4019 replies to this topic

[thedarkbobo]

Hmm 10mg ? MB is totally confusing From various reports you should aim at nanoscale first

http://www.longecity...methylene-blue/

 

Conclusion: MB is a strong but reversible MAO-A inhibitor. Recall that the MAO protein is located on the mitochondria! That means to me that even in the micro gram range 100 - 200 mug, enough MB reaches the mitochondria, to 'do something'. Now considering that we only need approx one MB molecule per cytrochrome c, to drive the mitochondria effect, this micro dose IS THE CORRECT DOSE. (To much MB per cytrochrome c and the effect reverses.)

 

Thanks Lostfalco for the list. I've tried Idra, Sunifiram and Unifiram many times and the effects are probably most safe with Idra, most pronounced(that's not sooo good when you are working with other people) and lasting 3 days for me with Suni and not sure, I think ok, but lacking the emotional part Unifiram.

 

The stack is reaallly long...I won't be able to check out all this in a resonable time lol, but will try. Caffeine in tablets or powder sounds really good, since I don't like to drink that. Any other PDE5 inhibitors (like in tablets/capsules/powder)? Found one only on teamtlr and price is similar, although for more mg's total, but it's selective soo maybe not what we need.

 

Tried ITPP but dropped because of unknown safety profile and price/storage of this powder vs any gain which was hard to notice.

I wonder, you do not plan to check out NSI? 

 

Edited by thedarkbobo, 03 January 2016 - 02:47 PM.

[EfeitoPlacebo]

what would be the ideal montelukast dosage?

[BieraK]

Hmm 10mg ? MB is totally confusing From various reports you should aim at nanoscale first

http://www.longecity...methylene-blue/

 

Conclusion: MB is a strong but reversible MAO-A inhibitor. Recall that the MAO protein is located on the mitochondria! That means to me that even in the micro gram range 100 - 200 mug, enough MB reaches the mitochondria, to 'do something'. Now considering that we only need approx one MB molecule per cytrochrome c, to drive the mitochondria effect, this micro dose IS THE CORRECT DOSE. (To much MB per cytrochrome c and the effect reverses.)

 

Thanks Lostfalco for the list. I've tried Idra, Sunifiram and Unifiram many times and the effects are probably most safe with Idra, most pronounced(that's not sooo good when you are working with other people) and lasting 3 days for me with Suni and not sure, I think ok, but lacking the emotional part Unifiram.

 

The stack is reaallly long...I won't be able to check out all this in a resonable time lol, but will try. Caffeine in tablets or powder sounds really good, since I don't like to drink that. Any other PDE5 inhibitors (like in tablets/capsules/powder)? Found one only on teamtlr and price is similar, although for more mg's total, but it's selective soo maybe not what we need.

 

Tried ITPP but dropped because of unknown safety profile and price/storage of this powder vs any gain which was hard to notice.

I wonder, you do not plan to check out NSI? 

Try to read the MB studies posted here, I also emailed some questions to Dr Golzalez-Lima about MB mechanism of action and interaction, the answers of Dr Gonzalez-Lima where shared here with his consent. Basically the supplement it is considered one of the most studied drugs, and safe for human and animals, it was created in the XIX century. The drug has opposite effects depending of the dose, low doses does not inhibit NO, low doses are considered in the range of 0.5-4 mg/kg. A study with adults with claustrophobia used 80 mg 3 times a day. 

Edited by BieraK, 03 January 2016 - 07:17 PM.

[Groundhog Day]

Hmm 10mg ? MB is totally confusing From various reports you should aim at nanoscale first

http://www.longecity...methylene-blue/

 

Conclusion: MB is a strong but reversible MAO-A inhibitor. Recall that the MAO protein is located on the mitochondria! That means to me that even in the micro gram range 100 - 200 mug, enough MB reaches the mitochondria, to 'do something'. Now considering that we only need approx one MB molecule per cytrochrome c, to drive the mitochondria effect, this micro dose IS THE CORRECT DOSE. (To much MB per cytrochrome c and the effect reverses.)

 

Thanks Lostfalco for the list. I've tried Idra, Sunifiram and Unifiram many times and the effects are probably most safe with Idra, most pronounced(that's not sooo good when you are working with other people) and lasting 3 days for me with Suni and not sure, I think ok, but lacking the emotional part Unifiram.

 

The stack is reaallly long...I won't be able to check out all this in a resonable time lol, but will try. Caffeine in tablets or powder sounds really good, since I don't like to drink that. Any other PDE5 inhibitors (like in tablets/capsules/powder)? Found one only on teamtlr and price is similar, although for more mg's total, but it's selective soo maybe not what we need.

 

Tried ITPP but dropped because of unknown safety profile and price/storage of this powder vs any gain which was hard to notice.

I wonder, you do not plan to check out NSI? 

 

What? There's the Reddit thread that basically says low mg doses are worthless, and lots of people pointing to studies where higher, 50+ mg doses were effective.

 

I'll have to study things a little more closely....I only planned on doing HBOT or MB one at a time but i'm intrigued by synergistic effect and ROS regulation.

[lostfalco]

What are your results with "god stack" lostfalco?

 

I'll answer your question, but first let me say that I've tried to make sure I link everything to studies and mechanisms so that everyone can come up with their own set of enhancements that work for them (I've previously posted studies, diagrams, and videos for almost all of The God Stack mechanisms). Some people might need more of 'x', some might need less of 'x'. I seem to do really well enhancing mitochondria (proton gradient), glutamatergic signaling (calcium gradient/signaling), and norepinephrine. My hope, however, is that the focus will be on the mechanisms and not on the mechanic. The ideas are MUCH more beautiful than I am anyway. =)

 

As I mentioned, it's a work in progress but so far it has been amazing. I can seriously study all day long and my brain doesn't get tired (I think endurance enhancement is an underrated aspect of nootropic advancement). My mood and motivation are excellent and my ability to focus/concentrate is off the charts. My memory is very good but not otherworldly (based on my Anki practice). Social skills are clicking and feedback from others has been extremely positive (making people laugh, people asking me how the hell I know so much, doing very well in school, etc.). 

 

Again, these are all anecdotes and I hope that the various mechanisms allow everyone reading to perform their own experiments and make adjustments based on what works given their own physiology. I'll discuss A LOT more mechanisms in the coming weeks but for now we have a pretty good (and frickin' expensive!) list to start from.

 

Edited by lostfalco, 04 January 2016 - 04:30 AM.

[lostfalco]

Anyone know if LLLT might help restore color to gray hair on your scalp, or prevent further graying haha?

Sorry magta, I haven't really looked into LLLT for gray hair. =)
 

[lostfalco]

Hmm 10mg ? MB is totally confusing From various reports you should aim at nanoscale first

http://www.longecity...methylene-blue/

Any other PDE5 inhibitors (like in tablets/capsules/powder)?

 

Tried ITPP but dropped because of unknown safety profile and price/storage of this powder vs any gain which was hard to notice.

 

I wonder, you do not plan to check out NSI? 

The "low" MB doses in the scientific literature are well above 10mg. I honestly wish that methylene blue thread didn't exist because this comes up over and over again. ha  

 

Icariin is an otc PDE5i. I've tried it but I've had much better results with sildenafil and tadalafil.

 

ITPP is the most questionable substance on the list for me. It might get dropped but I'm keeping it for now because it has a thoroughly unique moa. I'm currently experimenting with various doses so I'll keep everyone updated. I totally agree with you about the unknown safety profile...especially long term.

 

I'm very familiar with NSI but I've been unable to find the mechanism by which it increases neurogenesis/hippocampal volume by 20% (in rodents). A new study just came out but I'm still trying to find the free full text. If you have any literature for me regarding its moa then please share. =)

 

http://www.ncbi.nlm....pubmed/26643541

 

Mol Psychiatry. 2015 Dec 8. doi: 10.1038/mp.2015.178. [Epub ahead of print]

A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients.

Fava M^1,2, Johe K³, Ereshefsky L⁴, Gertsik LG⁵, English BA⁴, Bilello JA⁶, Thurmond LM⁶, Johnstone J⁷, Dickerson BC⁸, Makris N⁸, Hoeppner BB^1,2, Flynn M¹, Mischoulon D^1,2, Kinrys G^1,2, Freeman MP^1,2.

Author information

Abstract

We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4-20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions-Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort.Molecular Psychiatry advance online publication, 8 December 2015; doi:10.1038/mp.2015.178.

 

Edited by lostfalco, 04 January 2016 - 04:55 AM.

[lostfalco]

what would be the ideal montelukast dosage?

For our purposes...unknown. 5mg to 10mg is a typical dose for asthma but you could definitely start lower.

 

Edited by lostfalco, 04 January 2016 - 05:07 AM.

[lostfalco]

I'll have to study things a little more closely....I only planned on doing HBOT or MB one at a time but i'm intrigued by synergistic effect and ROS regulation.

 

 

Hey Groundhog Day, that's pretty cool that you have a hyperbaric chamber. I've never actually tried HBOT before. If you don't mind me asking...how long have you been using it and what has your experience been like with it?

 

Edited by lostfalco, 04 January 2016 - 05:15 AM.

[Bluecheer]

I'll discuss A LOT more mechanisms in the coming weeks but for now we have a pretty good (and frickin' expensive!) list to start from.

 

 

 

Amen to that!
But god that stack looks Interesting!! Is there by any chance a small selection of those supplements that give you say 80% of the benefit? or is it literally just working with a Syneregizing affect for 'you'... cause i dont know when ill be able to test all those at the same time.

[Bluecheer]

Actually lostfalco, I would be very interested in the amounts of these compounds you are taking? If you are not comfortable telling everyone do you think you could pm me? As i am going to try a number of them and would like a point of reference.

Regards,

And thank you for uploading that godstack post :D

[Bluecheer]

Actually lostfalco, I would be very interested in the amounts of these compounds you are taking? If you are not comfortable telling everyone do you think you could pm me? As i am going to try a number of them and would like a point of reference.

Regards,

And thank you for uploading that godstack post :D

Edited by Bluecheer, 04 January 2016 - 12:27 PM.

[Groundhog Day]

 

I'll have to study things a little more closely....I only planned on doing HBOT or MB one at a time but i'm intrigued by synergistic effect and ROS regulation.

 

 

Hey Groundhog Day, that's pretty cool that you have a hyperbaric chamber. I've never actually tried HBOT before. If you don't mind me asking...how long have you been using it and what has your experience been like with it?

 

 

 

I've had it around 6 months, using it 3 months, then 3 months of inactivity before I used it the other 2 days with MB. I used it probably 3-4 times a week on average for 90-120 minute sessions for the first month, then I was doing it maybe 2-3 times  a week for the 2nd and 3rd months. I stopped because I was worried about ROS and I was messing around with other things like MB and LLLT. 

 

I had a bad concussion almost 4 years ago and I've had severe insomnia for 10+ years so I thought it was time to try something like this. As far as benefits: it forces me to sit still and calm down and breathing is easier. I probably have low serotonin, which is involved in regulation of breathing, and I'm a "manual" breather most of the time. The HBOT makes it easier.

 

There was something I was doing earlier on that greatly helped my insomnia and allowed me to fall back asleep, I was doing HBOT and 1200mg NAC and something else, but I'm not well organized and I haven't been able to replicate it.

[magta39]

 

Anyone know if LLLT might help restore color to gray hair on your scalp, or prevent further graying haha?

Sorry magta, I haven't really looked into LLLT for gray hair. =)
 

 

 

Thanks...I am getting ready to soon try LLLT with the round 48LEDs as a preliminary experiment for cognitive enhancements and was wondering if it would possibly have other side benefits...we shall see.    With the LEDs you don't need protective goggles since it only comes on when in darkness or when you have it pressed against your head, correct? (and its not Laser light)
 

Edited by magta39, 04 January 2016 - 07:09 PM.

[thedarkbobo]

Was screening for some other compounds that might be of interest to us.

 

Since stress can shorten lifespan, healthspan and what not then this also looks neat:

FAAH inhibitors ex. URB597 for stress/anxiety & no adverse effect on memory

http://www.ncbi.nlm....pubmed/26713105

http://www.ncbi.nlm....pubmed/26558620

 

RESULTS:  One FAAH inhibitor, AM3506 (3 mg/kg), decreased accuracy in the memory task. Four other FAAH inhibitors (URB597, URB694, PF-04457845, and ARN14633) and a monoacylglycerol lipase inhibitor (JZL184, which blocks the degradation of the endocannabinoid 2-arachidonoylglycerol) had no effect. Testing of AM3506 in combination with antagonists for receptors known to be affected by anandamide and other fatty acid amides indicated that the impairment induced by AM3506 was mediated by cannabinoid CB1 receptors, and not by alpha-type peroxisome proliferator-activated receptors (PPAR-alpha) or vanilloid transient receptor potential cation channels (TRPV1).

--------------------------------------

Not so good

Tianeptine - also vs stress, not bad research about it but also quite bad user experiences overall - I don't think it will fit in your/mine agenda. Actually as everything that touches seretonin or dopamine?

http://www.ncbi.nlm....pubmed/23780498

http://www.ncbi.nlm....pubmed/23262120

http://www.longecity...e-side-effects/

Tianeptine inhibits activity of the enzyme nitric oxide synthase (NOS) in the hippocampus.(not good)

 

-------------------------

Barely researched.

5-HT5A receptor antagonists?

http://www.ncbi.nlm....pubmed/25837935

 

These results indicate that the 5-HT5A receptor is involved in learning and memory and that treatment with 5-HT5A receptor antagonists might be broadly effective for cognitive impairment associated with not only schizophrenia but also dementia.

http://www.ncbi.nlm....pubmed/23735322

 

All together this evidence suggests that the blockade of 5-HT5A receptor appear to be able to impair STM and LTM (24 h), while its stimulation might facilitate it. Of course further investigation is necessary, meanly with selective 5-HT5A compounds are necessary.

http://www.ncbi.nlm....pubmed/25108314

 

These results collectively suggest that ASP5736 is a novel and potent 5-HT5A receptor antagonist that not only ameliorates positive-like symptoms but also cognitive impairments in animal models of schizophrenia, without adverse effects. Present studies also indicate that ASP5736 holds potential to satisfy currently unmet medical needs for the treatment of schizophrenia by either mono-therapy or co-administered with commercially available antipsychotics.

http://www.ncbi.nlm....pubmed/20166946

 

currently only 2 (barely known?) substances. Might need to wait?

---------------------------------------------------------

Would be nice to keep listing alternative substances with same pathway action

 

For PDE5i we can list Icariin, sildenafil, tadalafil and other straight from wiki:

 

• avanafil
• lodenafil
• mirodenafil
• vardenafil
• udenafil
• zaprinast
• benzamidenafil

 

---------------------------------------------

For PDEi4 also Roflumilast (really this stuff is too expensive.)

 

is a potent, long-acting, selective PDE4 Inhibitor (PDE4i) displaying anti-inflammatory and cognitive enhancing/nootropic properties.

http://www.ncbi.nlm....pubmed/25038445

 

Here, we investigated possible preventive effects of ibudilast, as a pharmacologic phosphodiesterase inhibitor, currently used for treatment of inflammatory diseases such as asthma, on Aβ 1-42-induced neuroinflammatory, apoptotic responses and memory impairment. We found that pretreatment with ibudilast (4 or 12 mg/kg, i.p.) significantly ameliorated impaired spatial learning and memory in intracerebroventricularly (ICV) Aβ 1-42-injected mice, as evidenced by decrease in escape latency during acquisition trials and increase in exploratory activities in the probe trial in Morris water maze (MWM) task, and by increase in the number of correct choices and decrease in latency to enter the shock-free compartment in Y-maze test. Further study showed that ibudilast prevented generation of pro-inflammatory cytokines such as NF-κB p65 and TNF-α as well as pro-apoptotic molecule caspase-3 activation and anti-apoptotic protein Bcl-2 downregulation in both hippocampus and cortex of ICV Aβ 1-42-injected mice. Taken together, our findings suggest that ibudilast has preventive effects on Aβ-induced cognitive impairment via inhibiting neuroinflammatory and apoptotic responses.

---------------------------

What is your opinion -

Do we want to mess with serotonin via inhibition or rather not touch it at all?

[magta39]

 

 

Anyone know if LLLT might help restore color to gray hair on your scalp, or prevent further graying haha?

Sorry magta, I haven't really looked into LLLT for gray hair. =)
 

 

 

Thanks...I am getting ready to soon try LLLT with the round 48LEDs as a preliminary experiment for cognitive enhancements and was wondering if it would possibly have other side benefits...we shall see.    With the LEDs you don't need protective goggles since it only comes on when in darkness or when you have it pressed against your head, correct? (and its not Laser light)
OK I read back on page 19 of this thread and that answered my own question :-)

 

 

[Logic]

Botanical drug puerarin coordinates with nerve growth factor in the regulation of neuronal survival and neuritogenesis via activating ERK1/2 and PI3K/Akt signaling pathways in the neurite extension process.

...Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10-fold...

...Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process...

http://www.ncbi.nlm....ubmed/25310912/

 

Alpha-lipoic acid preconditioning reduces ischemia-reperfusion injury of the rat liver via the PI3-kinase/Akt pathway.

http://www.ncbi.nlm....pubmed/12816756

 

Niacin activates the PI3K/Akt cascade via PKC- and EGFR-transactivation-dependent pathways through hydroxyl-carboxylic acid receptor 2.

http://www.ncbi.nlm....pubmed/25375133

 

"...Limonene increased ERK1/2 activation by 30%..."

http://www.ncbi.nlm....pubmed/25622554

 

Edited by Logic, 05 January 2016 - 03:02 AM.

[Jochen]

Happy New Year folks ... hope everyone has a great journey in 2016.

 

Just throwing it out there as it appeared on my newsfeed: http://www.bioflexpersonal.com/

Dr Kahn has just released a personal laser therapy system. He uses 660 and 840 for these protocols (various body locations and different stages of treatment). His professional protocols are a bit more varied.

 

Doesn't come cheap though, but checking with them what a system like that actually entails. Only Canada (and US) at the moment though.

[lostfalco]

 

I'll discuss A LOT more mechanisms in the coming weeks but for now we have a pretty good (and frickin' expensive!) list to start from.

 

 

 

Amen to that!
But god that stack looks Interesting!! Is there by any chance a small selection of those supplements that give you say 80% of the benefit? or is it literally just working with a Syneregizing affect for 'you'... cause i dont know when ill be able to test all those at the same time.

 

Hey, what's up Bluecheer? So, the things I can obviously recommend to just about everyone are "The Big Six", the 20/10 method, and Anki. 

 

On the supplement side of things I really would start with PQQ (pgc-1a) and LLLT. Mitochondria are so ubiquitous that they end up affecting every other system.

 

The amino acids are cheap (glutamine, tyrosine, phenylalanine) and synergize to reduce kynurenic acid (synthesis and uptake into the brain). Also, make sure to get plenty of protein in your diet. If you need a little extra protein then whey is a good option for most. 

 

Your circadian rhythm is hugely important (it syncs up all of your body's systems). Make sure you go to bed and wake up at the same time every day and also eat your meals at the same time every day. Use the bright light device first thing in the morning to activate your intrinsically photosensitive retinal ganglion cells/suprachiasmatic nucleus and then avoid blue light in the evening so that melatonin production is not inhibited (use blue light blocking glasses and/or a blue light blocking computer program if you need to). 

 

All of these things will get you most of the benefits for a very low price and without taking any research chemicals. I think many people underestimate just how powerful non-pharmacological enhancements can be. 

 

http://www.ncbi.nlm....les/PMC4667098/

 

Front Psychol. 2015; 6: 1852. 

Published online 2015 Dec 2. doi:  10.3389/fpsyg.2015.01852

PMCID: PMC4667098

Pills or Push-Ups? Effectiveness and Public Perception of Pharmacological and Non-Pharmacological Cognitive Enhancement

Lucius Caviola1,* and  Nadira S. Faber1,2,*

Author information ► Article notes ► Copyright and License information ►

Go to:

Abstract

We review work on the effectiveness of different forms of cognitive enhancement, both pharmacological and non-pharmacological. We consider caffeine, methylphenidate, and modafinil for pharmacological cognitive enhancement (PCE) and computer training, physical exercise, and sleep for non-pharmacological cognitive enhancement (NPCE). We find that all of the techniques described can produce significant beneficial effects on cognitive performance. However, effect sizes are moderate, and consistently dependent on individual and situational factors as well as the cognitive domain in question. Although meta-analyses allowing a quantitative comparison of effectiveness across techniques are lacking to date, we can conclude that PCE is not more effective than NPCE. We discuss the physiological reasons for this limited effectiveness. We then propose that even though their actual effectiveness seems similar, in the general public PCE is perceived as fundamentally different from NPCE, in terms of effectiveness, but also in terms of acceptability. We illustrate the potential consequences such a misperception of PCE can have.

 

Edited by lostfalco, 06 January 2016 - 09:39 PM.

[lostfalco]

 

Actually lostfalco, I would be very interested in the amounts of these compounds you are taking? If you are not comfortable telling everyone do you think you could pm me? As i am going to try a number of them and would like a point of reference.

Regards,

And thank you for uploading that godstack post :D

 

No problem. =)

 

I've intentionally avoided putting dose amounts because I think it's very important for people to start low and work their way up with one (or a few) substances at a time. We all have different microbiomes (millions of genes), mitochondrial genes, nuclear genes, epigenomes, developmental histories, diets, etc. On top of that, all of these genomes interact with one another and with the substances we put into our bodies!  The complexity is staggering. I've tried to account for this by illustrating mechanisms (I'll connect all of them together soon) so that people can approach cognitive enhancement from many different angles with many different emphases (presynaptic, postsynaptic, astrocytic, intracellular, extracellular, receptors, transmitters, organelles, master regulators, networks, etc.).    

 

It's also a pretty delicate balancing act with this many substances and mechanisms at the same time. If I take more selegiline then I might take less modafinil and/or less ephedrine. When I try atomoxetine I will drop all three of them for a time before slowly adding them back in (maybe). You get the idea. =) It's constantly evolving and changing depending on what I'm focused on. But, just as a reference...I almost never take more than 1mg selegiline, 50mg modafinil, 25mg ephedrine, 2mg galantamine, 3 drops tadalafil, 10mg MK-677, etc. (per dose) and I always test a new substance with a tiny amount (for allergic reaction) before slowly increasing. Sorry to be a little vague, I just don't want someone to hurt themselves with doses that work for me. =) Unfortunately, with something this complex everyone is going to have to do a bit of tinkering.    

[lostfalco]

I've had it around 6 months, using it 3 months, then 3 months of inactivity before I used it the other 2 days with MB. I used it probably 3-4 times a week on average for 90-120 minute sessions for the first month, then I was doing it maybe 2-3 times  a week for the 2nd and 3rd months. I stopped because I was worried about ROS and I was messing around with other things like MB and LLLT. 

 

I had a bad concussion almost 4 years ago and I've had severe insomnia for 10+ years so I thought it was time to try something like this. As far as benefits: it forces me to sit still and calm down and breathing is easier. I probably have low serotonin, which is involved in regulation of breathing, and I'm a "manual" breather most of the time. The HBOT makes it easier.

 

There was something I was doing earlier on that greatly helped my insomnia and allowed me to fall back asleep, I was doing HBOT and 1200mg NAC and something else, but I'm not well organized and I haven't been able to replicate it.

 

Thanks for the info, Groundhog Day. I'm glad to hear that it seems to help a little. I hope you're able to get your insomnia solved. =)

Thanks...I am getting ready to soon try LLLT with the round 48LEDs as a preliminary experiment for cognitive enhancements and was wondering if it would possibly have other side benefits...we shall see.    With the LEDs you don't need protective goggles since it only comes on when in darkness or when you have it pressed against your head, correct? (and its not Laser light)

 

 

Hey magta, no goggles necessary. =)

[lostfalco]

Was screening for some other compounds that might be of interest to us.

 

What is your opinion -

Do we want to mess with serotonin via inhibition or rather not touch it at all?

Thanks for sharing your research!

 

It's complicated, but I think we are already messing with the serotonergic system with bright light therapy and a focus on circadian rhythms (this is somewhat debatable). When you say "serotonin via inhibition" are you referring to SSRIs? Something else? =)

[lostfalco]

Botanical drug puerarin coordinates with nerve growth factor in the regulation of neuronal survival and neuritogenesis via activating ERK1/2 and PI3K/Akt signaling pathways in the neurite extension process.

...Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10-fold...

...Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process...

http://www.ncbi.nlm....ubmed/25310912/

 

Alpha-lipoic acid preconditioning reduces ischemia-reperfusion injury of the rat liver via the PI3-kinase/Akt pathway.

http://www.ncbi.nlm....pubmed/12816756

 

Niacin activates the PI3K/Akt cascade via PKC- and EGFR-transactivation-dependent pathways through hydroxyl-carboxylic acid receptor 2.

http://www.ncbi.nlm....pubmed/25375133

 

"...Limonene increased ERK1/2 activation by 30%..."

http://www.ncbi.nlm....pubmed/25622554

Thanks for the info, Logic. I've taken ALA, niacin, and limonene but never purerarin. Have you tried it?

[lostfalco]

Happy New Year folks ... hope everyone has a great journey in 2016.

 

Just throwing it out there as it appeared on my newsfeed: http://www.bioflexpersonal.com/

Dr Kahn has just released a personal laser therapy system. He uses 660 and 840 for these protocols (various body locations and different stages of treatment). His professional protocols are a bit more varied.

 

Doesn't come cheap though, but checking with them what a system like that actually entails. Only Canada (and US) at the moment though.

Thanks, Jochen. That's an interesting device. Thankfully, we have options for a fraction of his price!

[lostfalco]

Update: My Dihexa arrived today. I'm reading back through all of the research before I start dosing but I'll let you guys know when I do. http://www.nyles7.co...80-d336112804bf

 

It's an allosteric modulator of HGF. 

 

"We hypothesize that AngIV analogs, such as Nle1-AngIV and dihexa, bind to and allosterically activate HGF better than HGF itself, forming an active heterodimer of HGF-dihexa."

 

 

http://www.ncbi.nlm....les/PMC4201273/

 

J Pharmacol Exp Ther. 2014 Nov;351(2):390-402. doi: 10.1124/jpet.114.218735. Epub 2014 Sep 3.

The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system.

Benoist CC1, Kawas LH1, Zhu M1, Tyson KA1, Stillmaker L1, Appleyard SM1, Wright JW1, Wayman GA2, Harding JW2.

Author information

Abstract

A subset of angiotensin IV (AngIV)-related molecules are known to possess procognitive/antidementia properties and have been considered as templates for potential therapeutics. However, this potential has not been realized because of two factors: 1) a lack of blood-brain barrier-penetrant analogs, and 2) the absence of a validated mechanism of action. The pharmacokinetic barrier has recently been overcome with the synthesis of the orally active, blood-brain barrier-permeable analog N-hexanoic-tyrosine-isoleucine-(6) aminohexanoic amide (dihexa). Therefore, the goal of this study was to elucidate the mechanism that underlies dihexa's procognitive activity. Here, we demonstrate that dihexa binds with high affinity to hepatocyte growth factor (HGF) and both dihexa and its parent compound Norleucine 1-AngIV (Nle(1)-AngIV) induce c-Met phosphorylation in the presence of subthreshold concentrations of HGF and augment HGF-dependent cell scattering. Further, dihexa and Nle(1)-AngIV induce hippocampal spinogenesis and synaptogenesis similar to HGF itself. These actions were inhibited by an HGF antagonist and a short hairpin RNA directed at c-Met. Most importantly, the procognitive/antidementia capacity of orally delivered dihexa was blocked by an HGF antagonist delivered intracerebroventricularly as measured using the Morris water maze task of spatial learning.

 

 

http://www.ncbi.nlm....pubmed/25649658

 

J Alzheimers Dis. 2015;45(4):985-1000. doi: 10.3233/JAD-142814.

The Brain Hepatocyte Growth Factor/c-Met Receptor System: A New Target for the Treatment of Alzheimer's Disease.

Wright JW1, Harding JW1.

Author information

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease increasing in frequency as life expectancy of the world's population increases. There are an estimated 5 million diagnosed AD patients in the U.S. and 16 million worldwide with no adequate treatment presently available. New therapeutic approaches are needed to slow, and hopefully reverse, disease progression. This review summarizes available information regarding an overlooked therapeutic target that may offer a treatment to slow and hopefully halt AD, namely the hepatocyte growth factor (HGF)/c-Met receptor system. Activation of the c-Met receptor stimulates mitogenesis, motogenesis, morphogenesis, the ability to mediate stem cell differentiation and neurogenesis, and protects against tissue insults in a wide range of cells including neurons. This growth factor system has recently been shown to induce dendritic arborization and synaptogenesis when stimulated by a newly developed angiotensin-based analogue, N-hexanoic-Tyr-Ile-(6) amino hexanoic amide (Dihexa). This small molecule was derived from the pre-prototype molecule Nle1-angiotensin IV and has shown promise in facilitating the formation of new functional synaptic connections and augmenting memory consolidation in animal models of AD. Dihexa is a first-in-class compound that is orally active, penetrates the blood-brain barrier, and facilitates memory consolidation and retrieval. This angiotensin-based small molecule may be efficacious as a treatment for AD.

 

Edited by lostfalco, 06 January 2016 - 11:01 PM.

[Bluecheer]

Thank you Lostfalco! I'm always so happy to see that theres new posts on this thread! :D And I highly appreciate the post! 

I must ask, because of my own eager-ness to take this substance for such a long time... the Mk-677 how effective is it? I know it may be hard to tell with such a quantity of other drugs in there but if there's any sudden notice? 
Also have you noticed any Anabolic sort of effects from this nasal spray, or any abnormalities? 
I realize this is personal but if you have seen a benefit from this, could it be related to your age?

Thanks again! I'm always watching this thread even if I don't post, forgive me but I am quite busy. I would love to discuss studies you post, constantly! But I know ill get to into it and it will end up taking away from other activities.

(p.s methyelene blue, worth it in reference to other substances? ) 

Thanks again, and sorry for all the questions
 

[Logic]

 

Botanical drug puerarin coordinates with nerve growth factor in the regulation of neuronal survival and neuritogenesis via activating ERK1/2 and PI3K/Akt signaling pathways in the neurite extension process.

...Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10-fold...

...Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process...

http://www.ncbi.nlm....ubmed/25310912/

 

Alpha-lipoic acid preconditioning reduces ischemia-reperfusion injury of the rat liver via the PI3-kinase/Akt pathway.

http://www.ncbi.nlm....pubmed/12816756

 

Niacin activates the PI3K/Akt cascade via PKC- and EGFR-transactivation-dependent pathways through hydroxyl-carboxylic acid receptor 2.

http://www.ncbi.nlm....pubmed/25375133

 

"...Limonene increased ERK1/2 activation by 30%..."

http://www.ncbi.nlm....pubmed/25622554

Thanks for the info, Logic. I've taken ALA, niacin, and limonene but never purerarin. Have you tried it?

 

 

Nope.  But you will!   
Seriously:  I'm a white South African.  Black Empowerment makes me unemployable...

 

You may also want to check out the Nilotinib threads here.
Mitophagy and autophagy by PARKIN upregulation and the elimination of misfolded proteins from the brain. (and probably the whole body)
 

Edited by Logic, 07 January 2016 - 10:31 AM.

[lostfalco]

Insulin can be purchased over the counter in the United States (sorry, not sure about other countries). Walmart has the cheapest that I've been able to find ($25)...just go to the pharmacy and ask the pharmacist for it. They keep it behind the counter. It has been connected to mood enhancement, self confidence, body fat reduction (in men), and long term memory enhancement (significantly) in healthy humans. The mood effects happen quickly but the memory effects take around 8 weeks at 4x40IU per day. It's surprisingly well studied but I'll just post one abstract to get you guys started if you want to look into it. =)

 

 

 

http://www.ncbi.nlm....pubmed/15288712

 

Psychoneuroendocrinology. 2004 Nov;29(10):1326-34.

Intranasal insulin improves memory in humans.

Benedict C1, Hallschmid M, Hatke A, Schultes B, Fehm HL, Born J, Kern W.

Author information

Abstract

Previous studies have suggested an acutely improving effect of insulin on memory function. To study changes in memory associated with a prolonged increase in brain insulin activity in humans, here we used the intranasal route of insulin administration known to provide direct access of the substance to the cerebrospinal fluid compartment. Based on previous results indicating a prevalence of insulin receptors in limbic and hippocampal regions as well as improvements in memory with systemic insulin administration, we expected that intranasal administration of insulin improves primarily hippocampus dependent declaration memory function. Also, improvements in mood were expected. We investigated the effects of 8 weeks of intranasal administration of insulin (human regular insulin 4 x 40 IU/d) on declarative memory (immediate and delayed recall of word lists), attention (Stroop test), and mood in 38 healthy subjects (24 males) in a double blind, between-subject comparison. Blood glucose and plasma insulin levels did not differ between the placebo and insulin conditions. Delayed recall of words significantly improved after 8 weeks of intranasal insulin administration (words recalled, Placebo 2.92 +/- 1.00, Insulin 6.20 +/- 1.03, p < 0.05). Moreover, subjects after insulin reported signs of enhanced mood, such as reduced anger (p < 0.02) and enhanced self-confidence (p < 0.03). Results indicate a direct action of prolonged intranasal administration of insulin on brain functions, improving memory and mood in the absence of systemic side effects. These findings could be of relevance for the treatment of patients with memory disorders like in Alzheimer's disease.

 

Edited by lostfalco, 09 January 2016 - 12:29 AM.

[lostfalco]

Interesting new full text article on BDNF mimetic 7,8 Dihydroxyflavone. It's orally bioavailable (5%), crosses the blood brain barrier, has a decent half-life, and activates TrkB receptors. It could possibly enhance learning and memory by slowing afterhyperpolarization (see Lynch's work).  

 

It's available here. http://www.amazon.co.../dp/B00O5N69EY/

 

http://translational...0035-015-0048-7

 

 

7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders

• Chaoyang Liu, 
• Chi Bun Chan and 
• Keqiang YeEmail author

Translational Neurodegeneration20165:2

DOI: 10.1186/s40035-015-0048-7

©  Liu et al. 2015

Abstract

Brain-derived neurotrophic factor (BDNF) regulates a variety of biological processes predominantly via binding to the transmembrane receptor tyrosine kinase TrkB. It is a potential therapeutic target in numerous neurological, mental and metabolic disorders. However, the lack of efficient means to deliver BDNF into the body imposes an insurmountable hurdle to its clinical application. To address this challenge, we initiated a cell-based drug screening to search for small molecules that act as the TrkB agonist. 7,8-Dihydroxyflavone (7,8-DHF) is our first reported small molecular TrkB agonist, which has now been extensively validated in various biochemical and cellular systems. Though binding to the extracellular domain of TrkB, 7,8-DHF triggers TrkB dimerization to induce the downstream signaling. Notably, 7,8-DHF is orally bioactive that can penetrate the brain blood barrier (BBB) to exert its neurotrophic activities in the central nervous system. Numerous reports suggest 7,8-DHF processes promising therapeutic efficacy in various animal disease models that are related to deficient BDNF signaling. In this review, we summarize our current knowledge on the binding activity and specificity, structure-activity relationship, pharmacokinetic and metabolism, and the pre-clinical efficacy of 7,8-DHF against some human diseases.

 

Edited by lostfalco, 09 January 2016 - 01:04 AM.

[lostfalco]

Recent 2015 free full text study on intranasal insulin.

 

It increases synaptogenesis, improves recall in aged rodents to the level of younger ones, reduces afterhyperpolarization (this mechanism has fascinated me for a while), has acute effects but even better chronic effects, modulates brain glucose utilization, is neuroprotective, interacts significantly with the brain melanocortin system, and has shown beneficial cognitive effects in humans with Alzheimer's disease as well as healthy humans. 

 

IGF-1 can also be administered intranasally and looks very interesting (especially for its neuroprotective properties). 

 

https://www.research...ts_on_Cognition

 

J Alzheimers Dis. 2015;47(3):715-28. doi: 10.3233/JAD-150307.

Central Nervous System Delivery of Intranasal Insulin: Mechanisms of Uptake and Effects on Cognition.

Salameh TS1,2, Bullock KM1, Hujoel IA1, Niehoff ML3,4, Wolden-Hanson T1, Kim J3, Morley JE3, Farr SA3,4, Banks WA1,2.

Author information

Abstract

Intranasal insulin has shown efficacy in patients with Alzheimer's disease (AD), but there are no preclinical studies determining whether or how it reaches the brain. Here, we showed that insulin applied at the level of the cribriform plate via the nasal route quickly distributed throughout the brain and reversed learning and memory deficits in an AD mouse model. Intranasal insulin entered the blood stream poorly and had no peripheral metabolic effects. Uptake into the brain from the cribriform plate was saturable, stimulated by PKC inhibition, and responded differently to cellular pathway inhibitors than did insulin transport at the blood-brain barrier. In summary, these results show intranasal delivery to be an effective way to deliver insulin to the brain.

 

Edited by lostfalco, 09 January 2016 - 05:55 PM.