34 replies to this topic

[fluidity]

After reading many of the reports on the sunifiram thread from last year I want to ask if anyone still uses the compound? Has anyone used it for over a week? A month? Has tolerance kicked in? Any significant benefits to cognition?

 

I would like to have some of these questions answered here rather than on the other thread for the sake of convenience. 

[jly1986]

Yes, many, many many months, no tolerance, no adverse effects, written extensively about it in other threads.

[fluidity]

Thanks do we have a consensus on why certain people had adverse effects while others didn't?? Could sunifiram be a compound that shouldn't be stacked with anything that also affects the glutamatergic system?

[Geoffrey]

I think it's wise not to stack with any glutamatergics and especially not with glutamate itself. I did find tolerance set in with sunifiram, unfortunately, although after a washout period I can reset to baseline quite easily. I've never had any of the effects Climactic reported -- i.e. long-lasting headache and what he thinks is excitotoxicity.What I did notice was a greatly increased need for a choline source to prevent the usual choline-depletion headache of the racetams/racerams. I've stacked with moderate amounts of (ar)modafinil without issue, but others believe this is a potentially excitotoxic combination, so exercise extreme caution. I also have come to believe that the current dosing recommendations of sunifiram are too high -- I find it to be very potent at about 2mg. For me, sunifiram works best for occasional use, as it builds up too fast if taking it every day. But everyone's mileage varies, so experiment and start with very low doses and work up (if needed).

[Jeoshua]

I've used it for a few weeks now, at 5-10mg, three times per day. No tolerance as of yet, and yes it does place a lot higher demand on the cholinergic pathways than it might suggest, by weight. I have noticed that a lot of the people complaining of bad effects were using upwards of 30mg per dose, or were using the provided spoonlet and not actually measuring their doses. With something active at such a low dose, that is a Bad Idea^TM.

One thing I would mention is that low doses of NMDA antagonists, such as 25% RDA of Magnesium or Zinc, or around 25mg of Agmatine Sulfate, seem to remove some of the stimulation feel while still retaining the focus and memory effects.

Edited by Jeoshua, 12 April 2014 - 04:59 PM.

[CholinergiX]

I gave it to few people, some have long-term nootropic effect from few doses, even measurable after more than 6 months, but in some people it have adverse effects.

 

I have permanent adverse effect from this compound, I took it for in 14 days 0.5mg once daily in August 2013 , it was good nootropic, but I have oversensitivity to caffeine and few other things since then(previously caffeine had no effect), I have sometimes very bad sharp temple headaches, I think it's grom GABA depletion because sulbutiamine solves this but not choline sources. CDP choline also can trigger that bad headache, and brahmi as it increases usage of GABA.

1 my friend have exactly same adverse effect and she had only 1 dose of 5mg.

 

some theories:

I think there is some connection with mercury poisoning and negative reactions. Maybe because mercury is destroying thiamine.

GABA depletion -> brain protecting itself from increased glutamate activity so it releases more GABA and deplete thiamine and other needed cofactors.

Both things in result completely deplete thiamine and this results into increased glutamate activity, sharp headache and possible neurotoxicity.

 

sorry my english

[formergenius]

Speaking of safety concerns, does anyone know why there are a bunch of Lithium references in the wiki article for the statement that Sunifiram protects against NDMAR excitotoxicity?

[Jeoshua]

Good question.

Actually I think you'll note that it's under "alternatives", and specifies that Lithium is an alternative to Sunifiram which protects against excitotoxicity.. That's honestly a section that should be revamped by someone with more knowledge about what "alternative" really means. Lithium is nothing like Sunifiram in effect, dosage, or mechanism. It is not an alternative, although low doses of it might make for a decent adjunct to Sunifiram usage to protect against excitotoxicity (much like I've found Magnesium, Zinc, and Agmatine to be).

As a matter of fact, since I have both of these substances right here, right now, and use them separated, I think I'll perform an n=1 personal study, right now. I've just taken Lithium Orotate 5mg (pill form), and Sunifiram 15mg (sublingual), and Alpha-GPC 500mg. Let's see how this plays out.

---

So far, 10 minutes in, I feel the Sunifiram coming on. Also, a slight headache that should subside once the GPC starts getting metabolized. I notice nothing except a touch of saltiness in the back of my throat from the Lithium (which is normal). Possibly the dosage of Lithium was too low to have any effects, but so far I feel nothing different than normal Sunifiram.

---

20 minutes, and as predicted, the choline has taken effect. I no longer have the mild headache. I also feel no real difference... wait. A touch of dizziness? That would be the Lithium Orotate. I always feel a slight lightheadedness from it. I normally take it before bed as this usually sweeps me off to sleep.

---

30 minutes. It does seem that the Lithium Orotate is having similar effects on the feel and my awareness as the other NMDA antagonists I have tried in conjunction with Sunifiram. I feel very clear headed, but not quite as stimulated as just Sunifiram + a choline source. The longer half life of Lithium might be useful, here, since one would only have to take a very small amount once per day, and be able to redose Sunifiram the requisite amount of times over the course of the day.

---

40 minutes. I've been trying to ignore it, but I have developed a bit of a tic in my eye, and a definite stomache upset. My mind doesn't feel as clear anymore, and I'm beginning to feel a bit woozy, actually. I take it back, if this is due to the combination of Lithium Orotate and Sunifiram, I do not think they are a good combo. Either way, I don't feel right.

---

50 minutes, and this will be the last update on this unless something drastic happens. It seems that somewhere around 40 minutes there was an interaction between the Sunifiram, the Alpha-GPC, and the Lithium Orotate. I did not like it. That has passed, I feel only a mild stomache upset, but the clear headedness is gone. I still feel the slight pressure that tells me the Sunifiram is still going strong, but I also feel a bit foggy. It's almost like the effects I get with a slight overdose of Sunifiram, but without the stimulation. It almost feels as if they are both in my mind right now, but the Lithium is cancelling out the Sunifiram. I haven't tested my memory, but it doesn't feel drastically improved. My typing speed, however, is.

Also, I feel a bit itchy. That happens with Lithium sometimes, or ALCAR, and I take it as a sign that BDNF has been released, as it seems to happen with me on almost everything that causes BDNF expression.

Overall, this stack might be good to prevent excitotoxicity, and to increase BDNF, but the side effects are somewhat uncomfortable. I'll be high-dosing on some Magnesium and a little Agmatine to try and cancel the effects (which normally works well).

Edited by Jeoshua, 12 April 2014 - 09:31 PM.

[normalizing]

never heard of zinc protecting against excitotoxicity. it probably matters what is chelated with zinc to have any good brain bioavailability anyway....

[Jeoshua]

Well it is a mild NMDA antagonist, as is Magnesium, and so I place it in the same category for this purpose, only. I have no studies to back it up except my own, and I have noticed it has much the same subjective effect on the effacity and mental feel of Sunifiram, cutting it's edge and making the ride a bit smoother.

[fluidity]

I gave it to few people, some have long-term nootropic effect from few doses, even measurable after more than 6 months, but in some people it have adverse effects.

 

I have permanent adverse effect from this compound, I took it for in 14 days 0.5mg once daily in August 2013 , it was good nootropic, but I have oversensitivity to caffeine and few other things since then(previously caffeine had no effect), I have sometimes very bad sharp temple headaches, I think it's grom GABA depletion because sulbutiamine solves this but not choline sources. CDP choline also can trigger that bad headache, and brahmi as it increases usage of GABA.

1 my friend have exactly same adverse effect and she had only 1 dose of 5mg.

 

some theories:

I think there is some connection with mercury poisoning and negative reactions. Maybe because mercury is destroying thiamine.

GABA depletion -> brain protecting itself from increased glutamate activity so it releases more GABA and deplete thiamine and other needed cofactors.

Both things in result completely deplete thiamine and this results into increased glutamate activity, sharp headache and possible neurotoxicity.

 

sorry my english

How are you feeling now? Also are you positive that the adverse effects you felt recently are solely from sunifiram? And how does mercury poisoning play a role in all of this?

Edited by fluidity, 13 April 2014 - 02:05 AM.

[formergenius]

Ha, didn't see that Jeoshua! Thanks for pointing that out.

[CholinergiX]

 

I gave it to few people, some have long-term nootropic effect from few doses, even measurable after more than 6 months, but in some people it have adverse effects.

 

I have permanent adverse effect from this compound, I took it for in 14 days 0.5mg once daily in August 2013 , it was good nootropic, but I have oversensitivity to caffeine and few other things since then(previously caffeine had no effect), I have sometimes very bad sharp temple headaches, I think it's grom GABA depletion because sulbutiamine solves this but not choline sources. CDP choline also can trigger that bad headache, and brahmi as it increases usage of GABA.

1 my friend have exactly same adverse effect and she had only 1 dose of 5mg.

 

some theories:

I think there is some connection with mercury poisoning and negative reactions. Maybe because mercury is destroying thiamine.

GABA depletion -> brain protecting itself from increased glutamate activity so it releases more GABA and deplete thiamine and other needed cofactors.

Both things in result completely deplete thiamine and this results into increased glutamate activity, sharp headache and possible neurotoxicity.

 

sorry my english

How are you feeling now? Also are you positive that the adverse effects you felt recently are solely from sunifiram? And how does mercury poisoning play a role in all of this?

 

 

I feel good now, because I am taking magnesium everyday and sometimes sulbutiamine, maybe once a week...

It is definitely from sunifiram, I never had this type of headache before.

Mercury is known to destroy thiamine.

[thedarkbobo]

Effects cumulated for me, and I think it changed my brain in the long term in some way. I'd say it made me more open to people and able to process short term info faster. On the downside I think my memory is bit worse now, or some kind of fogged. It all might be placebo.

I've taken unifiram in high dose(two green mini scoops provided by NSN) and have unpleasant feeling from time to time in last two days. It diminished when I've taken choline or noopept.

[fluidity]

 

 

I gave it to few people, some have long-term nootropic effect from few doses, even measurable after more than 6 months, but in some people it have adverse effects.

 

I have permanent adverse effect from this compound, I took it for in 14 days 0.5mg once daily in August 2013 , it was good nootropic, but I have oversensitivity to caffeine and few other things since then(previously caffeine had no effect), I have sometimes very bad sharp temple headaches, I think it's grom GABA depletion because sulbutiamine solves this but not choline sources. CDP choline also can trigger that bad headache, and brahmi as it increases usage of GABA.

1 my friend have exactly same adverse effect and she had only 1 dose of 5mg.

 

some theories:

I think there is some connection with mercury poisoning and negative reactions. Maybe because mercury is destroying thiamine.

GABA depletion -> brain protecting itself from increased glutamate activity so it releases more GABA and deplete thiamine and other needed cofactors.

Both things in result completely deplete thiamine and this results into increased glutamate activity, sharp headache and possible neurotoxicity.

 

sorry my english

How are you feeling now? Also are you positive that the adverse effects you felt recently are solely from sunifiram? And how does mercury poisoning play a role in all of this?

 

 

I feel good now, because I am taking magnesium everyday and sometimes sulbutiamine, maybe once a week...

It is definitely from sunifiram, I never had this type of headache before.

Mercury is known to destroy thiamine.

 

I also want to ask did you ever take an other nootropics/stimulants along with sunifiram?

And by mercury poisoning do you mean there was mercury in your sunifiram? Or that you suffered mercury poisoning from other sources?

[CholinergiX]

I've been taking sunifiram only in that time, and mercury poisoning is from other sources.

[fluidity]

Has anyone noticed any positive changed from suniifram? Either permanent or short term?

[Jeoshua]

The only downside and warning that I could give about Sunifiram after extensive testing is this:

 

Use a scale. Tolerance and bad effects only happen in the >30mg range, and that is really hard to eyeball. The powder is pretty dense, can clump, and you want to make sure you're getting the right dose. 10-15mg should be tops. 1-5mg is a good place to start.

[Duchykins]

I still take Sunifiram, not daily since I'm not taking daily noots at the moment, but I did take it for several weeks straight during the initial trial and I generally liked it. My doses were never more than 5mg at a time, sometimes twice a day, and I like it with 5-10mg coluracetam. No decrease in effectiveness noted. Small occasional doses of citicoline, less than 100mg. No additional choline. I usually have to take extra thiamine, cobalamin, zinc and methionine with noots to combat heightened histamine.


On HEADACHES:

If you are getting headaches with a nootropic and more choline does not help, then chances are your headache is coming from glutamate excess or imbalance of neurotransmitters. This can also drive up your histamine which brings its own problems, even if you have no history of histamine intolerance. In these cases, GABA and/or serotonin are too low and you should take steps to mitigate this when using noots. The GABA-glutamate balance is important, as is serotonin-norepinehrine. If glutamate gets too high it can drive down your GABA, additionally it is common for people to take stimulants like caffeine with their noots, caffeine interferes with GABA as well. Several GABAergic chemicals can be used to prevent glutamate excitoxicity.

For the guy musing about mercury poisoning - NO. Thiamine helped his headache because THIAMINE IS PART OF THE GABA SYSTEM. Too much glutamate can overwhelm GABA, rendering it ineffective. Nearly anything that boosts GABA can help for symptoms caused by excess glutamate.

Additionally, if anyone is noting increased irritability, anger, and increased difficulty controlling either, this is a strong indicator of excess norepinephrine, too-low serotonin, a state that is extremely easy to create in oneself by increasing their glutamate, acetylcholine and dopamine with nootropics and related supplementation -- without taking steps to counter it and attempt to keep a balance in neurotransmitters. Low serotonin is also an invitation for headaches to develop.

Edited by Duchykins, 17 April 2014 - 12:21 AM.

[fluidity]

Thanks for the info everyone. In any case I'm most likely going to try it once I'm done with my other stack of nootropics. 

[axonopathy]

What is the difference between sunifiram and domoic acid? Both directly activate AMPA receptors. Domoic acid is excitotoxic at very low doses, i.e., 50 micrograms. Moreover sunifiram is also a positive allosteric modulator of NMDAr. This two-pronged activity of sunifiram, whereby suni enhances acitivity at BOTH AMPA and NMDA receptors is almost sure to necrotize your hippocampus. Recall that piracetam allosterically enhances AMPAr activity; sunifiram is a direct agonist at AMPAr, just like α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and domoic acid, both of which are well-characterized excitotoxins and are used in animal models to induce neurodegeneration. It is also unlikely that you, the subject of your own self-experimentation will be able to detect hippocampal sclerosis. Cognitive reserve will likely compensate initially, but then as you deplete this reserve capacity during the aging process, cognitive deficits will be unmasked. 

 

Best,

RNApolymerase

[Jeoshua]

Sunifiram and Domoic acid don't have the same method of activity. Domoic acid acivates the Kainate receptors in the brain, a trick that Sunifiram doesn't.

[normalizing]

plot thickens.... [tense dramatic music]

[Geoffrey]

sunifiram is a direct agonist at AMPAr, just like α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and domoic acid

 

Do you have any evidence/research citation to show that sunifiram is a direct AMPAr agonist? I'm not aware of anything in the existing literature.

[Jeoshua]

Even with my great Google Fu, I could not find any actual studies that show Sunifiram being a direct agonist of AMPA, especially in comparison to AMPA, itself, or domoic acid.
 
I did, however, find a bunch of posts from people who had no studies to back anything they were saying up. Claims, not facts. Declarations, not science.
 
Piracetam has been known for decades, and we still have no proof or information on how, exactly it works. And you're claiming that this new drug which hasn't even had a good human trial published in a peer reviewed journal, that we know more about this one than we know about Piracetam? Your claims of sclerosis sound an awful lot like the claims people were making about MDMA causing similar lesions, even tho they had not and never were found in a single human being in any actual study, or the claims of teratogenic activity in LSD causing children to be born with webbed feet or hydroencephaly.
 
Please state your sources, give some links, or stop throwing around unsubstantiated claims about a substance we know so little about.
 
---
 
Oh, and you should note that AMPA receptor agonism causes an influx of Na⁺ and K⁺, while the excitoxic mechanism you are talking about requires an unchecked influx of Ca²⁺⁺ ions.

Edited by Jeoshua, 18 April 2014 - 02:54 PM.

[CholinergiX]

(...)

On HEADACHES:

If you are getting headaches with a nootropic and more choline does not help, then chances are your headache is coming from glutamate excess or imbalance of neurotransmitters. This can also drive up your histamine which brings its own problems, even if you have no history of histamine intolerance. In these cases, GABA and/or serotonin are too low and you should take steps to mitigate this when using noots. The GABA-glutamate balance is important, as is serotonin-norepinehrine. If glutamate gets too high it can drive down your GABA, additionally it is common for people to take stimulants like caffeine with their noots, caffeine interferes with GABA as well. Several GABAergic chemicals can be used to prevent glutamate excitoxicity.

For the guy musing about mercury poisoning - NO. Thiamine helped his headache because THIAMINE IS PART OF THE GABA SYSTEM. Too much glutamate can overwhelm GABA, rendering it ineffective. Nearly anything that boosts GABA can help for symptoms caused by excess glutamate.
(...)

 

Mercury has very big influence on CNS, increases levels of glutamate etc. I think sunifiram long-term upregulates AMPA/NMDA receptor, or does some epigenetic changes, thats why it causes these effects to me even after 8 months. So there is some synergy going on, sunifiram+mercury=excitotoxicity under right circumstances.

 

-CholinergiX

[Duchykins]

(...)
On HEADACHES:

If you are getting headaches with a nootropic and more choline does not help, then chances are your headache is coming from glutamate excess or imbalance of neurotransmitters. This can also drive up your histamine which brings its own problems, even if you have no history of histamine intolerance. In these cases, GABA and/or serotonin are too low and you should take steps to mitigate this when using noots. The GABA-glutamate balance is important, as is serotonin-norepinehrine. If glutamate gets too high it can drive down your GABA, additionally it is common for people to take stimulants like caffeine with their noots, caffeine interferes with GABA as well. Several GABAergic chemicals can be used to prevent glutamate excitoxicity.

For the guy musing about mercury poisoning - NO. Thiamine helped his headache because THIAMINE IS PART OF THE GABA SYSTEM. Too much glutamate can overwhelm GABA, rendering it ineffective. Nearly anything that boosts GABA can help for symptoms caused by excess glutamate.
(...)

 
Mercury has very big influence on CNS, increases levels of glutamate etc. I think sunifiram long-term upregulates AMPA/NMDA receptor, or does some epigenetic changes, thats why it causes these effects to me even after 8 months. So there is some synergy going on, sunifiram+mercury=excitotoxicity under right circumstances.
 
-CholinergiX

You'll get no argument from me on that.

[Duchykins]

Do you mind if I ask how old you are? And if other GABAergics had the same effect as thiamine?

Edited by Duchykins, 20 April 2014 - 09:15 PM.

[CholinergiX]

20 years old, no gabaergics, only bacopa, and it increases need for thiamine. THIAMINE IS ESSENTIAL, or derivates of...

 

[mattblack UK]

Tried some for the first time this week. Yesterday I dosed 10mg in the morning on an empty stomach and skipping breakfast, and felt absolutely nothing. Early afternoon yesterday I took an additional 15mg and still felt nothing.

 

Today I had a 5 egg omelette for breakfast then had a dose of 20mg 3 hours later at 10am. This time I definitely felt something - a slight stimulation and possibly some very slight euphoria building up inside. It also made me more sensitive to light and found the glare of my computer monitor and the indoor lighting too much. In terms of actual enhancement of anything - well.... I didn't notice anything else. I took an additional 10mg mid afternoon but haven't felt a thing from that other than an eventual mild headache. I certainly haven't felt this sunny colour enhancement that many people have noted. I'm only trialling these at the moment for a week or so. I'll make a decision then on whether it's' worth any further investment.