145 replies to this topic

[Googoltarian]

Apparently plant from which this flavonoid could be extracted is Godmania aesculifolia. But this information is from only one source: https://openwetware....-MS-natprod.pdf
Its listed on second page of this pdf document.

[ScienceGuy]

So a 75Kg person would be:

5mg x 75Kg = 375mg x 10 days = 3750mg

So at $363.30 per 50mg Would cost 3750/50 x 363.30 = $27 247.50

Depressing....

Of course we are talking mice so that will mess things up even further.

It's not quite as bad as that...

“The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight… For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.” [Reagan-Shaw, S., Nihal, M., Ahmad, N. Dose translation from animal to human studies revisited. FASEB J. 22, 659–661 (2007)]

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

⇒ HED for 7,8-dihydroxyflavone = 5 x (3 / 37) = 0.405 mg/kg

Hence, the recommended dosage for a 75Kg adult person = 30mg per day

[Reformed-Redan]

So a 75Kg person would be:

5mg x 75Kg = 375mg x 10 days = 3750mg

So at $363.30 per 50mg Would cost 3750/50 x 363.30 = $27 247.50

Depressing....

Of course we are talking mice so that will mess things up even further.

It's not quite as bad as that...

“The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight… For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.” [Reagan-Shaw, S., Nihal, M., Ahmad, N. Dose translation from animal to human studies revisited. FASEB J. 22, 659–661 (2007)]

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

⇒ HED for 7,8-dihydroxyflavone = 5 x (3 / 37) = 0.405 mg/kg

Hence, the recommended dosage for a 75Kg adult person = 30mg per day

Hey there ScienceGuy! Great to see you around!

I'm wondering about the quoted text. It says not to use HED to calculate equivalent doses; but, you did use it... Why's that? Man, this compound sounds like a winner. Too bad hard to get. I'm still willing to get this chem through escrow on lookchem from a verified vendor if there are people willing to share the cost... I could also send the product in hand to other people outside the US.

Edited by redan, 13 August 2012 - 03:12 PM.

[ScienceGuy]

Hey there ScienceGuy! Great to see you around!

I'm wondering about the quoted text. It says not to use HED to calculate equivalent doses; but, you did use it... Why's that?

Hi Redan,

To clarify:

1) HED (Human Equivalent Dose) is the "equivalent dose" and hence is precisely what we are interested in calculating here; unless of course you are interested in feeding this substance to your pet mouse

2) It does not in fact say "not to use HED to calculate equivalent doses", it says not to calculate the HED using a simple conversion based on body weight.

3) It goes on to instruct how to correctly calculate the HED (Human Equivalent Dose), wherein the correct formula for calculating the HED (mg/kg) = Animal Dose (mg/kg) x [Animal K_m / Human K_m]; and this is what I have calculated.

But you are forgiven already, since this is pretty confusing stuff!

Man, this compound sounds like a winner. Too bad hard to get. I'm still willing to get this chem through escrow on lookchem from a verified vendor if there are people willing to share the cost... I could also send the product in hand to other people outside the US.

I wholeheartedly agree that this appears to be a very exciting substance; however, I would urge caution in that, in my opinion, a singular RODENT STUDY is not enough to warrant such a call to action, in that we don't know if the positive effects translate to HUMANS, and we do not know what are the potential negative effects, including possible TOXICITY and SIDE EFFECTS.

I strongly advise waiting until after some further research is published before being tempted to start sprinkling it on your breakfast cereal... just sayin'

N.B. Since this subject keeps coming up, I have posted a new Thread on how to calculate the HED, which you can find HERE: How to convert dose from ANIMAL to HUMAN

Edited by ScienceGuy, 13 August 2012 - 04:02 PM.

[Reformed-Redan]

Hey there ScienceGuy! Great to see you around!

I'm wondering about the quoted text. It says not to use HED to calculate equivalent doses; but, you did use it... Why's that?

Hi Redan,

To clarify:

1) HED (Human Equivalent Dose) is the "equivalent dose" and hence is precisely what we are interested in calculating here; unless of course you are interested in feeding this substance to your pet mouse

2) It does not in fact say "not to use HED to calculate equivalent doses", it says not to calculate the HED using a simple conversion based on body weight.

3) It goes on to instruct how to correctly calculate the HED (Human Equivalent Dose), wherein the correct formula for calculating the HED (mg/kg) = Animal Dose (mg/kg) x [Animal K_m / Human K_m]; and this is what I have calculated.

But you are forgiven already, since this is pretty confusing stuff!

But, the citation recommends using the BSA method instead of the HED method; but, you still use the HED method. Well, anyway the dose isn't that bad. Will wait around for some more papers on 7,8-dihydroxyflavone.

[ScienceGuy]

Hey there ScienceGuy! Great to see you around!

I'm wondering about the quoted text. It says not to use HED to calculate equivalent doses; but, you did use it... Why's that?

Hi Redan,

To clarify:

1) HED (Human Equivalent Dose) is the "equivalent dose" and hence is precisely what we are interested in calculating here; unless of course you are interested in feeding this substance to your pet mouse

2) It does not in fact say "not to use HED to calculate equivalent doses", it says not to calculate the HED using a simple conversion based on body weight.

3) It goes on to instruct how to correctly calculate the HED (Human Equivalent Dose), wherein the correct formula for calculating the HED (mg/kg) = Animal Dose (mg/kg) x [Animal K_m / Human K_m]; and this is what I have calculated.

But you are forgiven already, since this is pretty confusing stuff!

But, the citation recommends using the BSA method instead of the HED method; but, you still use the HED method. Well, anyway the dose isn't that bad. Will wait around for some more papers on 7,8-dihydroxyflavone.

In short, NO; you are incorrect. It seems you are confused; but as I have alrady stated you are already forgiven this this is a very confusing subject

The pertinent information that you need to look at is: "Figure 1. Formula for dose translation based on BSA.", which is found in the bottom lefthand corner of page 660, which is the 2nd page of the published paper; wherein it clearly states that the "Formula for dose translation based on BSA" is as follows:

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

This is precisely what I have calculated

As such, I have calculated the HED using the 'BSA method', exactly as per the paper

Please kindly note that there is no "HED method", in that the HED (Human Equivalent Dose) is the parameter that we are calculating, not the method.

The BSA (Body Surface Area) is used to calculate the K_m factor that is used in the specified formula, wherein K_m = Body weight (kg) / Body Surface Area (BSA) (m²)

Hence, I reiterate that I have indeed calculated the HED using the 'BSA method', exactly as per the paper.

Edited by ScienceGuy, 14 August 2012 - 07:57 PM.

[Reformed-Redan]

Thanks for the clarification.

[arcticjoe]

redan, any news on sourcing 7,8-dhf?

[Reformed-Redan]

redan, any news on sourcing 7,8-dhf?

Right now I'm on a Zinc regimen. It's doing me good. Trying to keep cortisol levels (via Vit. C and such) also. Still interested in this compound; but, and wonderin about the agonist effect. Potential down-regulation? Cycling it would be something to do with this compound.

[nowayout]

Again, this is a patent, so don't go putting the cart before the horse. You can get a patent on almost anything you might imagine pulling out of your ass, and most patents today are essentially frivolous ideas filed just in case something might come of it in future. Appearing in a patent does not mean an idea has any therapeutic validity.

Edited by viveutvivas, 27 August 2012 - 03:50 PM.

[noos]

redan, any news on sourcing 7,8-dhf?

Right now I'm on a Zinc regimen. It's doing me good. Trying to keep cortisol levels (via Vit. C and such) also. Still interested in this compound; but, and wonderin about the agonist effect. Potential down-regulation? Cycling it would be something to do with this compound.

What is a zinc regimen and what does it treat?

Edited by noos, 28 August 2012 - 03:28 PM.

[Reformed-Redan]

Again, this is a patent, so don't go putting the cart before the horse. You can get a patent on almost anything you might imagine pulling out of your ass, and most patents today are essentially frivolous ideas filed just in case something might come of it in future. Appearing in a patent does not mean an idea has any therapeutic validity.

I understand; but, I first found out that lower BDNF levels are directly linked with many neurological disorders (depression mainly) and then looked for a compound that stimulated BDN-Factor or as some call it, Fertilizer.

redan, any news on sourcing 7,8-dhf?

Right now I'm on a Zinc regimen. It's doing me good. Trying to keep cortisol levels (via Vit. C and such) also. Still interested in this compound; but, and wonderin about the agonist effect. Potential down-regulation? Cycling it would be something to do with this compound.

What is a zinc regimen and what does it treat?

Check post 51.

[Verne]

What's the latest news on this compound? Have they begun human trials?

Plain old zinc appears to operate thru a similar mechanism. Not sure if it is as potent, but it sure is a lot cheaper and easier to obtain.
http://www.cnsspectr...?articleid=2558

Interesting. I'll have to look further into this.

[Psionic]

from wikipedia listed BDNF agonists:


BDNF (Brain-derived neurotrophic factor)
N-Acetylserotonin
Amitriptyline
7,8-dihydroxyflavone
4′-Dimethylamino-7,8-dihydroxyflavone

I am not sure how zinc relate to increased BDNF

[trance]

Here's a paper about zinc and depression pathways ...

 Zinc Depression Pathways.pdf   315.87KB   5 downloads

[Redux]

Another alternative ways to supercharge BDNF factor is physical exercise. Much better than any drug actually, and makes you look good naked.

BDNF relation to exercise:


https://cs.uwaterloo...c/Gomez2002.pdf

http://resulb.ulb.ac...ehaviorBDNF.pdf


On another note if you want to supercharge your BDNF even if its temporarily you might want to have a look at Ketamine:

http://www.youtube.com/watch?v=hNsIiq-5354

Paper: http://dx.doi.org/10...pbp.2007.07.027

Edited by Redux, 28 March 2013 - 02:47 PM.

[Redux]

Something went wrong with first scientific article link.

Here it is: https://cs.uwaterloo.../cc/Gomez2002.pdf

Definitely an interesting read.

Edited by Redux, 28 March 2013 - 06:57 PM.

[arcticjoe]

I dont think increase in BDNF is the most interesting aspect of this compound - I am far more interested in this because of its ability to restore transport of neurotransmitters both in animals genetically deficient in VMAT protein and in those exposed to neurotoxins... plus it's rapid anti-depressant effect.

Edited by arcticjoe, 29 March 2013 - 09:45 AM.

[Redux]

Another novel way to potentiate BDNF-factor - Sleep Deprivation

Rapid antidepressant effects of sleep deprivation therapy correlates with serum BDNF changes in major depression.

Abstract

Recent reports have suggested that brain-derived neurotrophic factor (BDNF) levels are reduced in individuals suffering major depressive disorder and these levels normalize following antidepressant treatment. Various antidepressants and electroconvulsive therapy are shown to have a positive effect on brain-derived neurotrophic factor levels in depressive patients. The aim of this study was to assess the effect of total sleep deprivation therapy on BDNF levels in major depressive patients. Patients were assigned to two treatment groups which consisted of 22 patients in the sertraline group and 19 patients in the total sleep deprivation plus sertraline group. Patients in the sleep deprivation group were treated with three total sleep deprivations in the first week of their treatment and received sertraline. Patients in sertraline group received only sertraline. BDNF levels were measured in the two treatment groups at baseline, 7th, 14th, and 42nd days. Patients were also evaluated using the Hamilton Rating Scale for Depression (HAM-D). A control group, consisting of 33 healthy volunteers had total sleep deprivation, BDNF levels and depression measured at baseline and after the total sleep deprivation. Results showed that serum BDNF levels were significantly lower at baseline in both treatment groups compared to controls. Decreased levels of BDNF were also negatively correlated with HAM-D scores. First single sleep deprivation and a series of three sleep deprivations accelerated the treatment response that significantly decreased HAM-D scores and increased BDNF levels. Total sleep deprivation and sertraline therapy is introduced to correlate with the rapid treatment response and BDNF changes in this study.

http://www.ncbi.nlm....pubmed/19576267

Sleep Deprivation Effects on Growth Factor Expression in Neonatal Rats: A Potential Role for BDNF in the Mediation of Delta Power


Abstract

The sleeping brain differs from the waking brain in its electrophysiological and molecular properties, including the expression of growth factors and immediate early genes (IEG). Sleep architecture and homeostatic regulation of sleep in neonates is distinct from that of adults. Hence, the present study addressed the question whether the unique homeostatic response to sleep deprivation in neonates is reflected in mRNA expression of the IEG cFos, brain-derived nerve growth factor (BDNF), and basic fibroblast growth factor (FGF2) in the cortex. As sleep deprivation is stressful to developing rats, we also investigated whether the increased levels of corticosterone would affect the expression of growth factors in the hippocampus, known to be sensitive to glucocorticoid levels. At postnatal days 16, 20, and 24, rats were subjected to sleep deprivation, maternal separation without sleep deprivation, sleep deprivation with 2 h recovery sleep, or no intervention. mRNA expression was quantified in the cortex and hippocampus. cFos was increased after sleep deprivation and was similar to control level after 2 h recovery sleep irrespective of age or brain region. BDNF was increased by sleep deprivation in the cortex at P20 and P24 and only at P24 in the hippocampus. FGF2 increased during recovery sleep at all ages in both brain regions. We conclude that cortical BDNF expression reflects the onset of adult sleep-homeostatic response, whereas the profile of expression of both growth factors suggests a trophic effect of mild sleep deprivation.

http://jn.physiology...91/4/1586.short


Seems Zinc does potentiate BDNF in very interesting levels:

Antidepressant-like activity of zinc: further behavioral and molecular evidence


ABSTRACT

Zinc exhibits antidepressant-like activity in preclinical tests (the forced swim test and tail suspension test) and in olfactory bulbectomy and chronic unpredictable stress; two models of depression. Zinc also enhances the treatment of depression in humans. In the present study we evaluated the antidepressant activity of zinc in another model of depression-chronic mild stress (CMS) and the effect of zinc treatment on BDNF protein and the mRNA level. In CMS zinc hydroaspartate (10 mg/kg) exhibited a rapid (after 1 week of treatment) antidepressant-like effect. Chronic treatment with zinc induced a 17-39% increase in the BDNF mRNA and protein level in the hippocampus. These data indicate a rapidly acting antidepressant-like activity of zinc in CMS and the involvement of zinc in the regulation of BDNF.

http://www.biopsychi...idepressant.htm

Edited by Redux, 30 March 2013 - 07:26 AM.

[Adamzski]

On another note if you want to supercharge your BDNF even if its temporarily you might want to have a look at Ketamine:

Ketamine as in the drug Special K? wow that is a trip,,,, it is the most dissociated I have been with the world an indescribable experience, I felt like, well I was standing at an open door on the edge of the universe and I had comprehension of how big the universe was, amazing. can not say it was a pleasurable experience but it was not scary.

[renfr]

Zinc has good neuroprotective and antidepressant activity however it should be carefully used as too much is neurotoxic, that's it's called the brain's dark horse.

[Reformed-Redan]

I'd redirect everyone over from this thread who was interested in a group buy over to the Dihexia thread:
http://www.longecity...a/page__st__150

[arcticjoe]

As much as dihexia sounds promising I wont be purchasing it until there are some human safety studies to back it up, as unfortunately it sounds like it may have some strong potential to promote brain tumor growth.
anyway, apparently 7,8-Dihydroxyflavone, is also known as Vitamin P... and its effects are working via a different path than BDNF:

Vitamin P as a Potential Approach for the Treatment of Damaged Motor Neurons
Apr. 2, 2013 — Biologists from the Ruhr-Universität Bochum have explored how to protect neurons that control movements from dying off. In the journal Molecular and Cellular Neuroscience, they report that the molecule 7,8-Dihydroxyflavone, also known as vitamin P, ensures the survival of motor neurons in culture. It sends the survival signal on another path than the molecule Brain Derived Neurotrophic Factor (BDNF), which was previously considered a candidate for the treatment of motoneuron diseases or after spinal cord damage.
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"The Brain Derived Neurotrophic Factor only had a limited effect when tested on humans, and even had partially negative consequences," says Prof. Dr. Stefan Wiese from the RUB Work Group for Molecular Cell Biology. "Therefore we are looking for alternative ways to find new approaches for the treatment of neurodegenerative diseases such as Amyotrophic Lateral Sclerosis."
Same effect, different mode of action
In previous studies, researchers hypothesised that vitamin P is an analogue of BDNF and thus works in the same way. This theory has been disproved by the team led by Dr. Teresa Tsai and Prof. Stefan Wiese from the Group for Molecular Cell Biology and the Department of Cell Morphology and Molecular Neurobiology headed by Prof. Andreas Faissner. Both substances ensure that isolated motor neurons of the mouse survive in cell culture and grow new processes, but what exactly the molecules trigger at the protein level varies. BDNF activates two signalling pathways, the so-called MAP kinase and PI3K/AKT signal paths. Vitamin P on the other hand makes use only of the latter.
The dose is crucial
However, vitamin P only unfolded its positive effects on the motor neurons in a very small concentration range.
"These results show how important an accurate determination of dose and effect is," says Prof. Wiese. An overdose of vitamin P reduced the survival effect, and over a certain amount, no more positive effects occurred at all. The researchers hope that vitamin P could have less negative side effects than BDNF. "It is easier to use, because vitamin P, in contrast to BDNF, can pass the blood-brain barrier and therefore does not have to be introduced into the cerebrospinal fluid using pumps like BDNF," says Wiese.

http://www.scienceda...30402101157.htm

Edited by arcticjoe, 03 April 2013 - 07:57 AM.

[Reformed-Redan]

Really interesting. I knew flavenoids must have been the main components of the positive effects of diets rich in fruits and vegetables.
Here's another nice study:

Emerging evidence suggests that a group of dietary-derived phytochemicals known as flavonoids are able to induce improvements in memory acquisition, consolidation, storage and retrieval. These low molecular weight polyphenols are widespread in the human diet, are absorbed to only a limited degree and localise in the brain at low concentration. However, they have been found to be highly effective in reversing age-related declines in memory via their ability to interact with the cellular and molecular architecture of the brain responsible for memory. These interactions include an ability to activate signalling pathways, critical in controlling synaptic plasticity, and a potential to induce vascular effects capable of causing new nerve cell growth in the hippocampus. Their ability to activate the extracellular signal-regulated kinase (ERK1/2) and the protein kinase B (PKB/Akt) signalling pathways, leading to the activation of the cAMP response element-binding protein (CREB), a transcription factor responsible for increasing the expression of a number of neurotrophins important in defining memory, will be discussed. How these effects lead to improvements in memory through induction of synapse growth and connectivity, increases in dendritic spine density and the functional integration of old and new neurons will be illustrated. The overall goal of this critical review is to emphasize future areas of investigation as well as to highlight these dietary agents as promising candidates for the design of memory-enhancing drugs with relevance to normal and pathological brain ageing (161 references).

Full study would be nice.

Edited by redan, 03 April 2013 - 08:40 PM.

[arcticjoe]

bump, i think i might have found a source for this. I've placed a test order for 5g and am quite curious to test this very promising substance.

[Reformed-Redan]

Keep us posted, thanks.

[addx]

Ketamine, Salvia Divinorum, Ibogaine, Corticosteroids and even Diclofen are able to stop depression immediately(and of course opioids). Of these, the first three have lasting results even when the drug is out of the system.

Experimental kappa opioid antagonists also stop depression, anxiety and anhedonia immediately. Please look at the JDTic thread guys.

I have explained stuff there in short and will provide studies to prove my claims if any of you thinks something is off.

[Reformed-Redan]

Ketamine, Salvia Divinorum, Ibogaine, Corticosteroids and even Diclofen are able to stop depression immediately(and of course opioids). Of these, the first three have lasting results even when the drug is out of the system.

Experimental kappa opioid antagonists also stop depression, anxiety and anhedonia immediately. Please look at the JDTic thread guys.

I have explained stuff there in short and will provide studies to prove my claims if any of you thinks something is off.

Anything supporting these claims? Salvia can induce lasting depersonalization disorder. Not that harmless as once thought.

[addx]

Ketamine has several case studies on the internet and this one refering to them

http://www.ncbi.nlm....pubmed/23825857

I will not look for other studies as this effect is well known and there are numerous studies trying to work out the mechanism by which ketamine achieves this, all on pubmed.


Salvia features a lot less official human testing than ketamine(for obvious reasons of ketamine being a very popular and usefull anaesthetic while salvia is just a psychedelic)

http://www.erowid.or..._journal3.shtml

There are several studies in rats of salvia

http://www.ncbi.nlm....pubmed/22926298

But Salvia is really just a kappa opioid agonist, a very pure and precise one at that - doesn't touch anything else. If you pubmed kappa opioid agonists and antagonists with the terms anxiety and depression you'll see what I'm talking about.

Ibogaine is well known, I don't think I have to explain that one. It detoxes heroin/meth/cocaine/alcohol/nicotine addicts in 36 hours. It will stop depression very fast even with a small dose. If you really want I'll search stuff about it but you can do it yourself.


I can't find cortef(corticosteroid) claims, dont have more time to search now, but I remember them. But cortef causes depression when withdrawing as well so this is kinda obvious. Also causes an instant switch to mania in a small percentage of people.

Diclofen is my personal experience, try it. I used it during a mononucleosis. It instantly gave me good mood and appetite in spite my lymph nodes being the size of golf balls and me not being able to swallow my own spit. I ate a loaf of bread within 3 minutes of taking a diclofen shot(not pills, the intramuscular shot). That's at least as safe as you can get. Now this was sickness induced depression but I kinda feel it would work pretty ok without the sickness causing the depression. Depression is considered by many to be an inflammation of the brain.

Check out the JDTic group buy thread, I made more claims there, some of theme explain stuff

Edited by addx, 12 August 2013 - 04:55 PM.

[addx]

Oh, btw. Ibogaine flood treatment causes months of upregulated BDNF in all the key areas of the brain. I think there's a pubmed study on this, gtg now