27 replies to this topic

[Robinvanpersie]

I want to ask is if someone knows about a drug addressing my dopamine levels, and that works similar to NSI-189 in that it permanently changes the brain so that I can take it for a few weeks and months and feel the effects for a long time after?

 

I'm pretty happy with my brain chemistry except that I think I'm my optimal self with a little more dopamine. Not a lot more since I'm not interested in going back to drugs similar to Adderall or Elvanse - they're making me way too addicted, too motivated and manic. Then I tried Bromantane and found it works really well for me - slight motivation increase, increase interest in people and conversations, no crashes or mania.

[John250]

I don’t think anything can permanently increase any neurotransmitter due to homeostasis

[metabrain]

How do you know you have an issue with Dopamine? 

 

Dopamine is a dangerous neurotransmitter to mess with. Your experience with Adderall will tell you that. You can also see the dangers when people with schizophrenia take anti psychotics for a long period of time (see https://en.wikipedia...ism_of_action) and it messes up their dopamine receptors.

 

Low Dose Naltrexone is one medication but it is used for opoid withdrawl and is dangerous. See previous posts on it.

 

You can try some of these options instead:

 

 

Modafinil, it is a weak dopamine reputake inhibitor.

An NDRI such as Bupropion

L-Tyrosine is a supplement that works on Dopamine.

[Painkillerrr]

the only way to permanently would be changing genes that encode for dopamine which is not currently possible

[MedMad]

Hello.. you say messing with dopamine lvls is dangerous.. I’m thinking of trying to fix brain damage caused by long term medication use & withdrawal using Mind Lab Pro & NSI-189 (I’m suffering acute meds withdrawal symptoms including depression, anxiety, confusion, physical pain) .. what are your thoughts on this ? please look up the ingredients at www.mindlabpro.com as I don’t know how to hotlink here.. I ask because quite a few ingredients of mind lab pro either increase or protect the decrease of dopamine & other neurotransmitters.. it also claims to help ‘fix’ brain damage, as apparently does NSI-189 also by increasing hippocampus quantity

[metabrain]

Hello.. you say messing with dopamine lvls is dangerous.. I’m thinking of trying to fix brain damage caused by long term medication use & withdrawal using Mind Lab Pro & NSI-189 (I’m suffering acute meds withdrawal symptoms including depression, anxiety, confusion, physical pain) .. what are your thoughts on this ? please look up the ingredients at www.mindlabpro.com as I don’t know how to hotlink here.. I ask because quite a few ingredients of mind lab pro either increase or protect the decrease of dopamine & other neurotransmitters.. it also claims to help ‘fix’ brain damage, as apparently does NSI-189 also by increasing hippocampus quantity

At high levels and over a long period of time yes, you see it with both recreational and pharmaceutical drugs such as Adderall.

 

The problem is though when people say they have deficient dopamine because symptom A or B, symptom A or B could be caused by something else.

The neurotransmitters also don't work in isolation, so if you do something with one neurotransmitters it may affect many others.

It gets even more complex when you take medications acting on multiple neurotransmitters. Unfortunately scientists don't understand this process fully and they discover new interactions all the time.

 

In your example you have depression, anxiety, confusion, and physical pain, that could be one of thousands of illnesses, could be malfunctioning neurotransmitter such as GABA or another neurotransmitter, could be dietary, could be anything.

 

You say in your post that you were on medication, what medication and how long? Could you still be withdrawing?

 

When you do have something wrong with dopamine you get things like Parkinsons, Serious memory loss, ADHD, Psychosis (increased), those are the kinds of conditions we talk about when we talk about Dopamine, dopamine is less likely than something else.

 

If you do want to test the neurotransmitters, test the common targets in succession, serotonin (SSRI), norepinephrine (SNRI) and then dopamine(L-DOPA/Carbidopa) but keep an open mind, don't just focus on neurotransmitters, try test various things in isolation.

[MedMad]

thx for your reply.. the most recently stopped meds cold turkey were Mirtazapine 45mg + Effexor 37.5 + Buspar 40mg .. was on them 11 weeks but did not help my symptoms, made me very aggressive & side effects were intolerable.. but since November last year was tried on many drugs.. all made me worse with intolerable side effects & withdrawals were (are) horrendous.. was tried on Annafranil 175 for 6 weeks.. made me very aggressive & agitated.. Seroquel 100mg for a number of weeks.. was brain dead, so sedated could not walk.. other Neuroleptics were the same.. before November was on Lamicdal 200mg, Abilify 5mg & moclobamide 150mg for 4 years.. was stable but my drs cold turkied me last February.. I’ve been very ill ever since.. tried giving me Abilify 5mg again but I had fits, palpitations, heart pains..

[Mike C]

Dancing/music works fantastically. Just gotta find the right tunes! Ones you really resonate with. Takes some work and effort. Get a good pair of earphones that’s important. Pills pills pills forget about it!

[davis89x]

Dancing/music works fantastically. Just gotta find the right tunes! Ones you really resonate with. Takes some work and effort. Get a good pair of earphones that’s important. Pills pills pills forget about it!

 

Drinking to that and answering also to OP, maybe it's not a medicine/substance but if you managed to get it you will arrive at what you want which is permanently increase in dopamine levels - just get schizophrenia for example    good luck

[Galaxyshock]

Dopamine receptor density correlates with increased social status. So being higher in a social hierarchy could mean long-term / permanent increased dopaminergic activity except if you lose that position.

[BieraK]

Dopamine receptor density correlates with increased social status. So being higher in a social hierarchy could mean long-term / permanent increased dopaminergic activity except if you lose that position.

Yes but specifically in the D2 receptor.

There are individuals with increased D2 receptor density due to genetic profile and there are individuals with motivational ADHD problems due to D2 receptor polymorphisms, in such case the D2 autoreceptor is unable to self detect dopamine levels so it does not releases more dopamine when a boring task is completed.
 

[BieraK]

There are some ways of permanently or semi-permanently increase dopamine, but with risks.

-Mr Happy Stack, this stack increases d2 receptor density (increases the amount of the d2 receptors), a guy on reddit report increased dopamine response after Uridine use, so for him less amount of dopaminergic substances or pleasurable stimulus are needed for achieve a response.

 

-Bromantine: This Russian drug banned in Olympics is one of the most fast acting anti-depressants and "life-enhancers". I've tried it and the effects are day and night.

One of the mechanism of action is an epigenetic effect on tyrosine hydroxylase enzyme, a crucial enzyme for producing dopamine from precursors, so with Bromantane the body starts to produce more dopamine and in some cases the changes in gene expression can be long-lasting

 

-9 Methyl Beta Carboline: This drug regenerates dopaminergic neurons in parkinson disease models in rats, if you have more dopaminergic neurons so your body will produce more dopamine in a natural way. I think this is highly experimental because continuous use of the drug for an extended period of time is needed for increasing the dopamine neurons quantity in a significative way for starting to feel differences, like 6 months and combined with a good diet exercise.

 

-PDE7 inhibitor: I don't know any compound right now out there that can inhibits PDE7, just only experimental research drugs. PDE7 inhibition produces dopaminergic neurogenesis even in a way more notorious compared to 9 methyl beta carboline.

Just search PDE7+Dopamine and you will see the research behind this area.

[Kimer Med]

There are ways to (semi-) permanently increase dopamine, but they're easier said than done. Things like being happier, being more satisfied with yourself and your life, laughing a lot, and so on.

 

One over-the-counter supplement that may help increase dopamine is Tyrosine, which is a precursor.

 

On the medication side, one option is dopamine agonists, such as Mirapex and Requip. Both are effective, although taking an occasional break is warranted. Without that, they can produce an unpleasant rebound effect.

 

Modafinil is an a-typical, non-addictive stimulant that might also be useful, but I wouldn't suggest it for the long term.

 

[Major Legend]

Op, you wanna start a Research Topic on Stardust.bio so we can work on this? This question gets asked a lot over and over again.

[jacobjerondin]

I think that Piribedil looks quite interesting for this purpose - unlike Mirapex and Requip, It's only a partial dopamine agonist (like hydergine). That seems to mean that it should be much safer to use long term without risking the notoriously terrible (and potentially permanent) DAWS.

 

Would love to know if anyone has any experiences with it.

[Galaxyshock]

Low-Dose Aspirin Upregulates Tyrosine Hydroxylase and Increases Dopamine Production in Dopaminergic Neurons: Implications for Parkinson's Disease.
Rangasamy SB1,2, Dasarathi S2, Pahan P2, Jana M1,2, Pahan K3,4.
Author information
Abstract
Increasing the function of residual dopaminergic neurons in the nigra of PD patients is an important area of research as it may eventually compensate the loss. Although tyrosine hydroxylase (TH) is the rate-limiting enzyme in the dopamine (DA) biosynthesis pathway, there are no effective drugs/molecules to upregulate TH and increase the production of DA in nigral dopaminergic neurons. This study underlines the importance of aspirin in stimulating the expression of TH and increasing the level of DA in dopaminergic neurons. At low doses, aspirin increased the expression of TH and the production of DA in mouse MN9D dopaminergic neuronal cells. Accordingly, oral administration of aspirin increased the expression of TH in the nigra and upregulated the level of DA in striatum of normal C57/BL6 mice and aged A53T α-syn transgenic mice. Oral aspirin also improved locomotor activities of normal mice and A53T transgenic mice. While investigating mechanisms, we found the presence of cAMP response element (CRE) in the promoter of TH gene and the rapid induction of cAMP response element binding (CREB) activation by aspirin in dopaminergic neuronal cells. Aspirin treatment also increased the level of phospho-CREB in the nigra of C57/BL6 mice. The abrogation of aspirin-induced expression of TH by siRNA knockdown of CREB and the recruitment of CREB to the TH gene promoter by aspirin suggest that aspirin stimulates the transcription of TH in dopaminergic neurons via CREB. These results highlight a new property of aspirin in stimulating the TH-DA pathway, which may be beneficial in PD patients. Graphical Abstract ᅟ.

→ source (external link)

[triguy]

Dancing/music works fantastically. Just gotta find the right tunes! Ones you really resonate with. Takes some work and effort. Get a good pair of earphones that’s important. Pills pills pills forget about it!

 

 

 

you are so correct!    I just started doing this & it has gave me a day long mood lift!   

Low-Dose Aspirin Upregulates Tyrosine Hydroxylase and Increases Dopamine Production in Dopaminergic Neurons: Implications for Parkinson's Disease.
Rangasamy SB1,2, Dasarathi S2, Pahan P2, Jana M1,2, Pahan K3,4.
Author information
Abstract
Increasing the function of residual dopaminergic neurons in the nigra of PD patients is an important area of research as it may eventually compensate the loss. Although tyrosine hydroxylase (TH) is the rate-limiting enzyme in the dopamine (DA) biosynthesis pathway, there are no effective drugs/molecules to upregulate TH and increase the production of DA in nigral dopaminergic neurons. This study underlines the importance of aspirin in stimulating the expression of TH and increasing the level of DA in dopaminergic neurons. At low doses, aspirin increased the expression of TH and the production of DA in mouse MN9D dopaminergic neuronal cells. Accordingly, oral administration of aspirin increased the expression of TH in the nigra and upregulated the level of DA in striatum of normal C57/BL6 mice and aged A53T α-syn transgenic mice. Oral aspirin also improved locomotor activities of normal mice and A53T transgenic mice. While investigating mechanisms, we found the presence of cAMP response element (CRE) in the promoter of TH gene and the rapid induction of cAMP response element binding (CREB) activation by aspirin in dopaminergic neuronal cells. Aspirin treatment also increased the level of phospho-CREB in the nigra of C57/BL6 mice. The abrogation of aspirin-induced expression of TH by siRNA knockdown of CREB and the recruitment of CREB to the TH gene promoter by aspirin suggest that aspirin stimulates the transcription of TH in dopaminergic neurons via CREB. These results highlight a new property of aspirin in stimulating the TH-DA pathway, which may be beneficial in PD patients. Graphical Abstract ᅟ.

→ source (external link)

 

I wonder what they consider low dose

I think that Piribedil looks quite interesting for this purpose - unlike Mirapex and Requip, It's only a partial dopamine agonist (like hydergine). That seems to mean that it should be much safer to use long term without risking the notoriously terrible (and potentially permanent) DAWS.

 

Would love to know if anyone has any experiences with it.

 

 

DAWS????

[John250]

It’s weird how all dopamine antagonists and agonists mainly cause fatigue yet dopamine reuptake inhibitors and stuff like amphetamines that push dopamine out of the synapses cause energy. If only there was a good safe agonist or antagonist that produced the euphoria and energy.

Maybe there is too much focus on dopamine for trying to achieve energy and not enough focus on norepinephrine and epinephrine. Has anyone experimented with any norepinephrine and/or epinephrine agonists or antagonists?

Edited by John250, 13 September 2018 - 08:03 PM.

[John250]

I will have to re-read this a few times but I find it interesting that they are now discovering amphetamines do not only damage the Dopamine system but play a huge role in glutamate and GABA.

https://www.ncbi.nlm...les/PMC4419710/

[jacobjerondin]

Been taking L-THP for the past few days, mainly for sleep which it seems to work well for, but also for potential dopamine receptor upregulation. It seems to be helping with that as well but it is a bit earlier to be sure.

[cat-nips]

It’s weird how all dopamine antagonists and agonists mainly cause fatigue yet dopamine reuptake inhibitors and stuff like amphetamines that push dopamine out of the synapses cause energy. If only there was a good safe agonist or antagonist that produced the euphoria and energy.

Maybe there is too much focus on dopamine for trying to achieve energy and not enough focus on norepinephrine and epinephrine. Has anyone experimented with any norepinephrine and/or epinephrine agonists or antagonists?

 

Wellbutrin, Coffee, Phentermine, Ritalin, Adderall and even Modafinil raise NE levels significantly.  Too much NE for too long could cause adrenal fatigue and massive anxiety.  I know NE is converted from D, but targeting it specifically could give you a ton of energy, but it's unfocused and anxiety ridden and kind of pointless.  That balance is crucial.  NE helps with energy and alertness and even planning, but does nothing for focus and creativity and can exacerbate irritability, due to its relationship to adrenalin and it being a stress hormone.  Because its a stress hormone, I wonder that if its chronically elevated, can it cause your parasympathetic system to have long-term issues as being constantly in fight/flight will shut down digestion and the function of your other organs to divert blood back to your heart and muscles. 

 

Wellbutrin made me turn into a raging, hostile, irritable, bitch.  The others can have that effect as well and I can usually differentiate now when it's too much NE and I start behaving differently because of it.  I find hot coffee/MCT/butter to be enough of a NE boost most of the time. 
 

[John250]

Been taking L-THP for the past few days, mainly for sleep which it seems to work well for, but also for potential dopamine receptor upregulation. It seems to be helping with that as well but it is a bit earlier to be sure.

What dosage are you taking and approximately how long before bed do you take it? How long after taking it does it make you sleepy? Thanks

[John250]

Wellbutrin, Coffee, Phentermine, Ritalin, Adderall and even Modafinil raise NE levels significantly. Too much NE for too long could cause adrenal fatigue and massive anxiety. I know NE is converted from D, but targeting it specifically could give you a ton of energy, but it's unfocused and anxiety ridden and kind of pointless. That balance is crucial. NE helps with energy and alertness and even planning, but does nothing for focus and creativity and can exacerbate irritability, due to its relationship to adrenalin and it being a stress hormone. Because its a stress hormone, I wonder that if its chronically elevated, can it cause your parasympathetic system to have long-term issues as being constantly in fight/flight will shut down digestion and the function of your other organs to divert blood back to your heart and muscles.

Wellbutrin made me turn into a raging, hostile, irritable, bitch. The others can have that effect as well and I can usually differentiate now when it's too much NE and I start behaving differently because of it. I find hot coffee/MCT/butter to be enough of a NE boost most of the time.

Several years ago I used 150mg Wellbutrin XR and for about 2 weeks I had amazing energy and felt great all the time. I was even able to lower my amphetamine dose. Then one day the energy and motivation just instantly went way. I had a friend who reported the same thing. Great for about 2-3 weeks then instantly gone. No idea why this happens but I sure wish it didn’t because it could have been a life saver for me.

[Galaxyshock]

Several years ago I used 150mg Wellbutrin XR and for about 2 weeks I had amazing energy and felt great all the time. I was even able to lower my amphetamine dose. Then one day the energy and motivation just instantly went way. I had a friend who reported the same thing. Great for about 2-3 weeks then instantly gone. No idea why this happens but I sure wish it didn’t because it could have been a life saver for me.

 

I remember somebody mentioning there is a trend with Wellbutrin where there's initial good effects first two weeks, then they fade but if you stick to it they come back around 8 week mark or so. Don't know why it works this way, but maybe give it a longer trial?

[John250]

I remember somebody mentioning there is a trend with Wellbutrin where there's initial good effects first two weeks, then they fade but if you stick to it they come back around 8 week mark or so. Don't know why it works this way, but maybe give it a longer trial?

I’m thinking about trying it again. I read a couple people said the dosage needs to be adjusted very frequently with Wellbutrin and your much better off using the instant release vs the extended release. I may pick some up and expierement a little.

[cat-nips]

Interesting, I haven't heard that about Wellbutrin suddenly stopping working. Maybe some kind of desensitization, but going upwards in dosage just increases the seizure risk and isn't really recommended above 300, or sometimes 450.  My friend who used it for smoking cessation reported that it "chilled her out", which totally baffled me.  I think at high enough dosages for some, it could trigger melatonin production?  I've tried it independently for smoking cessation a long time ago, and then more recently, in conjunction with Dexedrine.  It wasn't a very good combo for me as it just produced the negative side effects and a sort of dulling effect that I didn't get with those things when not combined.  My psychiatrist kept pushing me to keep with it, but it only got worse and I abandoned it after maybe 2 months.  I think there's a competitive aspect between them, so maybe that has something to do with the poop out effect you experienced. 

 

I've heard that Strattera, which works primarily on NE, can be helpful in combination with amps, but I can't comment on that as I was too turned off by the whole experience to try another NE dominant substance afterwards. 

 

On another note, my personal favorite for a long time was Dex/Ashwagandha/Coffee in the AMs.  The Ash took away any jitters from the Dex, and the Coffee counteracted any initial fatigue from the Ash and a few hours in, I noticed a clean, stable, focused energy that lasted throughout the day.  Effects are more subtle and you don't really notice it immediately until you've been taking it awhile, as it can make you sleepy at first, but it was really helpful for me at that time. 

Edited by cat-nips, 14 September 2018 - 05:41 PM.

[jacobjerondin]

What dosage are you taking and approximately how long before bed do you take it? How long after taking it does it make you sleepy? Thanks

 

Been experimenting with my 98% L-THP extract, even 50 mg seems to make a difference but I think something like 150-250 mg is best. It seems to start kicking within 30 min on a somewhat empty stomach with full effects by an hour.

[John250]

Been experimenting with my 98% L-THP extract, even 50 mg seems to make a difference but I think something like 150-250 mg is best. It seems to start kicking within 30 min on a somewhat empty stomach with full effects by an hour.

Very cool. I think I’ll try tonight but play it safe and only take the recommended dose of 30 mg for the first time. You take it sublingual?

Also if you want to do me a favor try taking a low dose like 20 mg during the day to see if it gives you energy instead of fatigue. I would do it myself but there’s not a single day where I could afford even a drop of fatigue with my lifestyle LOL

Edited by John250, 14 September 2018 - 10:12 PM.