1569 replies to this topic

[Passion]

So does Dihexa simulate BDNF or does it somehow create new neurons via its own mechanisms? If it acts as BDNF and interacts with the same receptors, this could lead to a downregulation nightmare:
http://www.ncbi.nlm..../pubmed/8752592

[Patrick Sylvester]

If it acts as BDNF and interacts with the same receptors, this could lead to a downregulation nightmare

this actually sounds like the downside of NZT scarily enough. except a faux brain-death replaces the actual death.

Thanks. What is your timeline? I would like to try this ASAP as I have only a few months to live (not too concerned about cancer).
... ...The physician who performed my stem cell treatment is moving on to gene therapy. His hope is that he has identified the neurotropic substances produced by stem cells and plans to reprogram the motor neurons to produce those substances themselves. I just need to buy some time to see if it works for the first human volunteer and then try it myself and dihexa seems like it could potentially do that.

im very sorry about your situation and my heart goes out to you. i don't know if it would help your position in anyway but there is currently a group buy awaiting synthesis completion of NSI-189. as far as i know all options have been filled however you more than likely can buy a member's share if (when?) they have second thoughts or wish to await trials of others first. a link for you, NSI-189 Started by hadora please ignore some of the later postings, the thread degenerated into a lot of heated opinions re: bio-ethics and secrecy, and some valid concerns. 189 promotes neurogenesis of the hippocampus and is investigated for treatment of massive depression disorder which has been speculated to have the effect of a damaged or shrunken hippocampus.
alternatively you can also look into Isoxazole-9 which supposedly promotes both neurogenesis and synaptogenesis through unknown properties. hope things work out for you.

[Xenix]

If it acts as BDNF and interacts with the same receptors, this could lead to a downregulation nightmare

this actually sounds like the downside of NZT scarily enough. except a faux brain-death replaces the actual death.

Thanks. What is your timeline? I would like to try this ASAP as I have only a few months to live (not too concerned about cancer).
... ...The physician who performed my stem cell treatment is moving on to gene therapy. His hope is that he has identified the neurotropic substances produced by stem cells and plans to reprogram the motor neurons to produce those substances themselves. I just need to buy some time to see if it works for the first human volunteer and then try it myself and dihexa seems like it could potentially do that.

im very sorry about your situation and my heart goes out to you. i don't know if it would help your position in anyway but there is currently a group buy awaiting synthesis completion of NSI-189. as far as i know all options have been filled however you more than likely can buy a member's share if (when?) they have second thoughts or wish to await trials of others first. a link for you, NSI-189 Started by hadora please ignore some of the later postings, the thread degenerated into a lot of heated opinions re: bio-ethics and secrecy, and some valid concerns. 189 promotes neurogenesis of the hippocampus and is investigated for treatment of massive depression disorder which has been speculated to have the effect of a damaged or shrunken hippocampus.
alternatively you can also look into Isoxazole-9 which supposedly promotes both neurogenesis and synaptogenesis through unknown properties. hope things work out for you.

Where did you read that ISX9 promotes synaptogenesis? I only found that it induces neurogenesis.

[Patrick Sylvester]

NSI thread pg6

a lecture by Amelia Eisch concerning Neurogenisis ...... but also significantly increase the dendride tree (synapses) that connect each neuron.
The research chemical ... is called: Isoxazole-9 ...
http://www.youtube.c...vl7xkuo#t=2709s ...

i think it warrents its own thread. is dihexa not any closer to being able for synthesis?

[Erebus]

I've recently tested a sample of Dihexa which Xenix was kind enough to send me. Of the sample, I can say the following things:

1. It's quite pure. I didn't detect any significant foreign substances or impurities.
2. The MW I've found matches perfectly with the 'expected' MW for this compound.
3. The fragmentation profile is unusual.

My results are attached. Due to #3, I sent the sample to another lab that I sometimes outsource work to. It took them a while, but they confirmed my findings in every particular: There are no meaningful impurities that we could detect, MW is as-expected, and the fragmentation profile is strange but perhaps not entirely out of the question.

Between both tests, we're both reasonably certain that Xenix's Dihexa is good. I say 'reasonably' because we don't have access to a Dihexa standard, and because we haven't run any further analytical tests. I would have liked to perform some NMR or Raman spectroscopy tests on it, which would be a great way to confirm the MS findings in lieu of a standard... But I'd need to outsource the NMR, which would be rather expensive in this case, and the Nicolet Raman instrument I have access to hasn't worked properly in many months. (A shame, as Raman can be an amazingly information-rich way to analyze small peptides.)
...I still have the sample, so perhaps in the near future...

Long story short: Unless his supplier sent him a 'decoy chemical' which can fool people who are running MS without a standard, and unless they didn't put together the right fragments in the wrong sequence, the Dihexa Xenix bought is good. Those 'what if' scenarios are very unlikely, but I can't rule 'em out unless I run some more tests.

Attached Files

•  Dihexa_1.pdf   356.06KB   31 downloads
•  Dihexa_2_frag.pdf   356.06KB   21 downloads
•  Dihexa_3.png   8.98KB   26 downloads

[Googoltarian]

But I'd need to outsource the NMR, which would be rather expensive in this case.

I can do it for free, on Bruker 700Mhz and I could also post FID file so anyone could interpret it on their computer

[daouda]

Where's the excitement? Isn't this big news?

[xks201]

Definitely interested in a group buy...

[jabowery]

nootlyinclinded has not reported in for quite a while, has he?

[Patrick Sylvester]

brain explosion
OR
he's busy making millions!

Edited by Patrick Sylvester, 07 June 2013 - 05:31 PM.

[Xenix]

Where's the excitement? Isn't this big news?

It still hasn't been proven to be as effective in humans as it is in rats...

[megatron]

Did you ingest it yet? Has Googoltorian been sent a sample and conducted the NRM-analysis? If, so has the legitimacy of the "Dihexa"-compound been established yet?

[daouda]

Where's the excitement? Isn't this big news?

It still hasn't been proven to be as effective in humans as it is in rats...

Well I guess we're now waiting on you to change this...

[Xenix]

I found this

http://www.ncbi.nlm....les/PMC3261279/

The validity for assigning disorder risk to an autism spectrum disorder (ASD) candidate gene comes from convergent genetic, clinical, and developmental neurobiology data. Here, we review these lines of evidence from multiple human genetic studies, and non-human primate and mouse experiments that support the conclusion that the MET receptor tyrosine kinase (RTK) functions to influence synapse development in circuits relevant to certain core behavioral domains of ASD. There is association of both common functional alleles and rare copy number variants that impact levels of MET expression in the human cortex. The timing of Met expression is linked to axon terminal outgrowth and synaptogenesis in the developing rodent and primate forebrain, and both in vitro and in vivo studies implicate this RTK in dendritic branching, spine maturation, and excitatory connectivity in the neocortex. This impact can occur in a cell-nonautonomous fashion, emphasizing the unique role that Met plays in specific circuits relevant to ASD.

I don't know what to think. I wonder if the researchers were aware of this. Hopefully I don't develop autism from using Dihexa. I've been taking 50mg/day for the past few days and I haven't noticed any significant changes yet -- whether I'm taking too low a dose, or if it takes a longer time to notice a difference, or if I have had a completely different compound synthesized -- I don't know. Synapse formation seems to tread a fine line between cognitive enhancement and disorder: too much/misfiring and it can lead to autism, too much pruning/loss and it can lead to schizophrenia.

[sunshinefrost]

I found this

http://www.ncbi.nlm....les/PMC3261279/

The validity for assigning disorder risk to an autism spectrum disorder (ASD) candidate gene comes from convergent genetic, clinical, and developmental neurobiology data. Here, we review these lines of evidence from multiple human genetic studies, and non-human primate and mouse experiments that support the conclusion that the MET receptor tyrosine kinase (RTK) functions to influence synapse development in circuits relevant to certain core behavioral domains of ASD. There is association of both common functional alleles and rare copy number variants that impact levels of MET exp<b></b>ression in the human cortex. The timing of Met exp<b></b>ression is linked to axon terminal outgrowth and synaptogenesis in the developing rodent and primate forebrain, and both in vitro and in vivo studies implicate this RTK in dendritic branching, spine maturation, and excitatory connectivity in the neocortex. This impact can occur in a cell-nonautonomous fashion, emphasizing the unique role that Met plays in specific circuits relevant to ASD.

I don't know what to think. I wonder if the researchers were aware of this. Hopefully I don't develop autism from using Dihexa. I've been taking 50mg/day for the past few days and I haven't noticed any significant changes yet -- whether I'm taking too low a dose, or if it takes a longer time to notice a difference, or if I have had a completely different compound synthesized -- I don't know. Synapse formation seems to tread a fine line between cognitive enhancement and disorder: too much/misfiring and it can lead to autism, too much pruning/loss and it can lead to schizophrenia.

How many doses still remain in your batch? If you have enough, could you stop right now and re-start later On when you feel more confident?

Have you started to test your performances ?

[sunshinefrost]

Xenix, if you decide to pursue, try to workout you brain as much as possible without worrying too much about this, you wouldn't want to activate/build or solidify the wrong neural networks. Time to workout! ... And enjoy !!

[OpaqueMind]

I found this

http://www.ncbi.nlm....les/PMC3261279/

The validity for assigning disorder risk to an autism spectrum disorder (ASD) candidate gene comes from convergent genetic, clinical, and developmental neurobiology data. Here, we review these lines of evidence from multiple human genetic studies, and non-human primate and mouse experiments that support the conclusion that the MET receptor tyrosine kinase (RTK) functions to influence synapse development in circuits relevant to certain core behavioral domains of ASD. There is association of both common functional alleles and rare copy number variants that impact levels of MET expression in the human cortex. The timing of Met expression is linked to axon terminal outgrowth and synaptogenesis in the developing rodent and primate forebrain, and both in vitro and in vivo studies implicate this RTK in dendritic branching, spine maturation, and excitatory connectivity in the neocortex. This impact can occur in a cell-nonautonomous fashion, emphasizing the unique role that Met plays in specific circuits relevant to ASD.

I don't know what to think. I wonder if the researchers were aware of this. Hopefully I don't develop autism from using Dihexa. I've been taking 50mg/day for the past few days and I haven't noticed any significant changes yet -- whether I'm taking too low a dose, or if it takes a longer time to notice a difference, or if I have had a completely different compound synthesized -- I don't know. Synapse formation seems to tread a fine line between cognitive enhancement and disorder: too much/misfiring and it can lead to autism, too much pruning/loss and it can lead to schizophrenia.

I have found that with substances that work primarily through neuro/synaptogenesis there is very little if any subjective shift in consciousness, the true colours of a compound emerging after a time, under a high/intense mental work-rate, and upon retrospective comparison.

[Xenix]

I found this

http://www.ncbi.nlm....les/PMC3261279/

The validity for assigning disorder risk to an autism spectrum disorder (ASD) candidate gene comes from convergent genetic, clinical, and developmental neurobiology data. Here, we review these lines of evidence from multiple human genetic studies, and non-human primate and mouse experiments that support the conclusion that the MET receptor tyrosine kinase (RTK) functions to influence synapse development in circuits relevant to certain core behavioral domains of ASD. There is association of both common functional alleles and rare copy number variants that impact levels of MET exp<b></b>ression in the human cortex. The timing of Met exp<b></b>ression is linked to axon terminal outgrowth and synaptogenesis in the developing rodent and primate forebrain, and both in vitro and in vivo studies implicate this RTK in dendritic branching, spine maturation, and excitatory connectivity in the neocortex. This impact can occur in a cell-nonautonomous fashion, emphasizing the unique role that Met plays in specific circuits relevant to ASD.

I don't know what to think. I wonder if the researchers were aware of this. Hopefully I don't develop autism from using Dihexa. I've been taking 50mg/day for the past few days and I haven't noticed any significant changes yet -- whether I'm taking too low a dose, or if it takes a longer time to notice a difference, or if I have had a completely different compound synthesized -- I don't know. Synapse formation seems to tread a fine line between cognitive enhancement and disorder: too much/misfiring and it can lead to autism, too much pruning/loss and it can lead to schizophrenia.

I have found that with substances that work primarily through neuro/synaptogenesis there is very little if any subjective shift in consciousness, the true colours of a compound emerging after a time, under a high/intense mental work-rate, and upon retrospective comparison.

That makes sense. I guess I'm hoping for a perfect scenario where I start forming/unfolding patterns in my life before my eyes... totally wishful thinking, I know. I just really have no idea what neuro/synaptogenesis is supposed to FEEL like, so I have no standard to base my experiences with the drug on -- sensation-wise. In terms of mentally challenging myself, though, I have been quite lazy lately.

What would you recommend I do to enhance my mental work-rate while taking 'Dihexa'? Dual-n-back? speed read books?

[daouda]

I always think that the best kind of mental exercise, in every way, is to learn a new language. Even better if it has a different "alphabet". I think that learning a language is fun but most importantly makes use of most areas of "intelligence", with the immense bonus of opening up a new culture and thus a different world view etc...
For audio-only methods I recommend the pimsleur and michel thomas methods. The assimil books+audio series are I think pretty good, among the best out there. Computer-based, "multimedia" methods : Rosetta stone is worthless imho, and I've read great things about "fluenz" (and based on the samples I've tried it does look pretty good).
Learning a musical instrument, and even better how to improvise with it, is also I think a very complete "brain workout" while still bringing you so much more than endless dual'n'back or lumosity exercises...

Edited by daouda, 13 June 2013 - 04:21 PM.

[Godof Smallthings]

If you are monolingual, learning a new language is a sure-fire way to boost your brain integration. If you are bi- or trilingual already, it is still beneficial, but less so than for people who are monolingual. Essentially, the rule seems to be that the more challenging the task for you personally, the greater the gain.

So if you are already fairly artistically minded, something more logic/maths-based might be a better idea - computer programming, a new area of maths, advanced statistics, etc.

[HappyPhysicist]

I am still waiting for my shipment. They keep promising it "next week".

Question for you peptide experts, I am looking at a peptide called NAP

NAP (davunetide) is an eight amino acid peptide (NAPVSIPQ) that has been shown to provide potent neuroprotection, in vitro and in vivo.

Would anyone know what info I would need to have this manufactured?

Thanks!

[Googoltarian]

I am still waiting for my shipment. They keep promising it "next week".

Question for you peptide experts, I am looking at a peptide called NAP

NAP (davunetide) is an eight amino acid peptide (NAPVSIPQ) that has been shown to provide potent neuroprotection, in vitro and in vivo.

Would anyone know what info I would need to have this manufactured?

Thanks!

Here you have molecular structure of your peptide:
 D09401.gif   6.31KB   25 downloads

It should be enough for peptide company to make it.

[Logic]

I am still waiting for my shipment. They keep promising it "next week".

Question for you peptide experts, I am looking at a peptide called NAP

NAP (davunetide) is an eight amino acid peptide (NAPVSIPQ) that has been shown to provide potent neuroprotection, in vitro and in vivo.

Would anyone know what info I would need to have this manufactured?

Thanks!

Why not talk to Sciwalk from the Epitalon thread.
He has been swatting up on peptides since starting epitalon and has close ties with the lab that made it.

[HappyPhysicist]

I'll check with Sciwalk. He mentioned Genscript so I went to their site and used the peptide builder assuming the letters NAPVSIPQ refer to the single letter designations. Waiting for the quote.

[Xenix]

Update: I was taking 'Dihexa' (I put it in single quotes as I am not 100% sure it is real Dihexa) for about 2 weeks orally -- 50mg/day on an empty stomach -- and did not notice any significant changes in my cognition or memory. Maybe there were some minor changes in my senses, but definitely nothing I couldn't pass off as placebo.

Naturally, I became a bit frustrated in not knowing whether my 'Dihexa' was real, or if I wasn't taking enough, etc.
I tried injecting a smaller amount (diluting 10mg of it with DMSO) intramuscularly (IM) but it only burnt my thigh (at the injection site) like crazy, and left me unable to walk properly for several days after. Note: I have injected the same (pure) DMSO directly into my thigh before at a much greater volumes (30mL) and besides an initial burning sensation, I had no further problems - it must have been due to the 'Dihexa' not breaking down correctly/irritating the injection site. There is *NO* way in hell I would ever take this stuff intravenously.

So, I took a break from capping and eating my 'Dihexa' for a few weeks, until I figured I had not yet tried the intranasal route (snorting the powder); yes, I joked about taking it this way on this thread a few pages back, but I am now being serious.

I did a quick search for "intranasal peptide" and found that it is indeed a legitimate method of peptide administration; although there are medical devices which somehow transform the chemical from its liquid form into a fine mist that one can inhale through their nostrils -- but instead I would just snort the powder through a straw.


Check it out:

Intranasal (IN) administration of drugs and medications is dependent on many drug factors but provides a convenient alternative to oral and intravenous (IV) or intramuslcular (IM) routes. When a drug is administered orally it is absorbed and enters the hepatic portal vein and goes to the liver before entering circulation within the rest of the body. This makes it subject to first-pass metabolism by the liver and this greatly reduces the bioavailability (how much of the drug enters circulation) of the drug. IV and IM administration of a drug avoids this problem entirely but it is very invasive for the subject and also more impractical for long term or daily use of a drug. IN administration offers several advantages in comparison to these two other routes of administration (ROA), including the potential to bypass the blood brain barrier altogether, and directly administer a drug to the brain and central nervous system.

...

When a drug in insufflated the material makes contact with the epithelial cells of the nasal membranes when it dissolves or mixes in the mucous. A drug can then be absorbed by one of two pathways, transcellular transport and paracellular transport. A drug that enters the body transcellularly passes into and through the cells that make up the membrane

...

Hydrophobic molecules of a low molecular weight tend to enter the tissue via the transcellular pathway, while hydrophilic molecules generally enter via the paracellular pathway

http://www.drugs-forum.com/forum/showwiki.php?title=Intranasal

************************************************

So, I insufflated (snorted) 25mg (half of the contents of a capsule) yesterday, I experienced this instant burst of euphoria and energy, mixed with a (subjectively) enhanced feeling of mental focus and clarity. The best way I can describe the feeling is by likening it to what I experience after an intense cardio session (treadmill running) at the gym - only much more pronounced. After a cardio session, I feel more 'alive' and things appear mentally 'clearer' - somewhat like Piracetam (which I am not currently taking). Maybe this is due to 'Dihexa' causing a BDNF-like protein to be over-expressed, maybe not. I'm not in a position to speculate.

Like Nootly said (before he disappeared off the board), I am starting to make/notice more associations between different entities: he used the analogy of an orange, and noticing more associations and better visualisations being formed between the orange. I thought of an orange and began to see one being dissected in my mind's eye; I saw cars drive past and noticed how they became 'one' with the road in a kind of tyre-tarmac symbiosis, or how the mat on my floor met the walls of my room to make wall-mat: really silly little things like this that I never really used to think about.

Thankfully there is not a single hint of burning when I snort 'Dihexa': only a chalky taste in the back of my throat after it has passed through my nasal cavity.

I took the remaining half of the 'dose' a few hours later and experienced similar effects. This morning I woke up many hours earlier than I normally would with lots more energy than usual.

I did some Lumosity brain training while 'on' it, and actually made some new high scores (memory matrix, lost in migration, by the rules, and word bubbles) -- for those of you who play.
I did some dual-n-back, too, and while I usually can never even get close to beyond n=3, I managed to breakthrough to the next level (n=4). It's too early to really make definitive assumptions yet, but my mind does feel clearer after only one day of IN administration.

I don't know with absolute certainty that this is not entirely (or least in part) due to placebo, but it certainly has a much, much, much more noticeable effect than compared to when I taking it orally.

Naturally, this is highly irresponsible and experimental and I do not recommend anyone to try it, but I am just sharing my experiences with this route so far. I am not claiming that this method works, IN just seems (so far) for me to be a much more effective way of taking this chemical than orally.

Edited by Xenix, 19 June 2013 - 03:28 PM.

[sunshinefrost]

Cool update ! Maybe you just broke down the initial barrier ? Is it possible that oral administration is fruitless compared to IN administration ?

How long will you pursue the experiment ?

[daouda]

You say "orally", but have you ever tried sublingually?
Also you should definitely wait a for few more days / doses of intranasal administration to assess wether the effects are placebo or not, as I have no doubt that snorting a white powder has great potential to exert some placebo effect...
But thanks for the updates so far, can't wait to read what's coming next

[Xenix]

Cool update ! Maybe you just broke down the initial barrier ? Is it possible that oral administration is fruitless compared to IN administration ?

How long will you pursue the experiment ?

I cannot say anything definitively yet, besides that it seems like a much more powerful way of consuming 'Dihexa'.

I now have just under 1,500mg (1.5 grams) to play with, so I have around 28 days left of experimentation (assuming I don't get too greedy) at 50mg/day of insufflation. If it turns out magically, then I will order more.

Again, too early to positively discern from placebo.

You say "orally", but have you ever tried sublingually?
Also you should definitely wait a for few more days / doses of intranasal administration to assess wether the effects are placebo or not, as I have no doubt that snorting a white powder has great potential to exert some placebo effect...
But thanks for the updates so far, can't wait to read what's coming next

I have not. I can only imagine that doing it under the tongue would be more or less the same as capping a dose and swallowing it (maybe less effective because it is broken down quicker - IDK).

I completely agree with you -- the placebo effect would be much greater due to this method than swallowing some capsules. But it's interesting that I felt next to nothing after 2 weeks from the capsules. Time will tell. In the meanwhile I'll try not to get overexcited, it could all be in my mind. I'll need objective evidence, not subjective feelings.

[daouda]

I can only imagine that doing it under the tongue would be more or less the same as capping a dose and swallowing it (maybe less effective because it is broken down quicker - IDK)

Quite the opposite actually! We say "sublingual" as opposed to "oral" because it is absorbed sublingually and thus avoids first pass metabolism and also potential destruction by stomach acids and bile plus much more enzymes than those in saliva. http://en.wikipedia...._administration
Not all substances absorb well sublingually though (should be lowish molecular weight and not too lipophilic), and also if ph is far from neutral it could be uncomfortable or even damaging to your teeth and gums.
You should give it a try with a little dose first.

Edited by daouda, 19 June 2013 - 04:01 PM.

[Xenix]

I can only imagine that doing it under the tongue would be more or less the same as capping a dose and swallowing it (maybe less effective because it is broken down quicker - IDK)

Quite the opposite actually! We say "sublingual" as opposed to "oral" because it is absorbed sublingually and thus avoids first pass metabolism and also potential destruction by stomach acids and bile plus much more enzymes than those in saliva. http://en.wikipedia...._administration
Not all substances absorb well sublingually though (should be lowish molecular weight and not too lipophilic), and also if ph is far from neutral it could be uncomfortable or even damaging to your teeth and gums.
You should give it a try with a little dose first.

Well it's good to know that I'm still learning :P how much would you recommend I try sublingually, and for how long should I hold it under my tongue for (before swallowing)? Luckily this stuff tastes really chalky and isn't god-awful like Piracetam. From my understanding, this peptide has no charge (is neutral) and extremely hydrophobic (to get it to solubilise I had to dilute in loads of DMSO).