1569 replies to this topic

[medicineman]

The idea of an effective transdermal dihexa turns me on.

is there a way we can confirm that it is working if someone tries it? I have ordered a nice amount, I wouldn't mind trialing half a gram or so if there is a way we can tell it's getting where it is needed (I'd rather an objective test, instead of random subjective reports of 'hearing is more amplified' or 'concentration is better') No point in trying with no goal in mind to confirm anything.

Edited by medicineman, 24 July 2014 - 11:20 PM.

[DHEXA]

Short of custom blood tests you'd have to do blinded trials.
Have someone give you placebo transdermal and oral dihexa or oral placebo and dihexa transdermal.
Repeat several times every few months (long half life) or trial it with multiple people.

[megatron]

Jesus! I take two weeks vacation from the forum after months of nothing happening, and then someone pops up start giving away samples and selling off Dihexa. Remember to quantify your results folks. For the people having reached their N-backing threshold previously, please resume or continue your testing. The Cambridgebrainsciences tests should be obligatory. 

[medicineman]

I don't believe nback means anything. Dihexa, theoretically, should improve information acquisition and retention. It should improve pure calculating power. My rat wants to read a quote once or twice and retain it... He wants to spot that potential fork being set up for him by his opponent. He wants to remember dates, develop better manual dexterity. Something noticeable. I don't want to wonder if it's placebo. When I was a child, as part of the curriculum, we would need to memorize long verses of the Quran, and say it out of memory. I used to be able to do this after once or twice of reading. Aging, stress, drug abuse, and now I am much slower. I want what I had as a middle schooler.

I really want the stuff in my rats blood, and in the most efficient (and safe) method available. I won't test or nback. I will gauge how I do everyday things. If there is something to it, noticeable cognitive results should show up in a few months.

[Nattzor]

n-back will only be effective for testing WM (and potentially fluid intelligence).

[88LS]

Would be really nice to see quantifiable results though.

[Strangelove]

Is it still for sale, do we have a price for it?

[Plasticperson]

so niles left with everyones money?

 

[cATsE]

so niles left with everyones money?

Is this something you've heard, or is it just an assumption on your part?

 

I'm part of this group buy and really would like to know what's going on. 

[tolerant]

Do we know anything about stability of Dihexa (in original powder form). I'm buying some but don't intend to use straight away. Will it remain potent in, say, 12 months, if stored properly? Would it make sense to refrigerate it?

[xks201]

No one said anyone left with anyone's money. It can be stored for a year at least. The colder the better.

[DHEXA]

No one said anyone left with anyone's money. It can be stored for a year at least. The colder the better.

Yup,

The original authors stored it as a powder at -20C. Humidity/moisture should be minimized.

[tolerant]

 

No one said anyone left with anyone's money. It can be stored for a year at least. The colder the better.

Yup,

The original authors stored it as a powder at -20C. Humidity/moisture should be minimized.

 

 

Is this how you guys store it for every day use? At -20C? I guess that would mean the freezer. And how do you minimize humidity/moisture in a freezer?

[megatron]

Anyone willing to pay DHEXA in bitcoins for me? 

[tolerant]

Anyone willing to pay DHEXA in bitcoins for me? 

 

I don't see why not. If you PayPal me the amount. Do you have a problem getting bitcoins where you live?

[DHEXA]

 

 

Is this how you guys store it for every day use? At -20C? I guess that would mean the freezer. And how do you minimize humidity/moisture in a freezer?

 

For long-term storage you'd want an airtight amber jar in a freezer. You could even go the extra mile and use argon cartridges to displace the air & humidity in the jar.

I wouldn't sweat about it for everyday use. Just store it in a dark, cool area; it should be fairly stable.

[tolerant]

I have been wondering. We practically know for sure that hippocampal neurogenesis is good, and we almost know for sure that it is good for depression, at least in certain populations. But just reading the name of this thread, it talks about synaptogenesis, not neurogenesis. Can someone who's researched it explain the difference? Can you have synaptogenesis in the absence of neurogenesis? It sounds like there will be more connections between neurons, but there's only so much neurotransmitters to go around, so will they have to be shared with more synapses. I clearly remember reading that one theory of how ECT works is by actually SEVERING connections between sections of the brain. How do we know increasing the amount of connections is a good thing?

[sk_scientific]

I have been wondering. We practically know for sure that hippocampal neurogenesis is good, and we almost know for sure that it is good for depression, at least in certain populations. But just reading the name of this thread, it talks about synaptogenesis, not neurogenesis. Can someone who's researched it explain the difference? Can you have synaptogenesis in the absence of neurogenesis? It sounds like there will be more connections between neurons, but there's only so much neurotransmitters to go around, so will they have to be shared with more synapses. I clearly remember reading that one theory of how ECT works is by actually SEVERING connections between sections of the brain. How do we know increasing the amount of connections is a good thing?

 

Neurogenesis is the creation of new neurons from stem cells, synaptogenesis is the creation of new synapses between neurons.  In the synaptic cleft (the gap area between synaptic knob and somas), neurotransmitters are exchanged to signal action potential.

 

So if NSI-189 signals the production of stem cells in the hippocampus, a chemical messenger must signal those stem cells to become new neurons.  Just because a neuron is signaled to manifest, it may not necessarily have function.  It must connect via dendrite, to synapse, to synaptic cleft to other functional neurons and be used with fair regularity, otherwise the neuron will likely be pruned.  Similar is true of dendrites, synapses and receptor sites in terms of 'use it or lose it'.

 

Dihexa, according to what we are told, signals dedritic spining, and therefore synapses, of which, some should find other nerves to communicate with.

 

Synaptogenesis happens throughout one's life time, especially in learning, however a 'vast explosion' of syanptogenesis occurs largely in youth during the critical developmental phase as pruning is quite high.  Pruning is good because it makes more efficient, your neurological network.  Dihexa, in theory, gives the adult brain an artificially provoked explosion of synaptogenesis similar to that of a child.

 

Neurogenesis largely happens during the pre-natal period, although in adult life some neurogenesis occurs, largely in the hippocampus and subventricular zone.  The reason for this is the concentration of stem cells in those areas.

 

I suppose, that if everything that I am reading of the drugs is correct, the sequence and schedule of drugs one would want to take to partially simulate an adolescent brain would be as follows:

 

1.) NSI-189 (for signaling of stem cell creation in available areas)

2.) ISX-9 (for signaling of available stem cells to neurons)

3.) Dihexa (for signaling of dendritic spines, and synapses from newly available neurons)

4.) Then the brain will do the rest in the way of pruning and reinforcement (probably good to take on new behaviors and courses of learning during this phase).

 

This is, of course, still a hypothesis as it's not necessarily proven that the above drugs will in fact have this action in the human brain, however data suggests they might.

Edited by sk_scientific, 27 July 2014 - 04:54 PM.

[tolerant]

Thanks for that summary. It gives me a good starting point if I ever want to research it further. However, if what you're saying about NSI-189 is correct (it merely signals the creation of new stem cells), then we would have no observable antidepressant or nootropic effect. Yet, clearly, we've observed both effects, both on these forums and in published Neuralstem data.

[sk_scientific]

Thanks for that summary. It gives me a good starting point if I ever want to research it further. However, if what you're saying about NSI-189 is correct (it merely signals the creation of new stem cells), then we would have no observable antidepressant or nootropic effect. Yet, clearly, we've observed both effects, both on these forums and in published Neuralstem data.

 

I'm not stating out right that this is all that NSI-189 does, however, I believe that this is what the company is suggesting it does.  I disagree with you, though, because the brain natively signals stem cells in those areas to develop into nerve cells, and the greater the density of stem cells, the more available the environment to the chemical messengers which signal them to become neurons.  This may explain the phenomenon of the beneficial effects of NSI-189 being oddly noticeable some months after cessation of the drug.  It takes time for stem cells to become neurons, mature, and be properly integrated into a neural network.  The more activation of a neuron (within a margin), the more reinforced and functionally integrated it becomes.

[tolerant]

Yes, good point about native signalling, I suppose. I just recently discovered, by the way, that new stem cells can be created (I think by way of division of other stem cells). Before I had a worrying thought that the amount of stem cells may be numbered and you may only use them so many times to create new neurons in the hippocampus to overcome a bout of depression for example.

[Strangelove]

 

 

I suppose, that if everything that I am reading of the drugs is correct, the sequence and schedule of drugs one would want to take to partially simulate an adolescent brain would be as follows:

 

1.) NSI-189 (for signaling of stem cell creation in available areas)

2.) ISX-9 (for signaling of available stem cells to neurons)

3.) Dihexa (for signaling of dendritic spines, and synapses from newly available neurons)

4.) Then the brain will do the rest in the way of pruning and reinforcement (probably good to take on new behaviors and courses of learning during this phase).

 

 

 

 

Nice, I hope we would have some feedback from people trying the combo above, are you maybe planning going for it?

 

I am thinking going for a combo of NSI, DIHEXA and maybe ISX-9, when I ll have the money, hopefully soon, but at the same time I have a hesitation as I am not aware of the mechanisms of how these drugs work and the theoretical possibility or no of any serious side effects, any thoughts at all on this?

[xks201]

I drink on social occasions maybe once per month. It has been around 4 to 5 days since the last dose and my alcohol tolerance is extremely high for some reason as of now. Was curious if anyone else had noticed any similar effect or could prove or disprove. In the name of experimentation and a generous bunch that brought the alcohol I wound up at about 15 shots and a beer and felt as if maybe I had drank one or two if that.

Edited by xks201, 27 July 2014 - 05:10 PM.

[Azz19]

I have been wondering. We practically know for sure that hippocampal neurogenesis is good, and we almost know for sure that it is good for depression, at least in certain populations. But just reading the name of this thread, it talks about synaptogenesis, not neurogenesis. Can someone who's researched it explain the difference? Can you have synaptogenesis in the absence of neurogenesis? It sounds like there will be more connections between neurons, but there's only so much neurotransmitters to go around, so will they have to be shared with more synapses. I clearly remember reading that one theory of how ECT works is by actually SEVERING connections between sections of the brain. How do we know increasing the amount of connections is a good thing?

Neurogenesis is the creation of new neurons from stem cells, synaptogenesis is the creation of new synapses between neurons. In the synaptic cleft (the gap area between synaptic knob and somas), neurotransmitters are exchanged to signal action potential.

So if NSI-189 signals the production of stem cells in the hippocampus, a chemical messenger must signal those stem cells to become new neurons. Just because a neuron is signaled to manifest, it may not necessarily have function. It must connect via dendrite, to synapse, to synaptic cleft to other functional neurons and be used with fair regularity, otherwise the neuron will likely be pruned. Similar is true of dendrites, synapses and receptor sites in terms of 'use it or lose it'.

Dihexa, according to what we are told, signals dedritic spining, and therefore synapses, of which, some should find other nerves to communicate with.

Synaptogenesis happens throughout one's life time, especially in learning, however a 'vast explosion' of syanptogenesis occurs largely in youth during the critical developmental phase as pruning is quite high. Pruning is good because it makes more efficient, your neurological network. Dihexa, in theory, gives the adult brain an artificially provoked explosion of synaptogenesis similar to that of a child.

Neurogenesis largely happens during the pre-natal period, although in adult life some neurogenesis occurs, largely in the hippocampus and subventricular zone. The reason for this is the concentration of stem cells in those areas.

I suppose, that if everything that I am reading of the drugs is correct, the sequence and schedule of drugs one would want to take to partially simulate an adolescent brain would be as follows:

1.) NSI-189 (for signaling of stem cell creation in available areas)
2.) ISX-9 (for signaling of available stem cells to neurons)
3.) Dihexa (for signaling of dendritic spines, and synapses from newly available neurons)
4.) Then the brain will do the rest in the way of pruning and reinforcement (probably good to take on new behaviors and courses of learning during this phase).

This is, of course, still a hypothesis as it's not necessarily proven that the above drugs will in fact have this action in the human brain, however data suggests they might.

I read somewhere that ISX-9 prevents stem cells from turning into non-nerve cells. Wouldn't ISX-9 be dangerous to take if that is the case?

[therein]

Anyone willing to pay DHEXA in bitcoins for me? 

 

I would be. How much do you have and how much are you asking for?

[megatron]

 

Anyone willing to pay DHEXA in bitcoins for me? 

 

I would be. How much do you have and how much are you asking for?

 

 

tolerant already agreed to do it, but thanks anyway.

[jabowery]

This bears directly on the dihexa faq's question:  

 

"What is the human equivalent dose?"

 

At present, the answer in the FAQ is:  

 

"Human equivalent dose is about 22mg per day for a 150lb male"

 

Obviously this is an over-dose if the half-life effect is of the magnitude estimated below.  

 

What we really need is single formula that takes into account not only the relationship between animal weight and dose per weight, but also animal weight and half-life so that the desired animal model results are expected from the human equivalent protocol.

 

Thus far the formulas we have are for:

 

Half-life:

log10[half-life in human]=0.906*log10[half-life in rat]+0.723

 

Human equivalent dose per kg:

HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]

Human Km = 37

Mouse Km = 3

Rat Km = 6

 

In the present instance since we're dealing with a rat model the Human equivalent dose per kg formula reduces to:

HED (mg/kg) = Rat Dose (mg/kg) x [Rat Km / Human Km]

HED (mg/kg) = Rat Dose (mg/kg) x [    6       /        37       ]

HED (mg/kg) = Rat Dose (mg/kg) x 0.162162...

 

Now the question is how to bring these two formulas together into a single formula?

 

Ancillary questions:

 

Are we trying to attain the same CNS concentration of dihexa in humans as for rats for the same amount of time?

 

Is the HED model really independent of the half-life model?

 

 

 

Hopefully samples should be arriving for most today or tomorrow. In the interest of harm reduction I'd like to reemphasize that this compound has an incredibly long half life.

SK_scientific and I dug a little bit more into the likely human half-life for dihexa. Here was our reasoning:
Due to metabolic and body composition differences, drugs administered to rats typically show a longer half-life when administered to humans.
The rat half life is 12.68 days[1]

SK_scientific was able to find an equation which allows you to estimate human kinetics based on rat kinetics. [2]

Here's some napkin math:
log10[half-life in human]=0.906*log10[half-life in rat]+0.723
[half-life in human]=antilog[0.906*log10[half-life in rat]+0.723]
[half-life in human]=antilog[0.906*log10[12.68*24]+0.723]
[half-life in human]=939.501 hours
[half-life in human]=39.1459 days

To put a 40 day half life into perspective. A common medication for hypothyroidism is levothyroxine. It has a rather long half life for a pharmaceutical - around 7 days. It takes 4-6 weeks to reach maximum serum concentration.

I couldn't find a documented method of determining maximum concentration from half life - though i can't imagine it's that hard. I finally just setup a basic spreadsheet and plotted it. I made the assumption that the dose is 20mgs once daily. On the y axis is mgs in circulation, on x is days. 

 

 

Don't take this as anything more than a rough estimate. What I'm trying to point out is that circulating levels rise (nearly linearly) for a long time. Maximum concentrations won't be reached until around 200 days of constant use! Reaching this point may be neither safe nor desirable. Additionally, if you do experience negative effects, they could take a very long time to subside, unlike most traditional pharmaceuticals.

[1] - Evaluation of Metabolically Stabilized Angiotensin IV Analogs as Procognitive/Antidementia Agents - page 147

[2] - The Prediction of Human Pharmacokinetic Parameters from Preclinical and In Vitro Metabolism Data - see figure 6

 

[fairy]

I'm having some problems with the editor so I'm gonna post a picture instead of the text. I would like to know the opinion of DHEXA.
 

 

 

%DIHEXA DECAY

d=22;
n=365;
x=1:n;
y=zeros(1,n);
for i=1:n,
    y(i)=q(i,d);
end
plot(x,y,'b--'); grid on
title('[DIHEXA] Exponential decay (?)');
xlabel('Days');
ylabel('Dihexa (mg)');

function a=q(i,k)
         t=24*60*60;
         l=log(2)/(12.68*t);
         v=zeros(1,i-1);
         for j=1:(i-1),
             v(j)=-l*t*j;
         end
         s=sum(exp(v));
         a=k*(1+s);

[Plasticperson]

matlab^^ <3

[DHEXA]

 

...

Now the question is how to bring these two formulas together into a single formula?

 

Ancillary questions:

 

Are we trying to attain the same CNS concentration of dihexa in humans as for rats for the same amount of time?

 

Is the HED model really independent of the half-life model?

 

I see what you're saying. Should we be seeking the equivalent concentrations of the rats as they demonstrated repair from scopolamine induced memory defects?

I can't really see a non-arbitrary way to determine a healthy human concentration at this point. Does anyone have ideas for this? It's necessary in order to determine dosage and timing.

The paper did indicate efficacy increased with concentration. But it would be irresponsible not to consider the possibility of too much of a good thing.

No biological systems will be truly independent. They do differ quite substantially in their mechanisms though. HED is based on differences in absorption, metabolism, body size, and presumably, body composition. 

The half life is determined again, on body composition (humans have more body fat, which may store some drugs), but mostly kidney filtration rate/efficiency and degrade enzymes.

 

 

I'm having some problems with the editor so I'm gonna post a picture instead of the text. I would like to know the opinion of DHEXA.
 
-snip-

Thanks for going over this fairy!

I think these are your calculations in the first paragraph.
Assuming 22mg is ingested every half life (every 39 days), and is fully absorbed.

22       =q1=22
33.0    =q2=22+22/2
38.5    =q3=22+22/2+22/4
41.25  =q4=22+22/2+22/4+22/8
42.625=q5=22+22/2+22/4+22/8+22/16

This looks right to me for a first order decay. It agrees with my calculations. I assumed a dose each day like this.

q1=22

q2=22+q1*.5^(1/39)=43.612

q3=22+q3*.5^(1/39)=64.844

q4=22+q4*.5^(1/39)=85.702

q5=22+q5*.5^(1/39)=106.192

I'm having trouble interpreting your second paragraph, which I think you intended to result in a graph similar to the one i posted earlier. Matlab is all gibberish to me. I did follow your links though. It looks like the functions given are for a second order decay. Second order decay, unlike single order, gives an increased half-life as concentration decreases. In other words, it results in a shorter half-life as concentration increases.

I could be wrong about all of this, or misinterpreting your work. Let me know If that's the case!

Edited by DHEXA, 28 July 2014 - 07:46 PM.