399 replies to this topic

[aphex]

 

This is interesting:

 

 

TrkB partial agonists: potential treatment strategy for epilepsy, mania, and autism.

Tsai SJ.

Author information

 

Abstract

Brain-derived neurotrophic factor (BDNF) is a member of a family of neurotrophins that, by activating a tyrosine kinase B receptor (TrkB), regulates a wide variety of processes in the nervous system, including neural development, function and survival. Evidence suggests that excess BDNF is involved in the pathogenesis of epilepsy, mania and autism. Thus, agents that can decrease BDNF-TrkB pathway signaling may be therapeutic for these diseases. However, blocking BDNF-TrkB pathways with TrkB antagonists may be harmful, as BDNF-TrkB deficiency has been related to major depression and Alzheimer's disease. A partial agonist is an agent that elicits a maximum response that is less than that of an agonist (e.g., the physiological ligand), so, in the presence of excess full agonist, a partial agonist would act as an antagonist. Interestingly, a dopaminergic partial agonist, aripiprazole, has been successfully developed for the treatment of psychotic disorders. Recently specific TrkB partial agonists have been synthesized by O'Leary and Hughes; it is proposed that these partial TrkB agonists may provide a novel strategy for the treatment of epilepsy, mania or autism, which may be associated with BDNF-TrkB hyperfunction.

 

 

 

I also recently stumbled across that study, indeed very interesting. Before I thought BDNF/neurogenesis/TrkB-agonism is all good, but mania, epilepsy and even cancer can be an issue. Involvement of BDNF in the pathogenesis of cancer is at least researched in colon cancer:

Biological influence of brain-derived neurotrophic factor (BDNF) on colon cancer cells.

http://www.ncbi.nlm....pubmed/24255678

I would also speculate that it could even be involved in brain cancer.

Functional characterization of human cancer-derived TRKB mutations.

http://www.ncbi.nlm....pubmed/21379385

I also experienced some manic states I think. They were not very severe but I was so overly active, productive (although not stimulated like with stimulants) that I sometimes thought it's too much and does harm.

I returned to more regular meditation and only take the DHF ocassionally now. I think you shoudn't  overdo it...

[Puppeteer]

Socialpiranha, I'm sure the lot of us involved in the group buy would greatly appreciate you checking in and just letting us know what's up. I private messaged you on the 19th and received no response, despite the fact that you were online at the time, and were last online on the 26th of June.

Even news of delays would be good, so long as we know there is progress. It would just be good to know that this is still all above board etc. As you received the sample at the beginning of June it seems reasonable to expect some details on your progress with getting it tested etc.?

Just a bit disconcerting to have all of these businesses cropping up around the place offering 7,8-DHF for immediate purchase and to still be in the dark about when (or even if) I'll eventually get my hands on the quantity I shelled out for 5+ months ago.

Cheers!

Edited by Puppeteer, 01 July 2014 - 11:49 AM.

[penisbreath]

 

 

This is interesting:

 

 

TrkB partial agonists: potential treatment strategy for epilepsy, mania, and autism.

Tsai SJ.

Author information

 

Abstract

Brain-derived neurotrophic factor (BDNF) is a member of a family of neurotrophins that, by activating a tyrosine kinase B receptor (TrkB), regulates a wide variety of processes in the nervous system, including neural development, function and survival. Evidence suggests that excess BDNF is involved in the pathogenesis of epilepsy, mania and autism. Thus, agents that can decrease BDNF-TrkB pathway signaling may be therapeutic for these diseases. However, blocking BDNF-TrkB pathways with TrkB antagonists may be harmful, as BDNF-TrkB deficiency has been related to major depression and Alzheimer's disease. A partial agonist is an agent that elicits a maximum response that is less than that of an agonist (e.g., the physiological ligand), so, in the presence of excess full agonist, a partial agonist would act as an antagonist. Interestingly, a dopaminergic partial agonist, aripiprazole, has been successfully developed for the treatment of psychotic disorders. Recently specific TrkB partial agonists have been synthesized by O'Leary and Hughes; it is proposed that these partial TrkB agonists may provide a novel strategy for the treatment of epilepsy, mania or autism, which may be associated with BDNF-TrkB hyperfunction.

 

 

 

I also recently stumbled across that study, indeed very interesting. Before I thought BDNF/neurogenesis/TrkB-agonism is all good, but mania, epilepsy and even cancer can be an issue. Involvement of BDNF in the pathogenesis of cancer is at least researched in colon cancer:

Biological influence of brain-derived neurotrophic factor (BDNF) on colon cancer cells.

http://www.ncbi.nlm....pubmed/24255678

I would also speculate that it could even be involved in brain cancer.

Functional characterization of human cancer-derived TRKB mutations.

http://www.ncbi.nlm....pubmed/21379385

I also experienced some manic states I think. They were not very severe but I was so overly active, productive (although not stimulated like with stimulants) that I sometimes thought it's too much and does harm.

I returned to more regular meditation and only take the DHF ocassionally now. I think you shoudn't  overdo it...

 

 

Yeah, it's disappointing; I've been looking for something to treat depression/anxiety that isn't directly monoanimergic and was hoping 7,8-DHF might be a viable substitute. It does seem to attenuate amphetamine stereotypy, which isn't a direct model for mania, I realize, but there is some overlap. 

[socialpiranha]

Sorry guys I've just had nothing to report really, still looking for a place to test it that i can afford, hoping someone else can help out on this as i'm very busy. I would understand if anyone had a problem with the delays and i'd be happy to issue a refund at any time

[aarfai]

Could we vote to skip testing entirely?! 

[neuroatypicow]

i got a quote last month from a lab to test the 7,8 DHF i got from THT, who could perform the analysis. that quote was $3800.00 to test a gram. but that included almost a dozen different tests.

is there just one test we can have performed that would give us a reasonable certainty of what this is or isn't? if so, i bet we could crowdfund the money to have that one test performed and it wouldn't individually strain our wallets.

i'm happy to help, if you guys can help me with the 'knowledges'.

~N

[Puppeteer]

Could we vote to skip testing entirely?! 

Yeah, I'm down with this. Assuming that this is legit from indofine I feel pretty damn confident that it's genuine, given that they were the supplier for those studies. I'd rather get my hands on the stuff ASAP then sort out testing at a later date as has been done with the NSI-189 buy. Is there any reason that's not possible?

Otherwise I may have to jump for that refund as I'm becoming more and more desperate as the year wears thinner and I don't really wanna wait another two or three months just to try something that may or may not be of use :/

[the_apollo]

i got a quote last month from a lab to test the 7,8 DHF i got from THT, who could perform the analysis. that quote was $3800.00 to test a gram. but that included almost a dozen different tests.

is there just one test we can have performed that would give us a reasonable certainty of what this is or isn't? if so, i bet we could crowdfund the money to have that one test performed and it wouldn't individually strain our wallets.

i'm happy to help, if you guys can help me with the 'knowledges'.

~N

 

Wouldnt it be possible for a lab to just isolate the molecule and confirm that it is 7,8 DHF by looking at it? For its structure and it being the same as depicted in reserach papers.

[neuroatypicow]

i don't know, i unfortunately know squat about chemistry beyond high school level. i did ask them to confirm not only composition, but also purity.

can those with greater knowledge than i in this department (which shouldn't be difficult) clarify just which tests/apparatus should be performed on our sample to assuage our concerns?

 

(socialpirahna, i'm in no way trying to step on your toes, just trying to help things along)

 

if it comes down to it, i suppose we could forego testing; it is indofine after all. probably none of the prior researchers who did the animal experiments sought 3rd party testing of the stock they fed their rats and mice. they used it on assumption that indofine has their shi+ together, right?

[Milkyway]

I know this is not the correct forum, but can anyone tell me what nsi 189 free base is as oppose to the phosphate as it is being advertised? Also, has anyone had any experience with the products from the new player on the block as they seem to be the only ones offering nsi 189 and 78 dihydroxyflavone. Does anyone know if their products are any good? Has anyone bought them and felt any positive effects?

[Milkyway]

Also, on Alibaba I compared prices for NSI-189 just to see.  Some people were advertising it as freebase which sounds like a very bizarre way to describe something that is supposed to be wholistic.  Also they were advertising it for some very outrageously low price if you bought an astronomical quantity which would make it very expensive.  Has anyone else seen these bizarre listings on Alibaba?  Perhaps it would be a good idea to stay away from Alibaba all together.  Just wondered if anyone else has seen these listings and can get a pulse on it?

[Amorphous]

Is this group buy still available? It seems like the organiser got the substance already, but analysis missing. Did indofine already do their analysis?

[lourdaud]

Could we vote to skip testing entirely?! 

 

Yeah, let's skip it!

[datrat]

I agree. I think in this case we could skip the independent analysis.

[neuroatypicow]

i'll go along with the prevailing opinion - skip the assay.

[aarfai]

Ok well there hasn't been any objections with skipping the testing and proceeding with the group buy... Could we please get an update social?

[socialpiranha]

I'm really hesitant to go that route because it still doesn't give people any peace of mind. It's all well and good that indofine is legit but if i can't prove myself to be, i can just imagine the accusations. At this point either someone takes care of the testing issue or we just call it off and refund

[neuroatypicow]

well, as i said before, i have a place that already supplied a quote to perform the analysis,

i just need you guys to tell me WHAT test(s) to ask for, to get a revised quote. if multiple tests are required, and its more than i can cover, i'll ask for contributions from the group members. but i need your chemistry knowledge guys.

[aarfai]

I am willing to contribute. Any ideas?

[neuroatypicow]

if you guys don't know off the top of your heads which tests would provide the best bang for the buck, perhaps you can point me to a member here who would have that knowledge?

[Flex]

if you guys don't know off the top of your heads which tests would provide the best bang for the buck, perhaps you can point me to a member here who would have that knowledge?

 

very likely joeyo and maybe ScienceGuy or Ceretropic

But the first two are busy, so perhaps a response could take time.

 

If those didnt response, then ask those Guys who had run a group buy. 

Maybe they could give some suggestions

Edited by Flex, 10 July 2014 - 09:00 PM.

[penisbreath]

Anyone still taking the tht stuff? Updates? I just placed a preorder with teamtlr ...

[Ezeon]

Anyone still taking the tht stuff? Updates? I just placed a preorder with teamtlr ...

 

I'm considering doing the same. I've also mailed a few of my nootropics suppliers to check if anyone has a plan to take it in. 7,8-Dihydroxyflavone is a natural flavone and not patentable. It would be great if more suppliers started to sell it.

[Al Capacino]

Anyone still taking the tht stuff? Updates? I just placed a preorder with teamtlr ...

I've just finished 1g in a month from tht and have noticed zero effects from it. I was taking 30mg sublingually per day. I was hoping to see a positive effect on my long term depression and severe Gad. But nothing. Waste of money for me.

[neuroatypicow]

sorry to hear that. i have some from them as well.

this is why it annoys me that there is no QC with these shops. we still don't know if this yellow-green powder is the real stuff, or a clever fake.

that's why group buys are better. or they should be.

[datrat]

 

Anyone still taking the tht stuff? Updates? I just placed a preorder with teamtlr ...

I've just finished 1g in a month from tht and have noticed zero effects from it. I was taking 30mg sublingually per day. I was hoping to see a positive effect on my long term depression and severe Gad. But nothing. Waste of money for me.

 

 

I don't blame you if you don't want to experiment with it anymore, but if you're still interested in it and get a chance to try some more I would suggest substantially increasing the dose. I had really good results with it at 60 mg sublingual 2x or 3x per day. When I cut back to 30 mg 2x per day due to limited amount the effect rather dramatically diminished. At 30 mg 1x a day I'm not sure if I would have noticed any results either. Also intranasally might be even more effective without increasing the dose that much.
 

[penisbreath]

what were the positive effects you noticed, datrat?

[datrat]

what were the positive effects you noticed, datrat?

 

Well, it wasn't my writing ability. Shouldn't have used the plural of result. I only noticed a very positive mood brightening effect. No cognitive plus or minuses or any other noticeable effect. But I'm definitely not complaining, the mood brightening effect alone was sufficient. It did decrease when I decreased the dosage and when I get some more I plan on using at least 60 mg BID sublingually, or maybe a lower dose intranasally, but I definitely want to use it again.
 

[tolerant]

Hello guys!

 

I've just forayed into the "Mental Health" sub-forum for the first time. I was hanging around in the general "Brain Health" forum, but this forum is probably more appropriate for me. In the "Brain Health" forum I get flamed for not continuing to experiment with a drug which makes my condition worse. I think healthy people who take nootropics to expand their intellectual abilities do not understand that people who are not well sometimes do not have that leeway for experimentation - if they feel worse from something, it can push them over the edge and they can't continue just for the sake of experimentation. I hope to find more understanding here.

 

So is this group buy still on or has it been called off?

 

[typ3z3r0]

Has anyone received anything yet from teamtlr? I contacted them regarding 7,8-DHF and they've said that they should have stock within 7-10 days.