47 replies to this topic

[fluidity]

I'm planning on using sulbutiamine/choline source as well as tyrosine to help improve my dopamine release and regulation. I heard choline can increase upregulation of dopamine receptors and so can sulbutiamine through decreasing the release of dopamine. And once I'm done with doing that for a few days I'm going to cycle and use tyrosine to increase my dopamine production, and then go back to upregulation for a few days. I also plan on using alcar and alpha gpc as well during all of this.

I just want to ask everyone what they think of this, and if this is an effective way of increasing dopamine?

[Mens]

Tyrosine and Sulbutiamine did not have any effect on me which is different for everyone so I don't want to discourage you to try it out.

Mucuna Pruriens did have a very profound effect for me. So you might look in to that as well. Mucuna Pruriens are velvet beans. It contains L-Dopa which is a precursor for the neurotransmitter dopamine.

Edited by Mens, 09 April 2013 - 04:14 PM.

[daouda]

Your approach looks interesting, but you should definitely take a look at the Uridine/DHA/Choline thread

[KoolK3n]

You won't feel anything from that. Lithium significantly upregulates TH (Tyrosine Hydroxylase) (Dopamine synthesis).
http://www.ncbi.nlm..../pubmed/9523597

[Reformed-Redan]

You won't feel anything from that. Lithium significantly upregulates TH (Tyrosine Hydroxylase) (Dopamine synthesis).
http://www.ncbi.nlm..../pubmed/9523597

The amount in the paper would work out to be around 58mg of lithium per kilogram in humans. Wayy too much.

[Galaxyshock]

Zinc is useful mineral to supplement:
http://www.ncbi.nlm....pubmed/19000913

So it's a dopamine reuptake inhibitor as long as the cells are excitable. It's also NMDA-antagonist.

[KoolK3n]

You won't feel anything from that. Lithium significantly upregulates TH (Tyrosine Hydroxylase) (Dopamine synthesis).
http://www.ncbi.nlm..../pubmed/9523597

The amount in the paper would work out to be around 58mg of lithium per kilogram in humans. Wayy too much.

Oh damn I didn't see that in the abstract. Thanks. I did a little more research and am finding conflicting results with its effect on neurotransmission. One says it unregulated serotonin synthesis while another says it shuts it down completely either way the doses are way to high as you pointed out.

[nowayout]

Doesn't tolerance occur quickly whatever you do to dopamine metabolism? (At least for some people, especially those with the genes to get addicted easily.) If someone could clarify this I'd appreciate it.

[chung_pao]

If our biochemistry works anything alike, Sulbutiamine will downregulate and cause withdrawal.
After daily use I started noticing that I was in a Parkinsonian-zombie state every day I didn't take sulbutiamine, kicking in at around the time I used to be dosing.
(The experience was exactly the opposite of what sulbutiamine would normally cause)

Edited by chung_pao, 10 April 2013 - 06:26 PM.

[renfr]

If our biochemistry works anything alike, Sulbutiamine will downregulate and cause withdrawal.
After daily use I started noticing that I was in a Parkinsonian-zombie state every day I didn't take sulbutiamine, kicking in at around the time I used to be dosing.
(The experience was exactly the opposite of what sulbutiamine would normally cause)

Sounds strange and unexpected from a compound that is supposed to upregulate D1 receptors.
Maybe it's because you're not used anymore to your pre-sulbutiamine state and therefore see it as a regression, it's like someone who has average vision and get some glasses to see a bit better and then when he removes the glasses he thinks that his vision has deteriorated but in fact it hasn't because he was used to optimal levels of sight.

If it did downregulate anything I would have noticed this, I've been using this compound for over a month and it still gives me the exact same effects as the first time! I take it everyday so it's unlikely that it has downregulated something.

[Dissolvedissolve]

Sounds strange and unexpected from a compound that is supposed to upregulate D1 receptors.
Maybe it's because you're not used anymore to your pre-sulbutiamine state and therefore see it as a regression, it's like someone who has average vision and get some glasses to see a bit better and then when he removes the glasses he thinks that his vision has deteriorated but in fact it hasn't because he was used to optimal levels of sight.

If it did downregulate anything I would have noticed this, I've been using this compound for over a month and it still gives me the exact same effects as the first time! I take it everyday so it's unlikely that it has downregulated something.

Your individual biochemistry may be different. There are many reports of withdrawal from sulbutiamine, so his should not come as a surprise. I personally feel a very definite come-down effect when sulbutiamine wears off and have never taken it for extended periods as to avoid such unpleasant withdrawal symptoms.

[**DEACTIVATED**]

I thought Sulbutiamine was very quick to adapt a tolerance to. Who knows though.. everyone success story is different.

Anyway, what's wrong with just taking Selegiline for more dopamine? The thread is titled "increasing dopamine production" and as far as I know Selegiline doesn't even down regulate dopamine receptors. So... what's the problem? I'd like to know for my own personal sake, if anything.

By the way I should mention I'm a total novice at this brain chemistry crapola. I can basically only repeat what more knowledgeable and reputable people write, so my posts could be expendable.

[renfr]

Sounds strange and unexpected from a compound that is supposed to upregulate D1 receptors.
Maybe it's because you're not used anymore to your pre-sulbutiamine state and therefore see it as a regression, it's like someone who has average vision and get some glasses to see a bit better and then when he removes the glasses he thinks that his vision has deteriorated but in fact it hasn't because he was used to optimal levels of sight.

If it did downregulate anything I would have noticed this, I've been using this compound for over a month and it still gives me the exact same effects as the first time! I take it everyday so it's unlikely that it has downregulated something.

Your individual biochemistry may be different. There are many reports of withdrawal from sulbutiamine, so his should not come as a surprise. I personally feel a very definite come-down effect when sulbutiamine wears off and have never taken it for extended periods as to avoid such unpleasant withdrawal symptoms.

Right individual chemistry may be a part of explanation though I don't see a lot of reports about withdrawals except those talking about tolerance.
But however it contradicts with current scientific data about sulbutiamine, it's true that it hasn't been researched thoroughsly though.

I thought Sulbutiamine was very quick to adapt a tolerance to. Who knows though.. everyone success story is different.

Anyway, what's wrong with just taking Selegiline for more dopamine? The thread is titled "increasing dopamine production" and as far as I know Selegiline doesn't even down regulate dopamine receptors. So... what's the problem? I'd like to know for my own personal sake, if anything.

By the way I should mention I'm a total novice at this brain chemistry crapola. I can basically only repeat what more knowledgeable and reputable people write, so my posts could be expendable.

Because it's an irreversible MAOI and it could overtime cause deadly hypertensive crisis overall if taken with tyraminergic foods.
Besides at high doses it inhibits strongly MAOB which is responsible for the rise in blood pressure, so it's not very practical on the long term, only short term use.

[Dissolvedissolve]

Right individual chemistry may be a part of explanation though I don't see a lot of reports about withdrawals except those talking about tolerance.
But however it contradicts with current scientific data about sulbutiamine, it's true that it hasn't been researched thoroughsly though.

There's one study showing the increase in D1 (I believe) receptors in the PFC. I think it needs to be verified, and the fact that it's increasing D1 receptor density in one brain region does not imply a broader increase in density. If we're specifically talking about reward or other mechanisms which would be implicated in sulbutiamine's benefits as well as its possible withdrawal, we'd be more interested in some specific regions, ie the VMPFC, rather than the PFC as a whole.

Because it's an irreversible MAOI and it could overtime cause deadly hypertensive crisis overall if taken with tyraminergic foods.
Besides at high doses it inhibits strongly MAOB which is responsible for the rise in blood pressure, so it's not very practical on the long term, only short term use.

The MAOI warning is justified, but at doses at or below 10 mg, it's selective for MAO-B and has very little risk of a tyramine effect. Any increase in BP should be relatively minor, especially once homeostasis is reached.

My more major criticism of selegiline is that there's risk of a substantial, perhaps even complete, tolerance. A longecity user discussed the development of a near-complete tolerance in this thread: http://www.longecity...r-adhd-reviews/

Edited by Dissolvedissolve, 10 April 2013 - 07:47 PM.

[**DEACTIVATED**]

renfr,

I think you meant MAOI-A at high doses. At doses above 10mg/day hypertension is possible, but you don't have to go that high to increase production of dopamine.

[nowayout]

Anyway, what's wrong with just taking Selegiline for more dopamine? The thread is titled "increasing dopamine production" and as far as I know Selegiline doesn't even down regulate dopamine receptors. So... what's the problem? I'd like to know for my own personal sake, if anything.

I don't know what's wrong with it, but studies have found that selegeline doesn't lift mood unless taken in doses that also inhibit MAO-A enough to raise serotonin and norepinephrine, indicating that it is not its effect on dopamine (at least not only) that causes people to feel better.

So maybe its effect on mood via dopamine is negligible or maybe its effect on dopamine leads to rapid tolerance.

I am still wondering why anybody should expect that any substance that either increases extracellular dopamine or increases dopamine receptors would not cause eventual habituation and tolerance.

[**DEACTIVATED**]

I'm not sure either. When I started a topic on Deprenyl and tolerance I was simply assured it was not an issue. Here's the thread: http://www.longecity...ving-tolerance/

As for the tolerance debate itself... I'm not sure who to believe. There are long-term users of the drug that state no such thing and there are others that do. Maybe dosages play a key role there, I don't know. But, the drug does increase dopamine.

[chung_pao]

Currently using Sulbutiamine again, successfully this time. Why? I decreased the dose. Whereas I would dose 500+ mg earlier I'm now dosing in the 100-200 mg intervall.
I think it's beneficial to use sulbutiamine as a b-vitamin with BBB-penetration, not a stimulant.

I use selegiline without noticeable tolerance. 0.5 - 1 mg /day. Deprenyl was erratic and occasionally unpleasant, but they're pretty similar. (aside from selegiline lacking side effects, in my experience)
I've been using it for weeks and it's definitely still effective in increasing levels of dopamine and PEA. (the second one is harder to tell, though)

[Reformed-Redan]

Has anyone had success in using selegiline and EGCG together?

[**DEACTIVATED**]

I get 200mg of EGCG through green tea extract everyday along with Deprenyl. Only 1 month in and everything feels fine.

I'm gonna try and report back on it in the future at a later date.

[Reformed-Redan]

I get 200mg of EGCG through green tea extract everyday along with Deprenyl. Only 1 month in and everything feels fine.

I'm gonna try and report back on it in the future at a later date.

Did you notice increased volition or anything like that? I know on selegiline I wanted to run a lot more and longer. Running was almost euphoric at times. That was a real benefit.

[**DEACTIVATED**]

I get 200mg of EGCG through green tea extract everyday along with Deprenyl. Only 1 month in and everything feels fine.

I'm gonna try and report back on it in the future at a later date.

Did you notice increased volition or anything like that? I know on selegiline I wanted to run a lot more and longer. Running was almost euphoric at times. That was a real benefit.

Haha, I've read it's great for endorphins but I haven't been doing any intense exercise lately! Gah, just one more reminder.

I don't really notice any volition but I will note that I've been supplementing with Spirulina at doses above 10g and about 1 - 1.5 hours later after ingesting I get a head rush. I wonder if it's from all the Phenylalanine in the Spirulina? I've read it's the dominant amino acid in the plant. But it wouldn't make sense for it to create any good feelings if there are other amino acids fighting for absorption through the blood brain barrier. Which there are.

[brainslugged]

Because it's an irreversible MAOI and it could overtime cause deadly hypertensive crisis overall if taken with tyraminergic foods.
Besides at high doses it inhibits strongly MAOB which is responsible for the rise in blood pressure, so it's not very practical on the long term, only short term use.

Selegiline lowers blood pressure; it is a strange, paradoxical effect. And if taken in low doses, it only inhibits B, so you don't have to worry about the food restrictions. Clinical patients on it do no follow the restrictions.

However, I have read that there may be concern about an increase in body temperature?

[Consistency]

Naturally... Retinoids(Vitamin A) regulate the dopamine system, like the dopamine D2 receptors.

searching google for "retinoids dopamine d2" will give you results.

You can either drink fresh squeezed carrot juice, or eat pumpkin, apricots or lettuce which will also includes Vitamin K.

Edited by Consistency, 13 April 2013 - 11:57 PM.

[chung_pao]

Has anyone had success in using selegiline and EGCG together?

Exercise on Selegiline/Rasagiline definitely becomes more enjoyable.
I've tried Selegiline with high doses of EGCG (500-1000 mg) and the COMT inhibition is very noticeable.
Executive function and "conscious thinking", the known functions of the PFC, seemed to be positively affected. Motivation increased aswell.
My guess is that it's due to more dopamine available, especially in this area.

Edited by chung_pao, 14 April 2013 - 11:25 AM.

[bugasman]

Nicotine increases reward sensitivity:
http://www.ncbi.nlm....pubmed/16192981

Chronic Oral Nicotine Normalizes Dopaminergic Function:
http://www.jneurosci...7/4681.full.pdf

Just research on google, lots of studies on nicotine. There are some drawbacks. But for me the positives >> negatives.

Another one to look is Catuaba, I never used it but will... Catuaba is very used in South America. I think this is a promissing natural. I read from a member that it increases dopamine sensitivity but did not found any study. This is a good one: http://www.ncbi.nlm....pubmed/15991001 , http://www.ncbi.nlm....les/PMC3095233/ (opiod activity?)

For a releasing agent you can use methylphenidate (MPH) or dextroamphetamine (DEX). I like both together, a low dose (5-10mg) of Ritalin combined with DEX (10-15mg) increases motivation, confidence, mood, self-control (executive function) and MPH prevents amphetamine toxicity. Many studies indicates that amphetamine increases sensitivity to dopamine. Maybe tolerance is due other factors like hormonal imbalances, nutrition, sleep...

Avoid cholinergics, serotonergics and dopamine agonists. Substances like Piracetam and high dose choline makes me suicidal and violent. Rhodiola (increases serotonin) makes me super-violent, super-depressed and suicidal. Dopamine agonists makes me lethargic and cancel the stimulant effects of MPH or DEX. It can cause DAWS (search this). Maybe a partial DA-agonist like Hydergine is a good option. Hydergine is interesting (powerfull anti-oxidant, reduces prolactin, anti-anhedonic, neuroprotective and slight psychedelic), but use very low dose because is anti-adrenergic (50-200 mcg) and fuction as a dopamine antagonist when used with DA releasers.

Maybe a good combo is l-phenylalanine daily (low dose 250mg to increase dopamine production), nicotine patch (low dose 1/24 of 21mg to regulate dopamine system), l-theanine (100mg - neuroprotective and relaxing, maybe upregulate dopamine), Catuaba (dopaminergic with speculated opioid activity) B-complex (maybe very low dose sulbutiamine 50 mg - you dont need much, just smell your urine after a normal dose of Arcalion 200mg), zinc, magnesium, anti-oxidants (found in yerba-mate, dark chocolate, coffee, fruits, vegetables...), good nutrition (Google "Ray Peat") a powerfull stimulant (MPH or DEX), and good downers (Wine, Marijuana, exercise, sex...)

Here we have a "NZT Lite"? I'm justing feeling invencible after a long depression using some of those substances. No, it's not mania... or? I hope not.

Edited by bugasman, 14 April 2013 - 12:54 PM.

[mait]

Gynostemma is my bet in improving my dopamine system:

6-Hydroxydopamine administration for 28 days (8 microg/2 microL) reduced the number of tyrosine hydroxylase (TH)-immunopositive neurons to 40.2% in the substantia nigra compared to the intact contralateral side. Dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and norepinephrine levels were reduced to 19.1%, 52.3%, 47.1% and 67.4% in the striatum of 6-hydroxydopamine-lesioned rats compared to the control group, respectively. However, an oral administration of herbal ethanol extracts from Gynostemma pentaphyllum (GP-EX) (10 mg/kg and 30 mg/kg) starting on day 3 post-lesion for 28 days markedly ameliorated the reduction of TH-immunopositive neurons induced by 6-hydroxydopamine-lesioned rat brain from 40.2% to 67.4% and 75.8% in the substantia nigra. GP-EX administration (10 and 30 mg/kg) also recovered the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and norepinephrine in post-lesion striatum to 64.1% and 65.0%, 77.9% and 89.7%, 82.6% and 90.2%, and 88.1% and 89.2% of the control group. GP-EX at the given doses did not produce any sign of toxicity such as weight loss, diarrhea and vomiting in rats during the 28 day treatment period and four gypenoside derivatives, gynosaponin TN-1, gynosaponin TN-2, gypenoside XLV and gypenoside LXXIV were identified from GP-EX. These results suggest that GP-EX might be helpful in the prevention of Parkinson's disease.

http://www.ncbi.nlm....pubmed/20428081

[tritium]

http://www.ncbi.nlm....pubmed/15146188

However, nicotine, like the nAChR antagonist
mecamylamine, suppressed release elicited by single pulses or low,
tonic frequencies (≤10 Hz), but selectively enhanced release by phasic
bursts (≥25 Hz; Fig. 1a–c). Thus nicotine, acting by nAChR desensitization,
enhanced the contrast between phasic- and tonic-evoked
[DA]o (Fig. 1d).

Nicotine, in effect, sets a high-frequency pass filter11 for impulsedependent
dopamine release.

Thus we show that nicotine, through nAChR desensitization, suppresses
dopamine release during non-reward,
low firing frequencies, and conversely, selectively
enhances reward-related dopamine
release by relieving short-term depression at
higher burst-like frequencies. The findings
suggest that nicotine will enhance the contrast
in [DA]o when dopamine neuron activity
switches from tonic to phasic firing, which
could be in response to salient primary
rewards or conditioned reward predictions7.

Nicotine lozenges or patches may be helpful according to the above study.

[Galaxyshock]

Interesting. Nicotine could help with anhedonia

Edited by Galaxyshock, 14 April 2013 - 06:39 PM.

[**DEACTIVATED**]

Because it's an irreversible MAOI and it could overtime cause deadly hypertensive crisis overall if taken with tyraminergic foods.
Besides at high doses it inhibits strongly MAOB which is responsible for the rise in blood pressure, so it's not very practical on the long term, only short term use.

Selegiline lowers blood pressure; it is a strange, paradoxical effect. And if taken in low doses, it only inhibits B, so you don't have to worry about the food restrictions. Clinical patients on it do no follow the restrictions.

However, I have read that there may be concern about an increase in body temperature?

I can confirm this, I am feeling hotter now a days. It's actually pretty nice for now, until Texas gets in the 100's. But I used to be "warm blooded" when I was younger and as I got older I've only gotten colder. Now after adding Deprenyl I get hotter faster, easier.

Not sure if its a bad thing.

On a related subject I bought a blood pressure monitor for fun but then returned it when I read there was an app that can do that now. Can anyone confirm that app? A good one?