4029 replies to this topic

[lostfalco]

Hey lostfalco, what's up??

 

I want to know if you still doing EC + IDRA 21 stack for focus and cognitiion, and some working memory.

 

I want to try ephedrine + idra 21 (I already do caff).

 

Thanks man!

Hey Lucas, that is a little stack I still like to use. The mental energy feels clean and focus is great for me. I usually use the typical EC stack doses with 10mg of IDRA. 

[lostfalco]

Hi Falco,

Thanks for the supportive post...I've posted links on several other alt-health boards with pretty much collective yawns from all so far. As everyone here must know, it's good to have company when trying out new protocols. I'll be interested to hear your results of testing the Lourdes machine. There's a facebook group, Hydrogen Water, which has discussions mainly between machine and pill salespeople (mostly MLM types, I think) and current or potential customers. They have a guideline against mentioning brand names there but I've seen posts that seem to imply the best machines get around 1.0 ppms or a little more. The Lourdes is one of the few that actually advertises a level for H2 produced...I think it's 1.2 ppms. I wish they all would cut to the chase and just document their H2 concentrations obtained with their machines under normal operation, since that seems to be the ONLY factor which, according to Tyler LeBaron, makes a difference in their therapeutic value. Then they could also publish a video showing someone testing the water since that's pretty hard evidence also. It might start to bring H2 Water supplementation out of the realm of wild claims of snake-oil hucksters to science based medicine with decent anecdotal reporting of perceived benefits. Peer-reviewed studies are great but I also like to hear user reviews. Big Pharma has steered clear of this technology so far, it seems, probably because they couldn't see how to make money selling the most abundant molecule in the universe.

 

If you decide to try the DIY method, it takes about 3 weeks to get the 5" rods delivered from the Ebay seller. This is definitely a drag and will keep some from trying it out. If anyone locates a better (faster) source, please share.  -Glen

 

No problem, Glen. I really liked your video and it makes H2 so much more affordable. My drops haven't arrived yet but I'll let you know as soon as they do so that we can compare. If the output of my machine is significantly lower than your method then I will be really interested in testing the differential effects between the two. I appreciate your willingness to share your experiment with everyone!

[lostfalco]

 

I've been using guanfacine for a while. Definitely, it increases spatial working memory, but not to a very extraordinary amount. Drowsiness and dry mouth is a killer. Idra-21, sunifiram, and coffee helped a little with somnolence. Dry mouth has no antidote. If there is a way to counteract dry mouth, increase in working memory and focus definitely worth to try to expand cognitive ability.

 

Thanks for the report, Amorphous! Did you get guanfacine through prescription?

Edited by lostfalco, 08 April 2016 - 02:58 PM.

[lostfalco]

Also, does anyone have any theories on what purpose PDE4 could have? It seems like PDE4i's are a mental panacea.

 

Hey bigyellow, almost forgot...here's a nice summary of PDE4i for cognition. http://www.ncbi.nlm....les/PMC4066988/

 

PDE4 has multiple subtypes expressed in different places throughout the body and its primary function is to hydrolyze cyclic-AMP (cAMP) and inactivate it. Here's how cAMP works (pay close attention to CREB and ultimately transcription): 

 

 

 

 

 

 

Edited by lostfalco, 09 April 2016 - 05:59 AM.

[lostfalco]

One last cAMP summary video and diagram. =)

 

Note: don't forget that PDE4i (esp subtype D in brain AND gut) is associated with severe vomiting/nausea (see Rolipram). The way around this is combining low doses of PDE4i and other substances (acetylcholinsterase inhibitors, PDE5i's, etc.).  http://www.longecity...100#entry767788

 

Note 2: Where do you think the ATP comes from which is subsequently turned into cAMP by adenylyl cyclase? Hint: it starts with 'mito' and ends with 'chondria'. =) Healthy mitos/hydrogen gradients are fundamental to just about everything. In fact, there is significant interaction between cAMP, CREB, and mitochondria. cAMP activates PKA activates CREB activates PGC-1a causes mitochondrial biogenesis (see PQQ mechanism).  http://www.ncbi.nlm....les/PMC3870303/

 

 

 

 

http://www.ncbi.nlm....les/PMC4066988/

Figure 2

PDE4 inhibition, cAMP signaling and brain function

Scheme illustrating the signaling events linking PDE4 inhibition to improved brain function. Inhibition of PDE4 triggers an increase in cAMP which in turn exerts its downstream effects via activation of protein kinase A (PKA), exchange proteins activated by cAMP (EPACs) and cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels. PKA is well known to phosphorylate a range of signaling proteins including CREB (cAMP response element binding protein), synapsin, DARPP32 (dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa) and tyrosine hydroxylase (TH) and thereby modulate gene expression, ion channel function, neurotransmitter synthesis and release as well as various other signaling events that regulate memory and cognitive processes. Recent evidence suggests that EPAC is involved in many of the same signaling paradigms previously associated with PKA, suggesting that some of the established effects of PDE4 inhibitors on memory and cognition might be mediated by EPAC rather than PKA activation [147-154]. Although a role for cyclic nucleotide-regulated channels (CNG and HCN) in brain function is well established [155,156], little is known thus far about the role of PDEs in regulating the pool of cAMP that controls the function of these channels. NT, neurotransmitter; AC, adenylyl cyclase; GsPCR, Gs protein-coupled receptor; GiPCR, Gi protein-coupled receptor; βAR, β-adrenergic receptor; αAR, α-adrenergic receptor; DR, dopamine receptor; 5HTR, serotonin type 1D receptor

 

Edited by lostfalco, 08 April 2016 - 07:09 PM.

[lostfalco]

This is so well written that I just figured I'd quote the whole thing. Subtleties like this are almost always the case with just about any system you attempt to modulate. Hence, my proclivity for low dosing. =) 

 

http://www.ncbi.nlm....les/PMC4066988/

"2.4. Not all cAMP signaling is procognitive

A complication in the development of PDE4 inhibitors as memory- and cognition-enhancing drugs is the fact that cAMP/PKA activation (in general, and after PDE4 inhibition in particular) does not exclusively exert procognitive effects. A case in point is the Drosophila dunce gene. The phosphodiesterase encoded by the dunce gene is the evolutionary ancestor of the mammalian PDE4s and its role in olfactory learning provided the first indication that PDE4s regulate CNS functions. However, while inhibition of the mammalian PDE4s is pursued as a way to improve memory and cognition, inactivating mutations in the dunce gene result in memory impairment, specifically impairment of early memory formation [12,14]. Although a large majority of studies attest to positive memory- and cognition enhancing effects of PDE4 inactivation, pharmacologic and/or genetic ablation of the mammalian PDE4s have also been shown to impair learning and memory in some paradigms [47,64-66]. Given the multitude of downstream targets and cellular functions regulated by cAMP/PKA signaling, it is not surprising that cAMP signaling does not exclusively exert beneficial effects on memory and cognition, but may also induce some untoward effects (see [67]).

 

Even in cAMP pathways that are therapeutically relevant, the level of PDE4 inhibition is critical to realize pro-cognitive effects. Physiological cAMP signals are generally short lived and the shape of cAMP transients is critical to induce the appropriate cellular responses [68]. Amplifying the cAMP transient may serve to amplify the cellular responses and thereby mediate therapeutic benefits. However, increasing cAMP levels above a certain threshold to supraphysiologic levels may essentially disrupt signaling, as downstream effectors are chronically switched on. Such conditions likely trigger compensatory mechanisms at other steps to desensitize the cAMP signaling cascade and these compensatory effects, rather than increased cAMP signaling per se, might induce memory and cognitive deficits (see for example [59]). This hypothesis fits well with some of the scenarios where PDE4 inactivation produces deficits. Memory deficits in R6 mice, a model of Huntington’s disease, for example, are associated with a reduced expression of hippocampal PDE4s and hyperactivation of PKA [64]. Importantly, while acute PDE4 inhibition is generally memory-enhancing, chronic treatment of wild type mice with high doses of Rolipram (22 days; 5 mg/kg/day i.p.) produced a similar upregulation of PKA activity and associated learning and memory deficits, but had no further effect in R6 mice [64]. Conversely, lower doses of Rolipram have shown neuroprotective effects in models of Huntington’s disease, including the R6 mice [69,70]. High doses of Rolipram also impaired prefrontal cortical function in aged, but not young monkeys, and the age-specific effects may be due to the fact that the cAMP/PKA pathway is already disinhibited in the aged prefrontal cortex [47,67]. Thus, PDE4 inhibition may exert deleterious effects on memory and cognition under conditions in which PDE4s are already downregulated and cAMP levels and PKA activity are elevated. On the other hand, targeting PDE4s can be expected to mediate beneficial effects in diseases characterized by cognitive deficits resulting from reduced/impaired cAMP/PKA signaling. Under these circumstances, PDE inactivation can serve to reverse memory and cognition deficits by restoring “normal” cAMP signaling. The untoward effects induced by cAMP/PKA hyperstimulation may also suggest that submaximal doses of PDE4 inhibitors that induce partial, rather than full inhibition of the enzymes might be more effective for memory- and cognition-enhancement."

Edited by lostfalco, 08 April 2016 - 06:53 PM.

[bigyellowlemon]

 

Why don't all humans have a ton more Nicotine receptors? Maybe we're messing with something we shouldn't.

 

I think Gwern brought this up as an example of why we can't reliably improve intelligence.

Hey bigyellow, explain the logic here. The 'number of nicotine receptors' somehow indicates what we should or shouldn't mess with? Morally? What will be most likely be effective? Something else? Not sure what the argument is here. =)

 

 

 

 

1. I've been wary lately of using nootropics.

 

2. Biology is so damn complex, and here we are so arrogantly thinking we know how to control it.

 

3. Maybe it's best to try to merely live a healthy life and let our own biology honed over millions of years do it's job. idk

1. I think you mentioned that you are 18, correct? I would humbly suggest that you don't take nootropics, actually (wait till 25, if ever). Of course, feel free to make your own choices. Just my two cents. =)

 

2. It is extremely complex. I would never assume that I know how to 'control it'. I've made it very clear over the years that I read massive amounts of scientific literature and use that to inform my 'guesses' about what may or may not work. There are always risks/unknowns and this is why I've always called myself 'a foolish self-experimenter who lives on pubmed'. If that makes me 'arrogant'...so be it. =)

 

3. I'm totally cool with this.  

 

 

haha no I don't think there's anything "wrong" with it at all.

My example was basically saying that if it improves cognition, why don't humans have more?
But then you could say the same thing about BDNF and other traits. They all come with a negative.

Ah I guess I answered my own question.

[bigyellowlemon]

Thanks for the stuff on cAMP!!! 

Edited by bigyellowlemon, 08 April 2016 - 08:26 PM.

[lostfalco]

Thanks for the stuff on cAMP!!! 

You're very welcome!

[lostfalco]

 

Ah I guess I answered my own question.

 

Yeah, I think you're on the right track. Also, I don't think there is any reason to think that humans have anything close to maximal intelligence so it seems reasonable to think that we might be able to improve a little. It's not an easy thing to do but it at least seems possible...to me at least. 

Edited by lostfalco, 08 April 2016 - 09:05 PM.

[lostfalco]

I was thinking that exactly, galantamine + ibudilast. Somewhat aside but I was wondering if you posted your experiments anywhere else like Gwern or Joe. It would be cool to check in occasionally and see what you've been up to instead of wading through several pages of Q&A.

 

 

Hey Nick, I've just started compiling info over at http://www.lostfalco.com

 

It's a complete mess right now but I'll be progressively organizing it in the coming weeks. Soon it will be a vision of pristine, organized beauty! =)

Edited by lostfalco, 09 April 2016 - 09:47 PM.

[MindExplorer]

Hi everyone! I've read all 102 pages of this thread and feel like part of the "team", but aside from a few PMs to lostfalco last year, I haven't actually contributed anything beyond my reading skills... I'll introduce myself and my results so far in a future post, but for now I'm just here to ask a question. I'm loving what you guys have done and are doing though, and I look forward to being a part of it.

Lostfalco, initially you reported great results from artichoke extract, I think primarily with regard to memory but perhaps other aspects of cognition, but you described it as almost too good and cautioned against using it frequently. Then, your focus seemed to shift more to PDE5 inhibitors, but more recently you've posted about other PDE4 inhibitors. If you don't mind, I'd love it if you could elaborate on what specifically you experienced from artichoke extract, what made it seem "too good" and why you suggested using it infrequently, what led you to move on from it, whether your initial experiences with it continued to be reproducible, how it compared to other PDE4 inhibitors that you've tried, how those have compared to PDE5 inhibitors, etc. Thanks in advance! And thanks for all the work you've done and shared!

[Nick Kyz]

 

I was thinking that exactly, galantamine + ibudilast. Somewhat aside but I was wondering if you posted your experiments anywhere else like Gwern or Joe. It would be cool to check in occasionally and see what you've been up to instead of wading through several pages of Q&A.

 

 

Hey Nick, I've just started compiling info over at https://lostfalco.com

 

It's a complete mess right now but I'll be progressively organizing it in the coming weeks. Soon it will be a vision of pristine, organized beauty! =)

 

It's already a big improvement, I'm looking forward to what you come up with.

[Judd Crane]

Has anyone experimented with LLLT on the radial and ulnar artery á la the Quantlet?

[bigyellowlemon]

I'm worried about galantamine down-regulating nicotinic receptors. Nicotine up-regulates them but I'm not sure if that's a good thing, maybe they're being sensitized?

 

Also Syrian Rue seems like the perfect nootropic. Acetylcholinestrase inhibiotor, benzo site GABA antagonist, MAOI-A/B, inhibits KYNA, increases histamine, increases normelatonin, and weakly inhibits serotonin re-uptake.

 

Combining nicotine with syrian rue seems like a good combination. Increase nicotine sensitivity + all of syrian rue's benefits. However, studies showing nicotines effects on the developing brain scare me.

 

This needs further research.

[Nuke]

I have my reservations about harmala alkaloids. If we plan to use it as a nootropic, I believe more research on its potential long term toxicity is necessary. I have not done any real research myself, just read about it when reading up on essential tremor.

 

https://en.wikipedia...ssential_tremor

https://en.wikipedia.org/wiki/Harmane

https://www.ncbi.nlm.../pubmed/8377927

http://web.ics.purdu...l Neurology.pdf

 

[bigyellowlemon]

I have my reservations about harmala alkaloids. If we plan to use it as a nootropic, I believe more research on its potential long term toxicity is necessary. I have not done any real research myself, just read about it when reading up on essential tremor.

 

https://en.wikipedia...ssential_tremor

https://en.wikipedia.org/wiki/Harmane

https://www.ncbi.nlm.../pubmed/8377927

http://web.ics.purdu...l Neurology.pdf

 

I believe the essential tremor comes from the GABA antagonism.

 

GABA antagonism should increase the chance of excitotoxicity as well, but if you are healthy than I believe it's not problem.

 

In fact, harmala alkallioids are neuroprotective by inhibiting KYNA, which would breakdown into quinolinic acid. Also,  harmala alkaloids inhbit nitric oxide synthase, which is neuroprotective as well. 

 

If you are healthy and don't have a family history of it than I bet essential tremor isn't a major concern.

[lostfalco]

I'm worried about galantamine down-regulating nicotinic receptors. Nicotine up-regulates them but I'm not sure if that's a good thing, maybe they're being sensitized?

 

Hey bigyellow, I think chronic nicotine generally downregulates receptors. 

 

https://www.ncbi.nlm.../pubmed/8371136

 

J Pharmacol Exp Ther. 1993 Sep;266(3):1268-76.

Downregulation of nicotinic receptor function after chronic nicotine infusion.

Marks MJ1, Grady SR, Collins AC.

Author information

Abstract

Chronic nicotine treatment generally results in tolerance to several actions of nicotine and a paradoxical increase in brain nicotinic receptor numbers. Receptor upregulation, it has been argued, arises as a consequence of functional desensitization. In the studies reported here, mice were chronically infused with saline (control) or one of five doses of nicotine (0.25-4.0 mg/kg/hr) for 10 days. This treatment resulted in a dose-dependent tolerance to nicotine-induced decreases in body temperature as well as decreases in locomotor and rearing activities in a Y-maze. The anticipated increase in [3H]nicotine binding was also observed. To assess functional status of the nicotinic receptors, nicotine-stimulated release of [3H]dopamine from striatal synaptosomes and 86Rb+ efflux from cortical and midbrain synaptosomes were also measured. Chronic nicotine infusion resulted in an infusion dose-dependent decrease in [3H]dopamine release from striatum and 86Rb+ efflux from midbrain; cortical 86Rb+ efflux was not affected by chronic nicotine treatment. Dose-response analyses of the release and efflux assays demonstrated that chronic nicotine infusion evoked decreases in the maximal effects of nicotine on the functional assays; potency was not altered by chronic drug treatment. These results are consistent with the hypothesis that behavioral tolerance to nicotine is a consequence of down-regulation of brain nicotinic receptor function.

[lostfalco]

I'm worried about galantamine down-regulating nicotinic receptors. 

Galantamine's effects are complicated but seem generally favorable for nicotinic receptor upregulation. 

 

https://www.ncbi.nlm...icles/PMC29386/

 

Galantamine: Effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning.

 

"These findings are consistent with a report (32) that also demonstrated a similar effect of chronic Gal therapy on nicotinic receptor density. Although Barnes et al. (32) did not find a significant improvement in spatial memory in their aged rats, they did find a significant positive correlation between the durability of long-term potentiation and the Bmax of nicotinic receptors within the hippocampus that was induced by chronic Gal therapy. Taken together with the results of the current study, these data suggest that chronic Gal therapy can effectively and consistently increase the density of nicotinic receptors in selected brain regions that are involved in learning and memory. It is our conclusion that this increase in nicotinic receptor number, and the resultant changes in electrophysiological indicators of neural plasticity (32), may underlie aspects of the cognitive benefits produced by long-term therapy with Gal in humans with AD."

Edited by lostfalco, 10 April 2016 - 05:15 PM.

[lostfalco]

Low dose lithium inhibits GSK3, activates Nrf2, and promotes longevity in fly model. 

 

We've talked a little bit about GSK3 inhibition in this thread. =)

 

Popular article:  http://www.medicalne...s/308830.php?tw

 

Free full text journal article from Cell: http://www.cell.com/...(16)30297-2.pdf

 

Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis 

 

SUMMARY

The quest to extend healthspan via pharmaco- logical means is becoming increasingly urgent, both from a health and economic perspective. Here we show that lithium, a drug approved for human use, promotes longevity and healthspan. We demonstrate that lithium extends lifespan in female and male Drosophila, when administered throughout adulthood or only later in life. The life- extending mechanism involves the inhibition of glycogen synthase kinase-3 (GSK-3) and activation of the transcription factor nuclear factor erythroid 2-related factor (NRF-2). Combining genetic loss of the NRF-2 repressor Kelch-like ECH-associated protein 1 (Keap1) with lithium treatment revealed that high levels of NRF-2 activation conferred stress resistance, while low levels additionally promoted longevity. The discovery of GSK-3 as a therapeutic target for aging will likely lead to more effective treatments that can modulate mammalian aging and further improve health in later life. 

 

Edited by lostfalco, 10 April 2016 - 06:53 PM.

[lostfalco]

Has anyone experimented with LLLT on the radial and ulnar artery á la the Quantlet?

Sorry Judd, I'm familiar with the Quantlet but haven't lasered at their locations. 

[lostfalco]

Hi everyone! I've read all 102 pages of this thread and feel like part of the "team", but aside from a few PMs to lostfalco last year, I haven't actually contributed anything beyond my reading skills... I'll introduce myself and my results so far in a future post, but for now I'm just here to ask a question. I'm loving what you guys have done and are doing though, and I look forward to being a part of it.

Lostfalco, initially you reported great results from artichoke extract, I think primarily with regard to memory but perhaps other aspects of cognition, but you described it as almost too good and cautioned against using it frequently. Then, your focus seemed to shift more to PDE5 inhibitors, but more recently you've posted about other PDE4 inhibitors. If you don't mind, I'd love it if you could elaborate on what specifically you experienced from artichoke extract, what made it seem "too good" and why you suggested using it infrequently, what led you to move on from it, whether your initial experiences with it continued to be reproducible, how it compared to other PDE4 inhibitors that you've tried, how those have compared to PDE5 inhibitors, etc. Thanks in advance! And thanks for all the work you've done and shared!

102 pages!?! You're a brave man, MindExplorer! I wonder how many times you've read me saying, "Hey, what's up..."? ha. 

 

Artichoke combined with TULIP + moda + pregnenolone, etc. (my stack back then) was quite stimulatory and I used it 3 years ago before I had extensive firsthand knowledge of the scientific literature on luteolin/artichoke extract (in humans when taken orally...I knew about cAMP and PDE4i). My reference to it being 'too good' is that generally things that are extremely stimulatory tend to cause downregulation of receptors over time. I've since moved on to substances that have greater evidence in humans for their actual mechanisms (artichoke has a low probability of inhibiting PDE4 in the human brain when taken orally...the stimulation I felt was likely through another mechanism). Tadalafil (PDE5i) and Ibudilast (PDE4i + other PDEs) have a lot more evidence in humans regarding their actual mechanisms when taken orally. I've just tried to increase my probability of actually adjusting the mechanism that I'm attempting to adjust. =)

 

Comparative effects are hard to ascertain due to the different stacks that I've tested each substance with. Our bodies are so interactive that adjusting X can have multiple downstream consequences and change the effects of adding Y, Z, etc...  Sorry about the vagaries, it's just the epistemic hand we're dealt. =)

 

Anyway, if you're interested in testing the effects of PDE5i or PDE4i I would recommend trying tadalafil/sildenafil or something like ibudliast (it's more of a pan-PDE but mainly targets PDE4). I hope that helps!

Edited by lostfalco, 10 April 2016 - 10:25 PM.

[MindExplorer]

Thanks for the reply! That does help, but my initial interest is more in trying to reproduce the amazing results you reported than in testing specific mechanisms like PDEi. Now that you no longer use modafinil daily, have you tried artichoke extract? I forget, do you still take pregnenolone? Even if it doesn't seem like the scarily positive effects you experienced from artichoke extract were from PDE4i as per Abelard Lindsay's hypothesis with CILTEP, do you think those results are still producible? If so, do you think they're producible just in conjunction with TULIP?

 

What type of stimulatory effects are we talking about? Wakefulness, motivation, mood, focus, all, other? Do you currently think artichoke was responsible for the apparent memory gains you quoted in the TULIP experiences thread or do you think that was just the result of TULIP or TULIP+pregnenolone? Has PDE5i been more consistent for memory enhancement in your experience? What about megadosing resistant starch? Has intranasal insulin's primary effects been limited to mood or have you experienced memory and/or other nootropic enhancement? Enough to outweigh metacresol unknowns?

 

Are there certain effects you reported early on that you now believe to be more the result of placebo than pharmacology? Do you still view TULIP as a real world analog of NZT? Basically, what recommendations would the page 102 lostfalco give to the page 1 lostfalco?

[lostfalco]

Thanks for the reply! That does help, but my initial interest is more in trying to reproduce the amazing results you reported than in testing specific mechanisms like PDEi. Now that you no longer use modafinil daily, have you tried artichoke extract? I forget, do you still take pregnenolone? Even if it doesn't seem like the scarily positive effects you experienced from artichoke extract were from PDE4i as per Abelard Lindsay's hypothesis with CILTEP, do you think those results are still producible? If so, do you think they're producible just in conjunction with TULIP?

 

What type of stimulatory effects are we talking about? Wakefulness, motivation, mood, focus, all, other? Do you currently think artichoke was responsible for the apparent memory gains you quoted in the TULIP experiences thread or do you think that was just the result of TULIP or TULIP+pregnenolone? Has PDE5i been more consistent for memory enhancement in your experience? What about megadosing resistant starch? Has intranasal insulin's primary effects been limited to mood or have you experienced memory and/or other nootropic enhancement? Enough to outweigh metacresol unknowns?

 

Are there certain effects you reported early on that you now believe to be more the result of placebo than pharmacology? Do you still view TULIP as a real world analog of NZT? Basically, what recommendations would the page 102 lostfalco give to the page 1 lostfalco?

haha That's a lot of questions. =)

 

Let me see if I can help you focus a bit (if not, just tell me to stfu =)). My guess is that your primary goal is to enhance your own cognition (not to hear my anecdotes). If that is the case, then I think your best bet is to start (after getting the Big 6 in order) by seeing if enhancements to your hydrogen gradient/mitochondria result in improvements in your cognition. LLLT is a great place to start because it is cheap, has a low probability of side effects, and results in more hydrogens (it's very fundamental: a photon interacts with an electron causing proton pumping) pumped across the inner mitochondrial membrane resulting in your body upregulating 100+ genes in response to the excess work done by the gradient. Once you have tested that out then you can seek to enhance it further (if it works for you) or drop it and try another approach if it doesn't work for you. 

 

I'm happy to answer your questions but my main goal is to help other self-experimenters guide their experiments rather than drone on (too much) about my own results. =) Everybody is individual and it kind of takes a piecemeal approach for each of us to figure out what does and doesn't enhance our particular cognition. I like to try to focus on fundamentals and then expand from there. What have you experimented with so far? 

Edited by lostfalco, 12 April 2016 - 03:32 AM.

[magta39]

 

1. Lostfalco, so do you think taking sublingual Pregnenolone would have different effects than if you just swallowed it to get the conversion to PS?  

 

 

2. Another question is do you think tadalafil is safe for women to take in the small doses for nootropic effects?

 

 

1. Yessir, I think so. 

 

2. In low doses (5mg) it seems relatively safe for women to test out. 

 

https://www.ncbi.nlm...pubmed/22612985

"Daily tadalafil 5 mg treatment seems to improve subjective sexual aspects and could be used to treat genital arousal disorder of premenopausal women with type 1 diabetes."

 

https://www.ncbi.nlm...pubmed/26797204

"PDE5is could be an effective treatment modality for female sexual dysfunction. Although there were significant increases in adverse events in comparison with placebo, PDE5is were still relatively safe."

 

 

Yes Lostfalco it seems the effects of sublingual pregnenolone and a swallowed tablet are very different..I have tried sublingually 2.5mg (quarter of tablet) several times in the past and the unwanted side effects for me include quick to anger and insomnia and vivid nightmare.  I have tried swallowing a 10mg tablet twice over the last few days and noticed none of this..I was in a good mood, memory was good and my wife says last night I was snoring 4 minutes after hitting the pillow which is very unusual for me to sleep that fast...so thank you again!

 

[lostfalco]

Yes Lostfalco it seems the effects of sublingual pregnenolone and a swallowed tablet are very different..I have tried sublingually 2.5mg (quarter of tablet) several times in the past and the unwanted side effects for me include quick to anger and insomnia and vivid nightmare.  I have tried swallowing a 10mg tablet twice over the last few days and noticed none of this..I was in a good mood, memory was good and my wife says last night I was snoring 4 minutes after hitting the pillow which is very unusual for me to sleep that fast...so thank you again!

 

No problem, magta. Glad that helped. =)

[resveratrol_guy]

Hey lostfalco, can you give us an update as to the state of readiness of lostfalco.com? In particular, it would be quite convenient to be able to read a more tidy and condensed version of your current thinking based on all the conversation here. Ideally, there would be one "special" blog entry which you would periodically update to be a summary of exactly that, with links out to the detailed posts. (But I realize how frustrating blog interfaces can be, for that purpose, as they're all geared to chronological journalling.)

 

[middpanther88]

Agreed with the concise summary of your findings and possible clear theories.

[Bluecheer]

Much appreciated lostfalco, as always. And I will definitely take your advice on board, although its hard when already experimenting and find things that help me perform at a higher wave length. When usually my intelligence has the grace of a fish out of a water... sigh :\

With that being said I am quite in a hurry to get some pregenolone powder as im moving over seas in a few months but would like to test it some more before I go... Unfortunately the source you use Or quoted on the god stack , Smart powders ... is all out, do you by any chance use another source?

Cheers!

[MindExplorer]

What have you experimented with so far?

 

Too many to list! I'll mention some highlights, and I'll include substances that fall outside some of the narrower definitions of "nootropic" as a noun. I'll start with focus promotion. Both modafinil and the L-theanine/caffeine stack (in a ratio greater than 1:1) significantly improve my focus but at the expense of motivation and creativity. 200mg modafinil gives me tunnel vision/laser-like focus but is intolerably emotionally dulling. It's also a bit cognitively impairing for me at that dose. 150mg modafinil, 75mg armodafinil, and something like 3:2 L-theanine/caffeine all enhance my ability to focus without forcing it à la tunnel vision, but they're still emotionally dulling enough to be a dealbreaker. Ephedrine seems to have similar focus-promotion effects for me with less emotional dulling. 50-100mg modafinil also has less emotional dulling for me (still some) but much less focus promotion and also less wakefulness promotion. Doses under 100mg seem to have very little wakefulness promotion for me.

 

For wakefulness, I've had better luck with various slow-releasing caffeine (plus other xanthine) sources like guarana, yerba mate, and guayusa. For me the first two are basically extended release coffee without the jitters or crash, and guayusa adds just enough L-theanine for some focus promotion without much emotional dulling. I'm not sure what the ratio is, but I'd guess it's around 6:5 L-theanine to caffeine. In higher doses (around 150mg caffeine worth) there's enough of a mood lift to fully negate my dislike of the emotional dulling. Phenylpiracetam gives me similar (but much shorter lived) focus promotion without emotional dulling at doses of 100mg and maybe up to around 150mg, but I find 200mg phenylpiracetam very similar both in emotional dulling and focus promotion to 3:2 L-theanine to caffeine. I do like 100mg phenylpiracetam stacked with a little caffeine, but I can't take it regularly due to phenylpiracetam tolerance. That's one of the only combinations of wakefulness and focus promotion that don't negatively impact my motivation. Phenylpiracetam also seems to improve my working memory or at least context switching. The only other focus promoter I've found that doesn't lower my motivation is Adderall (and presumably other DRAs), and the few times I tried it I got *strong* focus promotion (borderline tunnel vision) with an *increase* in motivation. That combination is amazing, but also scary and potentially neurotoxic, so I haven't sought a prescription.

 

I've also experimented with low doses of stimulating strains of kratom (those with higher ratios of mitragynine to 7-hydroxy-mitragynine). Some strains were focus promoting at the expense of motivation, some were motivation promoting without affecting focus, all were very slightly impairing (less so than modafinil), and all were too finicky to dose right for me to give them an adequate amount of experimentation. Kratom is a great analgesic to have on hand for emergencies, though.

 

I've also tried semax and n-acetyl-semax-amidate. I haven't used semax in a while, but it was very interesting. It didn't have any sort of forced focus promotion, but it seemed a lot easier to concentrate on it than normal. I felt a bit more detached but not emotionally dull, and cognitive tasks that I'd normally find boring felt less draining. I'll have to play around with it again. I found n-acetyl-semax-amidate very similar but slightly less effective for concentration and significantly more effective for wakefulness promotion. I only took it two or three times, so I'm not super confident in that assessment. Unlike semax, I've heard "NASA" can't be taken daily without tolerance buildup, at least to the stimulating effects, so I'm more interested in regular semax given that I did respond well to it.

 

I've tried a number of racetams beyond phenylpiracetam (piracetam, ani-, oxi-, and prami-), all of which give me significantly enriched sensory experience but very little in the way of observable nootropic value. Piracetam increases my confidence and mood, which can have downstream benefits on cognitive performance if confidence and mood are below baseline on a given day.

 

I've been playing around with TULIP for a couple of months and am still trying to figure out optimal dose of PQQ, dose and presence/absence of ubiquinol, "dose" of LLLT, time of day for LLLT, frequency of LLLT, and dose and presence/absence of supplements on non-LLLT days. I get pretty significant subjective effects after "lasering" (I'm using the 96 LED), but if anything my cognitive performance and/or productivity seem to decrease until 8-24 hours afterwards. That recovery period seems lower when I take 20mg PQQ and 200mg ubiquinol than when I take 10mg PQQ or 0-100mg ubiquinol, but the one time I tried 300mg ubiquinol I had a decent amount of brainfog for most of the day. I plan to continue to play around with these variables and collect more informal data before making strong conclusions about TULIP's effects in me. I'm also really tempted to try an actual laser like the Vetro and see if I get clearer results. I have more to say, but this post is long enough as is! I'll have more to say in the upcoming weeks at any rate.

P.S. I forgot to address the "Big Six"! I eat well. I have good sleep hygiene but typically struggle with insomnia 2-3 nights a week. I walk a lot but don't get enough real exercise. I intend to add regular HIIT and/or BBS in about a month. I stand a decent amount and take walking breaks whenever I feel I've been sitting too long. I don't use a standing desk though. I don't formally fast, but I often replace breakfast or lunch with an egg, avocado, high-oleic nut butters, or whole fruit, especially berries. I am able to achieve meditative ego loss at will but can't usually hold it for more than a second or two without the aid of cannabis or serotonergic psychedelics. That first part results in a general outlook on life that promotes a fairly high baseline for mood and excitement and a fairly low baseline for anxiety, but it also means I don't access much of the nootropic benefits of conventional, per-session vipassana/mindfulness meditation. I might start reserving 5-10 minutes a day for meditation sessions.

Edited by MindExplorer, 15 April 2016 - 01:13 AM.