home. 2 caps contain the following:

Phosphatidylcholine 48 mg
Phosphatidylethanolamine 40 mg
Phosphatidylinositol 28 mg
DMAE bitartrate 125 mg
Eleuthero root extract (.8% eleuthrosides) 100 mg
Ginkgo extract 60 mg
Gotu kola leaf extract 30 mg
Vinpo 5 mg
HupA 100 mcg

Plus a few vitamins, minerals and fatty acids.

If it were just underdosed I would gladly take more because, hey, it’s free product. But I’m concerned that it already has 100 mcg of hupA. So my question is, is it safe to go from 2 caps to 3 or 4 (not every day)? Or should I stick with the normal dose and throw in some extra vinpo?

31

Possibly the most important question is how much of a window there would be for taking piracetam or vinpocetine and being able to reduce cognitive disorders. So for instance, starting vinpo in the middle of Alzheimer’s might do nothing but taken once or twice a week from your 20s to 80s might do everything to prevent it. I doubt we will have those kinds of answers for a long time.

Insulin action in the brain is distinct from the periphery. It plays roles in mood, memory, energy homeostasis and appetite, in addition to being neurotrophic, but it is not fully understood. Researchers are just starting to study the effect of intranasal fast-acting insulin administration, but the early results are very interesting. It is hard for a diabetic to not want to pop open a vial, toss it in a nasal spray vial and give it a go… I mean after all, they say it elevates your mood…

A few reviews:

BMC Neurosci. 2008 Dec 10;9 Suppl 3:S5.
Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease.

Hanson LR, Frey WH 2nd.

ABSTRACT : Intranasal delivery provides a practical, non-invasive method of bypassing the blood-brain barrier (BBB) to deliver therapeutic agents to the brain and spinal cord. This technology allows drugs that do not cross the BBB to be delivered to the central nervous system within minutes. It also directly delivers drugs that do cross the BBB to the brain, eliminating the need for systemic administration and its potential side effects. This is possible because of the unique connections that the olfactory and trigeminal nerves provide between the brain and external environment. Intranasal delivery does not necessarily require any modification to therapeutic agents. A wide variety of therapeutics, including both small molecules and macromolecules, can be targeted to the olfactory system and connected memory areas affected by Alzheimer’s disease. Using the intranasal delivery system, researchers have reversed neurodegeneration and rescued memory in a transgenic mouse model of Alzheimer’s disease. Intranasal insulin-like growth factor-I, deferoxamine, and erythropoietin have been shown to protect the brain against stroke in animal models. Intranasal delivery has been used to target the neuroprotective peptide NAP to the brain to treat neurodegeneration. Intranasal fibroblast growth factor-2 and epidermal growth factor have been shown to stimulate neurogenesis in adult animals. Intranasal insulin improves memory, attention, and functioning in patients with Alzheimer’s disease or mild cognitive impairment, and even improves memory and mood in normal adult humans. This new method of delivery can revolutionize the treatment of Alzheimer’s disease, stroke, and other brain disorders.

Arch Physiol Biochem. 2009 May;115(2):112-6.
Insulin and the brain.

Laron Z.

Circulating insulin crosses the blood-brain barrier (BBB) into the central nervous system (CNS). There are many insulin receptors in various areas of the brain; they are expressed by both astrocytes and neurons. The two main insulin actions in the brain are (a) control of food intake and (b) effect on cognitive functions. In obesity there is a relative insulin deficiency in the CNS despite increased circulating levels. Insulin plays an important role in cognitive functions as demonstrated by the intranasal administration of insulin bypassing the liver. Brain insulin decreases with aging and may be related to the decrease in cognitive functions, as has also been reported in Alzheimer’s disease. Certain brain tumours over-express insulin receptors. Whether the larger insulin analogues pass the BBB is as yet not known.

Neuroendocrinology. 2007;86(2):136-42.
Intranasal insulin to improve memory function in humans.

Benedict C, Hallschmid M, Schultes B, Born J, Kern W.

BACKGROUND: Compelling evidence indicates that central nervous insulin enhances learning and memory and in particular benefits hippocampus-dependent (i.e., declarative) memory. Intranasal administration of insulin provides an effective way of delivering the compound to the central nervous system, bypassing the blood-brain barrier and avoiding systemic side effects. METHODS: Here we review a series of recent studies on the effects of intranasally administered insulin on memory functions in humans. In accordance with the beneficial effects of intravenously administered insulin on hippocampus-dependent declarative memory observed in hyperinsulinemic-euglycemic clamp studies, intranasal insulin administration similarly improves this type of memory, but in the absence of adverse peripheral side effects. RESULT AND CONCLUSION: Considering that cerebrospinal fluid insulin levels are reduced in patients suffering from Alzheimer’s disease, these results may be of considerable relevance for future clinical applications of insulin in the treatment of memory disorders. (c) 2007 S. Karger AG, Basel.

33

Ouch that’s awful. Like I said though, many years of use can be different than just a few days. From what I can tell AD seems to be more of result of poor metabolism than anything. Glucose control, metabolism and blood flow are all interdependent/related… anyways

I made this post last night and it wasn’t until after the post that I realized intranasal insulin apparently meets all of the qualifications to be included in the “Brain Function Boosters” thread. I can’t remember if I posted on it a long time ago or not? It would be nice if some people could experiment with it around here…

34

Hello everyone. I’ve been following the nootropics thread for a while now but this is my first post. The information is great and very interesting. How would this stack be for any everyday use (assuming that all vitamins are already taken care of):

Alpha-GPC 300mg
Phosphatidylserine 200mg
D-ribose 15mg
Vinpo 10mg

Any suggestions would be greatly appreciated

Thanx again.

35

I miss the Spike without the yohimbine. That stuff really worked well for me. With the added yohimbine, it puts me over the top. I know it is not suggested, but I have to take only half of the current Spike to give me all the great effects I am looking for to get me thru the day or ready for a great workout.

36

Just thought Id share some of my nootropic experiences. I got some piracetam a while back and used it for a good 2 months at least before calling it quits. Cant say I noticed anything, but wasent expecting a huge difference as its not known for that… But any dose over 2 grams pre workout would have me burping up all workout long. I must have gone up to 8 grams a day for weeks on end before calling it quits.

vinpocetine used at 10mg only on workout days does seem to help. I`ve tried using it twice a day and even off training days and preworkout seems to serve me best.

For a while I was using DMAE with my pre workout tyrosine. Seemed to get me in the zone, but Ive stopped it and cant say I notice anything since then. So I`m not so sure how effective it really it was me.

I may get some aniracetam and oxiracetam soon. Everybody seems to be looking for a place to buy the stuff. Is it not allowed to souce them? As far as I know they`re legal… Gonna throw in some huperzine at about 100mcg a day to see if it does anything as well.

39

Hey guys, I just received the piracetam I ordered about a week ago and I have a question about dosing. Since I don’t have a scale handy, does anyone have an approximate weight for a teaspoon of piracetam? I know density can change, but all I’m looking for is an approximation. Also, would that same approximation also be somewhat accurate for ani and oxr?

40

[quote]bushidobadboy wrote:

[quote]ts40925 wrote:
Hello everyone. I’ve been following the nootropics thread for a while now but this is my first post. The information is great and very interesting. How would this stack be for any everyday use (assuming that all vitamins are already taken care of):

Alpha-GPC 300mg
Phosphatidylserine 200mg
D-ribose 15mg
Vinpo 10mg

Any suggestions would be greatly appreciated

Thanx again.[/quote]

Should make a nice beginner stack. You have the choline source, an anti-cortisol source and the ever-important vinpocetine.

Good luck!

BBB
[/quote]

Are Racetams illegal/controlled in the US now?
It was indicated previously that 600mg of aniracetam 3x ed is ideal.
Would adding 200mg of Aniracetam per day to this stack be too little? Is the smallest effective amount 600mg?

Thanx for any info.