25 replies to this topic

[John250]

It seems that the number one drug to increase dopamine is Levodopa/carbidopa. If one wanted to restore dopamine permanently Ldopa wouldn’t be the choice as it’s synthetic and will cause further depletion after cessation. If Mucuna Pruriens contain natural levodopa would they also require Carbidopa to cross the BBB and be utilized efficiently? If so is there a natural source of carbidopa that’s just as effective(Fava Bean?)
If levodopa increases all of dopamines receptors, sub types and ligands wouldn’t Mucuna pruriens do the same? Wouldn’t this be the one and only supplement(that’s actually natural) to permanently and safely restore a damaged dopamine system?(dopamine system in its entire state)?

Edited by John250, 25 June 2018 - 08:39 AM.

[triguy]

what dosages were you thinking
?????

[John250]

what dosages were you thinking
?????

I use Now’s. 2caps is 800mg standardized for I believe 120mg L-Dopa. I just take 1-2 caps per day. Don’t really notice much at all from it. I think L-Dopa doses need to be much higher(>200mg) to notice but I believe they can suppress natural dopamine at that level.

[triguy]

now's 2 caps = 800mg.   This is mucuna??   120 mg standerdized "yields" 120mg of L-dopa from MUCUNA?

 

lol I am asking, is mucuna & l-dopa the same thing

 

 

All this advice, I should buy you lunch one day

[John250]

now's 2 caps = 800mg. This is mucuna?? 120 mg standerdized "yields" 120mg of L-dopa from MUCUNA?

lol I am asking, is mucuna & l-dopa the same thing


All this advice, I should buy you lunch one day

Yes Mucuna contains a % of natural L Dopa

[CWF1986]

Dopamine precursers won't be the answer to repairing dopamine pathways.  It might feel that way for a while but after some time the brain will reduce the amount of dopamine receptors to achieve homeostasis and if you ever want to quit those types of supps/meds you'll be in worse off shape than you were in the first place.  Yes, it is very possible to experience withdrawal from levodopa and this is a well known medical fact.  

 

I would focus on resensitizing my brain to dopamine and look into memantine and the uridine stack if this were something I wanted to do.  

 

Unfortunately, we don't have a silver bullet for fixing these types of things.  There might be some things that'll help you a little a long the way, but for the most part if you want to get back to baseline you're just going to have endure a long period of suck.  

 

If I wanted to make amphetamine withdrawal more tolerable, I would try bupropion which I have experience with and can make it easier to stop taking amphetamine.  Granted I was taking a low-moderate therapeutic dose of amp for ADHD.  What also might help is selegeline.  I mention selegeline very tentatively because even the PEA from a bar of dark chocolate can cause a strong high and addiction because of the way selegeline will amplify the effects.  

[gamesguru]

There is a strong cortisol-dopamine connection.  Working out for an hour and a half or more several days a week does the same thing to dopamine levels as masturbating too much, makes them plummet.  You might assume that's good because receptors will rise, but because of pre-synaptic sites it actually ends up being bad.

 

Whether a medicine will have greater effects on the synaptic or pre-synaptic sites is difficult to determine except through experiment, as it depends on many things, such as the type of neuron and the diffusion coefficient.  This is why amphetamines produce a long lasting up-regulation of dopamine receptor, while cocaine induces a down-regulation.

 

 

You can actually try some solutions that would be part of you and easy to digest up until your last days in hospice!  Magnesium, ginger,  grapefruit, all these are things with cumulative effects on the dopamine system that get better the longer you take it and originate from all the wonderful sub-constituents nature has to offer.  They all also property of being relative underdogs, things with real potential in parkinsons, ADHD, that just no one is taking seriously..

[John250]

I’m not so much concerned about the withdrawl as the first three days I can just sleep and it’s not like I’ll have chronic pain as you would with opioid with drawls. I’m more worried about the long lasting fatigue and anhedonia. And even more so the reality of going through life without having elevated dopamine all the time and achieving daily tasks and motivation. I think a lot of supplements I mentioned are more for preventative neurotoxicity while on amphetamines so I might eliminate those and just stick with supplements that will help restore natural dopamine. The one with the most promise so far seems to be Kb220z.

[CWF1986]

I’m not so much concerned about the withdrawl as the first three days I can just sleep and it’s not like I’ll have chronic pain as you would with opioid with drawls. I’m more worried about the long lasting fatigue and anhedonia. And even more so the reality of going through life without having elevated dopamine all the time and achieving daily tasks and motivation. I think a lot of supplements I mentioned are more for preventative neurotoxicity while on amphetamines so I might eliminate those and just stick with supplements that will help restore natural dopamine. The one with the most promise so far seems to be Kb220z.

 

Sorry, I loosely used the word withdrawal.  What I experience for some weeks after not having my therapeutic dose of adderall is fatigue, sleepiness, and brain fog.  That's the kind of thing I meant about withdrawal.  So I think we're actually on the same page there.  

[dopaminerush]

I think there is no magic supplement or drug for it.  if your talking about tolerance they say memantine,NAC, sulbutiamine works. And make you more sensitive to any stimulan and your own dopamine. 

 

But real way requires behavioral modification.

 

1-just be sure you dont have any vitamin mineral deffiency

2-increase your athletic performance (lift weights but at the same time have a high cardiovascular endurance, work capacity, do gpp work)

3-healty bodyweight.

4- Dont go overboard on modern day life joys. dont eat too much delicious foods, stay away from porn,masturbation, too much gaming etc.

5 -nofap can help too.

 

 

 

[metabrain]

To restore dopamine permanently the goal should not be to add more dopamine, instead you should focus on upregulating the receptors instead.

[John250]

To restore dopamine permanently the goal should not be to add more dopamine, instead you should focus on upregulating the receptors instead.

What could I take to do this? Thanks

[metabrain]

What could I take to do this? Thanks

 

You would need to be certain that your dopamine levels are low, a lot of people think their dopamine levels are low and dopamine is not at fault. One way you can tell is with Levadopa/Carbadopa, if symptoms improve you have an idea the receptor is at fault. Levadopa must be taken with Carbadopa as the levadopa will bind to areas outside of the brain (very very bad), get a proper prescription for it if possible. L-Tyrosine may also work as a test but it is not as reliable.

 

These are the only ones I know to upregulate, but I am betting there is many more:

 

Naltrexone an o1 opoid substitute up-regulates dopamine, it however is controlled and dangerous to take with an opoid or other medications.

 

SSRIS - Serotonin and Dopamine often compete, sometimes upregulating one will downregulate the other. (This is a complicated process)

 

Uridine + DHA + Choline (Not sure on this one)

[John250]

You would need to be certain that your dopamine levels are low, a lot of people think their dopamine levels are low and dopamine is not at fault. One way you can tell is with Levadopa/Carbadopa, if symptoms improve you have an idea the receptor is at fault. Levadopa must be taken with Carbadopa as the levadopa will bind to areas outside of the brain (very very bad), get a proper prescription for it if possible. L-Tyrosine may also work as a test but it is not as reliable.

These are the only ones I know to upregulate, but I am betting there is many more:

Naltrexone an o1 opoid substitute up-regulates dopamine, it however is controlled and dangerous to take with an opoid or other medications.

SSRIS - Serotonin and Dopamine often compete, sometimes upregulating one will downregulate the other. (This is a complicated process)

Uridine + DHA + Choline (Not sure on this one)

So the only medicine to help upregulate dopamine is levodopa?A dopamine agonist or antagonist will not do this? So basically if I feel better from it it’s something I would have to stay on forever as if I went off of it my levels would be depleted even further?

[Galaxyshock]

I don't think there's any compound that would strongly and selectively upregulate the dopamine receptors. Better just let time do the restoration and meanwhile take stuff that do good both short term and long term for the dopaminergic system like Cordyceps, Maca, Jiaogulan, and provide the precursors and micronutrients necessary for the neurotransmitter synthesis.

[gamesguru]

Cordyceps, Maca, Jiaogulan ... for the neurotransmitter synthesis.

 

muses.  wouldn't continued use simply result in unwanted downregulation? 

 

Flex and Area and I actually did find a few compounds that can upregulate them, I might be able to dust off those results on request

[Galaxyshock]

Well luckily the brain chemistry isn't all about some kind of zero-sum game where every boost in neurotransmission leads to downregulation, withdrawal, depression, divorce and death.

 

[metabrain]

So the only medicine to help upregulate dopamine is levodopa?A dopamine agonist or antagonist will not do this? So basically if I feel better from it it’s something I would have to stay on forever as if I went off of it my levels would be depleted even further?

No, levodopa only increases dopamine, since it is selective for dopamine you would be using that to see if your symptoms go away, if so then you would know it is dopamine and not something else. 2 weeks of levopdopa and you will know.

 

 

Actual Upregulation would be done by the following:

 

Naltrexone an o1 opoid substitute up-regulates dopamine, it however is controlled and dangerous to take with an opoid or other medications.

 

SSRIS - Serotonin and Dopamine often compete, sometimes upregulating one will downregulate the other. (This is a complicated process)

 

Uridine + DHA + Choline (Not sure on this one)

 

 

One thing you need to be aware of is that upregulation is actually not clear cut, for example if you take an SSRI short term you can get upregulation of dopamine but in the long term it can downregulate dopamine. 

 

Dopmaine agonist or antagonist may upregulate dopamine I am not sure to be honest

 

You have to investigate each medication or supplement on a case by case basis.

[John250]

So this is what I’m thinking. I’m sure it’s going to take years to fix my dopamine system and I don’t even have 3 months as I have a business and a family. When I used steroids it shut down my natural testosterone production which is very common with prolonged use. I take testosterone replacement therapy and everything is fine. I had two healthy kids and I feel great with it and it’s easy to monitor. I’m sure the dopamine system is much more complex but I wouldn’t be opposed to permanent dopamine replacement therapy as I don’t have time for my dopamine to recover and don’t even know if it will. Plus I’ve been on Lexapro for over seven years and need to stay on it so who knows if that is also depleting my dopamine. Are there any good options for permanent Dopamine replacement therapy? I have both naltrexone and ropinirol on hand and can order Levodopa if need be. Another thought is I could just stay on therapeutic doses of amphetamines but I don’t want the negative cardiovascular effects from them I would rather use something else to increase dopamine without those side effects. I realize I won’t get the high that I am used to getting but I also need to take something forever so I don’t experience the low.

[Galaxyshock]

If you really want to stay on stimulants or direct dopaminergics for life then maybe consult nickname Medievil as he is long term stimulant users with knowledge but I suspect it's a dead end. The cumulative damage is unpredictable. Adolf Hitler took daily injections of methamphetamine during the WWII and towards the end he had aged rapdily was drooling and barely standing. The damage from oral amp won't be that bad but you know what do you really think is "therapeutic use" long term? "Dopamine replacement" would be something similar to parkinson's treatment which are L-DOPA and dopamine agonists in increasingly higher doses leading to movement disorders and such. You're in your 30s so still somewhat young and looking at 50 years of healthy life ahead or dramatically longer if you believe in the principles of this site. Maybe I'm overly dramatic and you could manage to come up with a working protocol with DAergic drugs, but if I was you I would taper off the amphetamines, take the supps and perhaps resort to Iboga for addiction/psychological issues with the use.

[John250]

If you really want to stay on stimulants or direct dopaminergics for life then maybe consult nickname Medievil as he is long term stimulant users with knowledge but I suspect it's a dead end. The cumulative damage is unpredictable. Adolf Hitler took daily injections of methamphetamine during the WWII and towards the end he had aged rapdily was drooling and barely standing. The damage from oral amp won't be that bad but you know what do you really think is "therapeutic use" long term? "Dopamine replacement" would be something similar to parkinson's treatment which are L-DOPA and dopamine agonists in increasingly higher doses leading to movement disorders and such. You're in your 30s so still somewhat young and looking at 50 years of healthy life ahead or dramatically longer if you believe in the principles of this site. Maybe I'm overly dramatic and you could manage to come up with a working protocol with DAergic drugs, but if I was you I would taper off the amphetamines, take the supps and perhaps resort to Iboga for addiction/psychological issues with the use.

I just did an experiment today. I took my Vyvanse this morning and purposely left my Adderall at work. Right now I’m extremely tired and lethargic so I just tried .25mg ropinirole for the first time. It will take a few hours to kick in but I’m curious if I notice anything. It has a pretty short half-life of around 6hrs. Im an ultra metabolizers so for me probably like 4 hours. It’s typically dosed 3x/per day so if I just take it once a day and notice a difference it might be my answer short term while being off amphetamines. Then I can assess whether or not to taper off Ropinirole.

[metabrain]

So this is what I’m thinking. I’m sure it’s going to take years to fix my dopamine system and I don’t even have 3 months as I have a business and a family. When I used steroids it shut down my natural testosterone production which is very common with prolonged use. I take testosterone replacement therapy and everything is fine. I had two healthy kids and I feel great with it and it’s easy to monitor. I’m sure the dopamine system is much more complex but I wouldn’t be opposed to permanent dopamine replacement therapy as I don’t have time for my dopamine to recover and don’t even know if it will. Plus I’ve been on Lexapro for over seven years and need to stay on it so who knows if that is also depleting my dopamine. Are there any good options for permanent Dopamine replacement therapy? I have both naltrexone and ropinirol on hand and can order Levodopa if need be. Another thought is I could just stay on therapeutic doses of amphetamines but I don’t want the negative cardiovascular effects from them I would rather use something else to increase dopamine without those side effects. I realize I won’t get the high that I am used to getting but I also need to take something forever so I don’t experience the low.

Amphetamines will just continue to downregulate or even damage your dopamine neurons. Ideally we wouldn't want to put you on dopamine replacement therapy as that eventually fails with bad side effects. The goal really should be to upregulate and discontinue medication but only if it really is dopamine downregulation.

 

One thing about SSRIs is that serotonin competes with dopamine, increasing one can decrease the other. Have you tried coming off Lexapro for an extended period of time?

 

I would taper off everything, give yourself enough of a washout period, do this slowly to avoid withdrawal and to reset to a baseline.

 

Then go on Levadopa, and stay on that for 2-4 weeks. It is very easy to take. If you respond to it then you most likely have an issue with dopamine. This is just a feeler drug to see if you have issues with dopamine, so come off of it as soon as you know.

 

If you are going with Naltrexone, ask for a low dose, this will be easier and you can increase it as needed, and be careful with this medication. You can also use another medication to up-regulate but unfortunately I don't know much about dopamine to make a recommendation.

 

I would seriously recommending seeing a neurologist or doctor. I have been in the situation where I have needed to do this as part of my recovery and the neurologist was super helpful in helping me understand the complexity of what I was trying to do. Eventually for me it wasn't dopamine that was the issue at all, the Levadopa had been a useful testing tool to discount my assumption and that set me in a whole different direction.

[gamesguru]

dopamine replacement therapy is usually reserved for end-stage Parkinson's so let's not go there quite yet.  Dopamine is tricky, with different receptors and different localizations, it is hard to make sense of.  More or less you can take stuff that pushes it slightly one way, and back, and mix it with some other things and wait and stop and go and hope for the best.  Horny goat weed boosts TH, that's the enzyme that makes dopamine.  But the best thing is just time and not going too hard on any one thing

[MattH]

I actually think precursors work just fine for some basic restoration or regulation after I have given the receptors a blow/pushback by serotonin precursors, or acetylcholine/Huperzine - or by Uridine (sometimes very bad). No problem at all, also don't see why it should be bad to give a little extra dopamine to work with and stimulate receptors. Apparently dopamine receptors break easily, but not that easily, and it works for everything else too (serotonin).

Apparently I have used all three, all were fine: Mucuna Pruriens, Phenylalanin, L-Tyrosin. They are probably safest the less direct they are though, with Phenylalanin in the middle. Maybe that's how you avoid most negatives. Something else I've heard in that regard and to consider: the more direct (L-Dopa), the more it gets used in the body before it can reach the brain.

I also sometimes deplete serotonin beforehand by Beta-Alanin (which I've heard contributes to that). However you might not find this useful, if you have/want no serotonin issues.

Then you can look up some things which supposedly regrow dopamine receptors, like Forskolin, Inositol... Some seem to be wrong but probably rather serotonin boosters (St. John's Wort, Ashwaghanda), it's popular to casually claim both in many cases (also see coffee etc... hard to even find the real answer, but it's probably primarily serotonin).

Edited by MattH, 29 July 2018 - 11:39 PM.

[gamesguru]

A lot of us are looking for something we can take every day, safely, for the rest of our life.  The first three things don't fit that category.  But they are great in the short-term, as you found.  Forskolin arguably doesn't fit the category either, but regardless it breaks some of its own categories as some mutant stimulant and has question marks hanging from it everywhere.

 

Inositol is pretty tame for the healthy adult, as they get lots from their diet already.  I would go for ashwagandha before much of what was mentioned, but even there there is too much of a cholinergic component for my liking.  This is really a complicated problem that deserves some respect, you don't just go charging in like Gallahad

[MattH]

Well, I am not talking about taking it for the rest of one's life, but actual balance, which works no different than in all other things. Once you have balanced you can cut back on it. I'm talking about nothing else. It's not as "terrible"as it's made out to be, they are just some basic stimulation, which as we know has an effect, also longterm.

This "panic" I also had to struggle with and I think it causes pointless problems.

If you take anything else to "permanently change" it, I wouldn't recommend going without some precursors, which can make the process much more effective. They are just an ingredient, but generally nothing more "terrible" than that (or different to anything else just because it's the infamous dopamine system).

If I take two days Huperzone I'm messed up, which I can help by Dopamine. And that's almost the end of it. (In a nutshell.)

Edited by MattH, 29 July 2018 - 11:48 PM.