1569 replies to this topic

[jabowery]

Spoiler

 

 

He said he was using wxMaxima. The answer is correct.  jabowery, you should read this: http://www.math.com/...ls/more/b^x.htm  Remember that the logarithm of a number 0<x<1 will always be negative.

So did I give it the wrong formula to integrate.

Or is it that I need to summate rather than integrate since this is step-wise dosage per day?

 

Here's the summation for the accumulated bioavailable drug, on day 'day', of a bioavailable drug given as daily bioavailable doses of 'bioavailabledoseperday' and a half life of 'halflife':

sum(bioavailabledoseperday*((1/2)^(t/halflife)), t, 1, day), simpsum;

wxMaxima symbolically simplifies it to:

((bioavailabledoseperday*(1/2^((day+1)/halflife)−1/2^(1/halflife)))/(1/2^(1/halflife)−1)

A protocol of 10mg per day, assuming 1% bioavailability and half life of 40 days, yields the function:

bioavailabledose(day):=2^((day+1)/40)−2^(1/40)/((5*2^(41/40)−10)*2^((day+1)/40));

Evaluating for one month:

bioavailabledose(30);
-1.690492049259341

This is also nonsense.

 

Lets call the sum you want to calculate S, d-daily dosage,h-halflife, t-time(days). 
 
S= d+d*0.5^(1/h)+d*0.5^(2/h)+....+d*0.5^(t/h)= d(1+0.5^(1/h)+0.5^(2/h)+...+0.5^(t/h))=[It's a geometric progression]=d(1-0.5^((t+1)/h))/(1-0.5^(1/h)) 
 
d=10 
h=40
t=30
 
S=241.92 (w/o respect to any bioavailability)

 

That matches my numeric-only calculation in the prior comment with two caveats:

1) I applied the 1% bioavailability estimate to the 10mg dose to yield a 0.1mg bioavailable dihexa per daily dose.

2) The second significant digit in my calculation was 3 (2.3...), rather than your 4 (2.4...).

 

I'd still like to understand why the symbolic solution doesn't come out correctly for either integration or summation (from 1 so it shouldn't involve logs of numbers between 0 and 1 -- at least not in the variable being integrated or summed).

Edited by jabowery, 01 October 2014 - 11:04 PM.

[StevesPetRat]

I'm having a bit of trouble with wxMaxima integrating the halflife formula to get bioconcentration at a particular day given a particular bioavailable dose per day:

integrate(bioavailabledoseperday*0.5^(day/halflife),day)

it integrates to

−1.442695040888963*bioavailabledoseperday*halflife*0.5^(day/halflife)

Where does the - sign come from and does any of this look right?

That's an antiderivative. You forgot to evaluate at the lower limit (day = 0) to get the integral,

ln2*BADPD*t_half * (1-0.5^(d/t_half))

 

wheeee I'm helping

 

[meth_use_lah]

 

Spoiler

 

 

He said he was using wxMaxima. The answer is correct.  jabowery, you should read this: http://www.math.com/...ls/more/b^x.htm  Remember that the logarithm of a number 0<x<1 will always be negative.

So did I give it the wrong formula to integrate.

Or is it that I need to summate rather than integrate since this is step-wise dosage per day?

 

Here's the summation for the accumulated bioavailable drug, on day 'day', of a bioavailable drug given as daily bioavailable doses of 'bioavailabledoseperday' and a half life of 'halflife':

sum(bioavailabledoseperday*((1/2)^(t/halflife)), t, 1, day), simpsum;

wxMaxima symbolically simplifies it to:

((bioavailabledoseperday*(1/2^((day+1)/halflife)−1/2^(1/halflife)))/(1/2^(1/halflife)−1)

A protocol of 10mg per day, assuming 1% bioavailability and half life of 40 days, yields the function:

bioavailabledose(day):=2^((day+1)/40)−2^(1/40)/((5*2^(41/40)−10)*2^((day+1)/40));

Evaluating for one month:

bioavailabledose(30);
-1.690492049259341

This is also nonsense.

 

Lets call the sum you want to calculate S, d-daily dosage,h-halflife, t-time(days). 
 
S= d+d*0.5^(1/h)+d*0.5^(2/h)+....+d*0.5^(t/h)= d(1+0.5^(1/h)+0.5^(2/h)+...+0.5^(t/h))=[It's a geometric progression]=d(1-0.5^((t+1)/h))/(1-0.5^(1/h)) 
 
d=10 
h=40
t=30
 
S=241.92 (w/o respect to any bioavailability)

 

That matches my numeric-only calculation in the prior comment with two caveats:

1) I applied the 1% bioavailability estimate to the 10mg dose to yield a 0.1mg bioavailable dihexa per daily dose.

2) The second significant digit in my calculation was 3 (2.3...), rather than your 4 (2.4...).

 

I'd still like to understand why the symbolic solution doesn't come out correctly for either integration or summation (from 1 so it shouldn't involve logs of numbers between 0 and 1 -- at least not in the variable being integrated or summed).

 

 

2. 2.4 vs 2.3 comes from the fact that I calculate the amount directly after absorption (t=0) while you calculate immediately before dosage (t=1) (or you have taken the drug for 30 days and calculate the active amount on day 31.).

 

You have to put in the limits 0 and t. I=int(d*0.5^(x/h), 0, t)=d*h*0.5^(t/h)/ln(0.5)  -  d*h/ln(0.5)=d*h*(1-0.5^(t/h))/ln(2)    [ln(0.5)=-ln(2)]

 

d=0.1

h=40

t=30

 

I=2.34

 

Edited by meth_use_lah, 02 October 2014 - 07:07 AM.

[StevesPetRat]

That's an antiderivative. You forgot to evaluate at the lower limit (day = 0) to get the integral,
ln2*BADPD*t_half * (1-0.5^(d/t_half))
 
wheeee I'm helping

Shit, that should be 1/ln2. Guess I'm not helping anymore.
Anyway, the steady state concentration is BADPB*t_half/ln2. If you were feeling bold, you could take a loading dose of t_half/ln2 * the usual daily dose and BOOM you'd be right at the steady state concentration.

Or dead.

[xks201]

 

That's an antiderivative. You forgot to evaluate at the lower limit (day = 0) to get the integral,
ln2*BADPD*t_half * (1-0.5^(d/t_half))
 
wheeee I'm helping

Shit, that should be 1/ln2. Guess I'm not helping anymore.
Anyway, the steady state concentration is BADPB*t_half/ln2. If you were feeling bold, you could take a loading dose of t_half/ln2 * the usual daily dose and BOOM you'd be right at the steady state concentration.

Or dead.

 

 

And what is the loading and usual daily dose? lol 

[meth_use_lah]

 

 

That's an antiderivative. You forgot to evaluate at the lower limit (day = 0) to get the integral,
ln2*BADPD*t_half * (1-0.5^(d/t_half))
 
wheeee I'm helping

Shit, that should be 1/ln2. Guess I'm not helping anymore.
Anyway, the steady state concentration is BADPB*t_half/ln2. If you were feeling bold, you could take a loading dose of t_half/ln2 * the usual daily dose and BOOM you'd be right at the steady state concentration.

Or dead.

 

 

And what is the loading and usual daily dose? lol 

 

 

d*h*(1-0.5^(t/h))/ln(2) -> d*h/ln(2) as t-> infinity

 

d*h/ln(2) + d,      would be your loading dose where d- daily dose, h- half-life

 

the active amount in your body would then be

 

b*d*h/ln(2),      where b- bioavailability 

 

​for as long as you continue taking the daily dose d.

[resveratrol_guy]

Based on the relative number of thread followers, it looks like many of you have not been tracking J147, as described in this thread, where any replies should be directed. I only mention this because it would be highly likely that dihexa rats would be intereseted in this other compound as well, and we might be able to leverage what we learned with the dihexa group buy for J147 purposes.

 

[StevesPetRat]

And what is the loading and usual daily dose? lol

I don't have time to go back through the whole thread, but I believe it was estimated that the half life would be about 30 days, so you'd take 45 times the daily dose, which was 25-30 mg, or 1.1 - 1.3 g at once -- which you basically did already.

[jabowery]

 

And what is the loading and usual daily dose? lol

I don't have time to go back through the whole thread, but I believe it was estimated that the half life would be about 30 days, so you'd take 45 times the daily dose, which was 25-30 mg, or 1.1 - 1.3 g at once -- which you basically did already.

 

 

So now we see a rational for xks201's high dose -- not that I am, nor was nor is he, recommending that for others.

 

Anyway, thanks for putting your rat at risk (on behalf of the rest of us) xks201.  I'm sure now more people are going to be waiting with baited breath your reports.

 

I'm not going to go to that extreme, but the formulas I'm trying to compile should give us something to research.

Edited by jabowery, 03 October 2014 - 06:50 PM.

[sk_scientific]

I just wanted to check in with everyone and say hello.  Life is continuing and I haven't passed away owing to my "abuse" of neurological enhancers.  I would like to thank xks201 for making the irresponsible decision to ingest such a large amount of Dihexa in one sitting.  I can not say that his behavior is much different than my own as we're dabbling with compounds that haven't had human trials; He just took a whole hell of a lot more than I did in a go.

 

Where I will absolutely not encourage any one else to model their behavior after xks201's, I am very appreciative of his brave decision to take such a sizable amount  (that was rather brave of you, my friend) -- it does put my mind some what at ease regarding potential toxicity, though understand that this is one isolated case of such.

 

I hope you all are well and thank you for your continued support in the venture.

[Jbac]

700mg knocked me out and behaved sort of like a high dose of human growth hormone. I woke up now in a state of hyperfocus....tunnel focus. Feels like my brain is like ten times more capable than my body. This behaves very different at 700mg than even 50mg. It feels as if my brain is being rewired. I have zero trace of adhd which I have had severely for a while. I don't recommend anyone go over like 40mg until I figure out what exactly is happening here. It is extremely intense, almost like a psychedelic high without the hallucinations....how I described it to N is it feels like my brain is a one thousand pound paper weight over whatever train of thought I am having. It feels like an extreme parasympathetic stimulant. Not like a traditional stimulant....This is unlike anytjing I've seen before ...not even close. I'm not sure whether to rejoice or what at this moment as the hyperfocus Is ridiculous.

 

Still feeling the hyperfocus and anti-adhd?  Any brain rewiring?  How long did the effects of the 700 mg dose last?

[xks201]

The effects of the 700mg are still going and will most likely last another couple more months. Overall it's the same thing really..better body composition...much better stress resilience...probably still a lot more focus. The effects in cognitive enhancement seem cumulative. I don't get angry at stupid crap anymore. Cognition is definitely enhanced but to what degree at this exact moment I'm not sure. Overall I like it and if I have the ability to take it forever I probably will. I think more people will have to reach peak plasma levels with a loading dose to get a better of idea of how fast it works and in what. I have a ton of classes right now and literally have no room to breath let alone realize how my cognition is if that makes sense. I know it has to be better. I have been on cortisol for adrenal fatigue and I basically in the last few weeks have required none of it after using 20mg per day or so. It has to be doing something.

The effects of the 700mg are still going and will most likely last another couple more months. Overall it's the same thing really..better body composition...much better stress resilience...probably still a lot more focus. The effects in cognitive enhancement seem cumulative. I don't get angry at stupid crap anymore. Cognition is definitely enhanced but to what degree at this exact moment I'm not sure. Overall I like it and if I have the ability to take it forever I probably will. I think more people will have to reach peak plasma levels with a loading dose to get a better of idea of how fast it works and in what. I have a ton of classes right now and literally have no room to breath let alone realize how my cognition is if that makes sense. I know it has to be better. I have been on cortisol for adrenal fatigue and I basically in the last few weeks have required none of it after using 20mg per day or so. It has to be doing something. Like I said, it's doing what I expected it to slowly over time. I'm not sure if anyone is gonna reap the true benefits of it just taking 30mg per day unless you had a 10 gram order lol

Edited by xks201, 06 October 2014 - 12:10 PM.

[Jbac]

 

The effects of the 700mg are still going and will most likely last another couple more months. Overall it's the same thing really..better body composition...much better stress resilience...probably still a lot more focus. The effects in cognitive enhancement seem cumulative. I don't get angry at stupid crap anymore. Cognition is definitely enhanced but to what degree at this exact moment I'm not sure. Overall I like it and if I have the ability to take it forever I probably will. I think more people will have to reach peak plasma levels with a loading dose to get a better of idea of how fast it works and in what. I have a ton of classes right now and literally have no room to breath let alone realize how my cognition is if that makes sense. I know it has to be better. I have been on cortisol for adrenal fatigue and I basically in the last few weeks have required none of it after using 20mg per day or so. It has to be doing something. Like I said, it's doing what I expected it to slowly over time. I'm not sure if anyone is gonna reap the true benefits of it just taking 30mg per day unless you had a 10 gram order lol

 

 

Awesome. Are you still taking small doses of dihexa per day (20 mg?), or just waiting for the loading dose to wear off?  Btw please check your PM, I sent you my new mailing address. The old address will get returned to sender.

 

Also please explain what you mean by body composition; are you losing weight around your belly, gaining muscle, jaw getting bigger, etc.

Edited by Jbac, 06 October 2014 - 06:21 PM.

[jabowery]

I'm not sure if anyone is gonna reap the true benefits of it just taking 30mg per day unless you had a 10 gram order lol

 
Earlier you recommended people not exceed 40mg per day, apparently due to your reaction to the mega-dose.  You said:
 

I don't recommend anyone go over like 40mg until I figure out what exactly is happening here.

 
Now you seem to be saying something else altogether.  Is this because you have at least to some extent figured "out what exactly is happening here"?

[Jbac]

Sounds like he was waiting a couple weeks to see if there would be side effects from the 700 mg, and there were none.  After getting slow (or zero) results from 40 mg per day, then getting great results from the 700 mg loading dose with no side effects, it's obvious which one is better, unless the user really wants to play it safe and stick to the rat study dosage.

 

And of course you could try a 200 mg or 300 mg loading dose instead, if 700 sounds too scary.

Edited by Jbac, 06 October 2014 - 06:50 PM.

[xks201]

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good.

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good. I doubt anyone will feel much without a proper loading dose of around 500mg and up.

Edited by xks201, 06 October 2014 - 07:01 PM.

[DHEXA]

 

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good.

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good. I doubt anyone will feel much without a proper loading dose of around 500mg and up.

 

I tried this out the other day. 700mg left me feeling quite stimulated. Systolic BP increased ~10-15 points, pushing it into the pre-hypertension range. It also left me feeling quite ill for the rest of the day. Moderate Nausea made eating quite unpleasant.

I'm not feeling ill today, and my blood pressure seems to have lowered, though I need to take a couple more measurements.

In my honest opinion, 500mg is too much for a loading dose. Besides lowering or ignoring the loading phase completely, we may want to consider spreading high doses over a few days, in order to catch side effects before the entire amount is absorbed.

[Jbac]

^So is the dihexa helping you?

[jabowery]

 

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good.

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good. I doubt anyone will feel much without a proper loading dose of around 500mg and up.

 

The rationale for the high loading dose is not to "feel something" so much as to achieve a stead-state in vivo bioavailable concentration consistent with, say, 40mg/day oral.

 

Have we established a rationale for a particularly desirable in vivo bioavailable concentration?  Have we established the actual bioavailability of oral at 1% as previously suggested?

Edited by jabowery, 06 October 2014 - 09:01 PM.

[jabowery]

Spoiler

 

 

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good.

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good. I doubt anyone will feel much without a proper loading dose of around 500mg and up.

 

The rationale for the high loading dose is not to "feel something" so much as to achieve a stead-state in vivo bioavailable concentration consistent with, say, 40mg/day oral.

 

 

Have we established a rationale for a particularly desirable in vivo bioavailable concentration?  Have we established the actual bioavailability of oral at 1% as previously suggested?

 

 

This is no idle question on my part.  Jan's performance on Singing Coach as reached a limit as of a week ago (after increasing for almost a month) and the 10mg/day doses ceased as of yesterday.  Although I didn't inform her that the doses ceased she expressed frustration at Singing Coach today for the first time -- saying "It's not fun."  I'm terminating any further use of Singing Coach until the next batch of Dihexa arrives.  It is the only objective measurement that I've been able to find that she can tolerate so I don't want her becoming averse to it.  I'm considering upping the dose quite a bit.  The problem with that is if I do up her dose, I have to take even more as her "taster" to try to shield her from ill effects -- and that means I'll be going through the limited supply a lot faster than I had anticipated.  As it stands I'll be cutting into a supply that a friend originally got because he suffered some brain damage but he said Jan needed it more than he.

Edited by jabowery, 06 October 2014 - 11:47 PM.

[Infinite1]

Recently started following this. Has anyone proposed a feasible solution for the potentially pro-carcinogenic properties of this? If not I would consider this a priority. 

[Amorphous]

 

 

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good.

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good. I doubt anyone will feel much without a proper loading dose of around 500mg and up.

 

I tried this out the other day. 700mg left me feeling quite stimulated. Systolic BP increased ~10-15 points, pushing it into the pre-hypertension range. It also left me feeling quite ill for the rest of the day. Moderate Nausea made eating quite unpleasant.

I'm not feeling ill today, and my blood pressure seems to have lowered, though I need to take a couple more measurements.

In my honest opinion, 500mg is too much for a loading dose. Besides lowering or ignoring the loading phase completely, we may want to consider spreading high doses over a few days, in order to catch side effects before the entire amount is absorbed.

 

 

I think I am a little more sensitive to dihexa than you. I tried a 50mg dose and my DIASTOLIC pressure increased about 10 points. I don't remember how high is my systolics, but I think both are within prehypertensive range. 

How do you take dihexa? Did you take it with DMSO? or sublingually? or simply swallow it like xks201? Simply swallow it means you may have = or <1% of the amount being absorbed; that is 700 mg will deliver about 7 mg in blood, and if you are taking it while on Nexium or something similar, there will be even less absorption or not even absorbed at all. 

 

 

 

[DHEXA]

 

 

 

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good.

Yes. It appears quite benign and safe. I'd do a gram again soon no problem in the rat. I wouldn't recommend something before giving it a few weeks in my own rat. So far so good. I doubt anyone will feel much without a proper loading dose of around 500mg and up.

 

I tried this out the other day. 700mg left me feeling quite stimulated. Systolic BP increased ~10-15 points, pushing it into the pre-hypertension range. It also left me feeling quite ill for the rest of the day. Moderate Nausea made eating quite unpleasant.

I'm not feeling ill today, and my blood pressure seems to have lowered, though I need to take a couple more measurements.

In my honest opinion, 500mg is too much for a loading dose. Besides lowering or ignoring the loading phase completely, we may want to consider spreading high doses over a few days, in order to catch side effects before the entire amount is absorbed.

 

 

I think I am a little more sensitive to dihexa than you. I tried a 50mg dose and my DIASTOLIC pressure increased about 10 points. I don't remember how high is my systolics, but I think both are within prehypertensive range. 

How do you take dihexa? Did you take it with DMSO? or sublingually? or simply swallow it like xks201? Simply swallow it means you may have = or <1% of the amount being absorbed; that is 700 mg will deliver about 7 mg in blood, and if you are taking it while on Nexium or something similar, there will be even less absorption or not even absorbed at all. 

 

You could very well be more sensitive than I am. Perhaps the effects are attenuated since I've already used quite a bit. I'm still playing with DMSO, but dissolving the compound is tedious, and I'd rather not keep dihexa in solution if I don't have to. I generally try to consume it sublingually, but as i've mentioned before, it seems to clump up and not absorb in any appreciable amount. Because of this, I suspect most of it is being absorbed in the GI tract.

I remain a little skeptical of the claim that <1% is absorbed. This claim came from a PHD dissertation didn't it? It seems to directly contradict other published researchers.

[megatron]

You could however dissolve it in DMSO and take it sublingually like I do. 

[xks201]

How Does putting dmso under your tongue not make you gag? How much dmso per mg? Increased effects this way? I paid for one third of it as the other two thirds I guess aren't to N yet so I should have 30 something grams anyday I can begin shipping.

[Amorphous]

DMSO is one way to make dihexa more absorbable. I've never tried DMSO. Does DMSO actually dissolve it or just disperse it? I am currently using coconut oil to disperse and mechanically break down the particle size and make the size distribution more even. For hydrophobic drug, I understand that there are several ways that can improves drug absorption. The most important 3 that we can easily do are 1) an acidic environment 2) fat or oil content 3) drug particle size and size distributions. I think the arrangement of significance are 3>2>1. 

[PWAIN]

Would it dissolve in alcohol? Does alcohol do anything negative to the molecule? Might be a way to improve absorption.

[megatron]

Dihexa is very soluble in DMSO. The concentration I use is approx. 25mg Dihexa per 1mL DMSO. There are no chunks or anything left in the solution after having stirred or shaken it for a little while. DMSO should easily diffuse through the mucous membrane under the tongue. It is actually not that bad, as you don't taste the solution while holding it under your tongue. It is when swallowing it you get a good taste of it, but I've gotten quite used to it. 

[xks201]

Dihexa is very soluble in DMSO. The concentration I use is approx. 25mg Dihexa per 1mL DMSO. There are no chunks or anything left in the solution after having stirred or shaken it for a little while. DMSO should easily diffuse through the mucous membrane under the tongue. It is actually not that bad, as you don't taste the solution while holding it under your tongue. It is when swallowing it you get a good taste of it, but I've gotten quite used to it. 

Well how much of an increased effect do you notice via this route? 

[Amorphous]

Dihexa is very soluble in DMSO. The concentration I use is approx. 25mg Dihexa per 1mL DMSO. There are no chunks or anything left in the solution after having stirred or shaken it for a little while. DMSO should easily diffuse through the mucous membrane under the tongue. It is actually not that bad, as you don't taste the solution while holding it under your tongue. It is when swallowing it you get a good taste of it, but I've gotten quite used to it. 

 

I've just ordered some. If it can totally dissolve dihexa, it will definitely make it to systemic circulation in high %. When I use the method of administration I mentioned above, I definitely feel the hyperfocus state, but sometime when I get lazy and simply swallow the powder or do it sublingually, I simply feel nothing. However, disregard the state I felt I was in, there is no objective improvement in cognitive performance (dual n back).