1565 replies to this topic

[Introspecta]

So 3 people out of hundreds possibly thousands are having some excess glutamate issues and people are scared to take the product now. I feel we are being a little paranoid. Climatic why are you continuing to take supplements. Why don't you just stop everything and let your brain balance naturally rather than pumping more shit into your system? I do know how it is being semi addicted to taking supplements trying to gain extra energy or an edge but with the issues that you have I would think you would want to stear clear from everything for a bit until the symptoms go away. This is just a recomendation.

Is Isochroma still mega dosing Sunifiram with no ill results?

[3AlarmLampscooter]

According to the paper cited in this post, galantamine also activates PKCalpha. Why haven't we heard anything about this as a cancer risk? Similarly, Oxiracetam is said to activate PKC, although I haven't found a study where PKC-α is specified. Could this be a common mechanism of many nootropics?

It is possible that some nootropics are a Faustian bargain like NZT-48 in Limitless, however I still have not found anything directly tying increased PKCα to formation of new gliomas. Feel free to correct me if I'm wrong.

"Now the flame that burns twice as bright, burns only half as long"

Still in all, unless are talking about something like a tenfold increase in the risk of Gliomas, this is nothing likely to have a practical impact.

[Climactic]

So 3 people out of hundreds possibly thousands are having some excess glutamate issues and people are scared to take the product now. I feel we are being a little paranoid. Climatic why are you continuing to take supplements. Why don't you just stop everything and let your brain balance naturally rather than pumping more shit into your system? I do know how it is being semi addicted to taking supplements trying to gain extra energy or an edge but with the issues that you have I would think you would want to stear clear from everything for a bit until the symptoms go away. This is just a recomendation.

Guess what genius. I already tried discontinuing all my supplements. It did jack. I still have most of them discontinued, with the exception of those vitamins that are proven to help with excitotoxicity. I am not addicted to anything, not even caffeine, so be careful with your allegations. Since the incident, the only reason I tried sunifiram and modafinil independently once is to confirm they indeed were causative factors.

In case you forgot, a little paranoia is essential when dealing with experimental drugs. It's not you who is suffering. I think this is it for me and most untested experimental drugs. It's easy to ask someone to sit back and suggest to let things fix themselves, but not so easy to do when your head hurts like a mofo.

Now we have people [2.30.51.94] pointlessly whitewashing the Wikipedia article - removing perfectly well sourced statements. Did they actually think it would work?

Edited by Climactic, 20 June 2013 - 04:01 AM.

[Climactic]

According to the paper cited in this post, galantamine also activates PKCalpha. Why haven't we heard anything about this as a cancer risk? Similarly, Oxiracetam is said to activate PKC, although I haven't found a study where PKC-α is specified. Could this be a common mechanism of many nootropics?

It is possible that some nootropics are a Faustian bargain like NZT-48 in Limitless, however I still have not found anything directly tying increased PKCα to formation of new gliomas. Feel free to correct me if I'm wrong.

"Now the flame that burns twice as bright, burns only half as long"

Still in all, unless are talking about something like a tenfold increase in the risk of Gliomas, this is nothing likely to have a practical impact.

I still have faith in proper use of nootropics. One just mustn't go overboard. An analogy is overclocking your computer - a little works well, but overclock it too much and you'll fry it.

Also, one must be extra-cautious with untested experimental drugs, especially when they're new. I bet you that I will be hearing of more people having side effects from sunifiram.

Are you forgetting that gliomas are not the only cancer that PKCα is associated with? It affects practically the whole body.

The extent of PKCα activation may vary a thousand fold with current drugs. Sunifiram, I believe, is quite powerful. It may even vary a million fold with future drugs.

Edited by Climactic, 20 June 2013 - 04:01 AM.

[zongler007]

i take doses 60mg every day (sunifiram) bout 10 days and i feel great, lil doses dont work at me.

[Suirsuss]

One thing to point out, the expected rate of developing gliomas in the general population is 4.7/100,000 person-years (from http://www.ncbi.nlm....les/PMC1907421/)

thanks I was wondering about that. I would shy from megadosing suni of course but not all that worried about gliomas at 5mg bid when running low on money for noots.

[Climactic]

One thing to point out, the expected rate of developing gliomas in the general population is 4.7/100,000 person-years (from http://www.ncbi.nlm....les/PMC1907421/)

thanks I was wondering about that. I would shy from megadosing suni of course but not all that worried about gliomas at 5mg bid when running low on money for noots.

Considering a life-expectancy of 79 years, isn't that 4.7/1266 or 1/269 persons, or am I analyzing it wrong?

All old people will get cancers, but it doesn't mean that you must go out of your way to ensure your cancers are especially malignant. The practical goal is to keep them as local and slow-progressing as possible.

How do you know that 5mg is safe in the long term? There is no dosing study data available. Persistent headache side effects have occurred (reported to me just yesterday) at a dose as low as 4mg.

Edited by Climactic, 20 June 2013 - 05:26 AM.

[3AlarmLampscooter]

One thing to point out, the expected rate of developing gliomas in the general population is 4.7/100,000 person-years (from http://www.ncbi.nlm....les/PMC1907421/)

thanks I was wondering about that. I would shy from megadosing suni of course but not all that worried about gliomas at 5mg bid when running low on money for noots.

Considering a life-expectancy of 79 years, isn't that 4.7/1266 or 1/269 persons...

All old people will get cancers, but it doesn't mean that you must go out of your way to ensure your cancers are especially malignant. The practical goal is to keep them as local and slow-progressing as possible.

How do you know that 5mg is safe in the long term? There is no dosing study data available. Persistent headache side effects have occurred (reported to me just yesterday) at a dose as low as 4mg.

The breakdown by age/gender is even more interesting, Glioblastoma at least is by far the most prevalent for males from 50-85. http://www.cdph.ca.g...omaAdult-08.pdf

If there were one category who should really avoid Sunifiram due to possible cancer risk (if there is indeed any), I would probably say them. On the other hand, this category is hardest hit by cognitive decline as well.

[Climactic]

The breakdown by age/gender is even more interesting, Glioblastoma at least is by far the most prevalent for males from 50-85. http://www.cdph.ca.g...omaAdult-08.pdf

If there were one category who should really avoid Sunifiram due to possible cancer risk (if there is indeed any), I would probably say them. On the other hand, this category is hardest hit by cognitive decline as well.

But again, why is there the implied assumption that PKCa affects only brain cancers? It most definitely affects various other cancers as well.

Edited by Climactic, 20 June 2013 - 05:42 AM.

[xsiv1]

Have you been to see a doctor yet or had any blood work or scans done yet? I don't know if you have insurance so this may be prohibitive but here, it'd have gone and told the doc straight up as to what I did and request the correct testing including referral to a neurologist. I remember reading that they said (in the ER) there was no intracranial pressure found anywhere iirc. Regardless, is want a second opinion or further testing of the symptoms are still pronounced to this day. Glutamate excitotoxicity should diminish near daily with the cessation of the offending compound and normally, headaches aren't the primary symptom. You might have something else going on which is my concern Climactic.

Edited by xsiv1, 20 June 2013 - 10:44 AM.

[xsiv1]

I mean everyone is different, but glutamate, as you know is your body's chief excitatory neurotransmitter so you should be having symptoms akin to being in some sort of benzo withdrawal, i.e chills, flu-like symptoms, dreadful anxiety, insomnia, etc. I can only hope that the NMDARs were not permanently oversensitized in some fashion and by having tinnitus, it does seem to implicate their involvement but it has to be something else to it. If a brain scan revealed no encephalitis or other inordinate swelling of the brain, I'd be getting more thorough testing. How's cognition right now? And, to be sure, you're still experiencing an agonizing headache today? Dull ache all over or is it localized to the frontal/temple region of your head. I'm not defending Suni or saying the concoction you took was not the cause of your symptoms, but I'm concerned that we're overlooking something.

[ThePhoeron]

I finished my 14-day trial stack on tuesday, so I'm currently washing out. No come-down, crash, burnout, withdrawal, or detox symptoms as of yet. As I've mentioned before, the only issues I had with sunifiram were when I exceeded the dose of 5mg, and then I'd get brain fog or fatigue after about two hours. No headaches, no tinnitus, less sensitivity to pressure changes. The suni would wear off much faster when taken sublingually instead of orally, and it did make me more sensitive to caffeine, as others have reported.

As far as cognitive benefits, they were more noticeable in the first week—more subtle than my initial six-day high-dose piracetam trial, but more effective for programming. My thinking was clear, and I had the right mix of creativity and logic to solve some big problems in a few lines of very clean code. Most importantly, it all worked, bug-free, without having to run it through the test-debug-repair cycle several times. The second week felt more or less normal. Still got a lot done, very positive mood, no hypomania, relaxed and productive. That being said, I was substantially more sociable than normal.

So, I don't seem to have a problem with sunifiram or the other noots in that stack. But everyone's brain chemistry is at least a little different. It's probably also worth noting that I don't consume alcohol, ever, and I have no health or mental illness issues. I do, however, smoke and drink coffee, etc. All of these things could play a factor, not to mention diet, other medications, and supplements.

Obviously, if you react badly to a research compound, then you should stop taking it immediately. Maybe with more research we'll be able to narrow-in on the specific factors that control the efficacy or potential risk of ampakines like sunifiram, but that will obviously take years to do properly. None of our experiments are controlled, so all of our experiences are no more than anecdotal to the study of the compound as a whole—but a bad reaction isn't anecdotal for you personally. I found it to be effective for a reasonable duration of two weeks, and only got slightly (and briefly) cloudy and tired if I exceeded the maximum recommended dose for my body-mass of <5mg. I have not yet tested doses >25mg, so I don't know how my body wil react there, but it will be interesting to see.

[Suirsuss]

One thing to point out, the expected rate of developing gliomas in the general population is 4.7/100,000 person-years (from http://www.ncbi.nlm....les/PMC1907421/)

thanks I was wondering about that. I would shy from megadosing suni of course but not all that worried about gliomas at 5mg bid when running low on money for noots.

Considering a life-expectancy of 79 years, isn't that 4.7/1266 or 1/269 persons, or am I analyzing it wrong?

All old people will get cancers, but it doesn't mean that you must go out of your way to ensure your cancers are especially malignant. The practical goal is to keep them as local and slow-progressing as possible.

How do you know that 5mg is safe in the long term? There is no dosing study data available. Persistent headache side effects have occurred (reported to me just yesterday) at a dose as low as 4mg.

mang you dont just have 4.7/100,000 chance to get a glioma every year thats the age-standardidzed incidence rate from all ages...

there just not enough info to confidently take any of these ampakines asides from maybe piracetam. Oxiracetam has PKC action but the study didnt reveal the isoforms involved. It appears protein kinase C might be one of the mechanisms of nootropic action.

[Climactic]

Who is IP 2.30.51.94? He has been repeatedly censoring safety related information from the Wikipedia article on sunifiram. He has been deleting neutrally-stated well-sourced info about PKCa and cancer - perhaps he thinks it's better that you guys didn't know it, or that NMDA agonists can cause overactivation of NMDAR. He is wasting my time and I'll have to call a Wikipedia administrator.

Edited by Climactic, 20 June 2013 - 04:54 PM.

[xsiv1]

Who is IP 2.30.51.94? He has been repeatedly censoring safety related information from the Wikipedia article on sunifiram. He has been deleting neutrally-stated well-sourced info about PKCa and cancer - perhaps he thinks it's better that you guys didn't know it, or that NMDA agonists can cause overactivation of NMDAR. He is wasting my time and I'll have to call a Wikipedia administrator.

I'd say it's surely someone who has a vested interest in the sale or promotion of Suni...that, or an overzealously infatuated user of said compound. It happens all the time. I remember back in the GHB days over 15 years ago, when initial reports began to surface regarding it's dependence risk. Posts (I think on the bodybuilding forums) went missing or were entirely deleted. Any number of people may have an interest to preserve it's availability in the market. Same thing with Phenibut. Although it certainly has it's therapeutic properties, the likelihood of dependence is significantly high for those deemed "positive responders" it judicious use must be limited to a + or - 1 to 2 days a week depending on the individual and generally speaking. Both accounts are of dependence and it's associated risks like excitotoxicity, but not cancer. That's just something you don't want to mess with. I'd report it as a plausible link that's being edited out. They're likely inundated with requests like this though given their staffing levels.

[Suirsuss]

...that, or an overzealously infatuated user of said compound.

A certain longecity poster comes to mind hmm...

[xsiv1]

...that, or an overzealously infatuated user of said compound.

A certain longecity poster comes to mind hmm...

Meh. Remember all of the 'lurkers' out there as well...people who may not have even registered and LOVE the effects of Suni, but don't believe that the link can be drawn on what they believe to be limited data. I'm more of the belief it's someone with a financial interest in removing any inkling of Ampakines' potential link to cancer. For some vendors, it could mean their livelihood.

[ThePhoeron]

Who is IP 2.30.51.94? He has been repeatedly censoring safety related information from the Wikipedia article on sunifiram. He has been deleting neutrally-stated well-sourced info about PKCa and cancer - perhaps he thinks it's better that you guys didn't know it, or that NMDA agonists can cause overactivation of NMDAR. He is wasting my time and I'll have to call a Wikipedia administrator.

It's an IP address for London, England. Many handy sites come up in a search for 'ip address locator'.

Does that help narrow down the list at all?

[DorianGray]

In regard to the safety and cancer issue, I would be cautious with assertions, in both directions. Just the activation of a kinase and a specific pathway, does not mean, that you will get cancer from it. Several drugs do activate or supress cancer related proteins (which mostly are from pathways affecting proliferation, tumor suppression, apoptosis etc.) and receptors, like IGFR, the Akt pathway, but they do not cause cancer. Or more simple: They do not initiate cancer. They may have effects, which could enhance cancer formation or support the growth and further development of (pre-)malignant cells and so perhaps elevate the risk for developing cancer, but they usually do not initiate it.

It is not that simplistic as many think it is. It is not enough to induce a short, strong expression of such a protein and trigger cancer development. Perhaps through constant viral induced overexpression. Also the differences between various isoforms of PKC should be considered. Overexpression of PKCepsilon seems to lead to the formation of neoplastic leasons in mice prostata, while alpha and delta do induce cell death in prostata cancer. It is really not that simplistic, as there are a lot of other pathways, dependent and independent, which are involved in the regulation of proliferation and cell death.

Although I like to read Isochromas posts, especially for their illustrative manner and his love for the detail, he really does underestimate the danger and risks of experimental drugs. He is also not the only one, me included, as I have experimented with sunifiram too.

By the way I like it.

[Climactic]

In regard to the safety and cancer issue, I would be cautious with assertions, in both directions. Just the activation of a kinase and a specific pathway, does not mean, that you will get cancer from it. Several drugs do activate or supress cancer related proteins (which mostly are from pathways affecting proliferation, tumor suppression, apoptosis etc.) and receptors, like IGFR, the Akt pathway, but they do not cause cancer. Or more simple: They do not initiate cancer. They may have effects, which could enhance cancer formation or support the growth and further development of (pre-)malignant cells and so perhaps elevate the risk for developing cancer, but they usually do not initiate it.

It is not that simplistic as many think it is. It is not enough to induce a short, strong expression of such a protein and trigger cancer development. Perhaps through constant viral induced overexpression. Also the differences between various isoforms of PKC should be considered. Overexpression of PKCepsilon seems to lead to the formation of neoplastic leasons in mice prostata, while alpha and delta do induce cell death in prostata cancer. It is really not that simplistic, as there are a lot of other pathways, dependent and independent, which are involved in the regulation of proliferation and cell death.

Yes, but the question is - are you willing to needlessly gamble your brain and your life for it (with continued long-term consumption)?

It may help to think in terms of percentages. For example, you might argue that you may be willing to take up to a 3% risk of malignancy, and the risk of malignancy from sunifiram is say 1%, with the baseline risk being 0.25%. (These numbers are made up.)

Looking at cancer as a binary thing is an old and dated way of looking at it. The modern way of looking at it is in terms of how fast it grows and spreads.

Edited by Climactic, 20 June 2013 - 06:41 PM.

[DorianGray]

Yes, but the question is - are you willing to needlessly gamble your brain and your life for it (with continued long-term consumption)?

Gamble my brain and life by doing what? You have not shown anything substantial, any kind of connected evidence, or by experimental data supported theory in case of sunifiram and cancer. So why are we already speaking about gambling? PKCa is also activated by thought and memorizing processes, should I now stop learning?

Such a simplistic view on the complexity of intra- and interworking pathways regarding the development of cancer is even worse, then the binary way you mentioned.

[xsiv1]

The IP address won't have much to do with the user's actual location if they're aware of how to bypass that. The same precautions should have been held in the first place with a compound that's went untested in humans, whether it can be linked to cancer or not. The same goes for any of the numerous research chemicals out there - in my opinion of course. It's often the false assumptions of others or rather the short foresight that leads them to believe, well, if this person didn't die or fall down barfing, then I probably won't either without thinking of what the long-term ramifications of consistent use may be.

Edited by xsiv1, 20 June 2013 - 06:55 PM.

[DorianGray]

Or just to make it more clear: http://www.ncbi.nlm....pubmed/11602180
This is a study showing, that testosterone does increase the activity of PKCa. PKCa alpha is overexpressed in some cancers.
Ergo testosterone does induce or elevate the risk for cancer? (it does probably not, but this is still a subject of discussion)

PKCa is just involved in a response to testosterone, which does initiate some growth related pathways. Thats it.

Unrelated to this specific debate, yes we are all taking some risk by using substances, which were not evaluated in human studies for long term risk potential. Sunifiram is very probably not cancerogenic on its own, if the short term activation of a growth associated kinase does really represent a risk may and should be discussed, but without causing to much panic. Rather it is important to provide data and clear connected facts, which do support the one or the other opinion.

Edited by DorianGray, 20 June 2013 - 07:10 PM.

[ThePhoeron]

The IP address won't have much to do with the user's actual location if they're aware of how to bypass that.

Very true -- also, people on the forum don't necessarily state their location accurately, and it may not even be someone registered on the forum. As you and Climactic have said, it may very well be someone with a vested financial interest in selling the product. Wasn't there a new UK retailer that recently added Sunifiram to their catalogue?

[Nattzor]

Yes, but the question is - are you willing to needlessly gamble your brain and your life for it (with continued long-term consumption)?

Gamble my brain and life by doing what? You have not shown anything substantial, any kind of connected evidence, or by experimental data supported theory in case of sunifiram and cancer. So why are we already speaking about gambling? PKCa is also activated by thought and memorizing processes, should I now stop learning?

Such a simplistic view on the complexity of intra- and interworking pathways regarding the development of cancer is even worse, then the binary way you mentioned.

I agree fully with this. There is nothing scientific about 3 people on a random forum saying things, but not having any proofs. People have felt cranial pressure and headaches from piracetam too, that haven't stopped many from trying it. I also think the wiki page shouldn't have that info, it's just speculations that has not been proven. We've had (crazy) people on the forum taking WAAAAAAAAAAY more with other stims and not experiencing anything like that. It might just be "super responders" or something else. The first dude who reported it has taken TONS of supplements, no idea how they have been interacting.

[Climactic]

Or just to make it more clear: http://www.ncbi.nlm....pubmed/11602180
This is a study showing, that testosterone does increase the activity of PKCa. PKCa alpha is overexpressed in some cancers.
Ergo testosterone does induce or elevate the risk for cancer? (it does probably not, but this is still a subject of discussion)

PKCa is just involved in a response to testosterone, which does initiate some growth related pathways. Thats it.

Unrelated to this specific debate, yes we are all taking some risk by using substances, which were not evaluated in human studies for long term risk potential. Sunifiram is very probably not cancerogenic on its own, if the short term activation of a growth associated kinase does really represent a risk may and should be discussed, but without causing to much panic. Rather it is important to provide data and clear connected facts, which do support the one or the other opinion.

The link between testosterone and cancer is well theorized, although apparently not sufficiently studied. It is not up to you to say "probably does not", in the same way that I cannot say "probably does" for sunifiram.

There is presumably a threshold of PKCa, that if crossed, will contribute greatly to malignancy. Whether you cross this threshold may depend on the extent of your sunifiram and glutamatergics use. If you're only correcting deficiencies or overclocking just a little, it's probably safer than if you're dosing it 2x daily for life with glutamatergics.

Everybody knows not to overdo dopamine, serotonin, gaba, or acetylcholine. Why should we not exercise the same caution for glutamate receptor drugs? Numerous substances in our daily lives are such glutamatergics, including racetams, many stimulants, and various supplements.

Yes, I believe in presenting clear facts as they are. The risks people take with their lives are up to them.

Edited by Climactic, 20 June 2013 - 07:23 PM.

[3AlarmLampscooter]

The IP address won't have much to do with the user's actual location if they're aware of how to bypass that. The same precautions should have been held in the first place with a compound that's went untested in humans, whether it can be linked to cancer or not. The same goes for any of the numerous research chemicals out there - in my opinion of course. It's often the false assumptions of others or rather the short foresight that leads them to believe, well, if this person didn't die or fall down barfing, then I probably won't either without thinking of what the long-term ramifications of consistent use may be.

Wikipedia blocks any proxies they figure out are proxies. I port scanned this IP, and it doesn't appear to be a proxy off hand.

[ThePhoeron]

By the way---just noticed New Star has a limited quantity of Unifiram available, for those interested in checking out other ampakines.

[RawProduce]

The IP address won't have much to do with the user's actual location if they're aware of how to bypass that. The same precautions should have been held in the first place with a compound that's went untested in humans, whether it can be linked to cancer or not. The same goes for any of the numerous research chemicals out there - in my opinion of course. It's often the false assumptions of others or rather the short foresight that leads them to believe, well, if this person didn't die or fall down barfing, then I probably won't either without thinking of what the long-term ramifications of consistent use may be.

Wikipedia blocks any proxies they figure out are proxies. I port scanned this IP, and it doesn't appear to be a proxy off hand.

Stop port scanning me, kthnx.

[3AlarmLampscooter]

The IP address won't have much to do with the user's actual location if they're aware of how to bypass that. The same precautions should have been held in the first place with a compound that's went untested in humans, whether it can be linked to cancer or not. The same goes for any of the numerous research chemicals out there - in my opinion of course. It's often the false assumptions of others or rather the short foresight that leads them to believe, well, if this person didn't die or fall down barfing, then I probably won't either without thinking of what the long-term ramifications of consistent use may be.

Wikipedia blocks any proxies they figure out are proxies. I port scanned this IP, and it doesn't appear to be a proxy off hand.

Stop port scanning me, kthnx.

Alright, so you've seen nothing but positive effects from Sunifiram (as have I), but why are you removing well sourced statements from wikipedia?