145 replies to this topic

[dear mrclock]

i read this thread from top to bottom and i still dont fucking know from which plant 7,8-dihydroxyflavone is extracted from ?? i suppose just get the damn plant and extract it if they sell it too expensive.

[gamesguru]

Here's the full study: http://www.pnas.org/...53-e9aa7eb363f8.

Ye and Liu claim to know of more potent and hopefully less harmful derivatives of the lead compound, too, including 4′-dimethylamino-7,8-dihydroxyflavone: http://pubs.acs.org/....1021/jm101206p.

It's probably cheaper to synthesize the lead compound, though, because it probably requires fewer steps in the reaction. How much would 98% extract cost? I couldn't find any info on which plants naturally contain it either...this information might not be public yet.

The lead compound has some other mechanisms too, including NQO1 inhibition and trypanocidal activity: http://www.wikigenes...hem/e/1880.html. It is also being explored for PTSD, anxiety disorders, and psychopathology involving fear: http://www.healthemo...org/ressler.pdf & http://ajp.psychiatr...rticleID=102583. Might there be some toxicity that we're overlooking, though? I'm afraid to be the guinea pig so soon, when we know so little about this compound.

Edited by dasheenster, 23 July 2012 - 12:19 PM.

[dear mrclock]

i still dont fucking know from which plant is this extracted from

[Reformed-Redan]

That's why someone has to synthesize it. :/

[mycotheologist]

Its found in loads of plants. Green tea for instance. Only problem is its present in very low concentrations. Its not a very complex molecule, I'm fairly sure they synthesise it.

[gamesguru]

"It is likely that many people take in small amounts of 7,8-dihydroxyflavone in their diets," Ye says. "But drinking green tea or eating apples doesn't give you enough for a sustained effect."

"

7,8-dihydroxyflavone is a member of a family of antioxidant compounds naturally found in foods ranging from cherries to soybeans."

[Reformed-Redan]

Yeah, it is a simple compound and there are plenty of people who want to synth it. Just checking out the vendors.

[blighted]

I've managed to obtain some from research stock. While certainly not a controlled study, it seems to cause minimal acute affects (slight euphoria at high dose). My doses have not been carefully measured, but range from 100-500mg daily. I have begun experimenting with "snorting" smaller doses - any advice on the safety of that would be appreciated

After days to weeks, I do feel it has helped significantly with recovering from MDMA related neurotoxicity. While I am not 100%, I feel my working memory and vision has significantly recovered. Interestingly, my mood has trailed somewhat, but there is definitely less depression and my meditations are much easier.

Sorry that I can not reveal any supplier at this time as I fear they could shut off the supply for everyone if they receive too many inappropriate requests.

Depending on legalities, I would be very interested in performing some sort of informal controlled study.

Good luck.

Edited by blighted, 26 July 2012 - 12:13 AM.

[Reformed-Redan]

Can you list the price and amount you obtained? Just wondering what they are offering? Did they give you a HPLC with your purchase? Did you get it from Sigma, lol? 100mg to 500mg sounds like a waste and there shouldn't be any need for "snorting".

Edited by redan, 26 July 2012 - 03:05 AM.

[Reformed-Redan]

Ok I think I found a supplier. S/he has provided a COA with HPLC with purity to 99.4%. I will send the COA and HPLC to anyone seriously interested in the group buy. The total cost of 1 kg from this supplier would be $660 EMS or DHL included.

I have seen suppliers go as low as $200 and as high as $3500 for a kilogram; but, am not sure if they are for real or what the quality of the product would be (no purifying, no HPLC). If anyone wants to order the $200 and do a HPLC and quality test locally, let me know.

[mycotheologist]

Yeah, it is a simple compound and there are plenty of people who want to synth it. Just checking out the vendors.

Its not that simple though, semisynthesis may be more viable. Flavones are pretty ubiquitous in nature:
https://en.wikipedia.org/wiki/Flavone
I'm sure there are probably abundant natural sources of starting materials for 7,8-dihydroxyflavone. Total synthesis would be easy for a trained chemist in a well equipped lab but it may not be very economically viable or practical. Converting other flavones into it in a 1 or 2 step reaction would be far more viable.

I just noticed that its similar in structure to proanthocyanids:
https://en.wikipedia...roanthocyanidin
which are powerful antioxidants present in Maritime Pine bark.

[mycotheologist]

Ok I think I found a supplier. S/he has provided a COA with HPLC with purity to 99.4%. I will send the COA and HPLC to anyone seriously interested in the group buy. The total cost of 1 kg from this supplier would be $660 EMS or DHL included.

I have seen suppliers go as low as $200 and as high as $3500 for a kilogram; but, am not sure if they are for real or what the quality of the product would be (no purifying, no HPLC). If anyone wants to order the $200 and do a HPLC and quality test locally, let me know.

I want to get in on this group buy. I'm trying to find info on dosages at the moment but 1kg should be a large quantity. According to:
http://ajp.psychiatr...rticleID=102583
the dose they experimented with on mice was 5mg/kg. I'll research this now to try and estimate a safe and effective dose for humans. This is the first time I've done a group buy before, how does this work, will we all PM the buyer (the person who actually orders from the vendor)?

EDIT: According to that psychiatryonline article, the optimum dose to reverse fear conditioning in mice is 5mg/kg. I'll try and find some info on doses for depression.

Edited by mycotheologist, 26 July 2012 - 09:48 AM.

[mycotheologist]

I skimmed through this article:
http://www.ncbi.nlm....pubmed/21073191
and see that they were also dosing mice with 5mg/kg for their experiments. That article investigates 7,8-DHFs ability to induce neurogenesis and cure depression. In this article:
http://www.ecnp.eu/~...a-k/Bollen.ashx
they say:

The lowest effective dose was lower, i.e. 0.3 mg/kg, when 7,8-DHF was administered during the late consolidation phase compared to 1 mg/kg during early consolidation.

that article is about 7,8-DHF memory enhancing properties. The main problem here is I don't know if mice are more sensitive to the drug than humans or vice versa. If these doses also apply to humans, then my estimate is that therapeutic doses range between 1mg/kg and 15mg/kg. So in my case, since I weigh around 90kg, my doses would be 90mg - 1.3g. So $660 for 1kg isn't that bad. A kilo hypothetically contains around 1000 strong doses. Lets say 10 of us pitch in, that means we each put in $66 and get around 100 strong doses which would last over 3 months if using daily. So $60 for a 3 month supply of this stuff isn't bad at all considering all the beneficial properties it has. If chemical suppliers charge this much for bulk purchases, then I bet they will charge an arm and a leg for it if or when it becomes sold in pharmacies/health food shops.

It may be more economical for us to find a cheap analogue of this compound and turn it into 7,8-DHF ourselves. I'll look into it.

EDIT: The sigma-aldrich prices are ridiculous. Who in the name of God would pay €60 for 10mg of a simple organic compound.

Edited by mycotheologist, 26 July 2012 - 01:49 PM.

[Reformed-Redan]

Anyone know some domestic GC-MS testing place? Need to check this item when it comes in.

Edited by redan, 27 July 2012 - 02:36 AM.

[Reformed-Redan]

Here's an American supplier. 5 grams for 266 USD. 1 gram for 79 USD.
http://www.tcichemic...ity/D1916/.html

Edited by redan, 27 July 2012 - 05:02 AM.

[Reformed-Redan]

If the group buy goes well I will donate what I can to Longecity, just for being here.

[renfr]

I'm interested in the group buy, 1kg is largely enough for a lot of people. If I could get a small dose to start with.

I wonder if chronic use can cause downregulation of tyrosine kinase receptors, if that's the case caution should be taken with 7,8 dihydroxyflavone intake. Since it's an agonist it should.
Overactivation of RTK is linked with carcinogenesis : http://www.ncbi.nlm....pubmed/15229652
Some drugs to counter cancer growth use RTK inhibitors, correct me if I'm not right I'd like to hear an expert on that.

[gamesguru]

There's no study linking TrkB to cancer, but since there is research linking RKT-mediated dysregulated endocytosis and cancer (http://ajpendo.physi...296/5/E973.full & https://docs.google....sGuL0mkPDhW5jnA), and there is evidence linking TrkB abnormalities to dysregulated endocytosis (https://www.lablife....ser&id=14581459), we might suspect it to be dangerous. Provided we don't "overdo it", there shouldn't be an issue...in fact healthy activating might reduce cancer incidence. For example, does this research mean we ought to abandon turmeric and curcumin, since they boost BDNF, which probably results in receptor downregulation? I think the fact that these receptors are a double-edged sword remind us of the importance of cycling.

Keep in mind TrkB is one receptor in the subfamily of RKTs, a very large and diverse family. One poorly understood one is the LNGFR.

Edited by dasheenster, 27 July 2012 - 01:49 PM.

[Reformed-Redan]

Think, got enough people who are in the group buy. Might be enough. Will let you know how it goes.

[arcticjoe]

I too would be interested in buying some, - definitely looks like a promising compound.

Earlier this year, Emory medical school investigators, led by pathologist Keqiang Ke, found a compound that protects brain cells against the kind of damage seen in seizure, stroke, and PD, achieving what so many other experimental “neuroprotective” drugs have failed to do over the past decade. The compound, 7,8-dihydroxyflavone, is a member of the flavonoid family of chemicals, abundant in fruits and vegetables. Because of its ability to cross the blood-brain barrier, its selective action on specific cells once it arrives in the brain, and the different pathway it uses to achieve its actions (mimicking one of the brain’s own growth factors), the investigators believe the compound could be the founder of a new class of brain-protecting drugs. When Miller gave it to mice that had been treated with a toxin that kills the same neurons as those affected by Parkinson’s, it prevented nearly all of the damage. More studies are under way, but Miller believes this novel therapeutic agent can restore ability to transport neurotransmitters both in animals genetically deficient in VMAT protein and in those exposed to neurotoxins.

from: http://whsc.emory.ed...parkinsons.html

[cesium]

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

 

Zinc is an essential co-factor for over 100 enzymes. Clinical studies^6,7 have demonstrated the benefits of zinc sulfate monotherapy or supplementation for the treatment of attention-deficit/hyperactivity disorder and major depression, and it was well tolerated with a low rate of side effect. Chronic zinc treatment has been found to increase levels of BDNF mRNA in the rat cerebral cortex.⁸ Exposure to micromolar quantities of zinc robustly activated TrkB signaling in cultured cortical neurons.⁹

 

Recently, Sowa-Kuma and colleagues¹⁰ tested the antidepressant activity of zinc hydroaspartate in an animal model of depression and the effect of zinc treatment on BDNF protein and the mRNA level.  They found zinc hydroaspartate exhibited a rapid antidepressant-like effect and zinc treatment induced a 17% to 39% increase in the BDNF mRNA and protein level in the hippocampus.¹⁰ Furthermore, Franco and colleagues¹¹ indicated that chronic zinc treatment caused a significant antidepressant-like effect and produced an increase in BDNF expression in the cerebral cortex in rats.

 

[Reformed-Redan]

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

Zinc is an essential co-factor for over 100 enzymes. Clinical studies^6,7 have demonstrated the benefits of zinc sulfate monotherapy or supplementation for the treatment of attention-deficit/hyperactivity disorder and major depression, and it was well tolerated with a low rate of side effect. Chronic zinc treatment has been found to increase levels of BDNF mRNA in the rat cerebral cortex.⁸ Exposure to micromolar quantities of zinc robustly activated TrkB signaling in cultured cortical neurons.⁹

Recently, Sowa-Kuma and colleagues¹⁰ tested the antidepressant activity of zinc hydroaspartate in an animal model of depression and the effect of zinc treatment on BDNF protein and the mRNA level. They found zinc hydroaspartate exhibited a rapid antidepressant-like effect and zinc treatment induced a 17% to 39% increase in the BDNF mRNA and protein level in the hippocampus.¹⁰ Furthermore, Franco and colleagues¹¹ indicated that chronic zinc treatment caused a significant antidepressant-like effect and produced an increase in BDNF expression in the cerebral cortex in rats.

Nice find! Worth looking into. Only thing worries me is a daily dose of ~200mg of zinc.

Edited by redan, 29 July 2012 - 05:34 PM.

[gamesguru]

Zinc is easier to overdo than magnesium. Magnesium gets filtered by and excreted through the kidneys, whereas zinc has to be excreted by the intestinal cells in feces (http://nutrition.jbp...m?id=30&debug=0). It's kind of like the difference between fat soluble and water soluble vitamins. Water soluble ones are generally easier for the body to regulate when overdoses are concerned.

Zinc plasma levels tend to vary between 70-110 micrograms/dl--serum levels between 80-120. The study referenced by cesium doesn't mention how zinc supplementation affects people who are on the lower side vs. the higher side, or I'm overlooking it if it does.

[arcticjoe]

unfortunately higher doses of zinc make me feel like shit pretty quickly, i am far more interested in trying 7,8-hdf. Redan, how many people do you need for the group buy, and how much will it cost?

[Reformed-Redan]

I haven't collected any money yet from people; but, I've already payed for the product and am awaiting arrival. After that I'll be accepting payments. Still have a GS-MS to do when I get the product to check quality. Will let you guys/gals know how it plays out.

Edited by redan, 30 July 2012 - 09:56 PM.

[Reformed-Redan]

The amount was different for the purchase I made. Guess Chinese suppliers can do that.

No group buy, everyone. Can't organize the amount and let alone know if the product will arrive. Too risky.

Edited by redan, 31 July 2012 - 04:15 PM.

[arcticjoe]

ah shame. Oh well, hopefully some more encouraging research results pop up, which get some larger companies interested in this.

[Reformed-Redan]

I'm still getting some PM's of interest. This group buy should only be done through an escrow service so there are no issues with "trust". I got the COA from only one company for this compound out of like 100 "companies" that contacted me. According to them, they can provide 100 grams for $550. That's about it so far. Here's the COA. It's a big no-no to fake a government issued COA in China, so it might be real.
http://postimage.org/image/v3t6cjfh9/

[arcticjoe]

Is there any possibility of bartering the amount up to say 150g or cost down to $400? In the past when I used to buy RCs from Chinese vendors I could often make them an offer and get sometimes as much as 50% off the price.

[Googoltarian]

Here's the COA.

Looks totally calculated - not based in reality, just using computer programs. Let me show you:

It's a big no-no to fake a government issued COA in China, so it might be real.