4029 replies to this topic

[Q did it!]

I am Back!!! http://www.longecity...-back-on-track/

 

Also am on TULIP but only the 48 LED and Custom Laser i built atm. Sorry in a hurrry atm!!!

 

[lostfalco]

Stanislas Dehaene is doing very interesting work on the neural correlates of consciousness. Definitely worth checking out if you have the time. =)

 

Lecture starts at 3:38.

 

Edited by lostfalco, 17 August 2015 - 06:04 PM.

[lostfalco]

I am Back!!! http://www.longecity...-back-on-track/

 

Also am on TULIP but only the 48 LED and Custom Laser i built atm. Sorry in a hurrry atm!!!

 

Very nice, Q. Glad you're doing better. 

 

What are the strengths of each of your diodes?

[Amorphous]

After reading about methylene blue, I think I am going to try it. If it is synergistic with CoQ-10, it should also be that with Idebenone. It seems like the usual dosage is around 60 mcg, but some people suggesting that it is way too low to be effective. It is rather confusing in regard to dosing and proper source. Is Kordon really okay for human consumption? What is the best source available for human consumption? Pharmaceutical grade seems hard to get and need to invest in a huge quantity (20gm) which is not ideal for trying out. What's the best way to mix it is another question. Anyone has any suggestion? I know those are very low level questions about MB, but at this stage as a beginner, I am still trying to figure this out.

[Q did it!]

808nm 200mw. Less then $80 to build. And doing very well. Its put me back to ground zero these circumstances.

 

TULIP is still one of my favorite of all biohacks. I will become more active here with time for now ill simply lurk

[lostfalco]

Is Kordon really okay for human consumption? What is the best source available for human consumption? Pharmaceutical grade seems hard to get and need to invest in a huge quantity (20gm) which is not ideal for trying out. What's the best way to mix it is another question. Anyone has any suggestion? I know those are very low level questions about MB, but at this stage as a beginner, I am still trying to figure this out.

I would not use Kordon's. Unknown risk of contaminants. 

 

I've purcahsed MB from bluebrainboost and Nyles7 on ebay. Both seem legit to me. 

 

https://www.bluebrai...-blue-solution/

 

http://www.ebay.com/...=item27d8ca900e

 

Low dose MB in the scientific literature ranges from 0.5 to 4 mg/kg. So, if you weigh 70kg, then 35mg to 280mg. 

 

"But systemic low-doses (0.5–4 mg/kg) of methylene blue that stimulate mitochondrial respiration in vivo are safe and effective in both animals and humans."

http://www.ncbi.nlm....les/PMC4428125/

 

This human study used 260mg. http://www.ncbi.nlm....les/PMC4467026/

 

I'm currently testing bluebrainboost's droppers at 10 to 30mg/day. I'll try a 260mg dose of powder soon. 

[Bateau]

 

Is Kordon really okay for human consumption? What is the best source available for human consumption? Pharmaceutical grade seems hard to get and need to invest in a huge quantity (20gm) which is not ideal for trying out. What's the best way to mix it is another question. Anyone has any suggestion? I know those are very low level questions about MB, but at this stage as a beginner, I am still trying to figure this out.

 I'll try a 260mg dose of powder soon. 

 

 

The study used three doses of 86.66 mg to get the 260 mg and other studies (Phase II Rember Trial) had poor absorption issues at 100 mg but not 60 mg.

 

If I were you, I wouldn't push single doses much past that 86.66 mg dose.

[lostfalco]

The study used three doses of 86.66 mg to get the 260 mg and other studies (Phase II Rember Trial) had poor absorption issues at 100 mg but not 60 mg.

 

If I were you, I wouldn't push single doses much past that 86.66 mg dose.

 

Thanks for the heads up! =)

808nm 200mw. Less then $80 to build. And doing very well. Its put me back to ground zero these circumstances.

 

TULIP is still one of my favorite of all biohacks. I will become more active here with time for now ill simply lurk

Cool. Looks good, Q. 

[lostfalco]

A nice, simple video describing the relationship between AMPA and NMDA receptors. 

 

[Amorphous]

 

Is Kordon really okay for human consumption? What is the best source available for human consumption? Pharmaceutical grade seems hard to get and need to invest in a huge quantity (20gm) which is not ideal for trying out. What's the best way to mix it is another question. Anyone has any suggestion? I know those are very low level questions about MB, but at this stage as a beginner, I am still trying to figure this out.

I would not use Kordon's. Unknown risk of contaminants. 

 

I've purcahsed MB from bluebrainboost and Nyles7 on ebay. Both seem legit to me. 

 

https://www.bluebrai...-blue-solution/

 

http://www.ebay.com/...=item27d8ca900e

 

Low dose MB in the scientific literature ranges from 0.5 to 4 mg/kg. So, if you weigh 70kg, then 35mg to 280mg. 

 

"But systemic low-doses (0.5–4 mg/kg) of methylene blue that stimulate mitochondrial respiration in vivo are safe and effective in both animals and humans."

 

I'm currently testing bluebrainboost's droppers at 10 to 30mg/day. I'll try a 260mg dose of powder soon. 

 

Thanks for the source and dosing range. if the dosage is in 10 - 300 mg range, 20 gm is actually not that much.  

 

 

 

 

Is Kordon really okay for human consumption? What is the best source available for human consumption? Pharmaceutical grade seems hard to get and need to invest in a huge quantity (20gm) which is not ideal for trying out. What's the best way to mix it is another question. Anyone has any suggestion? I know those are very low level questions about MB, but at this stage as a beginner, I am still trying to figure this out.

 I'll try a 260mg dose of powder soon. 

 

 

The study used three doses of 86.66 mg to get the 260 mg and other studies (Phase II Rember Trial) had poor absorption issues at 100 mg but not 60 mg.

 

If I were you, I wouldn't push single doses much past that 86.66 mg dose.

 

So, it will be about 80 mg 3 times a day. In this case, It maybe quite difficult for me to do. I'll try 80mg twice daily then. Does late dose of MB affect sleeping? Should that be taken before LLLT or after? I usually do LLLT right before bed.

[Bateau]

So, it will be about 80 mg 3 times a day. In this case, It maybe quite difficult for me to do. I'll try 80mg twice daily then. Does late dose of MB affect sleeping? Should that be taken before LLLT or after?

 

If I were you, I'd either take a much smaller dose of MB, or stop using LLLT on the head while using MB.

 

Both of them are having their main effect by donating electrons to similar parts of the Electron Transport Chain, with LLLT directly effecting cytochrome C oxidase (Complex IV), while MB effects cytochrome C, both of which lead to increase in Complex IV, which is something you can only augment so much.

 

Using either MB or LLLT should get you near the upper limit of enhancing Cytochrome C oxidase, using both seems redundant if not dangerous.

 

Maybe alternate between them weekly?

 

Edited by Bateau, 19 August 2015 - 05:07 PM.

[lostfalco]

I would strongly recommend checking out this paper to everyone who has the time.  http://www.ncbi.nlm....les/PMC4033242/

 

It is one of the first roadmaps that I have found from a legitimate neuroscientist (Gary Lynch, UCI) that talks about qualitatively enhancing cognition in healthy humans. I have been testing out pretty much all of Lynch's ideas over the past few months with some very intriguing results that I will be talking about a lot more in the coming weeks. 

 

His basic idea is that we can attain supranormal cognition by activating a greater number of cortical networks by enhancing glutamatergic signaling. The primary elements are two (there are many more):

1. enhance presynaptic glutamatergic release by activating alpha4beta2 nicotinic receptors

2. enhance postsynaptic glutamatergic response by modulating AMPA receptors with ampakines

 

In monkeys, this allowed them to activate 3 cortical networks (frontal + temporal + parietal) instead of just 2 (frontal + temporal) and lead to the development of supranormal performance otherwise inaccessible to control animals. Very intriguing to say the least!  

 

Anyway, his work basically ties together all of the disparate elements that I have been talking about over the past few months and provides a plausible roadmap for future experimentation. Strongly recommended. =) 

Edited by lostfalco, 20 August 2015 - 03:35 AM.

[Amorphous]

 

So, it will be about 80 mg 3 times a day. In this case, It maybe quite difficult for me to do. I'll try 80mg twice daily then. Does late dose of MB affect sleeping? Should that be taken before LLLT or after?

 

If I were you, I'd either take a much smaller dose of MB, or stop using LLLT on the head while using MB.

 

Both of them are having their main effect by donating electrons to similar parts of the Electron Transport Chain, with LLLT directly effecting cytochrome C oxidase (Complex IV), while MB effects cytochrome C, both of which lead to increase in Complex IV, which is something you can only augment so much.

 

Using either MB or LLLT should get you near the upper limit of enhancing Cytochrome C oxidase, using both seems redundant if not dangerous.

 

Maybe alternate between them weekly?

 

 

Thanks. I see. Will definitely try "alternate weekly"

[middpanther88]

How does one increase the following:

His basic idea is that we can attain supranormal cognition by activating a greater number of cortical networks by enhancing glutamatergic signaling. The primary elements are two (there are many more):

1. enhance presynaptic glutamatergic release by activating alpha4beta2 nicotinic receptors

2. enhance postsynaptic glutamatergic response by modulating AMPA receptors with ampakines

 

 

[lostfalco]

 

Both of them are having their main effect by donating electrons to similar parts of the Electron Transport Chain, with LLLT directly effecting cytochrome C oxidase (Complex IV), while MB effects cytochrome C, both of which lead to increase in Complex IV, which is something you can only augment so much.

 

Using either MB or LLLT should get you near the upper limit of enhancing Cytochrome C oxidase, using both seems redundant if not dangerous.

 

Maybe alternate between them weekly?

 

Hey Bateau, the evidence actually points to LLLT working through 'electron excitation', not electron donation. The energy from a photon is absorbed by an electron causing the electron to jump to a higher energy shell. Here's Harvard scientist and LLLT expert Michael Hamblin:

 

"At the most basic level, LLLT acts by inducing a photochemical reaction in the cell, a process referred to as biostimulation or photobiomodulation. When a photon of light is absorbed by a chromophore in the treated cells, an electron in the chromophore can become excited and jump from a low-energy orbit to a higher-energy orbit." http://www.ncbi.nlm....les/PMC3288797/

 

This is a different mechanism from MB. 

 

​As far as combining them, we've been having this discussion for years now and BieraK actually emailed University of Texas scientist and Methylene Blue/LLLT expert Dr. Francisco Gonzalez-Lima and asked him this exact question. Here were Dr. Gonzalez-Lima's responses:

 

"The research takes into account only the use of one intervention at the same time because I am not aware of any combinations reported so far. But in principle they could be combined. The MB phototoxicity does not apply to near-infrared light as used for LLLT, and ketogenesis is also compatible with MB and LLLT."

 

"There is nothing to be concerned about low-dose MB with near-infrared light for transcranial LLLT. This is a concern apparently raised by some people that do not understand what they are talking about. In my previous reply I stated "The MB phototoxicity does not apply tonear-infrared light as used for LLLT"

Methylene blue is a "blue" dye when oxidized. Like all blue dyes, this means that by definition MB reflects light in the blue part of the visible light spectrum and absorbs light in the red part. And red light has much lower tissue penetration than near-infrared, so I recommend only near-infrared or infrared light for transcranial human brain studies of LLLT.  I used infrared (1064 nm) in my human studies:http://journal.front...2014.00036/full"       http://www.longecity...-80#entry727412

Edited by lostfalco, 20 August 2015 - 01:51 PM.

[Bateau]

"At the most basic level, LLLT acts by inducing a photochemical reaction in the cell, a process referred to as biostimulation or photobiomodulation. When a photon of light is absorbed by a chromophore in the treated cells, an electron in the chromophore can become excited and jump from a low-energy orbit to a higher-energy orbit." http://www.ncbi.nlm....les/PMC3288797/

 

This is a different mechanism from MB. 

 

​As far as combining them, we've been having this discussion for years now and BieraK actually emailed University of Texas scientist and Methylene Blue/LLLT expert Dr. Francisco Gonzalez-Lima and asked him this exact question. Here were Dr. Gonzalez-Lima's responses:

 

"The research takes into account only the use of one intervention at the same time because I am not aware of any combinations reported so far. But in principle they could be combined. The MB phototoxicity does not apply to near-infrared light as used for LLLT, and ketogenesis is also compatible with MB and LLLT."

 

"There is nothing to be concerned about low-dose MB with near-infrared light for transcranial LLLT. This is a concern apparently raised by some people that do not understand what they are talking about. In my previous reply I stated "The MB phototoxicity does not apply tonear-infrared light as used for LLLT"

Methylene blue is a "blue" dye when oxidized. Like all blue dyes, this means that by definition MB reflects light in the blue part of the visible light spectrum and absorbs light in the red part. And red light has much lower tissue penetration than near-infrared, so I recommend only near-infrared or infrared light for transcranial human brain studies of LLLT.  I used infrared (1064 nm) in my human studies:http://journal.front...2014.00036/full"       http://www.longecity...-80#entry727412

 

 

Thanks for the correction about donation vs excitation.

 

My point is still the same.

 

They both basically do the same thing by "providing" electrons to Cytochrome C Oxidase, therefore augmenting metabolism. Methylene blue is limitied in that it can only do this in neuronal tissue and has minor side effects. LLLT has no such limitations, except it doesnt transmit well through hair, limiting application to frontal lobes, or forcing you to go bald.

 

My point was providing electrons to Cytochrome C Oxidase has a limit to its benefits, and either treatment alone is more than likely to reach those upper limits. Combining therapies is essentally redundant, unless you merely want to use sup-optimal doses of each.

 

Gonzalez-Lima would likely agree with me, from his paper:

 

The purpose of this paper is to provide an update on the cellular mechanisms mediating the neuroprotective effects of low doses of methylene blue and near-infrared light, and to argue that the neurotherapeutic benefits of these two different interventions share the same cellular mechanism of action based on stimulation of mitochondrial respiration... We finish with a comparison of these two interventions and how they share a common cellular mechanism with similar properties such as energy transfer, low-dose hormetic dose-responses, and enhanced capacity for oxidative metabolic energy production, which serve to protect nervous tissue from degeneration.

→ source (external link)

 

Edited by Bateau, 20 August 2015 - 02:37 PM.

[lostfalco]

Thanks for the correction about donation vs excitation.

 

My point is still the same.

 

They both basically do the same thing by "providing" electrons to Cytochrome C Oxidase, therefore augmenting metabolism. Methylene blue is limitied in that it can only do this in neuronal tissue and has minor side effects. LLLT has no such limitations, except it doesnt transmit well through hair, limiting application to frontal lobes, or forcing you to go bald.

 

My point was providing electrons to Cytochrome C Oxidase has a limit to its benefits, and either treatment alone is more than likely to reach those upper limits. Combining therapies is essentally redundant, unless you merely want to use sup-optimal doses of each.

 

Gonzalez-Lima would likely agree with me, from his paper:

 

The purpose of this paper is to provide an update on the cellular mechanisms mediating the neuroprotective effects of low doses of methylene blue and near-infrared light, and to argue that the neurotherapeutic benefits of these two different interventions share the same cellular mechanism of action based on stimulation of mitochondrial respiration... We finish with a comparison of these two interventions and how they share a common cellular mechanism with similar properties such as energy transfer, low-dose hormetic dose-responses, and enhanced capacity for oxidative metabolic energy production, which serve to protect nervous tissue from degeneration.

→ source (external link)

 

No problem, man.

 

I'm with you that LLLT + MB is untested and it is questionable whether the combination would provide extra benefits. There is definitely an upper limit to mitochondrial enhancement. Totally agree. However, I've been surprised enough times by experiments to at least want to see what happens. =)

[lostfalco]

 

How does one increase the following:

His basic idea is that we can attain supranormal cognition by activating a greater number of cortical networks by enhancing glutamatergic signaling. The primary elements are two (there are many more):

1. enhance presynaptic glutamatergic release by activating alpha4beta2 nicotinic receptors

2. enhance postsynaptic glutamatergic response by modulating AMPA receptors with ampakines

 

 

VERY incomplete answer...I'll expound more later.

1. nefiracetam (potentiates α4β2) + galantamine (allosteric modulator of α4β2) (note: there is lack of specificity here AND canine testicular toxicity with nefiracetam. Human toxicity?)

2. IDRA-21 OR Aniracetam OR Sunifiram OR Unifiram (Combo? Others?)

 

High risk, obviously. 

 

 

 

 

 

Edited by lostfalco, 20 August 2015 - 03:45 PM.

[Bateau]

 

 

How does one increase the following:

His basic idea is that we can attain supranormal cognition by activating a greater number of cortical networks by enhancing glutamatergic signaling. The primary elements are two (there are many more):

1. enhance presynaptic glutamatergic release by activating alpha4beta2 nicotinic receptors

2. enhance postsynaptic glutamatergic response by modulating AMPA receptors with ampakines

 

 

VERY incomplete answer...I'll expound more later.

1. nefiracetam (potentiates α4β2) + galantamine (allosteric modulator of α4β2) (note: there is lack of specificity here AND canine testicular toxicity with nefiracetam. Human toxicity?)

2. IDRA-21 OR Aniracetam OR Sunifiram OR Unifiram (Combo? Others?)

 

 

+1 for galantamine

 

Shows more promise for enhancing cognition than other cholinergics.

 

 

Among the many cognition-enhancing drugs we have tested in 4-month-old rabbits (BMY-21502, donepezil, GTS-21, nefiracetam, nimodipine), Galantamine is the only drug that has facilitated learning in young rabbits.”

→ source (external link)

 

"Studies from this lab have also shown that, whereas other compounds facilitating Ach transmission, including the α 7 nicotinic partial agonist GTS-21 and the cholinesterase inhibitors donepezil and physostigmine, can significantly increase learning; treatment with Galantamine yielded even greater improvement"

→ source (external link)

 

AFAIK Aniracetam has never been shown to enhance cognition above baseline, just prevents decline. Not a promising cognitive enhancer. Have Aniracetams metabolites ever shown to potentiate AMPA? Ani doesnt make it to the brain in vivo in significant levels

Edited by Bateau, 20 August 2015 - 06:08 PM.

[lostfalco]

Goal: supranormal cognition. 

Means: enhance communication between cortical networks. (I know...VERY speculative) http://www.ncbi.nlm....es/PMC4033242/ 

Means: enhance glutamatergic signaling

Means: enhance presynaptic glutamate release AND enhance postsynaptic glutamate response

 

Another possible method for enhancing postsynaptic glutamate response: pregnenolone sulfate = more surface NMDA receptors + greater NMDA receptor response

 

Pregnenolone sulfate 1) traffics more NMDA receptors to the cell surface AND 2) positively allosterically modulates NMDA receptors. This increases the NMDA response by 200% to 400%.

https://www.ncbi.nlm...pubmed/23716622

 

1) "The number of functional cell-surface NMDARs in cortical neurons increases 60-100% within 10 minutes of exposure to PregS."

2) "When combined with the effect of rapid positive allosteric modulation, total enhancement of the NMDA response averages 200% but can reach up to 400% in a given neuron."

 

Oral pregnenolone is converted into pregnenolone sulfate. http://www.ncbi.nlm....icles/PMC23857/ 

 

"Orally ingested P probably largely is converted to PS in the intestine, which is rich in steroid-conjugating enzyme activity, the PS being absorbed rapidly into the blood."

 

Pregnenolone sulfate (intravenous) crosses the blood brain barrier in rats. http://www.ncbi.nlm..../pubmed/9408083  

 

"This study has yielded evidence that PeS injected i.v. can cross the blood-brain barrier without being hydrolysed to the more lipophilic Pe, and can thus be taken up by the brain."

 

Note: some of you may remember when we talked about this back in 2013. =)  http://www.longecity...e-8#entry593010

Note: obligatory excitotoxicity warning. 

 

 

Edited by lostfalco, 20 July 2016 - 06:26 PM.

[resveratrol_guy]

Note: obligatory excitotoxicity warning. 

 

 

For its part, galantamine also helps clear amyloid precursor protein from the BBB. So that much looks promising.

 

But... how would you know if any of these novel glutaminergic agents did in fact cause excitotoxicity, until you ended up with demyelination? And frankly how would you detect such demyelination, except by noticing a steep and likely irreversible cognitive decline? (Glutamate already has a bad name with respect to such hazards, on account of monosodium glutamate, but perhaps the indirect route of enhancing receptors instead of providing the actual neurotransmitter would be safer.)

As far as all those racetams are concerned, I have yet to find a single anecdote here of someone who uses them on a daily basis and has experienced sustained benefits for over a year. Whereas, there are plenty of anecdotes of irreversible burnout, despite some fantastic results in the near term. Could we just use a nicotine patch instead of nefiracetam, for instance? At least nicotine is much better characterized with respect to side effects.

 

You have been very clear about pointing out the potential risks. The essence of my question is whether we could perhaps achieve your pre- and postsynaptic glutaminergic enhancement in safer ways, albeit less efficiently. Secondly, what might those ways be? At least in that case, we could obtain confidence in the benefits of your theory, without so much excitotoxicity risk. And for the sake of statistical significance, more people would probably be interested in trying it.

Edited by resveratrol_guy, 23 August 2015 - 01:38 PM.

[lostfalco]

Preemptive warning: the highest of high risks. =)

 

Sorry about the lack of recent posts. My semester is insane this fall and my posting might be a little intermittent for a while.

 

Currently, my ampakine of choice is far and away IDRA-21. I've also been testing it with noradrenaline enhancers with some pretty impressive results.

 

Unfortunately, there are long term sustainability issues and potential cardiovascular risks with noradrenaline enhancers. Nevertheless, I wanted to test the concepts that we've been talking about and see if they work...even in the short term. The answer for me is a very resounding yes. Ymmv.

 

I've attached a full text pdf below that explains why noradrenaline enhancers are so effective at enhancing learning and memory. Read it if you have time...it's awesome! Pay special attention to how norepinephrine affects NMDA and AMPA receptors. It will suddenly make A LOT of sense why combining noradrenaline enhancers with ampakines is so effective. 

 

Best two stacks:

1. ephedrine (25mg) and caffeine (200mg) + IDRA-21 (start at 10mg)

2. prolintane + IDRA-21

 

I'll do a write up on IDRA-21 soon. It's a fascinating ampakine that probably works through a metabolite (when taken orally), has a plasma half life of 1 to 4 hours (depending on the study you read), and seems to have effects 48 hours after a single dose (in monkeys). Weird...but pretty damn cool.  

 

I'm also gonna try to take an IQ test soon and see if I notice any conspicuous increases. Obviously, I'm not blinding myself so the results will be anecdotal...but I'm still curious.  

 

http://www.ncbi.nlm....pubmed/26286656

 

Learn Mem. 2015 Aug 18;22(9):461-71. doi: 10.1101/lm.031088.113. Print 2015 Sep.

β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus.

O'Dell TJ1, Connor SA2, Guglietta R3, Nguyen PV4.

Author information

Abstract

Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the mammalian brain is norepinephrine (NE), which regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The mammalian hippocampus receives noradrenergic innervation and hippocampal neurons express β-adrenergic receptors, which are known to play important roles in gating the induction of long-lasting forms of synaptic potentiation. These forms of long-term potentiation (LTP) are believed to importantly contribute to long-term storage of spatial and contextual memories in the brain. In this review, we highlight the contributions of noradrenergic signaling in general and β-adrenergic receptors in particular, toward modulating hippocampal LTP. We focus on the roles of NE and β-adrenergic receptors in altering the efficacies of specific signaling molecules such as NMDA and AMPA receptors, protein phosphatases, and translation initiation factors. Also, the roles of β-adrenergic receptors in regulating synaptic "tagging" and "capture" of LTP within synaptic networks of the hippocampus are reviewed. Understanding the molecular and cellular bases of noradrenergic signaling will enrich our grasp of how the brain makes new, enduring memories, and may shed light on credible strategies for improving mental health through treatment of specific disorders linked to perturbed memory processing and dysfunctional noradrenergic synaptic transmission.

 

 b-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus.pdf   846.74KB   6 downloads

Edited by lostfalco, 28 August 2015 - 04:18 AM.

[Bateau]

Best two stacks:

1. ephedrine (25mg) and caffeine (200mg) + IDRA-21 (start at 10mg)

2. prolintane + IDRA-21

 

 

Make sure you've sufficiently quantified the cognitive boost from the EC stack and prolintane before you test the combo with IDRA-21

 

I recently decided to try the EC stack for the first time and was surprised how much of a boost in attention, subjective well being, and "forward thinking" (planning ahead) it provided. Really worked well for studying and such.

 

The combo is called a "dirty" stimulant due to the significant cardiovascular stimulation, but overall the cognitive stimulation feels pretty clean for me.

 

I might be pretty odd though, it gives me zero anxiety, it even seems to have some fear extinction effects, making me less anxious.

Edited by Bateau, 28 August 2015 - 02:37 PM.

[lostfalco]

 

Make sure you've sufficiently quantified the cognitive boost from the EC stack and prolintane before you test the combo with IDRA-21

 

I recently decided to try the EC stack for the first time and was surprised how much of a boost in attention, subjective well being, and "forward thinking" (planning ahead) it provided. Really worked well for studying and such.

 

The combo is called a "dirty" stimulant due to the significant cardiovascular stimulation, but overall the cognitive stimulation feels pretty clean for me.

 

I might be pretty odd though, it gives me zero anxiety, it even seems to have some fear extinction effects, making me less anxious.

 

Hey, what's up Bateau? I have tested EC, prolintane, and IDRA on their own. I've actually been at this all summer. =)

 

I totally agree on the EC stack. Very surprising to me too. Felt very clean, no anxiety, mood enhancing. Prolintane...not as clean but ability to focus was very good. 

 

Have you read over Lynch's work? I would love to hear your thoughts, feedback, etc. These three are good to start.  

http://www.ncbi.nlm....les/PMC4033242/

http://www.ncbi.nlm....les/PMC3114293/

http://www.ncbi.nlm....les/PMC3445784/

[lourdaud]

Noradrenaline! What an interesting subject.
lostfalco, are you still taking your armodafinil with the prolintane + IDRA-21 combo?

Regarding ephedrine, how effective would you say it is at boosting working memory? Would you compare it to levoamphetamine? I thought it mostly acted on the PNS.

Prolintane is probably one of the best cognitive enhancers I've tried but it's rather expensive. Where do you get yours? I've been nagging on Ceretropic to stock it but they seem a bit reluctant. Perhaps some of you guys could spur them on as well? https://www.reddit.c...pm1/prolintane/

 

[CitizenScientist]

Preemptive warning: the highest of high risks. =)

 

Sorry about the lack of recent posts. My semester is insane this fall and my posting might be a little intermittent for a while.

 

Currently, my ampakine of choice is far and away IDRA-21. I've also been testing it with noradrenaline enhancers with some pretty impressive results.

 

Unfortunately, there are long term sustainability issues and potential cardiovascular risks with noradrenaline enhancers. Nevertheless, I wanted to test the concepts that we've been talking about and see if they work...even in the short term. The answer for me is a very resounding yes. Ymmv.

 

I've attached a full text pdf below that explains why noradrenaline enhancers are so effective at enhancing learning and memory. Read it if you have time...it's awesome! Pay special attention to how norepinephrine affects NMDA and AMPA receptors. It will suddenly make A LOT of sense why combining noradrenaline enhancers with ampakines is so effective. 

 

Best two stacks:

1. ephedrine (25mg) and caffeine (200mg) + IDRA-21 (start at 10mg)

2. prolintane + IDRA-21

 

I'll do a write up on IDRA-21 soon. It's a fascinating ampakine that probably works through a metabolite (when taken orally), has a plasma half life of 1 to 4 hours (depending on the study you read), and seems to have effects 48 hours after a single dose (in monkeys). Weird...but pretty damn cool.  

 

I'm also gonna try to take an IQ test soon and see if I notice any conspicuous increases. Obviously, I'm not blinding myself so the results will be anecdotal...but I'm still curious.  

 

@lostfalco

 

If you're pursuing the AMPA + NE route, have you looked into exogenous L-lactate supplementation to trigger NE release?

 

I had been looking into L-lactate + caffeine for anabolic signalling and came across a study that may be of interest:

 

(Exogenous) L-lactate in the locus coeruleus is excitatory to the neurons, provoking NE release.  This appears to be cAMP-mediated, as the process is blocked by adenylyl cyclase / PKA inhibation.  It is also antagonised by D-lactate.

 

I'm not sure how localised the NE is. The glia-neuronal signalling paper is focused on the locus coeruleus, and accordingly, the forebrain noradrenergic activity.  I wonder if this means that NE-release triggered by exogenous L-lactate acts without peripheral hormonal / sympathetic activity?

 

(Conversely, is D-lactate a viable mechanism for NE inhibition by competing with L-lactate?  That is merely an afterthought, I'm not sure what the implications are.)

 

Reference

Lactate-mediated glia-neuronal signalling in the mammalian brain

Tang F, Lane S, Korsak A, Paton JF, Gourine AV, Kasparov S, Teschemacher AG.

doi: 10.1038/ncomms4284 PMID: 24518663

[lostfalco]

lostfalco, are you still taking your armodafinil with the prolintane + IDRA-21 combo?

Regarding ephedrine, how effective would you say it is at boosting working memory? Would you compare it to levoamphetamine? I thought it mostly acted on the PNS.

Prolintane is probably one of the best cognitive enhancers I've tried but it's rather expensive. Where do you get yours? I've been nagging on Ceretropic to stock it but they seem a bit reluctant. Perhaps some of you guys could spur them on as well? https://www.reddit.c...pm1/prolintane/

Hey, what's up lourdaud?

 

Tried multiple combos with armodafinil...haven't found anything that works yet. Even though I loved this study. http://www.longecity...-82#entry739179

 

I still haven't given up on astrocyte gap junction and hemichannel enhancement. Connexin 30 and Connexin 43 seem like prime targets to me for metabolic and glutamatergic enhancement. Modafinil affects connexin 30 and clenbuterol affects connexin 43 for anyone who wants to look into it. In my experiments I haven't been able to find anything I'm happy with at this point. 

 

Ephedrine definitely seems to affect focus and concentration (for me). I'd say that I've noticed a small bump in working memory. Ephedrine does mostly act on the PNS but it also crosses the blood barrier in small amounts. In my experience, that's been enough when combined with other things. 

 

I haven't taken levoamphetamine...though I've been surfing around the dark web lately. Still haven't pulled the trigger on that yet. I've only taken Adderall a handful of times (which is 25% levoamphetamine) and I don't currently have any. 

 

I got my prolintane from Newmind. https://newmind.com/...tane-0-3-g.html

 

I wonder why Ceretropic is dragging their feet on it? They certainly don't seem to shy away from dangerous chemicals. That's where I purchased my IDRA-21, btw. http://www.ceretropi...idra-21-powder/

[lostfalco]

@lostfalco

 

If you're pursuing the AMPA + NE route, have you looked into exogenous L-lactate supplementation to trigger NE release?

 

Reference

Lactate-mediated glia-neuronal signalling in the mammalian brain

Tang F, Lane S, Korsak A, Paton JF, Gourine AV, Kasparov S, Teschemacher AG.

doi: 10.1038/ncomms4284 PMID: 24518663

 

Hey Citizen, I have looked into it and tried a number of things so far. Nothing major to report but I'm still trying. Promising possibility though. 

 

Thanks for the study! I'll check it out. I think we definitely have to take into account the role of glial cells and their influence on pre ad post-synaptic neurons.

[lostfalco]

Since we're on the subject...here are astrocyte gap junctions and hemichannels. These will prove crucial to future learning and memory enhancements. 

 

 

[CitizenScientist]

 

@lostfalco

 

If you're pursuing the AMPA + NE route, have you looked into exogenous L-lactate supplementation to trigger NE release?

 

Reference

Lactate-mediated glia-neuronal signalling in the mammalian brain

Tang F, Lane S, Korsak A, Paton JF, Gourine AV, Kasparov S, Teschemacher AG.

doi: 10.1038/ncomms4284 PMID: 24518663

 

Hey Citizen, I have looked into it and tried a number of things so far. Nothing major to report but I'm still trying. Promising possibility though. 

 

Thanks for the study! I'll check it out. I think we definitely have to take into account the role of glial cells and their influence on pre ad post-synaptic neurons.

 

To be honest, the synaptic neurochemistry is a bit over my head.  But I'm seeing a recurring theme, being the role of cAMP / cGMP in enhanced cognition and memory.  As per the study I quoted, cAMP is a secondary messenger for the release of NE, and I've read some of your posts pertaining to phosphodiesterase inhibition (PDE4 and PDE5).  Do you include forskolin or arginine butyrate in your stacks?  Arginine butyrate in particular seems interesting, affecting NO pathways and HDAC inhibition.

 

On another note, I read the study you posted on enhancing cognition and memory.  The role of theta rhythms in the hippocampus for enduring LTP is very promising.  Especially if the neurochemistry is conducive.  Hippocampal theta seems to substantiate the spaced learning concept.  Have you got any ideas on how to implement it using electrical stimulation?  

 

 

 

More than a retrograde messenger: nitric oxide needs two cGMP pathways to induce hippocampal long-term potentiation.

Taqatqeh F, Mergia E, Neitz A, Eysel UT, Koesling D, Mittmann T.

J Neurosci. 2009 Jul 22;29(29):9344-50. doi: 10.1523/JNEUROSCI.1902-09.2009.

 

Tonic and phasic nitric oxide signals in hippocampal long-term potentiation.

Hopper RA, Garthwaite J.

J Neurosci. 2006 Nov 8;26(45):11513-21.