87 replies to this topic

[chrono]

Seems like the tolerance issue is real?
Is there any solid evidence?
...
Seems like no stimulant actually works long term. I seriously need stimulants because otherwise my vision is always blurred. Caffeine works for my vision as well as sulbutiamine, but tolerance develops. I also need the energy because I can't live a normal life without them (ie no motivation).

It seems like everyone reports a tolerance, so it's probably real. Have you been taking it for weeks in a row, still? If so, taking some time off will probably answer this question for you.

Can you describe the blurred vision more? Do you know what causes it, and does anything else help?

A cycle between sulbutiamine and caffeine is worth considering, since they both create tolerance. Three days of each, or EOD? With some days off when you can? And are you still taking ALCAR? How does it synergize, and does it help your vision? If so, that's another item to help with the tolerance cycle.

Edited by chrono, 10 September 2010 - 08:41 PM.
grammar police

[kurt]

Guys, some updates. I'm not sure if I were tolerant to sulbutiamine previously because I was concurrently suffering from nicotine withdrawal. The symptoms would be gone once I start puffing on a cigarette.
I've decided to quit smoking and I'm using some kind of a 'smokeless cigarette' that works like a nicotine dispenser to help wean off. Works great for withdrawal and nicotine itself is less addictive than smoking tobacco. I've yet to continue with the sulbutiamine cycle however.

The blurred vision has always been there. I'm always tired and the blurred vision is part of it I suppose. Coffee sharpens my vision very significantly. As well as tobacco. And that's about it, so far. I supposed my blurred vision has got something to do with my 'unstimulated' CNS.

Chrono, I can't take caffeine. I get severe anxiety and tremors, although the stimulant effects are really great. ALCAR works like a mild stimulant, but does nothing for my vision.

Edited by kurt, 18 February 2010 - 10:16 AM.

[425runner]

Kurt -

Have you seen an eye doctor? Ophtalmologist? What's wrong with your vision? There has to be a better explanation then blaming it on "unstimulated CNS"

Guys, some updates. I'm not sure if I were tolerant to sulbutiamine previously because I was concurrently suffering from nicotine withdrawal. The symptoms would be gone once I start puffing on a cigarette.
I've decided to quit smoking and I'm using some kind of a 'smokeless cigarette' that works like a nicotine dispenser to help wean off. Works great for withdrawal and nicotine itself is less addictive than smoking tobacco. I've yet to continue with the sulbutiamine cycle however.

The blurred vision has always been there. I'm always tired and the blurred vision is part of it I suppose. Coffee sharpens my vision very significantly. As well as tobacco. And that's about it, so far. I supposed my blurred vision has got something to do with my 'unstimulated' CNS.

Chrono, I can't take caffeine. I get severe anxiety and tremors, although the stimulant effects are really great. ALCAR works like a mild stimulant, but does nothing for my vision.

[chrono]

Have you seen an eye doctor? Ophtalmologist? What's wrong with your vision? There has to be a better explanation then blaming it on "unstimulated CNS"

Agreed, using one method of alleviating symptoms to make a diagnosis isn't the best way to go, especially when they're so seemingly unrelated. If you're trying to figure out how you can take stimulants (which you don't necessarily tolerate well) every day, I think you owe it to yourself to see a doctor about this. It's the kind of thing that could potentially be a symptom of something you'd want to know about.

Congratulations on quitting smoking. Have you thought about nicotine patches? Smokeless cigarettes are healthier than tobacco, but instant delivery of nicotine is the primary component of addiction. Not to mention that the ritual of "smoking" is a huge psychological component, and in my observations is one of the hardest things to give up. Best of luck!

[kurt]

Hi guys...my vision has improved. I'm do believe it is caused by nicotine withdrawal (fatigue/cns understimulation). I've been on 'smokeless cigarettes' for a while and it is really helping me, on top of helping me to quit. Mood is slightly improved (more stimulated/less brain fog). And maybe past alcohol abuse depleted my B12 stores. Therefore I'm also taking methylcobalamin. It helps to lessen the fatigue and also sharpens my vision.

Chrono: No worries, I'm consuming nicotine without a MAOI, which is present in tobacco. Nicotine without MAOI is much less addictive.

425runner: It seems to me that my poor vision is directly linked to fatigue (psychological). When my vision is blurred it would always be accompanied by fatigue and vice versa.

Does anybody know why?

My problem is probably psychological fatigue/lack of motivation and loss of zest/lack of inspiration (I'll think of ways to counter this). I've yet to continue on the sulbutiamine, but I'm thinking of giving it a try; taking it long term to increase dopamine receptors. Who knows, I might benefit from a long-lasting boost in motivation. So far sulbutiamine seems to be the only decent drug that directly counters fatigue and lack of motivation (via increase dopamine receptors). Can anybody think of a better alternatives?

Edited by kurt, 08 March 2010 - 03:34 PM.

[chrono]

No ideas about your vision, sorry.

I'm in the same boat motivation-wise. I find it very difficult to do even the things I love doing, because it's so hard to stay focused and feel "rewarded" by doing them; doing my favorite things sometimes feels like trying to memorize a phonebook. I think it's largely dopamine-related. The only time I feel I'm able to actually do what I desire is when I take adderall, but its attendant side effects and addictive properties make me very hesitant to take it any more.

I'm very anxious to try deprenyl, it sounds like the only long-term supplement that has a positive influence on dopamine. There are several other pharms that affect dopamine, but they all seem to have some downside. Other than that, there are things like sulbutiamine, which are good for sometimes-use, because of tolerance/downregulation.

I'm trying to be strategic about when to use dopamine agonists, and at other times working on the mental aspect and using things like ALCAR to do what I can.

[aLurker]

I tried 1 ml of sulbutiamine (should be about 320mg) this morning and didn't notice much, could be that I downed it with water and nothing else besides a few peanuts for breakfast.

I just downed 0.5ish ml (~160mg) dissolved in olive oil and fiber oatmeal, should be a better way to take this from the minimal amount of research I've done on this. Hopefully this will give better effects than a mild alertness and sense of well being. These mild effects might be enough to warrant a purchase for others but I'm looking for that motivational drive some people have reported on sulbutiamine.

Evidence for a modulatory effect of sulbutiamine on glutamatergic and dopaminergic cortical transmissions in the rat brain.

Chronic treatment of rats by sulbutiamine induced no change in density of N-methyl-D-aspartate (NMDA) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the cingular cortex, but a significant decrease of the kainate binding sites, as measured by quantitative autoradiography. In the same treated animals, an increase of D1 dopaminergic (DA) binding sites was measured both in the prefrontal and the cingular cortex, while no modification of the D2 binding sites was detected. Furthermore, an acute sulbutiamine administration induced a decrease of kainate binding sites but no change of the density of D1 and D2 DA receptors. Acute sulbutiamine injection led to a decrease of the DA levels in the prefrontal cortex and 3,4-dihydroxyphenylacetic acid levels in both the cingular and the prefrontal cortex. These observations are discussed in terms of a modulatory effect of sulbutiamine on both dopaminergic and glutamatergic cortical transmissions.

Increased D1 receptor density with chronic usage sounds totally awesome (as does the NMDA modulation I think I've read something about). I'm not that well read about D1 though, does anyone know what this might imply in terms of dopamine, receptor and reward sensitivity? Are the receptors up-regulated due to lack of dopamine or are there more of them but they are less sensitive? These are questions asked from a point of ignorance and I'd love for someone to explain this to me, the documented cognitive benefits which accompany chronic usage seem to indicate there might be some potential here even though the acute effects might be subject to tolerance according to the anecdotal accounts here. Any experiences from chronic users of this?

Edited by aLurker, 17 October 2010 - 10:11 AM.

[Thorsten3]

I tried 1 ml of sulbutiamine (should be about 320mg) this morning and didn't notice much, could be that I downed it with water and nothing else besides a few peanuts for breakfast.

I just downed 0.5ish ml (~160mg) dissolved in olive oil and fiber oatmeal, should be a better way to take this from the minimal amount of research I've done on this. Hopefully this will give better effects than a mild alertness and sense of well being. These mild effects might be enough to warrant a purchase for others but I'm looking for that motivational drive some people have reported on sulbutiamine.

Evidence for a modulatory effect of sulbutiamine on glutamatergic and dopaminergic cortical transmissions in the rat brain.

Chronic treatment of rats by sulbutiamine induced no change in density of N-methyl-D-aspartate (NMDA) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the cingular cortex, but a significant decrease of the kainate binding sites, as measured by quantitative autoradiography. In the same treated animals, an increase of D1 dopaminergic (DA) binding sites was measured both in the prefrontal and the cingular cortex, while no modification of the D2 binding sites was detected. Furthermore, an acute sulbutiamine administration induced a decrease of kainate binding sites but no change of the density of D1 and D2 DA receptors. Acute sulbutiamine injection led to a decrease of the DA levels in the prefrontal cortex and 3,4-dihydroxyphenylacetic acid levels in both the cingular and the prefrontal cortex. These observations are discussed in terms of a modulatory effect of sulbutiamine on both dopaminergic and glutamatergic cortical transmissions.

Increased D1 receptor density with chronic usage sounds totally awesome (as does the NMDA modulation I think I've read something about). I'm not that well read about D1 though, does anyone know what this might imply in terms of dopamine, receptor and reward sensitivity? Are the receptors up-regulated due to lack of dopamine or are there more of them but they are less sensitive? These are questions asked from a point of ignorance and I'd love for someone to explain this to me, the documented cognitive benefits which accompany chronic usage seem to indicate there might be some potential here even though the acute effects might be subject to tolerance according to the anecdotal accounts here. Any experiences from chronic users of this?

NMDA modulation? That sounds similar to Piracetam. Would they not clash? I though you took Pira?

Increased dopamine receptor density. If that was the case I would guess you'd need to give your dopamine receptors more fuel. Ultimate dopamine production/synthesis maybe through a methylation programme or something? That would be my line of approach, it could be totally wrong though. Maybe you antagonize them somehow to kick them back into gear? It would be interesting to hear from others on this. I suppose once that system is working well with increased capacity you'd reap the benefits and your rewarding life experiences would keep it juicy and flowing. Or have I lost the plot here?
I am also interested in what you mention above. Having an increase in any type of neurotransmitter system with increased sensitivity sounds delicious but how do we achieve this?
I remember reading a post from animal and he said it works in the same way as tianeptine does with the serotonin system. Upregulating it and increasing sensitivity. Maybe there is hope to draw from that? I wouldn't know this for sure though.

Edited by Thorsten, 17 October 2010 - 01:14 PM.

[Animal]

I tried 1 ml of sulbutiamine (should be about 320mg) this morning and didn't notice much, could be that I downed it with water and nothing else besides a few peanuts for breakfast.

I just downed 0.5ish ml (~160mg) dissolved in olive oil and fiber oatmeal, should be a better way to take this from the minimal amount of research I've done on this. Hopefully this will give better effects than a mild alertness and sense of well being. These mild effects might be enough to warrant a purchase for others but I'm looking for that motivational drive some people have reported on sulbutiamine.

Evidence for a modulatory effect of sulbutiamine on glutamatergic and dopaminergic cortical transmissions in the rat brain.

Chronic treatment of rats by sulbutiamine induced no change in density of N-methyl-D-aspartate (NMDA) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the cingular cortex, but a significant decrease of the kainate binding sites, as measured by quantitative autoradiography. In the same treated animals, an increase of D1 dopaminergic (DA) binding sites was measured both in the prefrontal and the cingular cortex, while no modification of the D2 binding sites was detected. Furthermore, an acute sulbutiamine administration induced a decrease of kainate binding sites but no change of the density of D1 and D2 DA receptors. Acute sulbutiamine injection led to a decrease of the DA levels in the prefrontal cortex and 3,4-dihydroxyphenylacetic acid levels in both the cingular and the prefrontal cortex. These observations are discussed in terms of a modulatory effect of sulbutiamine on both dopaminergic and glutamatergic cortical transmissions.

Increased D1 receptor density with chronic usage sounds totally awesome (as does the NMDA modulation I think I've read something about). I'm not that well read about D1 though, does anyone know what this might imply in terms of dopamine, receptor and reward sensitivity? Are the receptors up-regulated due to lack of dopamine or are there more of them but they are less sensitive? These are questions asked from a point of ignorance and I'd love for someone to explain this to me, the documented cognitive benefits which accompany chronic usage seem to indicate there might be some potential here even though the acute effects might be subject to tolerance according to the anecdotal accounts here. Any experiences from chronic users of this?

D1 receptor activity is primarily indicated in subjective feelings of energy and appetite suppression. There is minimal effect on mood and reward, mediated through it's modulation of D2 receptor neurotransmission.

In terms of motivation I expect it could have a moderate effect indirectly though increased energy levels, though this is dependent on the source of the amotivation i.e. if it originates from low mood there will be a negligible effect.

DA receptor activation with regards to endogenous ligand intrinsic activity is binary, so with increased density/volume comes increased neuro-synaptic sensitivity to ligand presence.

[Thorsten3]

I tried 1 ml of sulbutiamine (should be about 320mg) this morning and didn't notice much, could be that I downed it with water and nothing else besides a few peanuts for breakfast.

I just downed 0.5ish ml (~160mg) dissolved in olive oil and fiber oatmeal, should be a better way to take this from the minimal amount of research I've done on this. Hopefully this will give better effects than a mild alertness and sense of well being. These mild effects might be enough to warrant a purchase for others but I'm looking for that motivational drive some people have reported on sulbutiamine.

Evidence for a modulatory effect of sulbutiamine on glutamatergic and dopaminergic cortical transmissions in the rat brain.

Chronic treatment of rats by sulbutiamine induced no change in density of N-methyl-D-aspartate (NMDA) and (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the cingular cortex, but a significant decrease of the kainate binding sites, as measured by quantitative autoradiography. In the same treated animals, an increase of D1 dopaminergic (DA) binding sites was measured both in the prefrontal and the cingular cortex, while no modification of the D2 binding sites was detected. Furthermore, an acute sulbutiamine administration induced a decrease of kainate binding sites but no change of the density of D1 and D2 DA receptors. Acute sulbutiamine injection led to a decrease of the DA levels in the prefrontal cortex and 3,4-dihydroxyphenylacetic acid levels in both the cingular and the prefrontal cortex. These observations are discussed in terms of a modulatory effect of sulbutiamine on both dopaminergic and glutamatergic cortical transmissions.

Increased D1 receptor density with chronic usage sounds totally awesome (as does the NMDA modulation I think I've read something about). I'm not that well read about D1 though, does anyone know what this might imply in terms of dopamine, receptor and reward sensitivity? Are the receptors up-regulated due to lack of dopamine or are there more of them but they are less sensitive? These are questions asked from a point of ignorance and I'd love for someone to explain this to me, the documented cognitive benefits which accompany chronic usage seem to indicate there might be some potential here even though the acute effects might be subject to tolerance according to the anecdotal accounts here. Any experiences from chronic users of this?

D1 receptor activity is primarily indicated in subjective feelings of energy and appetite suppression. There is minimal effect on mood and reward, mediated through it's modulation of D2 receptor neurotransmission.

In terms of motivation I expect it could have a moderate effect indirectly though increased energy levels, though this is dependent on the source of the amotivation i.e. if it originates from low mood there will be a negligible effect.

DA receptor activation with regards to endogenous ligand intrinsic activity is binary, so with increased density/volume comes increased neuro-synaptic sensitivity to ligand presence.

That totally debunks my last post. I was writing assuming this stuff had an effect on mood (such as reward, wellbeing). I don't think anyone can scoff at its effects on motivation though. I think that's pretty useful for some.
Plus the effects on energy are very enjoyable for some. I may trial it again at some point. I just remember its effects being a bit dissapointing for me.

Edited by Thorsten, 17 October 2010 - 01:19 PM.

[Animal]

That totally debunks my last post. I was writing assuming this stuff had an effect on mood (such as reward, wellbeing). I don't think anyone can scoff at its effects on motivation though. I think that's pretty useful for some.
Plus the effects on energy are very enjoyable for some. I may trial it again at some point. I just remember its effects being a bit dissapointing for me.

Sulbutiamine has additional effects at DA receptor subtypes other then the overall increase in D1 receptor density with chronic administration. It does improve mood and motivation, but this is transitory, with tolerance developing rapidly in contrast to the D1 receptor up-regulation.

I wrote a post in the past going into extreme detail on the effects of sulbutiamine on the dopaminergic system as a whole, it has a fairly unique oscillating antagonism of D1 receptors. Look up that post if you want a more elaborate understanding of the receptor dynamics, I'm not writing it out again.

[aLurker]

Animal, chrono made a pretty good case for the importance of D1 in this post.

Since I generally enjoy your posts very much I dug up this excerpt from the very informative post you and Thorsten were referring to:

Sulbutiamine induces an increase in the density of D1 dopamine receptors in the prefrontal cortex due to a reduction in the release of dopamine. But because it has a positively charged thiazole moiety it can only be transported across the plasma membrane of dopaminergic neurons by high affinity carriers, what this means, especially in the brain because of it's anion activity, is that the rate of transport tends to fluctuate. So that you get an oscillation of dopamine release in the cortex, over a prolonged period (a few weeks) this oscillation will be compensated for through reactionary changes in endogenous dopamine production. The net result being the sulbutiamine's effectiveness will become negligible, and you'll be left with a dystonic dopaminergic system.

With regards to dopamine, agonists (particularly D1) are your best bet, but they are difficult to procure.

The D1 up-regulation is after chronic use and it doesn't explain the acute effects of sulbutiamine. The acute effects seemed to be lower DA and unchanged DA receptors... but with a decrease of kainate binding sites. Never even heard of kainate before. How would those acute changes account for the energy and motivation I've been hearing about? Seems paradoxical. Animal's oscillation hypothesis is by far the best one yet. It's also the only one I've heard, can't really say I understand it fully yet though.

A guess about the long-term effects would be that the acute lowering of DA would result in D1 up-regulation over time and that tolerance builds to the motivational aspects.

A wild and speculative hypothesis: When I've built a steady tolerance to the acute effects of sulbutiamine I might still benefit from chronic use by taking it nightly to up-regulate D1 receptors? Anyone thought of this or perhaps even tried it already?

Edited by aLurker, 17 October 2010 - 01:59 PM.

[Animal]

A wild and speculative hypothesis: When I've built a steady tolerance to the acute effects of sulbutiamine I might still benefit from chronic use by taking it nightly to up-regulate D1 receptors? Anyone thought of this or perhaps even tried it already?

Well like I indicated, the oscillation of dopamine release provides the acute effects of Sulbutiamine by causing a sustained consolidation/cascade dynamic that increases dopaminergic activity after the initial onset of effects which compensates for the cyclic reductions in DA release and D1 antagonism in the short term. Though this does tend to deplete endogenous catecholamine stores in a transitory way, which accounts for the 'crash' after the Sulbutiamine wears off.

Like you mention, when chronically dosing your neurology compensates for the modulation in dopaminergic activity, resulting in an absence of acute effects and a net reduction in DA production. This results in only the D1 antagonism having any psychoactive effect, a rather gradual but sustained up-regulation in D1 receptor density.

Hmmm, to be honest the subjective effects of long term usage of Sulbutiamine do not sound particularly pleasant, and I could imagine anxiety and over-stimulation would result during the day (if dosing at night) without concomitant stimulation of the D2 receptors. I'm also not sure how conducive the D1 antagonism would be to sleep, though it would make you tired, it could also make you hungry.

This kind of stuff is difficult to predict, I'd like to see someone experiment with it. There is the possibility overall energy levels and motivation may improve markedly after your dopaminergic system up-regulates in response to the decrease in endogenous DA production.

Edited by Animal, 17 October 2010 - 04:36 PM.

[aLurker]

Thanks for the simplified explanation Animal.

Yeah you're right; very difficult to predict what late chronic dosing would do. I've got 30 g of sulbutiamine though so perhaps I could try it myself if the side effects aren't too bad.

Edited by aLurker, 17 October 2010 - 04:51 PM.

[someidiot]

perhaps a round of Sulbutiamine after a stint of cabergoline or pergolide could prove beneficial? ...to offset D1 down regulation? Of course, D2 needs to be addressed....but I am too scared to fool around with the antipsychotics.

FYI: currently on 250mcg-500mcg pramipexole. i love it.

[chrono]

The D1 up-regulation is after chronic use and it doesn't explain the acute effects of sulbutiamine. The acute effects seemed to be lower DA and unchanged DA receptors... but with a decrease of kainate binding sites. Never even heard of kainate before. How would those acute changes account for the energy and motivation I've been hearing about? Seems paradoxical. Animal's oscillation hypothesis is by far the best one yet. It's also the only one I've heard, can't really say I understand it fully yet though.

A guess about the long-term effects would be that the acute lowering of DA would result in D1 up-regulation over time and that tolerance builds to the motivational aspects.

A wild and speculative hypothesis: When I've built a steady tolerance to the acute effects of sulbutiamine I might still benefit from chronic use by taking it nightly to up-regulate D1 receptors? Anyone thought of this or perhaps even tried it already?

My guess is that, since there are only 22 studies on sulbutiamine in medline, its mechanisms aren't fully elucidated, and trying to draw conclusions based on that one study concerned with DA might not be possible. Involvement of the cholinergic system [1] raises another possibility for acute mechanism, but the nature of the reports I've read make it sound pretty likely that DA is involved. So perhaps while acute administration decreases prefrontal DA, it is increased in subcortical areas (don't have the text yet, so I have no clue how many variables the study considered).

Looking forward to hearing more about your experience, as I've been curious about this one for a while. Many people seem to take a higher dose for acute stimulating/motivating effects, something like 600-1000mg, IIRC. People who mention the word "workout" seem to be happy with sub-500mg dosages. Chronic dosing would certainly be a worthwhile experiment, but I agree with Animal that many reports suggest that long-term usage sounds like it has some unpleasant drawbacks, at least in some cases. Though a few studies [2] [3] administered 600mg for 1-2 months, and mentioned no downsides in the abstracts.

In rats sul = no change in # of NMDA
In rats sul = decrease in kainate
In rats sul = no change in D1 density
In rats sul = decrease DA and decrease DOPAC

Is the reason for the decrease in DA and DOPAC because of hydrogen peroxide caused by sul?

The study did mention that chronic treatment increased D1 sites, while acute administration had no effect. Unless the full texts mention something, I didn't see anything to suggest that sulbutiamine increases H2O2 levels. In the absence of such data, it's probably more reasonable to assume that it effects modulation of DA through interaction with receptors or synthesis/release mechanisms, rather than destructive radical damage (which would probably have to be pretty heavy to change levels significantly, and would probably present other symptoms), though it's certainly not out of the question.

[Valor5]

In rats sul = no change in # of NMDA
In rats sul = decrease in kainate
In rats sul = no change in D1 density
In rats sul = decrease DA and decrease DOPAC

Is the reason for the decrease in DA and DOPAC because of hydrogen peroxide caused by sul?

Found this interesting point about hydrogen peroxide. Does anyone know much about hydrogen peroxide in the brain? Is this alleviated or exacerbated by antioxidants like vit. C, ALCAR, ALA, vit. E?

DOPAC (3,4-dihydroxyphenylacetic acid) is a metabolite of the neurotransmitter dopamine. DOPAC can be oxidized by hydrogen peroxide, leading to the formation of toxic metabolites which destroy dopamine storage vesicles in the Substantia nigra. This may contribute to the failure of Levodopa treatment of Parkinson's disease. A MAO-B inhibitor such as (deprenyl) can prevent this from happening.

I have read that it's better to avoid vitamins especially vitamin c when ingesting small doses of 3% H2O2, can't remember why.

Additionally, some animal research indicates that when H202 given orally combines with iron and small amounts of vitamin C in the stomach, hydroxyl radicals are created (J Inorg Biochem 89;35(1):55-69).

[longevitynow]

I've only occasionally thrown some into my morning stack, where I seem to have noticed that it perhaps added a little focus and sustained energy to the effect. This thread is encouraging me to re-experiment.

[chrono]

I split the discussion of H2O2 and peroxidation into a new thread, as I didn't see much connection with sulbutiamine's dopaminergic effects, in particular, and it seemed to be generating some discussion.

Here's something interesting I found in a very old M&M post:

Here is what a behavioral neuroscience grad student friend of mine had to say (keep in mind that this is all speaking in general terms):
it would increase motor behavior.
dopamine levels in the pfc and the nucleus accumbens are inversely related. stimulants primarily increase subcortical (nucleus accumbens) dopamine.
the effect of antipsychotics is to block the effect of dopamine subcortically, and actually to increase cortical dopamine.

The review cited is Seamans & Yang (2004), which like most papers, I don't have access to from my bedroom. It's an interesting possibility to explain the acute reward/motivational effects of sulbutiamine by an increase in NAc DA, with a downstream decrease in the PFC—or via prefrontal inhibition. (This is assuming that this possibility isn't discounted in the text of the Trovero et al dopamine paper by the examination of other brain regions).

Is anyone aware of any other drugs that increase NAc DA by/while also decreasing it in the PFC?

Edited by chrono, 21 October 2010 - 01:59 PM.

[Valor5]

I split the discussion of H2O2 and peroxidation into a new thread, as I didn't see much connection with sulbutiamine's dopaminergic effects, in particular, and it seemed to be generating some discussion.

Here's something interesting I found in a very old M&M post:

Here is what a behavioral neuroscience grad student friend of mine had to say (keep in mind that this is all speaking in general terms):
it would increase motor behavior.
dopamine levels in the pfc and the nucleus accumbens are inversely related. stimulants primarily increase subcortical (nucleus accumbens) dopamine.
the effect of antipsychotics is to block the effect of dopamine subcortically, and actually to increase cortical dopamine.

The review cited is Seamans & Yang (2004), which like most papers, I don't have access to from my bedroom. It's an interesting possibility to explain the acute reward/motivational effects of sulbutiamine by an increase in NAc DA, with a downstream decrease in the PFC—or via prefrontal inhibition. (This is assuming that this possibility isn't discounted in the text of the Trovero et al dopamine paper by the examination of other brain regions).

Is anyone aware of any other drugs that increase NAc DA by/while also decreasing it in the PFC?

Maybe apomorphine or procaine?

[Valor5]

Moreover, after a chronic
treatment of rats with sulbutiamine intracellular thiamine
derivatives were increased by respectively 250% (thiamine),
40% (ThMP), 25% (ThDP) and 40% (ThTP) [14].

Does anybody know if these derivatives are a good thing or a bad thing?

[kassem23]

I split the discussion of H2O2 and peroxidation into a new thread, as I didn't see much connection with sulbutiamine's dopaminergic effects, in particular, and it seemed to be generating some discussion.

Here's something interesting I found in a very old M&M post:

Here is what a behavioral neuroscience grad student friend of mine had to say (keep in mind that this is all speaking in general terms):
it would increase motor behavior.
dopamine levels in the pfc and the nucleus accumbens are inversely related. stimulants primarily increase subcortical (nucleus accumbens) dopamine.
the effect of antipsychotics is to block the effect of dopamine subcortically, and actually to increase cortical dopamine.

The review cited is Seamans & Yang (2004), which like most papers, I don't have access to from my bedroom. It's an interesting possibility to explain the acute reward/motivational effects of sulbutiamine by an increase in NAc DA, with a downstream decrease in the PFC—or via prefrontal inhibition. (This is assuming that this possibility isn't discounted in the text of the Trovero et al dopamine paper by the examination of other brain regions).

Is anyone aware of any other drugs that increase NAc DA by/while also decreasing it in the PFC?

IIRC, SSRIs activate 5-HT1A which reduces PFC activity and activates 5HT2C which reduces hedonic drive. IIRC, the 5HT2C is responsible for the decreased DA in the NAc's.

Edited by kassem23, 06 November 2010 - 07:25 PM.

[3 9 27]

trying to find a good source for Sulbutiamine... where do you guys purchase from?
thanks in advance.

[Animal]

I split the discussion of H2O2 and peroxidation into a new thread, as I didn't see much connection with sulbutiamine's dopaminergic effects, in particular, and it seemed to be generating some discussion.

Here's something interesting I found in a very old M&M post:

Here is what a behavioral neuroscience grad student friend of mine had to say (keep in mind that this is all speaking in general terms):
it would increase motor behavior.
dopamine levels in the pfc and the nucleus accumbens are inversely related. stimulants primarily increase subcortical (nucleus accumbens) dopamine.
the effect of antipsychotics is to block the effect of dopamine subcortically, and actually to increase cortical dopamine.

The review cited is Seamans & Yang (2004), which like most papers, I don't have access to from my bedroom. It's an interesting possibility to explain the acute reward/motivational effects of sulbutiamine by an increase in NAc DA, with a downstream decrease in the PFC—or via prefrontal inhibition. (This is assuming that this possibility isn't discounted in the text of the Trovero et al dopamine paper by the examination of other brain regions).

Is anyone aware of any other drugs that increase NAc DA by/while also decreasing it in the PFC?

IIRC, SSRIs activate 5-HT1A which reduces PFC activity and activates 5HT2C which reduces hedonic drive. IIRC, the 5HT2C is responsible for the decreased DA in the NAc's.

Yep, which of course accounts for the rather unpleasant SSRI initial adaptive phase. High affinity 5HT2C antagonists for everyone!

[ritch]

trying to find a good source for Sulbutiamine... where do you guys purchase from?
thanks in advance.

smartpowders.com I live in Canada and they always send express. They must be one of the cheapest places to get aniracetam also.

[J. Galt]

Would increasing dopamine receptor density help reverse stimulant tolerance (i,e. d-amp)?As I understand it, chronically elevated dopamine levels resulting from stimulant use results in receptor DOWNregulation, thus increasing tolerance by modulating the DA-associated subjective reward mechanism.

Would Memantine + Sulbutiamine synergize to help reverse amphetamine tolerance (via NMDA antagonism and DA receptor upregulation)?

Edited by J. Galt, 13 December 2010 - 05:48 AM.

[BlueCloud]

Sulbutiamine was one of the most useless things i ever tried. I got the real stuff , it's freely available OTC here under the name Arcalion from the lab that created it , Servier.
Never felt anything at all from it at any dose , i tried it for a week. In fact it's widely considered as placebo by most doctors and pharmacists here.
Once , i ate half the 30 pill box ( they're 200mg pills , they look and taste like M&M's :-) ) , probably 15 pills at once , so close to 3 grams. I should have bought some real M&M's instead.

Of course, YMMV.

[Justchill]

I also tried 600 mg of Sulbutiamine this saturday:

- I feelt good, motivated
- Energy
- Some focus
- No anxiety
- Though some small irritation

I will try 900mg this friday on a party with some other stuff

cheers

[m147]

I tried 1 ml of sulbutiamine (should be about 320mg) this morning and didn't notice much, could be that I downed it with water and nothing else besides a few peanuts for breakfast.

I just downed 0.5ish ml (~160mg) dissolved in olive oil and fiber oatmeal, should be a better way to take this from the minimal amount of research I've done on this.

sulbutiamine should be taken sublingually for max effect, it breaks down in the digestive tract if ingested

Edited by Michael, 28 June 2011 - 11:43 AM.

[The Human Meteorite]

I tried 1 ml of sulbutiamine (should be about 320mg) this morning and didn't notice much, could be that I downed it with water and nothing else besides a few peanuts for breakfast.

I just downed 0.5ish ml (~160mg) dissolved in olive oil and fiber oatmeal, should be a better way to take this from the minimal amount of research I've done on this.

sulbutiamine should be taken sublingually for max effect, it breaks down in the digestive tract if ingested

Citation? Thiamine sure doesn't and it is very similar...
Plus, I don't think anybody is capable of holding a powder this foul tasting in their mouth for 15 minutes.

Edited by Michael, 28 June 2011 - 11:44 AM.