95 replies to this topic

[GetOutOfBox]

I know people here almost universally reccomend cycling Sulbutiamine, however, I've been looking through the major studies regarding it, and they all seem to be for chronic usage, at least 2 weeks, often longer.

Reading the listed effects on Wikipedia, it sounds like something definitely worth taking regularly:

"Sulbutiamine is a lipophilic molecule that crosses the blood–brain barrier more easily than thiamine. Its metabolism in the brain leads to an increase in the levels of thiamine and thiamine phosphate esters.^[1][21] While the exact mechanism of action of sulbutiamine is unknown, it is thought to occur through the upregulation of the reticular activating system, which is the center of arousal and motivation in the brain.^[4] The administration of sulbutiamine potentiates cholinergic activity in the hippocampus.^[14] It also potentiates glutamatergic activity in the prefrontal cortex through a reduction in the density of kainate glutamate receptors, which may occur in response to a modulation of intrasynaptic glutamate.^[22] The facilitation of central glutamatergic transmission is a likely explanation for the ability of sulbutiamine to improve memory.^{[23][24][25][26]} In addition to its action on cholinergic and glutamatergic transmission, the administration of sulbutiamine reduces the release of dopamine in the prefrontal cortex, which increases the density of D₁ dopamine receptors through a compensatory mechanism.^[22] The modulation of dopaminergic transmission may also contribute to the ability of sulbutiamine to improve memory.^[27][28][29] A possible explanation for the pharmacodynamics of sulbutiamine is the increased availability of thiamine triphosphate (ThTP). Although the full physiological role of ThTP is unknown, it is an integral component of synaptosomal membranes,^[30] participates in the phosphorylation of proteins,^[31] and activates chloride channels that have a large unit conductance.^[32] The activation of chloride channels by ThTP may be involved in the modulation of receptor binding."

People seem to report that in the short term, it causes them huge boosts in motivation, but if they use it for more than a day or two in a row, they disappear. This seems to be the basis for the "builds tolerance really fast" theory, however it seems more likely to me that people reporting such effects are actually experiencing the placebo effect. I find that whenever the placebo effect is responsible for amazing effects, it's usually on the first day I take it, since I'm regularly thinking "Am I feeling anything?". Usually by the next day I don't think of it nearly as much. If the effects seem to persist despite the novelty fading, then I assume it's likely producing genuine benefits. However, if I suddenly stop feeling anything, it's likely just the fact that the initial excitement has worn off.

It seems unlikely that such tolerance could build so quickly to a non-stimulant (it's literally just a B vitamin that is capable of directly crossing the BBB), even aggressive medications like dopamine/GABA agonists usually take at least a week to produce any real tolerance/addiction. In fact, the evidence seems to point to it's effects being more subtle, proactive long term effects, such as modulating rather than dramatically increasing neurotransmitter activity. It also seems to upregulate several systems, suggesting that it could in fact have temporary negative affects (as a result of reducing dopamine), but with positive long term effects. Personally, I'm much more interested in upregulating receptors than finding various agonists. It seems like a more sustainable, proactive approach.

So what I'm saying is, that the temporary huge motivation boosts people are actually just the result of the placebo effect (or amplified by it), and that the real benefits arrive after at least 2 weeks usage. One other possible explanation is that people who have a mild B1 deficiency experience a rapid correction of that deficiency, as Sulbutiamine provides B1 directly to the brain bypassing intermediary metabolic processes, whereas traditional supplements require that it be transported indirectly to the brain, and even still according to this passage from Wikipedia's Thiamine article, it's normal form has a low availability to the brain:

"Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion.^[1] The brain requires a much greater amount of thiamine than in other cells of the body. Much of ingested thiamine never reaches the brain because of passive diffusion and the blood brain barrier. About 80% of intracellular thiamine is phosphorylated and most is bound to proteins. In some tissues, thiamine uptake and secretion appears to be mediated by a soluble thiamine transporter that is dependent on Na⁺ and a transcellular proton gradient."

Hence when Sulbutiamine is taken, this deficiency is immidietly corrected, allowing previously low neurotransmitters to return to baseline, which to someone who had dealt with neurotransmitter depletion for a long period of time, would feel amazing, almost euphoric at first (sort of like when you manage to clear clogged sinuses; an intense feeling of relief), but you would quickly adjust to the effects. That's not to say they're not still there, you just stop noticing the fact that your mood has stabilized. This also explains why some people react dramatically while others do not; someone who already has sufficient thiamine levels in the brain would probably still notice some benefits (according to the studies), but they would be much more subtle (though still quite interesting, it seems to positively affect several systems).

In my own personal experience taking Sulbutiamine, I noticed only a mild immediate affect, but ever since I started take a normal dose daily (200 mg morning, 200 mg afternoon, 400 mg total), I've been feeling a lot better lately. More stable (I have ADD-Pi, as well as mild comorbid depression at times). This seems to line up with the expected effects from the various literature. Just keep in mind that as it's fat soluble, it should be taken with a fatty food (but low-fiber, as foods with lots of fiber can reduce absorption when taken simultaneously with medication).

[xsiv1]

I've noticed the same thing with sulbutiamine in that, if I use it for more than 3 days in a row, I seem to develop a tolerance or, perhaps more accurately, the effects of it have been blunted to the point where any 'noticeable' focus/alertness is not the same as the initial days. So, having said that..how would you explain why taking 400mgs at a time produces a much more 'noticeable' lift? I'm not saying that tolerance actually occurs but am curious as to why I'm feeling the initial effects at a higher dose. Perhaps it's providing what is or continues to be a deficiency. In a sense, it could be likened to Vitamin B12. If you look at this...deficiencies are hard for traditional doctors to accurately assess, accurately treat and even to know when to stop or continue treatment. Perhaps some commonalities can be seen in this thread on it: http://forums.better...ed=1#post191131

Edited by xsiv1, 14 February 2013 - 08:03 PM.

[GetOutOfBox]

The thing is, I doubt that it has any immediate effect with the exception of someone who's deficient. I don't see any studies that found an actual dopamine agonist effect, reuptake inhibitor, or stimulating the release of dopamine. The only dopamine effect I've seen linked to it is upregulation of the dopinamergic system, and that would take a few weeks at least to happen. However, since most of the B vitamins are crucial to neurotransmitter synthesis (and overall neurological health), such a fast acting return to baseline levels would probably feel good, as you would go from low dopamine levels to normal.

As for why you're feeling the effects at a higher dose, well, that's just how the placebo effect works. Your mind assumes that more must be better, and hence expect it. I've been taking it for a while, haven't had any issues. I never had any initial effects myself, though I think over time it's contributed to the positive effects of my stack.

[xsiv1]

Hmm. Although I realize how powerful the placebo effect may be, I think it's more complex than that. I've tried all kinds of legal stimulants and maybe one illegal one in my lifetime and sulbutiamine was distinctly different than all of them. Like ALCAR, which is not a stimulant per se, you feel more alert. I felt more alert for sure. Have you ever tried 400mgs at a time? I also find it interesting that you never experienced any initial effects from taking it when you first tried it. I believe you and perhaps it has to do with deficiencies or not but it's one of the reasons I chose to purchase it again. I've been very judicious with it's use based on anecdotal reports.

[GetOutOfBox]

Well ALCAR is a precursor for Acetlycholine, as well as increasing glucose metabolism. So I'd expect it would have fairly noticeable effects. It lowers T4 though, which explains why some people have adverse reactions (exhaustion, brain fog, etc). They probably have mild hypothyroidism to start (or on the lower end of normal, but sub-clinical).

Yep, I've tried various doses of Sulbutiamine with milk (for the fat, as Sulbutiamine is fat soluble), including 200 mg, 400 mg, 600 mg, 800 mg. And yes, at first I did space the doses out based on the advice from the forums. However, after reading the studies that focused on chronic use, I decided to take doses throughout the day every day (400 mg two times a day). It's so cheap, it's sustainable at those doses.

I would say that how it's taken isn't a big deal, as it's very safe. There is no known upper limit in the dose (Though the manufacturer suggests no more than 600, it's often prescribed at more around 800), as the body is very capable of regulating thiamine levels. It's not addictive, and even if there are effects that fade with repeated use, there have definitely been very interesting (good) long term effects, such as upregulating the reticular activating system, which is associated with regulation of arousal and motivation.

[xsiv1]

Interesting. So how long have you been using it every day at 400mgs total? I may give it a whirl for a month or so. Does it ever adversely effect your sleep from what you can tell? Also, any noticeable irritability after 3 consecutive days using it?

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[Raza]

I like the research you dug up about the long-term effects, but like the poster above am dubious that the obvious immediate but quickly fading stimulant effect is all or mostly placebo. When I first took Sulbutiamine I didn't get the effects I expected at all, nor at the doses I expected them at, and what I got came along with unexpected side effects. It's feeling is rather specific, unusual in quality and completely reproducible so long as you wait between doses - which follows a tolerance pattern more than a placebo effect one. Plus, I'm not generally sensitive to placebo effects - I've tried a ton of white powder stimulants that I had similar hopes for with no noticeable effect.

I've also given it to someone else, once, who knew nothing about it except that it was to wake them up, and had them experience a bout of anxiety instead.

Edited by Raza, 15 February 2013 - 07:21 PM.

[GetOutOfBox]

Interesting. So how long have you been using it every day at 400mgs total? I may give it a whirl for a month or so. Does it ever adversely effect your sleep from what you can tell? Also, any noticeable irritability after 3 consecutive days using it?

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About 2 weeks, and I haven't experienced any negative effects. I do make sure to avoid taking it to close to bed, I've been dosing usually at 7:30am and 4pm. I never notice any stimulant effects. Btw, it's from Smart Powders, not some vague source, so I'm fairly certain it's legit.

I like the research you dug up about the long-term effects, but like the poster above am dubious that the obvious immediate but quickly fading stimulant effect is all or mostly placebo. When I first took Sulbutiamine I didn't get the effects I expected at all, nor at the doses I expected them at, and what I got came along with unexpected side effects. It's feeling is rather specific, unusual in quality and completely reproducible so long as you wait between doses - which follows a tolerance pattern more than a placebo effect one. Plus, I'm not generally sensitive to placebo effects - I've tried a ton of white powder stimulants that I had similar hopes for with no noticeable effect.

I've also given it to someone else, once, who knew nothing about it except that it was to wake them up, and had them experience a bout of anxiety instead.

Well I obviously can't say for certain there are no immediate effects, so if you really have spectacular short term effects, perhaps it's worth using it irregularly. However, since I never noticed any immediate effects, and the studies were all regarding long term usage, so I've been using it daily for the alleged long term benefits.

[Dissolvedissolve]

My experience is based on SP brand sulbutiamine at 300-400 mg.

I get a reliably stimulatory effect from it. It seems to be very motivating, rather than energizing. That is, there's little effect on energy, and no noticeable increase in heart rate or blood pressure (I do not have a heart rate monitor, so this is just my subjective opinion in comparison to other stimulants). More importantly, it always leaves me with a headache and pronounced tiredness. It's possible that I have very strange biochemistry, but it has these effects reliably for me.

It should always be noted that a dimer of a molecule does not necessarily have the same properties as each of its components. That is, sulbutiamine should not be presumed to work simply as a source of thiamine. Even if it is just a source of thiamine, its ability to cross the BBB may strongly impact the biosynthesis of various neurotransmitters.

[GetOutOfBox]

It should always be noted that a dimer of a molecule does not necessarily have the same properties as each of its components. That is, sulbutiamine should not be presumed to work simply as a source of thiamine. Even if it is just a source of thiamine, its ability to cross the BBB may strongly impact the biosynthesis of various neurotransmitters.

Well, all thiamine eventually makes it's way into the brain. It's just that normal forms have to pass through several metabolic processes/transporters to eventually diffuse into the brain, hence there's a much, much, lower bioavailability to that specific organ. However, it's still just thiamine. The fact that it permeates the BBB directly doesn't change how it would interact with the brain, just that we're talking a vastly greater supply at once vs normal forms of thiamine. I suspect that the reason for why a lot of people react very positively to it, while others feel little/nothing is that due to the low rates of thiamine availability to the brain vs the rest of the body means that people could theoretically have normal serum levels of thiamine, but a mild deficiency to the brain specifically. Or better put, someone could have no systemic deficiency of thiamine, but not enough to maintain adequate CNS levels. Hence why such a direct supply would produce such dramatic results; in those individuals, a nutritional deficiency would be corrected virtually immidietely, suddenly neurotransmitter levels would surge to normal levels again. However, as you'll often see in people who have such conditions alleviated, they quickly stop actively noticing the benefits.

However, there could be stimulatory effects that we don't know about. The sensation you described does have biological explanations, there are a bunch of different dopamine receptors, some of which produce more CNS stimulatory sensations, such as motivation/mood, when overstimulated, others that produce more PNS (Peripheral Nervous System) effects, such as motor effects (a literal energized feeling, more muscular than motivation).

[Dissolvedissolve]

Well, all thiamine eventually makes it's way into the brain. It's just that normal forms have to pass through several metabolic processes/transporters to eventually diffuse into the brain, hence there's a much, much, lower bioavailability to that specific organ. However, it's still just thiamine. The fact that it permeates the BBB directly doesn't change how it would interact with the brain, just that we're talking a vastly greater supply at once vs normal forms of thiamine. I suspect that the reason for why a lot of people react very positively to it, while others feel little/nothing is that due to the low rates of thiamine availability to the brain vs the rest of the body means that people could theoretically have normal serum levels of thiamine, but a mild deficiency to the brain specifically. Or better put, someone could have no systemic deficiency of thiamine, but not enough to maintain adequate CNS levels. Hence why such a direct supply would produce such dramatic results; in those individuals, a nutritional deficiency would be corrected virtually immidietely, suddenly neurotransmitter levels would surge to normal levels again. However, as you'll often see in people who have such conditions alleviated, they quickly stop actively noticing the benefits.

However, there could be stimulatory effects that we don't know about. The sensation you described does have biological explanations, there are a bunch of different dopamine receptors, some of which produce more CNS stimulatory sensations, such as motivation/mood, when overstimulated, others that produce more PNS (Peripheral Nervous System) effects, such as motor effects (a literal energized feeling, more muscular than motivation).

I mostly agree with you, but I have just a few minor, nitpicky points.

It's not accurate to say "all thiamine eventually makes its way into the brain." Most thiamine is eliminated in urine, and most thiamine in the body is not in the brain. The brain would normally have an extremely small amount of thiamine present - for reference, the total amounts of most NTs in their active forms at any one time is approximately a few mgs (IIRC). So taking hundreds of mgs of thiamine is a major change to the normal equilibrium. Thus, large doses of sulbutiamine overcome the homeostatic balance of the body, which is adapted to the fact that thiamine is water soluble and thus not capable of penetrating the BBB.

There are definitely different kinds and distribution of DA receptors - the literature on DA receptor subtypes is very interesting. But the thing to keep in mind is DA by itself is not stimulatory. Think of the effects of L-DOPA in Parkinson's patients, for instance. DA itself increases willingness to deal with a barrier for a reward. So high DA mice will deal with an obstacle to get a larger reward, and low DA mice will get the small, easily-accessible reward. DA is often associated with energy because many of its mechanisms are shared with NE, which is a metabolite. So when you increase DA or inhibit its reuptake, you're likely affecting NE as well. But those energy-related effects have little to with DA itself.

Edited by Dissolvedissolve, 16 February 2013 - 09:11 AM.

[renfr]

I experimented sulbutiamine for something like 1 month last year but I was mixing it with several racetams, picamilon, etc... so I'm not sure if it did bring effects. Dosage was between 600-900mg.
I remember taking it in the morning after taking GHB in the night one day and I got a huge dopamine rush, I was feeling overmotivated, maybe was it starting to work? I'm not sure if the GHB played a role in that, maybe it did...
Now I'm starting that again (without the GHB though), 600mg sulbutiamine a day, been 3 days, I still feel some stimulant effects for now but I'm more interested in long term effects.
However I won't take more than 600mg as it increases food craving (due to stress, it gives a slight anxiety indeed) though I already took up to 2000mg a day without severe adverse effects.

[xsiv1]

I experimented sulbutiamine for something like 1 month last year but I was mixing it with several racetams, picamilon, etc... so I'm not sure if it did bring effects. Dosage was between 600-900mg.
I remember taking it in the morning after taking GHB in the night one day and I got a huge dopamine rush, I was feeling overmotivated, maybe was it starting to work? I'm not sure if the GHB played a role in that, maybe it did...
Now I'm starting that again (without the GHB though), 600mg sulbutiamine a day, been 3 days, I still feel some stimulant effects for now but I'm more interested in long term effects.
However I won't take more than 600mg as it increases food craving (due to stress, it gives a slight anxiety indeed) though I already took up to 2000mg a day without severe adverse effects.

They still have GHB out on the streets huh? Wow. I remember those days. It can actually be a very therapeutic compound when used as designed. I've heard sodium oxybate is not nearly as euphoric but I thought they were the same chemically. I haven't used sulbutiamine in more than a 400mg dose but I find the lift to come on smooth and disappear quite subtly.

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Edited by xsiv1, 16 February 2013 - 09:22 PM.

[renfr]

I experimented sulbutiamine for something like 1 month last year but I was mixing it with several racetams, picamilon, etc... so I'm not sure if it did bring effects. Dosage was between 600-900mg.
I remember taking it in the morning after taking GHB in the night one day and I got a huge dopamine rush, I was feeling overmotivated, maybe was it starting to work? I'm not sure if the GHB played a role in that, maybe it did...
Now I'm starting that again (without the GHB though), 600mg sulbutiamine a day, been 3 days, I still feel some stimulant effects for now but I'm more interested in long term effects.
However I won't take more than 600mg as it increases food craving (due to stress, it gives a slight anxiety indeed) though I already took up to 2000mg a day without severe adverse effects.

They still have GHB out on the streets huh? Wow. I remember those days. It can actually be a very therapeutic compound when used as designed. I've heard sodium oxybate is not nearly as euphoric but I thought they were the same chemically.

Sent from my MB860 using Tapatalk 2

Nope. I bought GBL from a reliable seller within the EU then converted it myself with sodium hydroxyde, it's a very simple reaction.
I still have some GBL now, I use it very rarely therefore I don't convert it to GHB anymore.
The first time I took GHB? Yes it was extremely euphoric, pure euphoria if you ask me but then it wears off pretty quickly and you only get the anti-anxiety/alcohol buzz effect.
GHB receptors downregulate pretty quickly, and even after months of GHB abstinence I am unable to recreate that euphoric effect I first had.
Sodium oxybate = Sodium GHB, it's exactly the same thing, most of GHB is bound with sodium.

[renfr]

Concerning the sulbutiamine :
Also I remember that yesterday I was starting an exercise but only went through one question, incredibly the day after I managed to remember all the data of the exercise without looking at the paper. I usually recall some facts but not all of them, here it was really all of them, I guess sulbutiamine is starting to have effects.

When compared to control subjects, sulbutiamine treated mice learned the task at the same rate in a single session but showed greatly improved performance when tested 24 hr after partial acquisition of the same task.

I guess this statement is quite true.
Also I've read that a bodybuilder experienced wild headaches after several months of use, according to this study, this could be because of choline depletion (which causes headaches) :

Parallel neurochemical investigations showed that the treatment induced a slight (+ 10%) but significant increase in hippocampal sodium-dependent high affinity choline uptake.

Therefore I think that supplementing choline along with sulbutiamine is recommended. (not too much though)

There's also no noticeable difference between Arcalion and the sulbutiamine I bought from SP, it's the same strenght to me.

[GetOutOfBox]

Well, all thiamine eventually makes it's way into the brain. It's just that normal forms have to pass through several metabolic processes/transporters to eventually diffuse into the brain, hence there's a much, much, lower bioavailability to that specific organ. However, it's still just thiamine. The fact that it permeates the BBB directly doesn't change how it would interact with the brain, just that we're talking a vastly greater supply at once vs normal forms of thiamine. I suspect that the reason for why a lot of people react very positively to it, while others feel little/nothing is that due to the low rates of thiamine availability to the brain vs the rest of the body means that people could theoretically have normal serum levels of thiamine, but a mild deficiency to the brain specifically. Or better put, someone could have no systemic deficiency of thiamine, but not enough to maintain adequate CNS levels. Hence why such a direct supply would produce such dramatic results; in those individuals, a nutritional deficiency would be corrected virtually immidietely, suddenly neurotransmitter levels would surge to normal levels again. However, as you'll often see in people who have such conditions alleviated, they quickly stop actively noticing the benefits.

However, there could be stimulatory effects that we don't know about. The sensation you described does have biological explanations, there are a bunch of different dopamine receptors, some of which produce more CNS stimulatory sensations, such as motivation/mood, when overstimulated, others that produce more PNS (Peripheral Nervous System) effects, such as motor effects (a literal energized feeling, more muscular than motivation).

I mostly agree with you, but I have just a few minor, nitpicky points.

It's not accurate to say "all thiamine eventually makes its way into the brain." Most thiamine is eliminated in urine, and most thiamine in the body is not in the brain. The brain would normally have an extremely small amount of thiamine present - for reference, the total amounts of most NTs in their active forms at any one time is approximately a few mgs (IIRC). So taking hundreds of mgs of thiamine is a major change to the normal equilibrium. Thus, large doses of sulbutiamine overcome the homeostatic balance of the body, which is adapted to the fact that thiamine is water soluble and thus not capable of penetrating the BBB.

There are definitely different kinds and distribution of DA receptors - the literature on DA receptor subtypes is very interesting. But the thing to keep in mind is DA by itself is not stimulatory. Think of the effects of L-DOPA in Parkinson's patients, for instance. DA itself increases willingness to deal with a barrier for a reward. So high DA mice will deal with an obstacle to get a larger reward, and low DA mice will get the small, easily-accessible reward. DA is often associated with energy because many of its mechanisms are shared with NE, which is a metabolite. So when you increase DA or inhibit its reuptake, you're likely affecting NE as well. But those energy-related effects have little to with DA itself.

Well that's what I said :P Any form of thiamine will enter the brain, but Sulbutiamine is unique in that it can cross the BBB directly, whereas there is a much lower availability for other forms of thiamine. My point is that the effects of normal thiamine should translate to the effects of Sulbutiamine, we're just talking much more powerful results. But in the end, Sulbutiamine is just thiamine, it shouldn't act any differently.

As for whether dopamine is "stimulatory", it really depends on what kind of effects you're talking about, i.e wakefulness, high attention, etc. Increasing dopamine is by nature stimulating, it is not merely a pleasure compound, but has a multitude of effects on the CNS and PNS, depending on the receptors. Technically no neurotransmitter has a direct connection to "energy levels" as that's in the realm of mitochondria health, ATP production, etc.

[Dissolvedissolve]

Well that's what I said :P Any form of thiamine will enter the brain, but Sulbutiamine is unique in that it can cross the BBB directly, whereas there is a much lower availability for other forms of thiamine. My point is that the effects of normal thiamine should translate to the effects of Sulbutiamine, we're just talking much more powerful results. But in the end, Sulbutiamine is just thiamine, it shouldn't act any differently.

As for whether dopamine is "stimulatory", it really depends on what kind of effects you're talking about, i.e wakefulness, high attention, etc. Increasing dopamine is by nature stimulating, it is not merely a pleasure compound, but has a multitude of effects on the CNS and PNS, depending on the receptors. Technically no neurotransmitter has a direct connection to "energy levels" as that's in the realm of mitochondria health, ATP production, etc.

I think at this point, this confusion is mostly semantic. In any case, I'm just saying that when you have a common substance at an uncommon concentration, that is quite different from having it at its typical concentration. So an obvious example would be that if you drink gallons of water back-to-back, it will literally kill you. Obviously, sulbutiamine is not going to kill you (at least without having grams and grams of it), but I think it's safe to say that it cannot be regulated by the same homeostatic mechanisms as thiamine as easily since it behaves differently (it's fat-soluble and crosses the BBB).

I agree that DA can create some sense of wakefulness and whatnot. What I was getting at is the NE is responsible for increases in HR and BP, enhanced physical energy, loss of appetite, and many other stimulatory effects. So I guess it would be better to say that both NE and DA are very important in creating a stimulant effect.

[renfr]

After five days of chronic use I can definetely tell a difference in cognitive function, for instance my memory has been performing better than ever and even while sleep deprived.
Concerning sleep, sulbutiamine doesn't make it difficult to sleep however with Sleepcycle I saw that my sleep was much more lighter, stage 1 and 2 were increased a lot, I can reach stage 4 but there's definetely an higher prevalence of light sleep stages in my sleep. (note : I always take my sulbutiamine in the morning)
I will keep up with 600mg, for the moment I reached no tolerance, when I take an higher dose my speech is a bit slurry which might be the indication that there is indication glutamate agonism on kainate receptors, not sure if downregulation will lead my cognitive functions back to baseline.

[Godof Smallthings]

Any aggression/irritability?

[GetOutOfBox]

I will keep up with 600mg, for the moment I reached no tolerance, when I take an higher dose my speech is a bit slurry which might be the indication that there is indication glutamate agonism on kainate receptors, not sure if downregulation will lead my cognitive functions back to baseline.

That's actually one thing that should be emphasized, long term Sulbutiamine usage has been associated with kainate receptor downregulation. This could result in a minor negative effect on plasticity, however as kainate receptors play a minor role in comparison to AMPA/NMDA, this shouldn't be a big problem. However, if you're more interested in just cognitive improvements, perhaps Sulbutiamine isn't worth it for you. I'm more interested improving mood/motivation, so I'm willing to sacrifice a little bit of cognition for the motivation improvements (upregulation of D1 receptors in the Prefrontal-Cortex) as well as the unique (as far as I can tell) effect of upregulating the Reticular Activating System, resulting in possibly reducing Psycho-Behavioral Inhibition (long term patterns of timidness when confronted with new stimuli, such as meeting new people, trying new experiences, etc). I've definetly noticed that I hold back a little less now, talking to new people and actually trying to get to know them (rather than just sitting there frozen, unable to decide whether it's worth "the risk" to introduce myself), though of course that could just be the placebo effect.

[renfr]

Any aggression/irritability?

Nope, not for me. I do get a bit more irritable and agressive when I only sleep 2-3 hours a night but it's really mild and is not related with sulbutiamine.
In the best case, sulbutiamine probably alleviates this effect.

I will keep up with 600mg, for the moment I reached no tolerance, when I take an higher dose my speech is a bit slurry which might be the indication that there is indication glutamate agonism on kainate receptors, not sure if downregulation will lead my cognitive functions back to baseline.

That's actually one thing that should be emphasized, long term Sulbutiamine usage has been associated with kainate receptor downregulation. This could result in a minor negative effect on plasticity, however as kainate receptors play a minor role in comparison to AMPA/NMDA, this shouldn't be a big problem. However, if you're more interested in just cognitive improvements, perhaps Sulbutiamine isn't worth it for you. I'm more interested improving mood/motivation, so I'm willing to sacrifice a little bit of cognition for the motivation improvements (upregulation of D1 receptors in the Prefrontal-Cortex) as well as the unique (as far as I can tell) effect of upregulating the Reticular Activating System, resulting in possibly reducing Psycho-Behavioral Inhibition (long term patterns of timidness when confronted with new stimuli, such as meeting new people, trying new experiences, etc). I've definetly noticed that I hold back a little less now, talking to new people and actually trying to get to know them (rather than just sitting there frozen, unable to decide whether it's worth "the risk" to introduce myself), though of course that could just be the placebo effect.

Indeed but kainate receptors are not the most numerous glutamate receptors, also no one knows precisely their function so I guess their downregulation is not really a concern, besides agonization of glutamate receptors is not a bad thing as reversal is pretty fast.
This study says that in fact sulbutiamine is good for cognitive function and I do experience a huge cognitive boost but afterall this is also all about motivation, if sulbutiamine makes you more motivated then it will lead to cognitive enhancement.

About the RAS upregulation, I read that on wikipedia and this is the study that justify the sentence : http://www.ncbi.nlm....pubmed/12973384
I don't see any explicit mention of the RAS in this study, there is probably a link between asthenia and the RAS but it doesn't seem that obvious.
But if you say that it gave you a huge motivation/social boost then it probably upregulates the RAS, which dose do you currently use and for how much time have you been doing that?

[brainslugged]

I had a trial run of sulbutiamine a while ago.

I was expecting a strong, "drug like" effect, but was fairly dissapointed. The mild stimulation was orobably placebo.

However, it did have a few effects that started to happen almost a week in.

Firstly, I was previously having a bit of trouble getting it up and had no sexual drive. That was cured and then some. I felt like I was in middle school, random occurences. However, since the lack of libido happens in cycles, it is possible that I just happened to come out of it, but I have never had rebound like that.


There was also a general feeling of wellbeing and slight increase in talkativeness and sociability.

The feelings were very spotty, though. It wasn't strong enough to really make much of a difference even at 700mg, and the side effect was horrible.

Time was super dialated. Think racetam, but magnitudes stronger. Days were like weeks, and weeks like months. It was absolute torture. I felt like time was never going to progress, and even people's sentences seemed to be enlongated. Maybe if my life was more eventful, it would have been a good thing, but I ended up refreshing news sites and twitter constantly, feeling like hours between each post or update when it was really only 10 or so mins.

I assume that is because of increased episodic memory. My other memory was unaffected as far as I could tell.

I had no significant increased ability to concentrate, as I would expect from a stim. I only tried it for a week and a half, stopping when I ran out of pills. Maybe I will make some more pills and try it for longer.

[GetOutOfBox]

Any aggression/irritability?

Nope, not for me. I do get a bit more irritable and agressive when I only sleep 2-3 hours a night but it's really mild and is not related with sulbutiamine.
In the best case, sulbutiamine probably alleviates this effect.

I will keep up with 600mg, for the moment I reached no tolerance, when I take an higher dose my speech is a bit slurry which might be the indication that there is indication glutamate agonism on kainate receptors, not sure if downregulation will lead my cognitive functions back to baseline.

That's actually one thing that should be emphasized, long term Sulbutiamine usage has been associated with kainate receptor downregulation. This could result in a minor negative effect on plasticity, however as kainate receptors play a minor role in comparison to AMPA/NMDA, this shouldn't be a big problem. However, if you're more interested in just cognitive improvements, perhaps Sulbutiamine isn't worth it for you. I'm more interested improving mood/motivation, so I'm willing to sacrifice a little bit of cognition for the motivation improvements (upregulation of D1 receptors in the Prefrontal-Cortex) as well as the unique (as far as I can tell) effect of upregulating the Reticular Activating System, resulting in possibly reducing Psycho-Behavioral Inhibition (long term patterns of timidness when confronted with new stimuli, such as meeting new people, trying new experiences, etc). I've definetly noticed that I hold back a little less now, talking to new people and actually trying to get to know them (rather than just sitting there frozen, unable to decide whether it's worth "the risk" to introduce myself), though of course that could just be the placebo effect.

Indeed but kainate receptors are not the most numerous glutamate receptors, also no one knows precisely their function so I guess their downregulation is not really a concern, besides agonization of glutamate receptors is not a bad thing as reversal is pretty fast.
This study says that in fact sulbutiamine is good for cognitive function and I do experience a huge cognitive boost but afterall this is also all about motivation, if sulbutiamine makes you more motivated then it will lead to cognitive enhancement.

About the RAS upregulation, I read that on wikipedia and this is the study that justify the sentence : http://www.ncbi.nlm....pubmed/12973384
I don't see any explicit mention of the RAS in this study, there is probably a link between asthenia and the RAS but it doesn't seem that obvious.
But if you say that it gave you a huge motivation/social boost then it probably upregulates the RAS, which dose do you currently use and for how much time have you been doing that?

Well keep in mind that's just the abstract from the study, I'm sure if the notes were available we'd see more information regarding it's effects on the RAS. I suspect that the effects are most dramatic in sufferers of asthenia, since the RAS is specifically implicated in that disorder, and Sulbutiamine is unique in that is specifically targets the cause, with minimal side-effects if any.

I suspect that in healthy people, the improvements are much less dramatic. When it comes to most non-stimulant nootropics, there is a roughly logarithmic curve of improvement relative to your health. People with brain disorders or damage tend to show very visible improvements, as the drugs bring them back to baseline, allowing them to function in ways we consider normal. People who are fairly healthy already tend to show relatively minor improvements, as increasing the efficiency of the neurotransmitter systems in the brain tends to be limited by physical brain structure.

In my case, I can't say whether Sulbutiamine alone has had a very positive impact on me, but my dopamine-optimizing stack has had a very large impact on the quality of my life (Uridine UMP 250 mg+2 grams fish oil x3 daily: modulates dopaminergic neuron firing, as well as many other beneficial effects on brain health, Tyrosine: precursor to Dopamine, and through the metabolism of Dopamine, adrenal hormones/neurotransmitters, Sulbutiamine: upregulates various dopamine receptors, hence sensitizing one to normal dopamine levels and especially occasional stimulant use). It's not dramatic like after taking that stack, suddenly I was working like a maniac, it's more that I find myself satisfied by less stimulating things. I've been diagnosed with ADD-Pi for years now, I've been on Adderall and Ritalin with little to no effect from either (not even hyper, it was almost like they were doing nothing. My friend tried 10 mg ritalin, and was bouncing off the walls for 6 hours, whereas I notice literally nothing, even when I was just starting). I used to have massive trouble doing any sort of work, it was like I had zero motivation to do anything that required mental effort, even the things I loved, like programming. After about a month on that stack, I've started noticing a return in my motivation, I still sort of have to force myself to sit down and work, but it's so much easier, I even enjoy it now. You see, before, I never understood how it felt to derive satisfaction from working on a hobby. Friends would talk about enjoying doing art or music, whereas for me, the only reward came when I was finished, the work itself wasn't satisfying, even though I liked it, if that makes any sense. Now, I feel like less stimulating things are more pleasurable, I enjoy working on my hobbies. My moods have also stabilized, I wouldn't describe my old self as Bipolar, but I used to have mild mood fluctuations, such as feeling happy, then suddenly losing that happiness for no reason. I never had manic or hypomanic episodes, but it seemed like my mood didn't take much to push it into irritability or mild depression (and I wasn't going through depression, I mean on a per-mood basis. I'd be happy thinking about something I was looking forward to, then suddenly, boom, happiness gone, for no reason). I also used to have odd bursts of rage (which I always was able to suppress, but nevertheless, I'd feel them) triggered by exercise. For example, I'd be riding my bike for a few km, and feel a growing sense of irritability. Anything that happened during that mood that was mildly irritating would cause this burst of anger, yet I rationally would have no idea why I was angry. This could have been a sign of adrenal issues.

I suspect the Tyrosine is what's helped with my moods primarily, as although I do eat healthy, I don't eat a lot. I definitely don't have lots of meat in my diet, if I ever eat meat, it's usually for dinner, and even then, some days my meals just don't have a lot of it. Since meat is pretty much the only good source of proteins/amino-acids for humans (aside from a few vegetables that have "complete protein", that is, all of the essential amino-acids for humans), it's not unreasonable that I could have had a mild amino-acid deficiency, or perhaps I just don't metabolize Phenylalanine very well, and hence the Tyrosine get's around that. I'm sure the Uridine has also helped to stabilize my dopaminergic system, smoothing out the highs and lows.

Still, due to Sulbutiamine's upregulating nature, I'd say it definetly has long term uses. I personally am more interested in upregulating my dopaminergic system, it seems like a much more sustainable goal. With stimulants, you always have the issue of tolerance, as well as rebound-effects as the drug wears off. And once you've built tolerance, you start having issues like inconsistent effects due to various factors preventing full absorption. This way, I'm actually increasing the number of receptors, so that my natural dopamine levels are sufficient.

[xsiv1]

Any aggression/irritability?

Nope, not for me. I do get a bit more irritable and agressive when I only sleep 2-3 hours a night but it's really mild and is not related with sulbutiamine.
In the best case, sulbutiamine probably alleviates this effect.

I will keep up with 600mg, for the moment I reached no tolerance, when I take an higher dose my speech is a bit slurry which might be the indication that there is indication glutamate agonism on kainate receptors, not sure if downregulation will lead my cognitive functions back to baseline.

That's actually one thing that should be emphasized, long term Sulbutiamine usage has been associated with kainate receptor downregulation. This could result in a minor negative effect on plasticity, however as kainate receptors play a minor role in comparison to AMPA/NMDA, this shouldn't be a big problem. However, if you're more interested in just cognitive improvements, perhaps Sulbutiamine isn't worth it for you. I'm more interested improving mood/motivation, so I'm willing to sacrifice a little bit of cognition for the motivation improvements (upregulation of D1 receptors in the Prefrontal-Cortex) as well as the unique (as far as I can tell) effect of upregulating the Reticular Activating System, resulting in possibly reducing Psycho-Behavioral Inhibition (long term patterns of timidness when confronted with new stimuli, such as meeting new people, trying new experiences, etc). I've definetly noticed that I hold back a little less now, talking to new people and actually trying to get to know them (rather than just sitting there frozen, unable to decide whether it's worth "the risk" to introduce myself), though of course that could just be the placebo effect.

Indeed but kainate receptors are not the most numerous glutamate receptors, also no one knows precisely their function so I guess their downregulation is not really a concern, besides agonization of glutamate receptors is not a bad thing as reversal is pretty fast.
This study says that in fact sulbutiamine is good for cognitive function and I do experience a huge cognitive boost but afterall this is also all about motivation, if sulbutiamine makes you more motivated then it will lead to cognitive enhancement.

About the RAS upregulation, I read that on wikipedia and this is the study that justify the sentence : http://www.ncbi.nlm....pubmed/12973384
I don't see any explicit mention of the RAS in this study, there is probably a link between asthenia and the RAS but it doesn't seem that obvious.
But if you say that it gave you a huge motivation/social boost then it probably upregulates the RAS, which dose do you currently use and for how much time have you been doing that?

Well keep in mind that's just the abstract from the study, I'm sure if the notes were available we'd see more information regarding it's effects on the RAS. I suspect that the effects are most dramatic in sufferers of asthenia, since the RAS is specifically implicated in that disorder, and Sulbutiamine is unique in that is specifically targets the cause, with minimal side-effects if any.

I suspect that in healthy people, the improvements are much less dramatic. When it comes to most non-stimulant nootropics, there is a roughly logarithmic curve of improvement relative to your health. People with brain disorders or damage tend to show very visible improvements, as the drugs bring them back to baseline, allowing them to function in ways we consider normal. People who are fairly healthy already tend to show relatively minor improvements, as increasing the efficiency of the neurotransmitter systems in the brain tends to be limited by physical brain structure.

In my case, I can't say whether Sulbutiamine alone has had a very positive impact on me, but my dopamine-optimizing stack has had a very large impact on the quality of my life (Uridine UMP 250 mg+2 grams fish oil x3 daily: modulates dopaminergic neuron firing, as well as many other beneficial effects on brain health, Tyrosine: precursor to Dopamine, and through the metabolism of Dopamine, adrenal hormones/neurotransmitters, Sulbutiamine: upregulates various dopamine receptors, hence sensitizing one to normal dopamine levels and especially occasional stimulant use). It's not dramatic like after taking that stack, suddenly I was working like a maniac, it's more that I find myself satisfied by less stimulating things. I've been diagnosed with ADD-Pi for years now, I've been on Adderall and Ritalin with little to no effect from either (not even hyper, it was almost like they were doing nothing. My friend tried 10 mg ritalin, and was bouncing off the walls for 6 hours, whereas I notice literally nothing, even when I was just starting). I used to have massive trouble doing any sort of work, it was like I had zero motivation to do anything that required mental effort, even the things I loved, like programming. After about a month on that stack, I've started noticing a return in my motivation, I still sort of have to force myself to sit down and work, but it's so much easier, I even enjoy it now. You see, before, I never understood how it felt to derive satisfaction from working on a hobby. Friends would talk about enjoying doing art or music, whereas for me, the only reward came when I was finished, the work itself wasn't satisfying, even though I liked it, if that makes any sense. Now, I feel like less stimulating things are more pleasurable, I enjoy working on my hobbies. My moods have also stabilized, I wouldn't describe my old self as Bipolar, but I used to have mild mood fluctuations, such as feeling happy, then suddenly losing that happiness for no reason. I never had manic or hypomanic episodes, but it seemed like my mood didn't take much to push it into irritability or mild depression (and I wasn't going through depression, I mean on a per-mood basis. I'd be happy thinking about something I was looking forward to, then suddenly, boom, happiness gone, for no reason). I also used to have odd bursts of rage (which I always was able to suppress, but nevertheless, I'd feel them) triggered by exercise. For example, I'd be riding my bike for a few km, and feel a growing sense of irritability. Anything that happened during that mood that was mildly irritating would cause this burst of anger, yet I rationally would have no idea why I was angry. This could have been a sign of adrenal issues.

I suspect the Tyrosine is what's helped with my moods primarily, as although I do eat healthy, I don't eat a lot. I definitely don't have lots of meat in my diet, if I ever eat meat, it's usually for dinner, and even then, some days my meals just don't have a lot of it. Since meat is pretty much the only good source of proteins/amino-acids for humans (aside from a few vegetables that have "complete protein", that is, all of the essential amino-acids for humans), it's not unreasonable that I could have had a mild amino-acid deficiency, or perhaps I just don't metabolize Phenylalanine very well, and hence the Tyrosine get's around that. I'm sure the Uridine has also helped to stabilize my dopaminergic system, smoothing out the highs and lows.

Still, due to Sulbutiamine's upregulating nature, I'd say it definetly has long term uses. I personally am more interested in upregulating my dopaminergic system, it seems like a much more sustainable goal. With stimulants, you always have the issue of tolerance, as well as rebound-effects as the drug wears off. And once you've built tolerance, you start having issues like inconsistent effects due to various factors preventing full absorption. This way, I'm actually increasing the number of receptors, so that my natural dopamine levels are sufficient.

I've experienced the very symptoms you've described in terms of mood. I'm not sure that they'd be considered at clinical levels, but sometimes I believe they should. I've found my own cocktail that works well, on and off. Mostly on. In fact, any time I use fat burning supplements that are typically stims, I can become enraged for no 'good' reason. Other times, I'm in a good mood and then have it go to flatness and more rarely dysphoria. I've also had issues with motivation during office work but when it comes to other things, I'm ok. Anyways, it's always good to read the accounts of others to fine tune what one is already taking and may be considering. I typically switch things up every few months barring some of my staple supplements. If you don't mind me asking, where do you purchase your Uridine UMP 250 mg? I've looked at iherb and it seems to me that it can get pricey. I already take 2 grams of fish oils per day along with a good multi, b-complex, Methyl B12, & C. I'd like to look into this combo further since I see upregulating better than agonizing receptors as well in the long run..although, admittedly, I've tried both...concurrently lol.

[GetOutOfBox]

I've experienced the very symptoms you've described in terms of mood. I'm not sure that they'd be considered at clinical levels, but sometimes I believe they should. I've found my own cocktail that works well, on and off. Mostly on. In fact, any time I use fat burning supplements that are typically stims, I can become enraged for no 'good' reason. Other times, I'm in a good mood and then have it go to flatness and more rarely dysphoria. I've also had issues with motivation during office work but when it comes to other things, I'm ok. Anyways, it's always good to read the accounts of others to fine tune what one is already taking and may be considering. I typically switch things up every few months barring some of my staple supplements. If you don't mind me asking, where do you purchase your Uridine UMP 250 mg? I've looked at iherb and it seems to me that it can get pricey. I already take 2 grams of fish oils per day along with a good multi, b-complex, Methyl B12, & C. I'd like to look into this combo further since I see upregulating better than agonizing receptors as well in the long run..although, admittedly, I've tried both...concurrently lol.

I, as well as most Uridine users, get it from Superior Nutraceuticals. I bought 25 grams bulk powder for $40, which is good value. At most, I take 500 mg a day total. Superior Nutraceuticals is pretty much the only reliable place I could find to get Uridine UMP, the one's you saw on iHerb were probably the TAU (Triacetyluridine) version, which although it is fat soluble and requires much less per dose theoretically, many users report not responding to it, but responding to UMP (Uridine-5'-Monophosphate). Plus you can take the UMP sublingually.

Although Superior Nutraceutical's website looks shabby, I actually had a good experience with them, it shipped fast, and was the real stuff (at least it looks and tastes like Uridine's supposed to). Plus they have a good reputation here.

[renfr]

Been one week on sulbutiamine, taking around 600-1200mg and it's pretty fine.
I did notice an enhancement in my memory, I'm not sure if it's still there. Apart from that my talkativeness, spontaneity and sociability have increased really a lot which is good.
I also have that time dilating effect which is rather good to me.
I will keep taking it and plan to do it on very long term (1 year if I don't experience bad side effects after prolonged use, I have found a source--sun nootropics, its cost for a 500g batch is $10/month for 1g), I will however make a 1 week abstinence after 1 month to see if there are withdrawal symptoms. (I think it's unlikely, I didn't experiment any withdrawal syndrome after may 2012).
But I'm not sure if this must be mixed up with dopaminergics such as tyrosine or NALT, upregulation is made through a compensatory mechanism so it would be counterproductive to add a dopaminergic with it.

Edited by renfr, 21 February 2013 - 08:54 PM.

[GetOutOfBox]

Been one week on sulbutiamine, taking around 600-1200mg and it's pretty fine.
I did notice an enhancement in my memory, I'm not sure if it's still there. Apart from that my talkativeness, spontaneity and sociability have increased really a lot which is good.
I also have that time dilating effect which is rather good to me.
I will keep taking it and plan to do it on very long term (1 year if I don't experience bad side effects after prolonged use, I have found a source--sun nootropics, its cost for a 500g batch is $10/month for 1g), I will however make a 1 week abstinence after 1 month to see if there are withdrawal symptoms. (I think it's unlikely, I didn't experiment any withdrawal syndrome after may 2012).
But I'm not sure if this must be mixed up with dopaminergics such as tyrosine or NALT, upregulation is made through a compensatory mechanism so it would be counterproductive to add a dopaminergic with it.

Well, keep in mind that L-Tyrosine(or NAL-Tyrosine)/Phenylalanine do not directly raise dopamine levels, as they are simply precursors. The brain has a self-limited metabolic process to convert them to catecholamines, you could chug an entire bottle of Tyrosine, and the real concern would be the effects it would have on your liver/kidneys than brain. Some individuals may initially have elevated dopamine as a result of adding precursors, but the hydroxylase will downregulate before the receptors themselves can.

I personally take the tyrosine supplement simply so I can be sure I have an adequate amount of precursors, since I don't eat a ton of meat, hence don't consistently get a lot of protein. I don't actually expect or really desire any direct effect from them.

[renfr]

Vitamin D is known to enhance l tyrosine conversion to l dopa for instance.
concerning sulbutiamine,
I'm starting to think that maybe it should be cycled during the week like taking it parcingly 2-3 days in a week, because dopamine upregulation means depletion then there should be days where dopamine levels return to baseline so that we can feel the effects.

[xsiv1]

Thanks for that link GetOut. I'll give it a go. I havent exceeded 400mgs of Sulbutiamine IIRC, perhaps 600 in one day and at this point (8th day straight), I don't feel the effects to the same degree. Ill break from it starting tomorrow.

[renfr]

Would adding inositol a good thing? There's an interesting study :

chronic inositol induced a significant increase in striatal D(2) receptor density (B(max)) with a slight, albeit insignificant, increase in 5HT(2) receptor density.

http://www.ncbi.nlm.nih.gov/pubmed/11267629