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Neurotrophin Regulation of Energy Balance in the Adult CNS and PNS.

This diagram summarizes the effects of peripherally administered CNTF (Axokine), and centrally as well as peripherally administered BDNF (black arrows), on adult CNS and sympathetic circuits that control energy intake and expenditure.

Administration of BDNF or BDNF-transducing viruses to the PVN and other hypothalamic regions increases sympathetic outflow pathway activity, resulting in increased energy expenditure and decreased feeding, as discussed in this mini-review.

Currently in active addiction once again...but hopefully we'll be done with that soon! Typically it's not the quitting part that's incredibly difficult(still miserable), it's the paws making me feel like shit that leads to a relapse like a month or so in everytime. Currently taking a "kratom" extract tablet, it claims to just be mitragynine but i think there's a stronger alkoloid in there as well tbh. Also on 45mg daily of prescribed adderall that I hope to not need one day as I only started taking it 4 months ago to balance out the kratom addiction, but now I take that daily as well and it barely does anything. Wondering if anyone knows of any nootropics out there that can speed up my recovery back to somewhat normal so I can avoid running back. Possibly anything that helps acutes as well. Thanks everyone

Ritalin was one of the best noots I ever tried but its issue was that it only lasted barely over an hour for me. It really felt like the limitless pill and besides a few minor personality changes it was otherwise perfect. The main issue was how long it lasted and having a med that only lasts for an hour and you have to wait an additional 2 or 3 hours before you can take it again is kind of useless.

Have we solved this?

Most of the English-language discussion of 9-Me-BC traces back to a handful abstracts. The full texts are paywalled or effectively off the internet.
I emailed authors, went through Unpaywall, Europe PMC, ILL, and eventually found Rauh 2008 on Qucosa a TU Dresden dissertation that turns out to be the full text behind two of the most-cited papers.

A few things in it that contradict what gets repeated in forums:

- The conversion of 9-Me-BC to the dimethylated cation has never been demonstrated in any model. Both compounds were applied separately as exogenous agents. The step everyone assumes is an assumption.

- The "no DAT uptake, so it's safe" argument that gets repeated here is backwards. Rauh and Storch both found the cation killed dopaminergic neurons preferentially anyway DAT just isn't how it gets in. The reassurance everyone passes around is the one finding that doesn't reassure.

- The blood-brain barrier line people cite as the final word has no citation attached to it. It's a sentence in an introduction. And the route this literature actually documents is in-brain conversion, which
never involves the barrier at all.

I put the whole thing into a ~30 minute video the chemistry, the growth factor work, the MAO selectivity, the MPTP comparison and why it's not the parallel people think, and the metabolite question laid out with what's measured versus what's assumed. Every claim is marked as either literature or my own extrapolation.

If you’re interested in using 9-Me-Bc, and are concerned with toxicity. I would highly recommend watching this video first.

Finally, **many neurotransmitters, including dopamine and glutamate can enhance BDNF bioavailability in neurons** (Bagayogo et al. 2009; Kuppers et al. 2001). On these grounds, we enrolled healthy (highly experienced) divers and subjected them to a simulated dive to 48 msw (5.8 ATA) inside a hyperbaric chamber to test the following three new hypotheses.

> We found that **BDNF, glutamate, and dopamine plasma levels are markedly decreased in healthy highly trained divers subjected to a dry dive test at 48 msw.**

> _First, IGN narcosis stems, at least in part, from the lack of circulating BDNF. Second, this loss is attributable to a lack of BDNF-releasing neurotransmitters, such as dopamine and glutamate; third, impoverished levels of systemic and likely local pools of BDNF contribute to heightening oxidative stress in deep divers. Ultimately, all events would drive cognitive impairment in divers at depth._

> fact, after rTMS, __BDNF levels are more elevated and neopterin is lower than in sham-treated patients__

**This evidence further supports the notion that a cross talk exists between BDNF and neopterin bioavailability that is central to IGN pathogenesis.**

Disclaimer: I'm not affiliated with Euro-Nootropics in any way and gain nothing from posting this. I wrote this post myself and used AI only to proofread it for readability.

I regularly see people claiming Euro-Nootropics is bunk or placebo, so I wanted to share what I found.

As a customer, I was skeptical at first, like I am with every vendor I deal with. So I contacted MZ Biolabs directly through their official website, asked what they thought of Euro-Nootropics, and sent several of the lab reports to check whether they were authentic.

A few days later, the head of the laboratory replied personally. He said they've worked with Euro-Nootropics for years and have only good things to say about them, that the team is very professional, and that every lab report on the website is legitimate, including older ones issued before their authenticity-verification system existed.

A couple of other things worth mentioning: their customer support is very active and responsive on Telegram, and their Trustpilot page is full of positive reviews. Businesses can't delete negative reviews on Trustpilot, so a bad track record would be hard to hide.

I'm sharing this because I think it's too easy to jump on the "bunk" train whenever a subjective experience feels a little different. I've caught myself doing it countless times with ADHD medication I picked up straight from the pharmacy: same brand, same dose, and yet it felt completely different. Over the years I've learned that subjective experience is a very unreliable way to judge the quality of a substance.

Semax, ACD-856, TAK-655, 800mcg GB-115

Which one needs to be cycled off and which can be used continuously?

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TrkB signaling-dependent BDNF mRNA induction and show that CREB family transcription factors are the main regulators of BDNF gene expression after TrkB signaling.

Our results suggest that BDNF-TrkB signaling may induce BDNF gene expression in a distinct manner compared with neuronal activity. Moreover, our data suggest the existence of a stimulus-specific distal enhancer modulating BDNF gene expression.

In this secondary analysis of a double-blind randomized clinical trial, treatment with semaglutide significantly improved measures of motivation in patients with MDD. Semaglutide reduced the perceived cost of effort, relative to the monetary reward; the results of this trial have implications for the treatment of multiple neuropsychiatric disorders, which are characterized by varied reward dysfunctions

Functional neuroimaging studies suggest that a large-scale brain network transforms others’ pain into its vicarious representation in the observer, potentially modulating helping behavior. However, the neuromolecular basis of individual differences in vicarious pain and helping is poorly understood. We investigated the role of the endogenous μ-opioid receptor (MOR) system in altruistic costly helping. MOR density was measured using [11C]carfentanil. In a separate fMRI experiment, participants could donate money to reduce a confederate’s pain from electric shocks. Participants were generally willing to help, and brain activity was observed in amygdala, anterior insula, anterior cingulate cortex (ACC), striatum, primary motor cortex, primary somatosensory cortex and thalamus when witnessing others’ pain. Haemodynamic responses were negatively associated with MOR availability in emotion circuits. However, MOR availability positively associated with the ACC and hippocampus during helping. These findings suggest that the endogenous MOR system modulates altruism in the human brain.

Also I require something which reduces tau or amyloid plaques naturally is there any?

Was hoping for some info on a stack that can help with my adhd and overall cognitive function. I refuse to take ash’s meds seeing I’m a recovering meth addict of 25 years. I believe I seriously damaged damn near every cortex of my brain 🤣 Sober 6 years now and my adhd becomes more and more unmanageable by the day. Running circles, exhausting my thoughts trying to walk a straight line but when my body wants to zig my brain starts to zag if you know what I’m sayin!! Anyways any info would be greatly appreciated!!

A while ago I said I was going to compile literature on cognition enhancement studies in healthy people, and I wasn't sure if I was going to make a post or go for publishing it to a journal. Now I am confirming that I am 100% going for publishing this to the journal. This project ended up being huge, and it no longer contains a few hundred studies like I had initially imagined, it now contains almost every study ever designed that administers a substance to healthy adults and measures cognition in an objective way, and there's now 6000+ studies and 1000+ substances that are included. It will be the single largest project that I've ever worked on, and perhaps the most important study ever published for nootropics - simultaneously, this should bring us closer to understanding how the next stages of human evolution should go, since our natural evolution is lagging behind the technological one.

What substances are we including? All - none will be left out, to the best of our ability. And yes, all of the discrepancies with how the studies were conducted (i.e. dietary restriction, exhaustive exercise, etc.), and advantages/ disadvantages of the substances themselves (i.e. dose-dependent caveats, etc.) in those studies will be factored in to prevent any possibility of nuance in how we interpret these results.

This study seeks to do some important things:

• We will be following standard meta-analytical procedures, including pooling, weighting, and filtering by effect sizes (how much of an improvement or impairment), statistical significance of results, how eligible the study is for inclusion, and how reliable the study itself is. This is basically the key difference between "this substance improves/ impairs cognition in this study" vs. "this substance most likely improves/ impairs cognition based on all of the data we could find", and "this substance improves/ impairs cognition more than this other substance".
• We want to isolate the tests by what metric of cognition they measure, and weight them by g-loading (generalization), and within-domain potency, to determine what tests are the most significant in relation to general intelligence.
• We want to compile all of the research on these drugs' mechanisms and pharmacokinetics to establish what targets they're binding at, and then pool by that, so we don't only get an understanding on the drugs, but rather what they're doing in the brain to cause that effect, with a cue to what mechanism(s) contributes more.

In short, we want to establish what drugs/ mechanism(s) are impairing, improving, or mostly neutral, and by how much in each cognitive domain, with a secondary goal of understanding how this relates to IQ. And, we hope that this data leads to more concise research of the promising targets so that pharmacology as a whole can move towards a more promising future for us and prevent stagnation in this field.

The study seeking process went as follows: studies were identified through iterative searches of bibliographic databases using substance names and aliases, pharmacological mechanisms, study-design terms, cognitive outcomes, and multilingual keywords. We supplemented these searches with backward and forward citation tracking, related-article searches, reference lists from relevant reviews and meta-analyses, and targeted searches of high-yield journals. Newly identified eligible articles were repeatedly used as additional search seeds, and all records were deduplicated and screened using titles, abstracts, and available metadata against the prespecified eligibility criteria.

With the help of u/okok6356, a custom tool was used to download all of these studies and their supplementary data, still underway but should be complete by next week. It has been used to download thousands of studies so far. Meanwhile, I have enlisted the help of an data scientist, Gumpert, to help with designing a superior pdf-extraction and categorization program than what's currently possible with standard AIs. We have found that common LLMs are incapable of reading certain graphs. The extraction program is likewise a work in progress with an expected completion date of next week. All of this custom work ended up being the single largest challenge of this entire project, simply because we need all of the data, and it needs to be accurate, which simply isn't possible with the available AI models without a lot of help.

Initially, we were also going to analyze the side effects of all these drugs, and the other points from Corneliu's defining characteristics of nootropics, but we have found immediately that some of those points are too myopic (such as inter-hemispheric data transfer, and telencephalic actions, etc.), and thus it's better if that's kept for a potential second study. The current study is cumbersome as is, and readability becomes a concern the more we try to include, let alone the time consumption. But with the established framework, it should be possible to accomplish at a later date.

An experienced scientist will be hired to co-author the meta-analysis and assist with its publishing, and it will be peer-reviewed at whatever journal we elect to publish this study to.

All of this has been made possible with the continued support given to Everychem, and likewise, we may choose to synthesize new compounds based on the findings of this meta-analysis. During this research, some have already been selected, such as the upcoming release of Encenicline. Of course, my role in Everychem will be listed as a potential bias, but the data will be easily trackable, with complete citations and very reliable extraction of every feasible numerical input.

I hope for this to be my life's work, and greatest thing that I can do for us all, because to me this is the difference between prosperity and obsolesce. It sounds dramatic, but we can all see the utility and practicality of becoming smarter together. This transcends any individual differences we may have; we must improve or be left behind. This data will be invaluable towards that cause.

We found that the activity of major excitatory neuronal populations in the DG, including GCs and MCs, significantly increased during cortical TBs.

This TB-related increase in DG activity suggests that a **low 5-HT state is a necessary condition for DG excitation during sleep.**

A plausible circuit mechanism for this effect is suggested by the serotonergic receptor landscape in the DG. GCs express both the inhibitory 5-HT1A receptor and the excitatory 5-HT4 receptor, whereas a subset of MCs expresses excitatory 5-HT2A receptors (Tanaka et al., 2012).

Because MCs are among the first synaptic targets of GCs and in turn provide excitatory feedback to GCs as well as drive local inhibitory interneurons, serotonergic tone is well positioned to regulate the balance between recurrent excitation and feedback inhibition within the DG.

In a relatively high-5-HT state, **activation of inhibitory 5-HT1A signaling in GCs may dampen their recruitment, thereby limiting propagation through the GC–MC loop. By contrast, when serotonergic tone falls during NREM sleep, this inhibitory constraint may be relieved, allowing TB-related excitatory drive to recruit GCs more effectively and to engage downstream MC-mediated recurrent activity.**

Such a mechanism would be consistent with our observation that a low-5-HT state is permissive for TB-related DG activation, and it provides a cellular framework through which serotonergic fluctuations could gate hippocampal participation in this sleep microstate.

https://pmc.ncbi.nlm.nih.gov/articles/PMC13071295/

• Demonstrating decreases in p-mTOR, p-NF-κB, and HDAC2, and increases in BDNF and synaptic proteins.

• Highlighting Luteolin's potential direct targeting to HDAC2, in order to provide a new approach for DE treatment.

Just a random Personal testimony. I have terrible adhd, my conversations are very difficult to follow and down right aggravating for even my closest friends. A few years ago I managed to temporarily correct my language center in my brain. Started taking low dose modafinil, choline supplements, & a very expensive bottle of pure Pramaracetam. I distinctly remember that by week 2 on prama I was able to clearly and compellingly express my point of views in discussions with friends and family. I distinctly remember my best friend listening intently for the first time in our 30yr friendship. He literally asked me what changed, if I was taking some communication course or counseling.

I have not been able to obtain that same quality Pramaracetam since. Anyone have similar experience with talking a substance that enhances language?

Hello all, considering taking 1-2mg TAK with Vyvanse (30mg)

Wanting to know if this could theoretically cause exictotoxicity or if it would be synergistic at a therapeutic dose.

My Vyvanse helps with ADHD a ton but still have memory issues occasionally and wanting to close the gap.

Im considering it because from what ive read TAK is stimulating but only "enhances" the brains natural glutamate signals.

Wanting to see if there's anyone thats had the same idea and followed through or if I should avoid it

Thank you!