# Dopamine Levels in Brain May Determine Social Status



## crayzyMed (Nov 2, 2006)

FRIDAY, Feb. 5 (HealthDay News) -- The makeup of your brain may influence your social standing, a new study suggests.








Researchers conducted PET scans of the brains of healthy volunteers and assessed their levels of social status and social support. The results suggest that social status and social support are associated with the density of dopamine D2/D3 receptors in an area of the brain called the striatum, which plays a major role in reward and motivation.

"We showed that low levels of dopamine receptors were associated with low social status and that high levels of dopamine receptors were associated with higher social status. The same type of association was seen with the volunteer's reports of social support they experience from their friends, family or significant other," Dr. Diana Martinez, of the New York State Psychiatric Institute, said in a news release.

People who achieve greater social status are more likely to find life rewarding and stimulating because they have more targets for dopamine to act upon within the striatum, Martinez explained. Dopamine is a chemical that transmits signals between brain cells.

The study was published in the Feb. 1 issue of Biological Psychiatry.

"These data shed interesting light into the drive to achieve social status, a basic social process," said journal editor Dr. John Krystal. "It would make sense that people who had higher levels of D2 receptors, i.e., were more highly motivated and engaged by social situations, would be high achievers and would have higher levels of social support."

The study also may help improve understanding about why certain people are more likely to abuse alcohol and drugs. Previous studies have suggested that lower levels of social status and social support contribute to the risk of substance abuse.

SOURCE: Biological Psychiatry, news release, Feb. 3, 2010
http://www.nlm.nih.gov/medlineplus/news/fullstory_94981.html


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## Narcissus (Aug 28, 2007)

I wouldn't say we're genetic uh, anomalies. Societies always have members with different roles and specialisations. Not everyone can be at the top. That said, it's not always great being down here in the trenches. :b


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## Akane (Jan 2, 2008)

I've been seeing more and more studies showing dopamine and gaba have a greater role in social situations, depression, and other disorders than serotonin which most medicines for SA or depression are based off of.


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## GnR (Sep 25, 2009)

The idea that my brain may not be wired for success pisses me off.


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## lonelygirl88 (Dec 25, 2009)

GnR said:


> The idea that my brain may not be wired for success pisses me off.


if you keep that distorted mentality...then you should be pissed off. 
its just a generalized article.


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## Akane (Jan 2, 2008)

Personally I don't find being high in social status success and being low in social status failure.... Anyone judging you by your number of friends or contacts doesn't have an opinion worth listening to.


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## UltraShy (Nov 8, 2003)

So highly successful people have loads of dopamine that losers like me would need amphetamines to get.


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## 2Talkative (Nov 1, 2007)

UltraShy said:


> So highly successful people have loads of dopamine that losers like me would need amphetamines to get.


I'm glad I wasn't the only one that thought of amphetamines right away.

Too bad about the side effects otherwise I'd be on them. :blank


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## UltraShy (Nov 8, 2003)

2Talkative said:


> I'm glad I wasn't the only one that thought of amphetamines right away.
> 
> Too bad about the side effects otherwise I'd be on them. :blank


Which side effect(s) concern you the most?


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## 2Talkative (Nov 1, 2007)

Nervous System problems and the included impotence and changes in libido aren't very welcoming either. I've done them(twice) and had the sides first hand. I guess alot of the meds out there do this though... I guess it's why I don't bother with any. :help


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## crayzyMed (Nov 2, 2006)

Akane said:


> I've been seeing more and more studies showing dopamine and gaba have a greater role in social situations, depression, and other disorders than serotonin which most medicines for SA or depression are based off of.


Yep, I'm not even convinced of the role of GABA in SA either, imo are glutamate and dopamine the biggest issues in social anxiety.


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## Ehsan (Mar 21, 2009)

download original paper here:
http://download.journals.elsevierhealth.com/pdfs/journals/0006-3223/PIIS0006322309009652.pdf


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## crayzyMed (Nov 2, 2006)

Ehsan said:


> download original paper here:
> http://download.journals.elsevierhealth.com/pdfs/journals/0006-3223/PIIS0006322309009652.pdf


Thx


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## euphoria (Jan 21, 2009)

Yeah, life isn't at all fair.



2Talkative said:


> Nervous System problems and the included impotence and changes in libido aren't very welcoming either. I've done them(twice) and had the sides first hand. I guess alot of the meds out there do this though... I guess it's why I don't bother with any. :help


A lot of the bad side effects come from noradrenaline release. Most of us social phobics would just need the dopamine. A pure dopaminergic would cause the opposite to impotence.


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## crayzyMed (Nov 2, 2006)

UltraShy said:


> So highly successful people have loads of dopamine that losers like me would need amphetamines to get.


Yes i personally do beleive that amphetamine is the most promosing treatment for social anxiety. However not on its own.
Social anxious people have higher levels of glutamate in the brain wich amphetamine will only make worse as it releases glutamate too and i also beleive that glutamate plays a key role in tolerance to amphetamine.
Therefor the combination of a NMDA antagonist (riluzole would be better, but memantine seems to lower the ammount of glutamate too) and amphetamine could be a novel and effective way to treat social anxiety.

Ive also been thinking that glutamate is responsible for the increase in anxiety amphetamine's sometimes cause, i'm not sure about that tough.


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## Vini Vidi Vici (Jul 4, 2009)

crayzyMed said:


> Yes i personally do beleive that amphetamine is the most promosing treatment for social anxiety. However not on its own.
> Social anxious people have higher levels of glutamate in the brain wich amphetamine will only make worse as it releases glutamate too and i also beleive that glutamate plays a key role in tolerance to amphetamine.
> Therefor the combination of a NMDA antagonist (riluzole would be better, but memantine seems to lower the ammount of glutamate too) and amphetamine could be a novel and effective way to treat social anxiety.
> 
> Ive also been thinking that glutamate is responsible for the increase in anxiety amphetamine's sometimes cause, i'm not sure about that tough.


Dextroamphetamine + Memantine/Riluzole + MAO-B Inhibitor + 5ht1a Agonist + CCKB Antagonist + 5ht2c Antagonist (maybe not necessary).

Mice lacking 5ht2c receptors show a Locomotor response to mCPP, while Normal mice get the Opposite. I thought that was cool.....5ht2c is lame.

I wonder what would happen if someone took low dose Pramipexole with Amphetamine, youd get more D2 activity, maybe less Social Anxiety? and still get the regular DA release from Amphetamine, maybe inhibited a Tad, but it would still work. Not considering Psychosis that might develop of course


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## crayzyMed (Nov 2, 2006)

Vini Vidi Vici said:


> Dextroamphetamine + Memantine/Riluzole + MAO-B Inhibitor + 5ht1a Agonist + CCKB Antagonist + 5ht2c Antagonist (maybe not necessary).
> 
> Mice lacking 5ht2c receptors show a Locomotor response to mCPP, while Normal mice get the Opposite. I thought that was cool.....5ht2c is lame.
> 
> I wonder what would happen if someone took low dose Pramipexole with Amphetamine, youd get more D2 activity, maybe less Social Anxiety? and still get the regular DA release from Amphetamine, maybe inhibited a Tad, but it would still work. Not considering Psychosis that might develop of course


It would inhibit amphetamine at first as dopamine neurotransmission is reduced, however after 2 weeks the body adapts. Possibly less social anxiety as result, id be carefull of developping psychosis tough.


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## Nae (Nov 10, 2003)

or, social status influences dopamine.


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## Ehsan (Mar 21, 2009)

the problem is reduced D2/D3 receptor binding. it may be result of reduced dopaminergic neurons' count or reduced receptor count per neuron.
we can't increase the number of dopaminergic neurons or dopamine receptors' count per neuron permanently.
is there any way?
does an increase in dopamine help?


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## crayzyMed (Nov 2, 2006)

Ehsan said:


> the problem is reduced D2/D3 receptor binding. it may be result of reduced dopaminergic neurons' count or reduced receptor count per neuron.
> we can't increase the number of dopaminergic neurons or dopamine receptors' count per neuron permanently.
> is there any way?
> does an increase in dopamine help?


The only way to counteract this is increasing dopamine with a stimulant, as amphetamine is a VERY effective treatment for social anxiety, this method seems to be pretty good.


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## Ehsan (Mar 21, 2009)

crayzyMed said:


> The only way to counteract this is increasing dopamine with a stimulant, as amphetamine is a VERY effective treatment for social anxiety, this method seems to be pretty good.


there are evidences that suggest reduced number of dopaminergic neurons in SAD.
so i should *warn amphetamine users* about its neurodegenerative properties that may kill dopamine neurons and this may describe why SAD is seen within healthy ones after heavy amphetamine abuse!
beside its short term useful effects, the long-term effect may worsen SAD permanently.
i think Dopamine Reuptake Inhibitors are more safe.

*Amphetamine Misuse and Social Phobia *


> Ms. A, a 26-year-old woman, was seen after 2 months of flushing, sweating, palpitations, and shortness of breath, which occurred in a range of social situations. The first episode happened in a staff canteen, when he became aware of her colleagues staring at her and felt embarrassed. At her assessment she had given up work and had started avoiding various activities for fear of reexperiencing similar feelings. She had no past psychiatric history, and before these attacks she had been confident and extroverted. She had been taking 1.5 g of street amphetamine orally almost daily for 6 years. Initially, she felt good while taking the drug, but she currently used it to help her "get going." There was no temporal relationship between her anxiety symptoms and her amphetamine ingestion; the attacks occurred specifically in social situations. She showed no symptoms of affective disturbance or psychotic symptoms. A diagnosis of generalized social phobia was made.


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## meyaj (Sep 5, 2009)

Ehsan said:


> there are evidences that suggest reduced number of dopaminergic neurons in SAD.
> so i should *warn amphetamine users* about its neurodegenerative properties that may kill dopamine neurons and this may describe why SAD is seen within healthy ones after heavy amphetamine abuse!
> beside its short term useful effects, the long-term effect may worsen SAD permanently.
> i think Dopamine Reuptake Inhibitors are more safe.
> ...


Oh give me a break. Amphetamine typically has, at worst, negligible long-term effects at therapeutic doses.

What you quoted has two issues:


It's "street" amphetamine. For all we know there could be the far more neurotoxic methamphetamine or any number of stims in the product.
Even if they could prove that the entire 6 years she was just taking pure unadulterated amphetamine, 1.5g a day is INSANE. A typical daily Dexedrine prescription is only 1/100th of that amount at ~15mg. Of course, the street product was not likely pure, but for it to be in line with a therapeutic dose, it would have to be 99% inert cuts... which is totally absurd.


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## meyaj (Sep 5, 2009)

My experience with Dexedrine, having both ADHD-I and pretty damn severe SAD, is that yes, it's anxiogenic. I also have GAD, and it does exacerbate it a bit, but I find that Dexedrine is by far less anxiogenic than the alternatives. It's pretty slight, actually.

But... generalized anxiety and social anxiety are two VERY different monsters, and they sound a lot more similar than they really are. In my experience, the anxiogenesis does not extend to the SAD. Yes, I feel slightly more anxious and wired on it, but socially, it just makes me feel motivated to do and say things before I can even give myself time to stress about it. And once it's out in the air, I no longer care and just move on to the next thing.

It's very liberating. My personality basically smashes right through the wall I've built up around myself my whole life. And every time I have a good opportunity to do so, it increases my confidence a tiny bit because I realize that people don't react to the real me in such a negative fashion like I normally tend to imagine. And through that, any increased anxiety is often diminished to even less than my baseline.

Then again, I am on an MAOI which tends to actually lower NE in the first place. But I'm still at a rather small dose, and I don't think the effect is that significant from it yet. The only issue I have with Dexedrine (and really stimulants in general), is that they're not 24/7 drugs like an SSRI/tricyclic/MAOI would be. I get maybe 4-5 hours of not caring about revealing myself to the world and then it's back to being terrified of people making judgments of every little thing I might say or do. Back to the hermit lifestyle.

It's incredibly helpful for the ADHD alone but even long-term for SAD, I can see potential for it as some form of exposure therapy.


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## Ehsan (Mar 21, 2009)

meyaj said:


> Oh give me a break. Amphetamine typically has, at worst, negligible long-term effects at therapeutic doses.
> 
> What you quoted has two issues:
> 
> ...


we had another case report here:
http://www.socialanxietysupport.com/forum/f30/tried-everything-82441/

and here:
Dopamine and social anxiety disorder


> Members of our group have previously reported on amphetamine misuse just before the onset of social phobia, raising the consideration that dopamine depletion may be a predisposing factor.


Dextromethorphan potentiation of d-amphetamine-induced behavior and neurodegeneration in rats.

New mechanism found for neurodegenerative effects of amphetamines in mice

Brain Region-Specific Neurodegenerative Profiles Showing the Relative Importance of Amphetamine Dose, Hyperthermia, Seizures, and the Blood-Brain Barrier

The neurotoxicity of amphetamines: Bridging drugs of abuse and neurodegenerative disorders 

the "high dose" is a key surely but in SAD which "reduced dopamine neurons" is suggested a low dose can damage in long time imo.

i think we should switch to DRIs because they are not toxic and have long term effects on dopamine level too(like SSRIs).

another method is to decrease dopaminergic neurodegeneration and to increase neurogenesis.


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## meyaj (Sep 5, 2009)

In a perfect world I'd be able to take a long-acting, non-cardiotoxic SNDRI cocaine derivative, but at best that's still a decade away...

As it stands now, (N)DRIs like Ritalin are far too anxiogenic in my experience and don't have the same benefits, so dextroamphetamine is still ideal IMO as there's no sound clinical evidence that lower, therapeutic doses actually do any significant damage.


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## Vini Vidi Vici (Jul 4, 2009)

Ehsan said:


> another method is to decrease dopaminergic neurodegeneration and to increase neurogenesis.


I always thought It might be really cool to inhibit Dopamine-beta hydroxylase, not strongly but just weakly. You get more Dopamine, and less Norepinephrine and Adrenaline, in like one drug. Kinda like taking a Stimulant with a beta-blocker. Maybe thered be alot of postural hypotension during normal situations, but in anxiety-inducing Social situations it would be cool. Disulfiram seems like an easy thing 2 get, especially if one is already an alcoholic. Hypericin (the non-active ingredient in St. Johns Wort) might inhibit DbHy also.

At the same time, why not Inhibit COMT too? By itself COMT inhibition looks cool, but combined with DA-beta hydroxylase inhibition = Large DA increase, and NA levels could be brought back closer to baseline, so as not to cause hypotension. Entacapone and Tolcapone both have problems, But high doses of pure EGCG might work really well.

Then at the same time (of course) inhibit MAO-B, I don't see any purpose for MAO-B in the first place, really. Selegiline is cheap, Rasagiline is also gettable but Expensive. The combination of the 3 different mechanisms is actually doable/possible....at least it looks like it. It would really stink tho, If people ended up getting tolerant to the DA regardless of how DA is being increased...which is what would probably happen


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## Ehsan (Mar 21, 2009)

Guide 4 Dummies said:


> Ehsan, which DRI are you interested in?


i don't like ritalin because of its short half-time and its anxiogenic property.
Wellbutrin is the only option but it at best occupy 30% DAT transporters and has a little bioavailibility.

i use wellbutrin + fluoxtine that you said hasn't worked for you.
how many days did you take it?
i believe wellbutrin+fluoxetine is unlikely to cause europhia(at least 60% DAT occupancy needed) however i'm sure it works to some extent if be used for enough days and dose(i'have some experiences).
i'll report my experiences soon.


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## Ehsan (Mar 21, 2009)

Vini Vidi Vici said:


> I always thought It might be really cool to inhibit Dopamine-beta hydroxylase, not strongly but just weakly. You get more Dopamine, and less Norepinephrine and Adrenaline, in like one drug. Kinda like taking a Stimulant with a beta-blocker. Maybe thered be alot of postural hypotension during normal situations, but in anxiety-inducing Social situations it would be cool.
> 
> At the same time, why not Inhibit COMT too? By itself COMT inhibition looks cool, but combined with DA-beta hydroxylase inhibition = Large DA increase, and NA levels could be brought back closer to baseline, so as not to cause hypotension.
> 
> Then at the same time (of course) inhibit MAO-B, I don't see any purpose for MAO-B in the first place, really. The combination is actually doable/possible....at least it looks like it. It would really stink tho, If people ended up getting tolerant to the DA regardless of how DA is being increased


me too. 
however i have two problems:
1- i haven't access to DBH inhibitors(disulfram ,...). i read somewhere that hyperforin is a DBH inibitor!
2- we don't know how much increase in dopamine and decrease in NE we would have.


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## Ehsan (Mar 21, 2009)

Guide 4 Dummies said:


> 28 days and then gave up on it.
> 
> Interesting ideas, VVV.


i had tried wellbutrin+fluoxetine+sertraline before and it caused me awake all the night.
it's important to take wellbutrin about 1 hour after SSRIs.
maybe your liver has more CYP2B6 than me(not so strange). ticlopidine is far stronger than fluoxetine however.


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## Vini Vidi Vici (Jul 4, 2009)

Molecular modelling study of the mechanism of high-potency inhibition of human catechol-O-methyltransferase by (-)-epigallocatechin-3-O-gallate.



> The molecular mechanism of inhibition of human catechol-O-methyltransferase (COMT) by (-)-epigallocatechin-3-O-gallate (EGCG), which is a modest substrate of COMT but an ultra-potent inhibitor of this enzyme, was studied. EGCG has an IC(50) value of 70 nM for inhibiting human liver COMT-mediated O-methylation of 2-hydroxyestradiol, which was 210-760 times more potent than catechin, epigallocatechin and epicatechin. Kinetic analyses showed that EGCG had a strong component of non-competitive inhibition of the O-methylation of 2-hydroxyestradiol. Computational molecular modelling studies showed that the B- and D-rings of EGCG can bind tightly to the human COMT in four different modes (i.e. D-para-OH, D-meta-OH, B-para-OH, and B-meta-OH). The binding geometry of EGCG in these binding modes was found to be less than ideal to form perfect Mg(2+) coordination for the catalysis of its own methylation. It is concluded that the very tight binding interaction of EGCG with COMT makes it a potent non-competitive inhibitor, but its imperfect geometry makes it a poor substrate for methylation by this enzyme.


http://www.ncbi.nlm.nih.gov/pubmed/18197555


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## euphoria (Jan 21, 2009)

Vini Vidi Vici said:


> I always thought It might be really cool to inhibit Dopamine-beta hydroxylase, not strongly but just weakly. You get more Dopamine, and less Norepinephrine and Adrenaline, in like one drug. Kinda like taking a Stimulant with a beta-blocker. Maybe thered be alot of postural hypotension during normal situations, but in anxiety-inducing Social situations it would be cool. Disulfiram seems like an easy thing 2 get, especially if one is already an alcoholic. Hypericin (the non-active ingredient in St. Johns Wort) might inhibit DbHy also.
> 
> At the same time, why not Inhibit COMT too? By itself COMT inhibition looks cool, but combined with DA-beta hydroxylase inhibition = Large DA increase, and NA levels could be brought back closer to baseline, so as not to cause hypotension. Entacapone and Tolcapone both have problems, But high doses of pure EGCG might work really well.
> 
> Then at the same time (of course) inhibit MAO-B, I don't see any purpose for MAO-B in the first place, really. Selegiline is cheap, Rasagiline is also gettable but Expensive. The combination of the 3 different mechanisms is actually doable/possible....at least it looks like it. It would really stink tho, If people ended up getting tolerant to the DA regardless of how DA is being increased...which is what would probably happen


DBH also metabolises phenethylamine, so DBH inhibitor + MAOB inhibitor could give a large increase in PEA.


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## Ehsan (Mar 21, 2009)

Guide 4 Dummies said:


> If Parnate didn't work I may consider trying a higher dose Wellbutrin + Zoloft + Buspirone.
> 
> For some reason, if I take Buspirone + SSRI before bedtime it gives me massive amount of energy for 30 minutes after waking up. It's better than Nicotine + Caffeine + Selegiline.
> 
> SSRI alone doesn't give me massive energy, I must add Buspirone. So it's an interesting drug for me.


another thing that i forgot.
there isn't any study for bioavailability of wellbutrin in humans but its bioavailability in animals is about 4%
to increase bioavailability to 20% you can take it after a fatty meal(don't know why).


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## Vini Vidi Vici (Jul 4, 2009)

Ehsan said:


> me too.
> however i have two problems:
> 1- i haven't access to DBH inhibitors(disulfram ,...). i read somewhere that hyperforin is a DBH inibitor!


yeah that is the only problem, especially since it appears to not be Generic yet. Yeah and even if hypericin or hyperforin inhibit DbHy, youd want 2 have only the single chemical not all the other weird stuff in St. Johns Wort. Hyperforin Would be AWESOME, if only it didnt also inhibit the Reuptake of Glutamate (which sucks) . Lol, i cannot seem 2 find anything that will inhibit DbHy,...this is lame.:sus



Ehsan said:


> 2- we don't know how much increase in dopamine and decrease in NE we would have.


Lol, Im not particularly worried about the DA increase-- Its the NA that would concern me if it got Raised higher/moreso than DA. Well actually your concern is well founded, things could become "problematic" :twisted if DA levels were raised by 300% or something.


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## crayzyMed (Nov 2, 2006)

Ehsan said:


> there are evidences that suggest reduced number of dopaminergic neurons in SAD.
> so i should *warn amphetamine users* about its neurodegenerative properties that may kill dopamine neurons and this may describe why SAD is seen within healthy ones after heavy amphetamine abuse!
> beside its short term useful effects, the long-term effect may worsen SAD permanently.
> i think Dopamine Reuptake Inhibitors are more safe.
> ...


:sus
I hope you see the difference between 1,5 gram daily and normal therapeutic doses of pharmaceutical amphetamine.

Whats next, using heroine abuse as an argument against pain meds? LOL


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## crayzyMed (Nov 2, 2006)

1. Wellbutrin and ritalin arent neurotoxic but the unfortionate truth is that they arent very effective for social anxiety, they may help but nothing like amphetamine.
2. Amphetamine may be a mild neurotoxin (wich i doubt) HOWEVER it IS possible to prevent this from happening.
3. If there is a effective treatment, why not focus on how to FIX the issues instead of trying a wannabe alternative?

Memantine+Amphetamine+Deprenyl = Dopamine boosted without any neurotoxiticy and a potential very safe and effective treatment.


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## crayzyMed (Nov 2, 2006)

Ritalin is neuroprotective[1] it may be ideal for us, however its too anxiogenic to be usefull, i wonder if it can be made prosocial in combination with other meds.


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## Ehsan (Mar 21, 2009)

crayzyMed said:


> :sus
> I hope you see the difference between 1,5 gram daily and normal therapeutic doses of pharmaceutical amphetamine.
> 
> Whats next, using heroine abuse as an argument against pain meds? LOL


i've responded to similar question so i only copy and paste my response:

seems we have another case report here:
http://www.socialanxietysupport.com/forum/f30/tried-everything-82441/

and here:
Dopamine and social anxiety disorder


> Members of our group have previously reported on amphetamine misuse just before the onset of social phobia, raising the consideration that dopamine depletion may be a predisposing factor.


Dextromethorphan potentiation of d-amphetamine-induced behavior and neurodegeneration in rats.

New mechanism found for neurodegenerative effects of amphetamines in mice

Brain Region-Specific Neurodegenerative Profiles Showing the Relative Importance of Amphetamine Dose, Hyperthermia, Seizures, and the Blood-Brain Barrier

The neurotoxicity of amphetamines: Bridging drugs of abuse and neurodegenerative disorders 

*the "high dose" is a key surely but in SAD which "reduced dopamine neurons" is suggested as a mechanism a low dose can damage in long term imo.*

i think we should switch to DRIs because they are not toxic and have long term effects on dopamine level too(like SSRIs).

another method is to decrease dopaminergic neurodegeneration and to increase neurogenesis.


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## crayzyMed (Nov 2, 2006)

I'l check those references out.



Ehsan said:


> i think we should switch to DRIs because they are not toxic and have long term effects on dopamine level too(like SSRIs).
> 
> another method is to decrease dopaminergic neurodegeneration and to increase neurogenesis.


*BUT* DRIs arent as effective for social anxiety, they are far from as effective as amphetamine.
Therefor it would be much easier to focus on how to PREVENT the neurotoxiticy instead of going to fairly ineffective treatments. (well maybe not ineffective, but far from as good as amphetamine from all the anecdotes i read, and they often cause an increase in anxiety).

I agree that decreasing dopaminergic neurodegeneration is a good idea.


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## euphoria (Jan 21, 2009)

The effect from Ritalin changes after chronic treatment I believe, similar to chronic SSRI use. A comparison of acute Ritalin vs. acute amphetamine wouldn't be fair.


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## crayzyMed (Nov 2, 2006)

euphoria said:


> The effect from Ritalin changes after chronic treatment I believe, similar to chronic SSRI use. A comparison of acute Ritalin vs. acute amphetamine wouldn't be fair.


Give me anecdotes of ppl with social anxiety that take ritalin on a daily basis for social anxiety, small pilot studies or anything else, you can convince me. So far i havent read many positive anecdotes about it and my personal experience doesnt help much either.

Ive taken ritalin for a few months daily so ive got enough experiences with it myself.


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## euphoria (Jan 21, 2009)

I don't know if it works for SA, just checking that you tried it longer than acutely. I agree, reuptake inhibitors aren't as good as releasing agents.


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## IllusionalFate (Sep 10, 2008)

Due to the pharmacokinetics I assume, short-acting NDRIs such as cocaine and methylphenidate don't work on a chronic dosing schedule. Benefits are noticed right away which indicates postsynaptic receptors downregulate more quickly than the presynaptic autoreceptors.


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## meyaj (Sep 5, 2009)

euphoria said:


> I don't know if it works for SA, just checking that you tried it longer than acutely. I agree, reuptake inhibitors aren't as good as releasing agents.


I don't think it's as simple as that. Cocaine is a reuptake inhibitor and is unbelievably effective. The drug itself isn't very anxiogenic at all, although many of the active cuts used to increase street profits ARE. Cocaine analogues and SNDRIs in general, under development, seem to have a great deal of promise.

Concepts like therapeutic index and the ratio of effects on different receptors are hugely important too.

As an example of the former, something like bupropion (not metabolized into other active metabolites, for arguments' sake), has a pretty damn good DA:NE ratio, but the overall effectiveness you can get from it is limited by safety constraints, as higher doses can dramatically lower the seizure threshold.

As an example of the latter, well... just look at Ritalin vs Adderall vs Dexedrine. Anxiogenesis is obviously not a desired trait when treating an anxiety disorder, so better DA:NE ratios are likely to be the most effective. To get a similar benefit from the dopamine RI/RA properties of these drugs, you have to deal with different levels of adrenergic effects, and it might just be way too much. This is why Dexedrine in particularly is the most preferred, and in fact, at lower doses, it actually acts much more like a reuptake inhibitor than a releasing agent anyways.


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## IllusionalFate (Sep 10, 2008)

meyaj said:


> I don't think it's as simple as that. Cocaine is a reuptake inhibitor and is unbelievably effective.


Due to its pharmacokinetics. It's fast-acting and therefore accumulates monoamines in their respective synapses before the autoreceptors can get a chance to control the release and as a result provides a quick "rush" as a high.



> To get a similar benefit from the dopamine RI/RA properties of these drugs, you have to deal with different levels of adrenergic effects, and it might just be way too much. This is why Dexedrine in particularly is the most preferred, and in fact, at lower doses, it actually acts much more like a reuptake inhibitor than a releasing agent anyways.


I've read that calcium channel influx is the mechanism that mediates amphetamine's reuptake inhibition, but even at low therapeutic doses I feel the same type of effects as higher doses (just obviously not as strong). Ritalin, at any dose, doesn't feel smooth or even calming and anxiolytic like amphetamine does. Even if amphetamine works primarily through reuptake inhibition at 5mg, I have a feeling membrane transporter inversion prevents it from feeling like an actual RI.


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## Ehsan (Mar 21, 2009)

imo, hydroxybupropion causes seizure not bupropion itself. when i take bupropion without CYP2B6 inhibitors i have some tremor but when i use CYP2B6 inhibitors it takes a long time to feel similar effect.
bupropion has some problems:
1- low affinity for DAT
higher dose
2- low bioavalibility
i read a case report about nasal administration which had caused seizure
3- high metabolism
inhibitors:clopidogrel>ticlopedine>paroxetine>sertraline>norfluoxetine...



Guide 4 Dummies said:


> One could take an antiepileptic/anticonvulsant agent with it to prevent seizures. How about valproic acid + snorting wellbutrin? lol would be interesting to read about and they may make wellbutrin illegal if it actually worked.


 Bupropion-induced convulsions: Preclinical evaluation of antiepileptic drugs
clonazepam is suggested as a possible adjunct to inhibit convulsions.


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## UltraShy (Nov 8, 2003)

meyaj said:


> Oh give me a break. Amphetamine typically has, at worst, negligible long-term effects at therapeutic doses.
> 
> What you quoted has two issues:
> 
> ...


Yeah, I too would note that doesage seems to be a major issue here. This woman would have been consuming the equivalent of *150* of my pills to equal 1.5 grams.

This is like warning about alcohol consumption based upon somebody who managed to consume 150 drinks per day and say that's what happens if you have two glasses of wine with dinner.


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## Phibes (Mar 8, 2009)

Akane said:


> Personally I don't find being high in social status success and being low in social status failure.... Anyone judging you by your number of friends or contacts doesn't have an opinion worth listening to.


Amen sister!


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## euphoria (Jan 21, 2009)

Snorting anything on a long term basis would be a pretty bad idea...


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## euphoria (Jan 21, 2009)

I tried snorting it once myself, I think it was a lot more dopaminergic than normal bupropion.


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## Ehsan (Mar 21, 2009)

i think it's very hard to snort bupropion or use sublingually cause it's irritant and extremely bitter.
i wanna substitute fluoxetine with sertraline. sertraline is better for SAD and occupy 12% of dopamine transporters itself.


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## crayzyMed (Nov 2, 2006)

meyaj said:


> I don't think it's as simple as that. Cocaine is a reuptake inhibitor and is unbelievably effective. The drug itself isn't very anxiogenic at all, although many of the active cuts used to increase street profits ARE. Cocaine analogues and SNDRIs in general, under development, seem to have a great deal of promise.
> 
> Concepts like therapeutic index and the ratio of effects on different receptors are hugely important too.
> 
> ...


Cocaine is completely useless for me, amphetamine still is the gold standard for my anxiety.


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## meyaj (Sep 5, 2009)

crayzyMed said:


> Cocaine is completely useless for me, amphetamine still is the gold standard for my anxiety.


You live in Belgium, dude. What you call cocaine is almost certainly not actually cocaine. Maybe partially, but it's an expensive drug even within most of the Americas, and so even here, closer to the source, it's cut to all hell with countless other stimulants and often lidocaine as well to simulate the numbing feeling. Seizures of large amounts of cocaine entering the United States have even shown us that the drug is massively adulterated before it even gets into the country.

Unless you've had a bunch of experience with the drug in countries like Colombia, Peru, Panama, and Costa Rica, it's very unlikely that you have a good grasp of just exactly what the drug is like. And I say a bunch of experience because even in such countries, while I have come across very high quality product, I've sometimes received poor quality stuff even there.

That being said, cocaine has limited usefulness because the duration is very short, less than 90 minutes for most people. That would require a lot of redosing. Although even the Dexedrine I'm on only lasts 4-5 hours, it's certainly not a 24/7 miracle drug. This can be improved upon with an extended release formulation such as Dexedrine Spansules (which I don't take because if I want XR my insurance will only cover Adderall), but for obvious reasons we're not going to see a pure, unadulterated, extended-release formulation of cocaine showing up on the streets of North America and Europe anytime soon...


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## crayzyMed (Nov 2, 2006)

Yeah i agree that i would need to try it in those countries.


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## meyaj (Sep 5, 2009)

crayzyMed said:


> Yeah i agree that i would need to try it in those countries.


To be entirely honest, I find the feeling to be closer to that of good quality MDMA than just a straight up stimulant. And as far as miracle cures for SA go, MDMA is without a doubt tops. The neurotoxicity is just way too much of an issue for it to be seen as a viable solution though.


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## crayzyMed (Nov 2, 2006)

meyaj said:


> To be entirely honest, I find the feeling to be closer to that of good quality MDMA than just a straight up stimulant. And as far as miracle cures for SA go, MDMA is without a doubt tops. The neurotoxicity is just way too much of an issue for it to be seen as a viable solution though.


Ive been playing with the idea of using MDMA in daily therapeutic doses (dont try this at home kids!) its not the neurotoxiticy thats the biggest issue as i beleive that would be negliable in low doses, the 5HT2B agonism is tough;

In case of coke the cardiotoxiticy is a huge issue;

So far they are only good as recreational substances; At this point i'm not able to give up recreational substances (i'm capable of taking breaks of a few months tough) as stimulants completely ABOLISH my social anxiety, so there's 1 time a week i'm able to feel like MYSELF, to not act like an idiot and for the first time enjoy life instead of trying to enjoy life but not being able tough;

MDMA is a very prosocial drug, but i dont find it more effective then amphetamine or other stimulants for social anxiety as they all tend to abolish my issues (dopamine is my main issue it seems);


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## meyaj (Sep 5, 2009)

crayzyMed said:


> Ive been playing with the idea of using MDMA in daily therapeutic doses (dont try this at home kids!) its not the neurotoxiticy thats the biggest issue as i beleive that would be negliable in low doses, the 5HT2B agonism is tough;
> 
> In case of coke the cardiotoxiticy is a huge issue;
> 
> ...


Ah. Amphetamine does undoubtedly do a great job for me too, and there's no doubt in my mind that dopamine is my main issue as well, because strictly serotonergic and/or noradrenergic drugs don't do much on their own. But SNDRAs/SNDRIs like cocaine and especially MDMA turn the very pro-social effects into and absolute love and desire for human interaction and an increased capacity for empathy and understanding. I already consider myself a very empathic individual, but on MDMA, it's a totally unreal experience. I wish I could go to my therapy and psychiatrist appointments on the stuff, I think progress would be much more rapid, and it's a reasonable compromise to not having to be on the stuff 24/7.

As it stands, even though my Dexedrine prescription is supposed to be for ADHD-I, I take it before these appointments anyways and, without at first knowing that I was doing this, both my social worker and psychiatrist remarked at how much more open, communicative, and perky I was, and I've been able to talk about stuff that had been impossible for me to do for over a year, even though I feel more comfortable with those people than my own family. I'm normally just a very closed-off person, and so the whole process has been frustrating for everyone involved. Amphetamine is definitely starting to change that.

And that's not even to speak of the countless ways it's been improving other aspects of my life...


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## crayzyMed (Nov 2, 2006)

I have the same issues, i CANT talk about anything and i'm extremele closed up, i find it impossible to talk about my problems with ppl and amphetamine helps alot with that for me too.

How long have you been om amp? i'm worried that tolerance may start developping as that may start a lot faster then tolerance to the focus enhancing effects.
Imo is memantine the key for that tough.


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## meyaj (Sep 5, 2009)

crayzyMed said:


> I have the same issues, i CANT talk about anything and i'm extremele closed up, i find it impossible to talk about my problems with ppl and amphetamine helps alot with that for me too.
> 
> How long have you been om amp? i'm worried that tolerance may start developping as that may start a lot faster then tolerance to the focus enhancing effects.
> Imo is memantine the key for that tough.


I believe it's been close to 3 months now. My prescription is to take 7.5mg daily at the moment, but that was just as I was titrating my own dose, cautiously, because I'm also on Parnate. I just met with my psychiatrist today and my Parnate dosage is to be doubled starting today. I'm interested to see how that will affect things

She prescribes me the Dexedrine too, but does not actually make the decisions involving it. She originally sent me for a consult to a developmental/learning disorder specialist (very busy guy, takes forever to get an appointment with him), and he strongly diagnosed me with ADHD and wrote my initial prescription. My psychiatrist basically just follows his recommendations.

I'm scheduled to meet with the guy again in a few weeks and, from what my psychiatrist told me today, she's already talked with him and it's likely he'll be letting me take 7.5-10mg twice a day. As it's technically a prescription for ADHD and tolerance isn't as huge of an issue with symptoms specific to that disorder, it's probably not a wise idea for me to even ask for memantine.

But in agreement with one of your previous posts, I'm just not ready to give up recreational drugs yet either. With the amphetamine I find going over the therapeutic dose is unpleasant for me anyways though, so it's not like I have any incentive to abuse it, and being on an MAOI limits much of what I can do. I've been quite a polydrug abuser though and all my psychiatrists have been aware of that, it's not something I hide, but despite all the stuff I do I absolutely CANNOT handle weed. People find that really strange. So for the most part right now though, as far as I can tell, I'm limited to ketamine and opioids, both of which I enjoy, but I have a bit of a legitimate need for opioids right now so abusing those would be stupid too! So ketamine has been the main thing I've been interested in, and while I used to have no problem acquiring it, it's been impossible for me to find lately. It's a pretty damn escapist drug, and although many people don't like it, I find it's an interesting way to relax and de-stress. It also have proven, potent antidepressant qualities (FOLLOWING the experience, not during), and as it's a strong NMDA antagonist, I imagine it could have quite a bit of benefit in mitigating amphetamine tolerance as well. So it's pretty damn unfortunate I haven't been able to find it lately!! I haven't gone this long without a recreational drug since I started doing them altogether!

But still... my mental health is vastly more important. I could easily just get off the Parnate in favor of being able to do stuff like MDMA, LSD (those two in combination are unbelievably mind-blowing), DMT, and even South American cocaine (my parents have a place down there, a trip would cost me next to nothing), but I'm a totally non-functional mess of a human being, even since before I ever touched a drug, and it's bad enough that I would have absolutely no reason to keep on living if I didn't have the prospect of attaining some semblance of mental health and becoming a functional, independent, and at least moderately happy human being.


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## Ehsan (Mar 21, 2009)

UltraShy said:


> Yeah, I too would note that doesage seems to be a major issue here. This woman would have been consuming the equivalent of *150* of my pills to equal 1.5 grams.
> 
> This is like warning about alcohol consumption based upon somebody who managed to consume 150 drinks per day and say that's what happens if you have two glasses of wine with dinner.


street amphetamines are impure. 60% of them are below 10% purity and the average purity is about 14%.
http://www.idmu.co.uk/amphetuse.htm

what's the recreational dose of amphetamine?


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## crayzyMed (Nov 2, 2006)

I cant handly weed either, were completely the same in that part.

I can understand you man, i personally dont have any issues with depression and just feel good everyday apart from my anhedonia, so i can handly life without much problems, if i had depression that would be differend.
The biggest reason i take memantine now is that it reduces my OCD and GAD significantly, i actually started it for tolerance and didnt expect this lol, i'm very happy with it and i would like to start experimenting in higher doses with it soon.

I wish i could get diagnosed with ADHD as easily as in the US, it seems that a pdoc can just say youv got ADHD and give you amp's, in my country its a whole proces of differend appointments (they have to talk to my parents too) tests etc...


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## shadowmask (Jun 22, 2009)

Hell yeah Dopamine. Gotta get me some of that.


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## meyaj (Sep 5, 2009)

Ehsan said:


> street amphetamines are impure. 60% of them are below 10% purity and the average purity is about 14%.
> http://www.idmu.co.uk/amphetuse.htm


14% pure amphetamine in 1.5 grams is still pretty crazy. That's 210mg of pure amphetamine, which is still ridiculous. For the sake of argument, let's go with something of even lower purity than even the 10%. I'll choose 7% simply because it's half of that 210mg - 105mg. Keep in mind also statements from the page you linked to such as the following:


```
Given the low purity of most street powders, larger
quantities of street amphetamine powder are required to
produce the desired effect. [U]A typical 'recreational' dose
of 50mg pure drug[/U] would require 1g of 5% powder, or 
5 grams of 1% powder. [U]A heavily tolerant and dependent 
user seeking to consume 600mg of pure amphetamine per 
day[/U] a person would need to use 12 grams of 5% 
amphetamine powder, 6 grams of 10%, or 3 grams of 20% 
powder.
```



Ehsan said:


> what's the recreational dose of amphetamine?


The recreational doses of amphetamine are variable depending on the user and are represented in some of the charts on the very page you linked. I assume you meant what is the typical therapeutic dose? That's a bit more consistent. 10mg of Dexedrine is pretty typical.

But strictly speaking, Dexedrine as measured in mg isn't pure amphetamine either. It's a salt, and roughly 27% of that mass is actually sulfate (sulfuric acid.) So we're looking at a typical daily dose of maybe 7.3mg for therapeutic purposes. 7.3mg or 10mg, the difference is ultimately of little consequence when looking at recreational doses.... but for the sake of accuracy I thought I'd take it into account anyways.

Now compare that to even my rather lowball estimate of what 1.5g of street amphetamine would be - 105mg. That's nearly 15 times as much! If the stuff was 14% which YOU call average purity, it would be about 30 times as much! And it could just as easily be stronger than average purity as it could be weaker than average, we don't really know. So we could even be looking at doses as high as 50 times as much, and possibly even beyond that!

To roughly equate 1.5g to a therapeutic dose, you'd have to have such a crappy product that it would be less than 0.5% pure! The chances of somebody willingly buying such a consistently poor amphetamine product for 6 years straight is so unlikely that it's a pretty safe bet that nobody in history has EVER done that, let alone the subject of this study in particular. Anybody that's ever used recreational drugs more than just a few times knows it's a waste of time, money and possibly even detrimental to your health to keep buying from somebody who supplies sub-par drugs, and 0.5% is just outrageously beyond subpar. NOBODY would put up with that for 6 years. Even on the extremely remote chance that this woman did, it just cannot be reasonably assumed anyways, so that particular study says absolutely nothing about the effects a normal therapeutic dose has on the brain.

And again, this is all an impossibly ideal scenario. 6 years of purchasing street amphetamine for use on a daily basis, and it's practically inevitable that other, even more toxic chemicals are going to be cut into the powder. Finding other stimulants in the mix is pretty common. And even the non-psychotropic cuts that are assumed to be inert and are merely used to bulk up the product could potentially cause harm. There's absolutely no way this was controlled for using street product over a span of 6 years.

I'm not trying to be close-minded here, and I accept that therapeutic doses of amphetamine could be mildly neurotoxic, but all the current literature using carefully controlled doses suggests that any such effect is negligible. Citing case studies of a single person using an unknown amount of what ever drugs and other assorted chemicals might have been added in along the supply chain is as unscientific as it gets, especially when the one thing we CAN reasonably assume is that even under the most ideal of conditions, the doses being used were at least an order of magnitude greater. It's just absurd to throw a decades and decades of quite soundly conducted scientific studies out the window just to be scared by something of absolutely no relevance to therapeutic users.

If I start seeing solid research indicating serious problems for long-term ADULT patients using therapeutic doses, I'd have no problem reconsidering my stance, but considering the mountain of evidence to the contrary, I don't think this is likely to ever happen. Not with this particular problem anyways...


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## mohammed (Feb 12, 2010)

if this idea were true, schizophrenics would be in highest status due to their high dopamin levels.


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## crayzyMed (Nov 2, 2006)

mohammed said:


> if this idea were true, schizophrenics would be in highest status due to their high dopamin levels.


Thats not true, as passed a certain point you get problems, lots of dopamine is good but the same rule applies, too much= bad.
Apart from that i dont really understand shizophrenia, but its certainly not a good argument against this study.


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## euphoria (Jan 21, 2009)

mohammed said:


> if this idea were true, schizophrenics would be in highest status due to their high dopamin levels.


Schizophrenics have an imbalanced dopamine system - they commonly experience anhedonia (lack of pleasure, related to low dopamine), yet they also suffer "positive symptoms" like hallucinations and thought disorder characteristic of high dopamine. I don't think it's as simple as high dopamine vs. low dopamine; what matters is where dopamine is high or low. I think there is more to schizophrenia than just dopamine levels. It may be related to abnormal tryptophan metabolism interfering with NMDA receptors.


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## crayzyMed (Nov 2, 2006)

meyaj said:


> 14% pure amphetamine in 1.5 grams is still pretty crazy. That's 210mg of pure amphetamine, which is still ridiculous. For the sake of argument, let's go with something of even lower purity than even the 10%. I'll choose 7% simply because it's half of that 210mg - 105mg. Keep in mind also statements from the page you linked to such as the following:
> 
> 
> ```
> ...


+1
Besides those that use amphetamine daily allways looks for the best quality and then stay with that dealer, so we can assume that addicts take speed of the better quality on the streets. (Possibly cut with other garbage too).

Ive had street amphetamine that was active in the 10mg range. If you know where to look youll get amphetamine that is ALOT purer then 14%.


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## CoconutHolder (Oct 13, 2007)

GnR said:


> The idea that my brain may not be wired for success pisses me off.


I hear ya. 

Very interesting article.

I always thought it was me that no one in my family or my "friends" could ever seem to show me a tiny bit of social support. . .when it seemed like my life mission to continue to support them my whole life over and over. Only to not get emotional support back, ever ~but to be emotionally abused over and over. Now I know, it is me. :/

Take care, everyone.


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## euphoria (Jan 21, 2009)

> I hear ya.
> 
> Very interesting article.
> 
> I always thought it was me that no one in my family and none of my friends could ever seem to show me a tiny bit of social support when I supported them my whole life over and over. Only to not only get emotional support ever but to be emotionally abused over and over. Now I know, it is me. Feels great.


Your family should always support you, and even more so if you have emotional problems. You've got it the wrong way round if you're blaming yourself for their failures.


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## Ehsan (Mar 21, 2009)

have you perceived any change in your motor skills when you are on dopaminergics.
i think low dopamine is associated with low "motor skill learning" which can be used as a diagnosis method.
a complex computer game that requires controlling several keys... at once is an example of a complex motor activity.
am i true?
are you good at "motor skill learning" when you are not on dopaminergics.


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## n1kkuh (Jul 11, 2008)

"I try to help others be happy, so that is why I act and do most of the things I do. Most of the time it only backfires - go figure. . ."

People aren't always ready to receive advice, when they aren't they'll usually do something rude.


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## meyaj (Sep 5, 2009)

Ehsan said:


> have you perceived any change in your motor skills when you are on dopaminergics.
> i think low dopamine is associated with low "motor skill learning" which can be used as a diagnosis method.
> a complex computer game that requires controlling several keys... at once is an example of a complex motor activity.
> am i true?
> are you good at "motor skill learning" when you are not on dopaminergics.


Amphetamines decrease the time needed to get motor skill function back in physical therapy, so it makes a lot of sense.

I think a lot of your motor skill learning is done as a kid though and, even as a young adult, any further refining of your motor skills needs to be done through at least semi-intentional effort. I don't think it's just going to happen on its own.

That being said, I DO see a correlation between clumsiness and certain disorders where dopamine deficiencies are implicated (ADHD, social anxiety, etc). Interesting thought.


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## steelpenguin79 (Feb 13, 2010)

UltraShy said:


> So highly successful people have loads of dopamine that losers like me would need amphetamines to get.


Yep. I believe that I'm in the same boat. I have done well so far but I know I could've done better if I had that wiring. I supervised Financial Advisors for several years until I lost my job this past October because of a merger. Oh well. At least they gave my a 5 month severance package. Anyways, to get back on track, the best Financial Advisors made over one million in commissions a year and I'm willing to bet that their dopamine levels are naturally sky high. That lets them talk to people and network for success. When I was on tramadol for my back I felt like I could do that and I felt great mentally. I read that it rasies dopamine activity in the brain but it has nasty side effects. I can't wait to go to the mental health specialist this week to start my evaluation process because my general doctor has struck out with giving me Celexa, Alprazolam, and ambian for sleep. I don't even need the ambian and I have not taken it in months. Same goes for Alprozolam, it makes me sleepy and that's not good!


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## meyaj (Sep 5, 2009)

steelpenguin79 said:


> Yep. I believe that I'm in the same boat. I have done well so far but I know I could've done better if I had that wiring. I supervised Financial Advisors for several years until I lost my job this past October because of a merger. Oh well. At least they gave my a 5 month severance package. Anyways, to get back on track, the best Financial Advisors made over one million in commissions a year and I'm willing to bet that their dopamine levels are naturally sky high. That lets them talk to people and network for success. When I was on tramadol for my back I felt like I could do that and I felt great mentally. I read that it rasies dopamine activity in the brain but it has nasty side effects. I can't wait to go to the mental health specialist this week to start my evaluation process because my general doctor has struck out with giving me Celexa, Alprazolam, and ambian for sleep. I don't even need the ambian and I have not taken it in months. Same goes for Alprozolam, it makes me sleepy and that's not good!


Well you've already got a leg up most people, getting both Xanax AND Ambien, from a GP no less! But even though you may be seeing a specialist, new doc means new attitudes and for all you know your meds will be regressed. I wish you luck in getting dopaminergics if you really think they might help you, but damn it's tricky, especially without diagnosed ADHD/narcolepsy to give you a damn good reason.


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## steelpenguin79 (Feb 13, 2010)

meyaj said:


> Well you've already got a leg up most people, getting both Xanax AND Ambien, from a GP no less! But even though you may be seeing a specialist, new doc means new attitudes and for all you know your meds will be regressed. I wish you luck in getting dopaminergics if you really think they might help you, but damn it's tricky, especially without diagnosed ADHD/narcolepsy to give you a damn good reason.


Yeah, that's why I'm going to see the specialist to see if I am ADHD because from everything I've read it points to the symptoms that I'm having. Especially the concentration issue that is getting worse as time goes on. Nothing that he perscribed helped with my concentration problems and mild fatigue problems.


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## Classified (Dec 7, 2004)

Nae said:


> or, social status influences dopamine.


This is what I was thinking. I haven't read the paper, but they had better explain the 'chicken & the egg' problem and why their findings are correct.

Basically, if you send one of these high dopamine people to the middle of nowhere with no human contact, does their dopamine levels decrease or stay the same? Do dopamine levels go down after a breakup or a falling out with friends or family?


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## Ehsan (Mar 21, 2009)

I think "reduced motor learning" is associated with low dopamine activity
 Also a large change in "spontaneous eyeblink rate" with dopaminergics is a good test for dopamine abnormalities.​


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## crayzyMed (Nov 2, 2006)

Excellent post rocknroll (regarding the amp neurotoxiticy, i still havent seen any convincing evidence, and have yet to see reports of ppl that have gotten depression, social anxiety etc from taking normal dexedrine doses.) The doses that were used proven neurotoxic in rats are HUGE, kinda like IV'ing 6 gram daily if your a human.

Very interesting post man, i learned alot from that!


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## steelpenguin79 (Feb 13, 2010)

Classified said:


> This is what I was thinking. I haven't read the paper, but they had better explain the 'chicken & the egg' problem and why their findings are correct.
> 
> Basically, if you send one of these high dopamine people to the middle of nowhere with no human contact, does their dopamine levels decrease or stay the same? Do dopamine levels go down after a breakup or a falling out with friends or family?


 
Good question. Now if my hypothesis of highly successful Financial Advisors is true then I would have to say that a breakup or falling out with friends would not effect them that much. They reason I believe that is because they hear the word NO more than most people when they are trying to drum up business. When I first got out of College I tried to be a Financial Advisor but...well as you could expect with my anxiety and concentration issues I could not handle people telling me no. Now if they had no human contact....well I don't know about that one. Anyone want to tackle that?


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## crayzyMed (Nov 2, 2006)

Ive been thinking that the combination of amisulpride and a dopamine agonist may proof to be usefull, the ami would antagonize the presynaptic receptors and knock the dopamine agonist to the postsynaptic receptors (if the affinity of ami is higher for the presynaptic receptors).

It kinda worked with a combination of ami and trivastal i tried yesterday, however it wasnt very significant, so i would need to try in higher doses of the dopamine agonist.


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## Upekkha (Dec 10, 2009)

rocknroll714 said:


> Now to address some of the posts in this thread..
> 
> 1) Amphetamines and other NDRAs are potent dopaminergic neurotoxins. This has been demonstrated time and time again in scientific research in both rodents and primates, including humans. Furthermore, there are countless anecdotal/subjective reports of these drugs inducing long-lasting mental problems such as apathy/anhedonia, depression, and social anxiety, among others. You can say that they are only mildly toxic or that the damage is not present with lower doses, but when it comes down to it, we don't really know the true facts regarding these claims. Taking amphetamines is essentially playing with fire.


 It has been in use for almost 80 years without any evidence that it produces any detectable damage in humans at therapeutic doses. In rodents there is evidence that it actually has a nutritive effect on the brain in low doses. Calling it playing with fire seems highly excessive. There is no alarm in the psychiatrist community with these drugs with all the evidence on the table. They give them to children and adults and they are considered safe at recommended dosages.

How do you explain the lack of alarm? I would explain it because the drugs have been used medicinally longer than any other psychiatric medication I am aware of without producing recongizable harm when used as directed.


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## crayzyMed (Nov 2, 2006)

Upekkha said:


> It has been in use for almost 80 years without any evidence that it produces any detectable damage in humans at therapeutic doses. In rodents there is evidence that it actually has a nutritive effect on the brain in low doses. Calling it playing with fire seems highly excessive. There is no alarm in the psychiatrist community with these drugs with all the evidence on the table. They give them to children and adults and they are considered safe at recommended dosages.
> 
> How do you explain the lack of alarm? I would explain it because the drugs have been used medicinally longer than any other psychiatric medication I am aware of without producing recongizable harm when used as directed.


Exactly!


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## crayzyMed (Nov 2, 2006)

> Blood pressure drug also 'rejuvenates brain' in Parkinson's
> By Mike Nagle, 11-Jun-2007
> 
> Related topics: Emerging targets, Drug discovery
> ...


http://www.drugresearcher.com/Emerg...re-drug-also-rejuvenates-brain-in-Parkinson-s



> Ecstasy as a brain booster for Parkinson's?
> 
> 27 October 2006
> Magazine issue 2575. Subscribe and get 4 free issues.
> ...


http://www.newscientist.com/article/mg19225754.800-ecstasy-as-a-brain-booster-for-parkinsons.html


> Program#/Poster#: 756.16/DD18
> Title: MDMA (Ecstasy) enhances dopamine cell survival and neurite outgrowth in vitro
> Location: Georgia World Congress Center: Halls B3-B5
> Presentation Start/End Time: Wednesday, Oct 18, 2006, 11:00 AM -12:00 PM
> ...





> E. Neuronal growth and reorganization
> 
> In contrast to the administration of high doses of MDMA that act as a selective serotonergic neurotoxin in animals, the administration of low concentrations of MDMA produce the opposite effect, stimulating neuronal growth. MDMA's release of serotonin modulates receptor enzymes and stimulates astrocytes to release Neurotrophic Growth Factors (NGF). These actions, in turn, cause neurons to develop and innervate new target areas in the brain. (75-77)
> 
> Stimulating neurons to morphologically reorganize, known as neuroplasticity, has the potential to correct underlying causes of neurochemical imbalances. It may be possible to re-engineer neuronal structures and activity to create a biochemical state of lasting well being and happiness. (7


MDMA and isradipine for dopamine health?

(Dont start taking mdma folks, still some interesting research).


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## crayzyMed (Nov 2, 2006)

> Dopamine D2 receptor upregulation in rat neostriatum following in vivo infusion of forskolin
> Wanderoy, Maria H.; Westlind-Danielsson, Anita; Ahlenius, Sven
> Abstract
> INTRACEREBROVENTRICULAR (i.c.v.) forskolin infusion for 5 days resulted in a concentration-dependent increase in rat striatal dopamine (DA) D2 receptors measured with [3H]raclopride. In animals given 50 nmol/h forskolin, the highest concentration used, raclopridemediated suppression of spontaneous locomotor activity was attenuated, and (±)-7-hydroxy-dipropyl-aminotetralin HBr (7-OH-DPAT)-mediated inhibition of striatal DA synthesis, as estimated by the accumulation of DOPA following inhibition of cerebral decarboxylase, was enhanced. These data suggest that the DA D2 receptor increase comprises receptors localized both postand presynaptically. The density of striatal DA D1 receptors was also changed with the forskolin treatment, in a concentration-dependent fashion, but in the opposite direction to DA D2 receptors. These findings suggest that striatal DA receptor sensitivity can be changed by manipulation at the second messenger level (e.g. independent of direct neurotransmitter-receptor interactions) in vivo.


Forskolin is available as a herb, could it be usefull for us?


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## No Surprises (Nov 1, 2009)

Rocknroll714, I thank you kindly for your extensive contributions to this forum. You're only 19 and yet you sound like you're about ready to author a psychopharmacology text.


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## Ehsan (Mar 21, 2009)

*Comparisons between bupropion and dexamphetamine in a range of in vivo tests exploring dopaminergic transmission.*

forget bupropion:no
*
*


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## korey (Apr 25, 2006)

Ehsan said:


> forget bupropion


It's better than nothing.:blank


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## Ehsan (Mar 21, 2009)

korey said:


> It's better than nothing.:blank


btpropion is a very weak dopamineric becuse it is metabolized in body using several enzymes and about 5% of drug that remains unchanged recieve brain.
1-CYP2B6 which has a great role in hydroxy-bupropon production
2- *unknow enzymes* that convert bupropion to erythro and threo hydrobupropion

it is possible to inhibit above mentioned enzymes to have almost pure bupropon but
1- you should take high doses of several different pills in a short time to get a weak dopaminergic effect
2- when you ihibit metabolization, bupropion's plasma concentration goes high and higher(like when you are badly overdosed) and you may develop a convulsion(like me:haha)
3- bupropion even(in high dose) blocks DAT trasporters to some extent because it has a very week affiity for DAT(520uM)
4- at the best it can improve your concentration and motor but not pleasure or motivation.

anyway, it is not worth the problems it cause, there are man better dopaminergics


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## crayzyMed (Nov 2, 2006)

Yes, bupropion sucks.

What other dopaminergics did you have in mind? for me its simple, amphetamine, but you are concerned about neurotoxiticy, what alternatives are there?


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## euphoria (Jan 21, 2009)

Selegiline + low dose bupropion might be worth exploring. I've heard selegiline boosts the good effects of Ritalin by 5x without much increase in bad effects. But bupropion on its own is very very mild and close to useless for me.


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## crayzyMed (Nov 2, 2006)

euphoria said:


> Selegiline + low dose bupropion might be worth exploring. I've heard selegiline boosts the good effects of Ritalin by 5x without much increase in bad effects. But bupropion on its own is very very mild and close to useless for me.


Probably useless for SA, may be good for depression.


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## Ehsan (Mar 21, 2009)

euphoria said:


> Selegiline + low dose bupropion might be worth exploring. I've heard selegiline boosts the good effects of Ritalin by 5x without much increase in bad effects. But bupropion on its own is very very mild and close to useless for me.


i've tried bupropion+selegiline without seccess.
forget bupropion. it's NRI and useless.


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## euphoria (Jan 21, 2009)

Ehsan said:


> i've tried bupropion+selegiline without seccess.
> forget bupropion. it's NRI and useless.


Oh ok, fair enough.


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## crayzyMed (Nov 2, 2006)

> The results suggest that social status and social support are associated with the density of dopamine D2/D3 receptors in an area of the brain called the striatum, which plays a major role in reward and motivation.


After i found all that studies showing that NMDA antagonists upregulate D2 receptors in the striatum, id say that memantine would be a very promosing treatment for social anxiety. (Also because we tend to have higher levels of glutamate in the brain[1], i wonder wheter this extra glutamate caused our dopamine receptors to desentisize, simular to what happened in ALS patients?[2])

Studies have shown that memantine is not effective as an antidepressant in doses of 20mg and less, however in 30mg or 40mg doses its effective for major depression, i assume that are the minimal doses needed for significant dopamine upregulation.
I cant wait to try higher doses of it.


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## Ehsan (Mar 21, 2009)

*Chronic administration of NMDA antagonists induces D2 receptor synthesis in rat striatum.*

but in contrast:

*Glutamate Promotes Proliferation of Striatal Neuronal Progenitors by an NMDA Receptor-Mediated Mechanism *
*
*


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## Vini Vidi Vici (Jul 4, 2009)

N-desmethylclozapine = Agonist at Delta-Opioid, M1, M3, .. Partial Agonist at D2/D3, .. Antagonist at 5-HT2c ,...... I can't figure out whether it is an antagonist at 5-HT2a also....ive found multiple articles citing it is a selective 5-HT2c antagonist, but then other articles say it Is a potent antagonist at 5-HT2a also.

Lol....Maybe they are all are citing the same article or something, ..and doing experiments Assuming that a specific compound is selective to a certain receptor, when actually the compound isn't selective. apparently Ketanserin was supposed to be selective to 5-HT2a....then somebody figured out it also antagonized 5-HT2c. Im not complaining tho, I always make assumptions based on inconclusive evidence, ...actually, i make alot of conclusions on nonexistent evidence.

I found a really cool article, i dunno if it means anything, but maybe Metergoline is weak at blocking overall 5-HT2a activity and alot stronger at blocking 5-HT2c....or maybe its metabolized into something else, i dunno, but it looks awesome, --

*Increased self-administration of d-amphetamine by rats pretreated with metergoline.* 



> Rats trained to self-administer d-amphetamine were pretreated with metergoline, a long-acting 5-hydroxytryptaminergic antagonist, and immediately placed in self-administration cages for 8 hours. During the first 3 hours after metergoline the normal pattern of d-amphetamine self-administration was unaltered, but thereafter the rate of self-injections was increased. Between 4 and 6 hr the self-injections in metergoline-treated rats were increased in a regular fashion and subsequently (7-8 hr) in a stereotyped manner, i.e., rapid bursts of lever presses with little space between injections. *In amphetamine-naive rats the levels of striatal and nucleus accumbens dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, rose with time after metergoline injection.* Levels of 5-hydroxyindoleacetic acid remained unchanged in these brain areas. The neurochemical results suggest a correlation between the dopaminergic actions of metergoline and d-amphetamine self-administration.


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## crayzyMed (Nov 2, 2006)

Ehsan said:


> *Chronic administration of NMDA antagonists induces D2 receptor synthesis in rat striatum.*
> 
> but in contrast:
> 
> ...


I dont think the effect of NMDA antagonists on embryos could be translated to normal use, there's no evidence that nmda antagonists have a negative effect in normal doses in developped brains.
Besides is memantine a partional antagonist and is therefor known to not interfere with normal glutamate transmission.
Memantine even raises N-acetyl aspartate wich has been corrolated with intelligence.

Memantine turning us in highly intelligent and socially succesfull ppl? That may be a bit of wishfull thinking haha.
http://www.jaoa.org/cgi/content/full/106/6/358#REF2


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## crayzyMed (Nov 2, 2006)

Anyway, these are our options:

Increasing dopamine

Dopamine agonists (Trivastal, pramipexole,...)
Dopamine antagonists to block presynaptic dopamine receptors (Amisulpride, altough the prolactin may be an issue and it appears that 5HT7 antagonism is responsible for the antidepressant effect)
LDOPA/Cardidopa (Look at euphoria's thread)
DARI's (altough ritalin sucks, desoxy may be good but its largely uninvestigated)
DRA's (Amphetamine, altough for some ppl neurotoxiticy is an issue)

Dopamine upregulation

NMDA antagonists (Memantine)
Forskolin [1]
Inositol [2]

The combination of an agent to agonize/increase dopamine and 1 to upregulate dopamine seems like the best strategy.
If anyone has any other idea's id like to hear them.


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## euphoria (Jan 21, 2009)

COMT inhibitors (including rhodiola)
MAO inhibitors
mu, delta opioid agonists
Kappa opioid antagonists
GHB agonists

Actually there are too many things to list... But most things affecting dopamine are not usually available for anxiety, anhedonia and depression.


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## crayzyMed (Nov 2, 2006)

MAO inhibitors dont seem to be a good option because of the reason rocknroll mentioned.


> For whatever reason, selegiline does not increase dopamine in the mesolimbic and mesocortical pathways, the pleasure pathways,


Do COMT inhibitors raise dopamine in the reward area's?


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## euphoria (Jan 21, 2009)

Selegiline did have a mild hedonic effect on me, it's not the same as stimulants but it's useful for boosting other drugs.


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## Ehsan (Mar 21, 2009)

positive:


> Chronic treatment with low doses of the selective monoamine oxidase (MAO) type B inhibitors selegiline [(7)-deprenyl] and rasagiline, causes elevation in extracellular level of 3,4-dihydrox-yphenylethylamine (dopamine) in the rat striatum in vivo





> Amphetamine-induced increase in striatal extracellular dopamine level was attenuated by one day and by chronic (21 days) treatment with selegiline


negative:


> Striatal levels of DAT were elevated after 1 and 21 days treatment with selegiline,


i have not perceived any positive or negative from selegiline


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## euphoria (Jan 21, 2009)

It seems entacapone is only a peripheral COMTI, and the other two are reserved as a last resort in Parkinson's due to liver toxicity. But still, I've read that rhodiola is a COMTI and that correlates well with my experience of it being a stimulant in higher doses.


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## Ehsan (Mar 21, 2009)

source


> Autoradiographic analysis of [3H]7-OH-DPAT and [3H]raclopride binding revealed a significant up-regulation of dopamine D2 and D3 receptors in the rat nucleus accumbens upon repeated treatment with tramadol.


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## crayzyMed (Nov 2, 2006)

Ehsan said:


> source


Interesting.


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## crayzyMed (Nov 2, 2006)

I forgot, tramadol is a NMDA antagonist, i gues this property explains the upregulation of those receptors.[1]


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## Ehsan (Mar 21, 2009)

Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study


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## meyaj (Sep 5, 2009)

Ehsan said:


> Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study


That's not surprising if it's looked at as a rebound/homeostatic effect. And kind of useless in utility too. The antipsychotics would have to be used longer to block dopamine than they'd be effective in bumping receptor binding up. In other words, the treatment will only make us feel a lot WORSE the majority of the time. Not what I'd call ideal.

Not to mention antipsychotics tend to block dopamine for a reason. Psychotic people, schizophrenics, etc, tend to have a very high baseline for dopamine binding. What you end up with upon abrupt cessation is rebound psychosis... yikes.

But hey, if you think that's a good idea, be my guest.


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## crayzyMed (Nov 2, 2006)

Ehsan said:


> Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study


Antipsychotics increase D2 density because D2 antagonism increases cyclic AMP, increasing cyclic AMP with forskolin has the same effect.
The use of antipsychotics also isnt very practical as they make us feel alot worse.


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## miko (Jul 5, 2009)

I'm taking requip (ropinirole) 1mg 2 x day, and it's the only dopamine med that I can take without bad side effects. And the only med that helps with my anxiety/anhedonia without excessive sweating and worse anxiety.

And it's decreasing my seborrhea...


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## crayzyMed (Nov 2, 2006)

miko said:


> I'm taking requip (ropinirole) 1mg 2 x day, and it's the only dopamine med that I can take without bad side effects. And the only med that helps with my anxiety/anhedonia without excessive sweating and worse anxiety.
> 
> And it's decreasing my seborrhea...


How long did it take before it started working? What side effects did you have when you started using it?


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## miko (Jul 5, 2009)

One week. Side effects - little nausea for one, two days... and little drowsy - that's all.


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## crayzyMed (Nov 2, 2006)

miko said:


> One week. Side effects - little nausea for one, two days... and little drowsy - that's all.


I see your still on a low dose, are you planning to go any higher? The max dose for parkinson is 24mg a day.


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## miko (Jul 5, 2009)

I know. Maybe gradually? I'm afraid of possible sleep attacks on higher doses.


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## crayzyMed (Nov 2, 2006)

miko said:


> I know. Maybe gradually? I'm afraid of possible sleep attacks on higher doses.


Yeah if you go very gradually it should work out.


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## miko (Jul 5, 2009)

Try this med and play your favorite music  Interesting feelings, music sounds deeper !


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## crayzyMed (Nov 2, 2006)

Sounds good


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## euphoria (Jan 21, 2009)

Don't despair guys, if it's a chemical imbalance at the root of your problems, then it can be solved with drugs.


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## crayzyMed (Nov 2, 2006)

euphoria said:


> Don't despair guys, if it's a chemical imbalance at the root of your problems, then it can be solved with drugs.


Exactly.


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## NicktheQuik (Nov 9, 2009)

The only problem is getting a hold of the RIGHT drugs. If you're seeing a doc about Depression/Social Anxiety, as far as I know at least (which really isn't that much) there are very few good dopamine related drugs you can get prescribed. 

My friend has plenty of adderall which works wonders on me, I just don't wanna go through life doing that when none of my family or doctor know about it.


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## crayzyMed (Nov 2, 2006)

NicktheQuik said:


> The only problem is getting a hold of the RIGHT drugs. If you're seeing a doc about Depression/Social Anxiety, as far as I know at least (which really isn't that much) there are very few good dopamine related drugs you can get prescribed.
> 
> My friend has plenty of adderall which works wonders on me, I just don't wanna go through life doing that when none of my family or doctor know about it.


Its a matter of finding the right doc (for example call around and ask if i doc would be willing to prescribe a dopamine agonist, ldopa, memantine etc, dont ask for anything addictive, once you found one you have open minded doc wich could help you with alot of things.)

Its indeed quite sad that not one of those dopamine based drugs that could help us is aproved for SA while there is ALOT of evidence pointing to dopamine problems and not serotonine or gaba.


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## miko (Jul 5, 2009)

Yes, sad, but I'm thanks God, that I have found dopamine agonists, by myself. And I have found doc with open mind, that prescribed me this meds! Now I know, that I'm alive !


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## crayzyMed (Nov 2, 2006)

*Pramipexole*
Lots of potential..



> Comparison of pramipexole, fluoxetine, and placebo in patients with major depression.
> Corrigan MH, Denahan AQ, Wright CE, Ragual RJ, Evans DL.
> 
> Pharmacia & Upjohn, Inc., Global Clinical Research, Bridgewater, NJ 08807-0995, USA.
> Pramipexole, a dopamine D2 receptor agonist, was tested in 174 patients with major depression, with or without melancholia and without psychotic features. Three daily dose levels (0.375 mg, 1.0 mg, and 5.0 mg) were compared to fluoxetine (Prozac) at 20 mg and placebo in a randomized, double-blind, parallel-group study. After a 1 week placebo run-in period, patients were treated for 8 weeks, had a post-study follow-up (week 9), and were evaluated primarily with the Hamilton Psychiatric Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinician's Global Impressions-Severity of Illness scale (CGI-SI). All patients who received one dose of study medication were included in the observed-case analysis (no missing data were replaced). *Results indicated that by endpoint (week 8), patients receiving pramipexole at the 1.0 mg per day dose had significant improvement over baseline compared to the placebo group by measure of the HAM-D, MADRS, and CGI-SI. Significant improvement in this dose group was seen at other timepoints as well. The most obvious improvement was seen in the pramipexole 5.0 mg group, although a substantial dropout rate for this group precluded statistical tests vs. placebo late in the study. *Patients taking fluoxetine also showed significant improvements at endpoint on the MADRS and earlier in the study on the HAM-D. No new or unusual safety concerns were generated during this study. Pramipexole helped safely alleviate the symptoms of depression at 1.0 mg per day and especially in those patients who could tolerate the escalation to 5 mg per day.





> Pramipexole in treatment-resistant depression: a 16-week naturalistic study.
> Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB.
> 
> Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa, Italy. [email protected]
> OBJECTIVE: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2-D3 dopamine agonist, in patients with drug-resistant depression. METHODS: The study sample consisted of in-patients with major depressive episode, according to the DSM-IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a > 50% reduction of the Montgomery-Asberg Depressive Rating Scale (MADRS) total score and a score of I or 2 on the Clinical Global Impression scale (CGI-1) at endpoint. Side-effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). RESULTS: Thirty-seven patients were enrolled. Of these. 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses. 19 completed the 16-week follow-up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 +/- 8.4 at baseline to 13.9 +/- 11.5 at endpoint (p < 0.001) and the CGI-S decreased from 4.6 +/- 0.8 at baseline to 2.8 +/- 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI-I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. CONCLUSIONS: *These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.*





> Pramipexole for bipolar II depression: a placebo-controlled proof of concept study.
> Zarate CA Jr, Payne JL, Singh J, Quiroz JA, Luckenbaugh DA, Denicoff KD, Charney DS, Manji HK.
> 
> Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institute of Health, Department of Human and Health Services, Bethesda, Maryland, USA.
> ...





> Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression.
> Goldberg JF, Burdick KE, Endick CJ.
> 
> Department of Psychiatry, Weill Medical College of Cornell University, New York, NY, USA. [email protected]
> OBJECTIVE: Previous studies suggest that the dopamine agonist pramipexole may possess antidepressant properties. The authors conducted a preliminary randomized, placebo-controlled trial to determine the safety and antidepressant efficacy of pramipexole in treatment-resistant bipolar depression. METHOD: Twenty-two depressed outpatients with DSM-IV nonpsychotic bipolar disorder were randomly assigned to receive placebo or flexibly dosed pramipexole (mean maximum dose=1.7 mg/day, SD=1.3) added to existing mood stabilizers for 6 weeks. The primary outcome measure was response, defined as improvement in Hamilton Depression Rating Scale score of 50% or more over the baseline score; secondary analyses involved changes in Clinical Global Impression (CGI) severity scores. RESULTS: More patients given pramipexole (10 [83%] of 12) than patients given placebo (six [60%] of 10) completed the study. Eight (67%) of 12 patients taking pramipexole and two (20%) of 10 taking placebo had an improvement of at least 50% in their Hamilton depression scale scores. The mean percentage of improvement from baseline Hamilton depression scale scores was greater for patients taking pramipexole (48%) than for those taking placebo (21%). Mean improvements in CGI severity were also greater with pramipexole than placebo. No patients discontinued the study because of adverse events except for one patient who became hypomanic while taking pramipexole. CONCLUSIONS: *Pramipexole was a safe and effective antidepressant among patients with bipolar depression. Larger randomized, controlled trials are needed to affirm these initial observations.*


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## crayzyMed (Nov 2, 2006)

Part2



> Mechanism of synergistic action following co-treatment with pramipexole and fluoxetine or sertraline in the forced swimming test in rats.
> Rogóz Z, Skuza G.
> 
> Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. [email protected]
> The aim of the present study was to examine the effect of combined treatment of male Wistar rats with pramipexole and fluoxetine or sertraline in the forced swimming test. The obtained results showed that co-treatment with pramipexole (0.1 mg/kg) and fluoxetine (10 mg/kg) or sertraline (5 mg/kg) (in doses inactive per se) exhibited antidepressant-like activity in the forced swimming test. Sulpiride (a dopamine D(2/3) receptor antagonist) and WAY 100635 (a 5-HT(1A) receptor antagonist), either being ineffective in the forced swimming test, inhibited the antidepressant-like effect induced by co-administration of pramipexole and fluoxetine or sertraline. However, SCH 23390 (a dopamine D(1) receptor antagonist) only partly did not alter the effect of pramipexole given jointly with antidepressant drugs; on the other hand, S 33084 (a dopamine D(3) receptor antagonist) only partly decreased (in a statistically insignificant manner) that effect. Moreover, progesterone and BD 1047 (a sigma(1) receptor antagonist) counteracted the antidepressant-like effect induced by co-administration of pramipexole and sertraline (but not pramipexole and fluoxetine). In that test, active behavior did not reflect the increases in general activity, since combined administration of pramipexole and fluoxetine or sertraline failed to enhance the locomotor activity of rats. None of the tested drugs (SCH 23390, sulpiride, S 33084, WAY 100635, BD 1047 and progesterone) - alone or in combination with pramipexole and fluoxetine or sertraline - changed locomotor activity. *The results described in the present paper indicate that co-administration of pramipexole and fluoxetine or sertraline may induce a more pronounced antidepressive activity than does treatment with pramipexole alone, and that in addition to other mechanisms, dopamine D(2/3) and 5-HT(1A) receptors may contribute to the antidepressant-like activity of pramipexole and fluoxetine or sertraline in the forced swimming test in rats. Moreover, sigma(1) receptors may constitute one of the possible mechanisms by which co-administration of pramipexole and sertraline induces antidepressant-like activity in that test.*





> [The Role of Low-Dose Pramipexole in the Treatment of Treatment-Resistant Bipolar Depression: A Case Report.]
> [Article in Turkish]
> 
> Akdenız F, Aldemır E, Vahıp S. Despite a wide range of various drugs, a significant proportion of depressed bipolar patients fail to respond to the treatment strategies. Novel theraupetics for bipolar depression are needed. Preliminary studies suggest that pramipexole a dopaminergic agent that has been used in the treatment of Parkinson's disease and restless leg syndrome may have antidepressant properties in unipolar and bipolar depressed patients as well as neurotrophic properties. The optimal antidepressant daily dose of pramipexole is not known. It has been suggested to be used between 0.125 to 9.0 mg/day. In double blind placebo controlled bipolar depression treatment studies, the average daily dose of pramipexole was 1.7 mg. Manic switches have been reported with depressive subjects and with subjects without any mental disorders. We report two cases of treatment resistant bipolar depression. Despite different treatment strategies and treatment adherence, the patients did not give optimal response to the treatments and continue to experience depressive relapses. *They have been treated with low dose (0.5-0.75 mg/day) pramipexole augmentation successfully. The severity and the duration of the depressive episodes were decreased. No serious adverse event has been reported with pramipexole during the maintenance treatment.*
> ...





> Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease.
> Lemke MR, Brecht HM, Koester J, Reichmann H. Center of Psychiatry and Neurology, Rhine Clinic Bonn, Germany. [email protected]
> 
> Depression affects approximately 45% of all patients with Parkinson's disease, reduces quality of live independent of motor symptoms and seems to be underrated and undertreated. Pramipexole shows D(3)- versus D(2)-receptor preference at cortico-frontal dopamine receptors and neurotrophic effects which seem to relate to its antidepressant and anti-anhedonic properties in Parkinson's disease and bipolar depression found in controlled studies. In the present study, effects of pramipexole were investigated under routine clinical conditions. Anhedonia was measured in patients with Parkinson's disease (n=657) using the self-rated Snaith-Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated Short-Parkinson's-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all patients and in 79.7% of the depressed patients with Parkinson's disease. Mild depression was present in 47%, moderate to severe depression in 22% of the patients. At the end of the study period of 9 weeks on an average, the mean dosage of pramipexole was 1.0+/-0.6 mg/d (range 0.3 to 4.2). *Frequency of depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well as motor deficits were significantly reduced during treatment with pramipexole. Drop-outs due to adverse events occurred in 3.5%. Future studies should investigate specificity of anti-anhedonic and antidepressive properties of pramipexole.*
> ...





> Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study.
> Rektorová I, Rektor I, Bares M, Dostál V, Ehler E, Fanfrdlová Z, Fiedler J, Klajblová H, Kulist'ák P, Ressner P, Svátová J, Urbánek K, Velísková J. First Department of Neurology, Masaryk University, St Anne's Teaching Hospital, Brno, Czech Republic. [email protected]
> 
> An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. *Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.*
> ...





> Pramipexole has astrocyte-mediated neuroprotective effects against lactacystin toxicity.
> Imamura K, Takeshima T, Nakaso K, Ito S, Nakashima K. Department of Neurology, Institute of Neurological Sciences, Tottori University, Faculty of Medicine, Yonago, Tottori, Japan. [email protected]
> 
> Pramipexole, a dopamine D2/D3 receptor agonist used in the treatment of Parkinson's disease, has been reported to have neuroprotective potential. We investigated the effect of pramipexole against cell death induced by a proteasome inhibitor, lactacystin, using primary mecencephalic neuronal cultures and SH-SY5Y cells. In E14 rat primary mesencephalic cultures, the number of surviving tyrosine hydroxylase (TH)-positive neurons and microtubule associated protein 2 (MAP2)-positive neurons was decreased by exposure to 1-5 microM lactacystin in a dose-dependent manner. Pretreatment with 100 microM pramipexole rescued TH-positive neurons and MAP2-positive neurons from the toxicity of lactacystin. The protective effect of pramipexole was not selective for TH-positive dopaminergic neurons. However, the treatment with 100 microM pramipexole did not protect SH-SY5Y cells against lactacystin-induced cell toxicity and proteasome dysfunction. We hypothesized that the protective effect of pramipexole against the lactacystin-toxicity was not direct but a secondary effect mediated by astrocytes. Therefore, we investigated the efficacy of conditioned medium collected from mecencephalic astrocytes treated with pramipexole. The conditioned medium increased the viability of SH-SY5Y cells against the toxicity of lactacystin. Pramipexole increased the levels of brain derived neurotrophic factor (BDNF) in the conditioned medium of astrocyte cultures. These protective effects were not significantly inhibited by dopamine D2 or D3 receptor antagonists. *We demonstrated that pramipexole had the protective effect against lactacystin toxicity, mediated by a neurotrophic effect of astrocyte-produced factors including BDNF.*
> ...


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## crayzyMed (Nov 2, 2006)

Part3


> Pramipexole in psychiatry: a systematic review of the literature.
> Aiken CB. Department of Psychiatry, Wake Forest University School of Medicine, Winston-Salem, NC, USA. [email protected]
> 
> OBJECTIVE: To assess the risks and benefits of pramipexole in psychiatric populations. DATA SOURCES: A PubMed search was performed using the keywords pramipexole and ropinirole, which identified 500 articles. STUDY SELECTION: All clinical studies in psychiatric populations were included in the primary review (24 articles). Studies involving other populations were then reviewed to evaluate potential risks and benefits not identified in the psychiatric studies. DATA EXTRACTION: Effect sizes were calculated from controlled studies. Rates of intolerable side effects and manic switching were estimated by pooled analysis of controlled and uncontrolled studies. DATA SYNTHESIS: Pramipexole has a large effect size (0.6-1.1) in the treatment of both bipolar and unipolar depression with a low short-term rate of manic switching in bipolar patients (1% mania, 5% hypomania). The pooled discontinuation rate for all reasons was 9%. Pramipexole is neuroprotective and exerts beneficial effects on sleep architecture. Pramipexole is associated with 3 rare but serious side effects: sleep attacks, which have only occurred in Parkinson's disease; compulsive behaviors and pathologic gambling, which have occurred in Parkinson's disease and restless legs syndrome; and psychosis, which has occurred in both psychiatric and neurologic populations. CONCLUSIONS: *Pramipexole is an important therapeutic option for treatment-resistant bipolar and unipolar depression; further studies are warranted to evaluate its safety in psychiatric patients.*
> ...





> Sustained administration of pramipexole modifies the spontaneous firing of dopamine, norepinephrine, and serotonin neurons in the rat brain.
> Chernoloz O, El Mansari M, Blier P. Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada. [email protected]
> 
> Pramipexole (PPX) is a D(2)/D(3) receptor agonist that has been shown to be effective in the treatment of depression. Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems are known to be involved in the pathophysiology and treatment of depression. Due to reciprocal interactions between these neuronal systems, drugs selectively targeting one system-specific receptor can indirectly modify the firing activity of neurons that contribute to firing patterns in systems that operate via different neurotransmitters. It was thus hypothesized that PPX would alter the firing rate of DA, NE and 5-HT neurons. To test this hypothesis, electrophysiological experiments were carried out in anesthetized rats. Subcutaneously implanted osmotic minipumps delivered PPX at a dose of 1 mg/kg per day for 2 or 14 days. After a 2-day treatment with PPX the spontaneous neuronal firing of DA neurons was decreased by 40%, NE neuronal firing by 33% and the firing rate of 5-HT neurons remained unaltered. *After 14 days of PPX treatment, the firing rate of DA had recovered as well as that of NE, whereas the firing rate of 5-HT neurons was increased by 38%. It was also observed that sustained PPX administration produced desensitization of D(2)/D(3) and 5-HT(1A) cell body autoreceptors, as well as a decrease in sensitivity of alpha(2)-adrenergic cell body autoreceptors. These adaptive changes are implicated in long-term firing rate adaptations of DA, NE and 5-HT neurons after prolonged PPX administration. In conclusion, the therapeutic action of PPX in depression might be attributed to increased DA and 5-HT neurotransmission.*
> ...





> Synergistic effect of pramipexole and sertraline
> in the forced swimming test
> by
> Maj J, Rogoz Z.
> ...





> Pramipexole in treatment-resistant depression:
> An extended follow-up
> by
> Cassano P, Lattanzi L, Soldani F, Navari S,
> ...





> Potential antidepressant properties of pramipexole detected in locomotor and operant behavioral investigations in mice
> by
> Lehr E.
> Department of Pulmonary Research,
> ...


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## crayzyMed (Nov 2, 2006)

*Trivastal*



> Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors
> by
> Brocco M, Dekeyne A, Papp M, Millan MJ.
> aPsychopharmacology Department,
> ...





> Psychomotor and cognitive effects of piribedil,
> a dopamine agonist, in young healthy volunteers
> by
> Schuck S, Bentue-Ferrer D, Kleinermans D,
> ...





> Effects of a dopamine agonist piribedil in depressed patients: relationship of pretreatment homovanillic acid to antidepressant response
> by
> Post RM, Gerner RH, Carman JS, Gillin JC, Jimerson DC, Goodwin FK, Bunney WE Jr.
> Arch Gen Psychiatry. 1978 May;35(5):609-15.
> ...


A collection of anecdotal reports:



> Great Stuff. 50 mg first thing in the morning.





> Hey everyone,
> 
> It's been a long time since I've posted here. Anyways, has anyone else ever tried Trivastal(piribedil)? I tried it for the first time today. I've noticed better concentration, improvement with information processing, verbal fluency, etc. It's completely different than any other dopamine agonist I've tried. Hopefully, the effects continue. Has anyone had experience with it?





> Yes, I've been using Trivastal (piribedil) for quite some time, and have to say its the best dopaminergic drug out there, without side-effects. Pretty much same effects as yours + libido over the roof ;-)





> Yeah, I've found most dopamine agonists to be somewhat sedating(Mirapex, Bromo, Cabergoline). I don't notice any sedating effect with Trivastal though. I think it's because of the additional noradrenergic properties. I'm interested to hear if other people have a similar experience.





> I tried trivestal briefly, and I HATED it. Both times I tried it I descended into a hopeless depression-like feeling which lasted for the rest of the day. I lied huddled under blankets shivering on my couch, eating take out food with a kind of desperation. To each his own, I have 27 tablets left if anyone (US preferred) wants to take them off my hands for $45 shipping included.





> ok...took it 50mg dose with breakfast before going to work.
> 
> 30-40 minutes later i star getting ranndom erections on the office.
> 
> ...





> 50mg feedback:
> 
> I took it just with my regular vitamins, and a little green tea.
> 
> It feels like C+Y almost, no measurable increase in focus, feel a lot more agitated and "excitotoxic" and worse, I feel no serotonine whatsoever. dissapointed thus far. what is the HL of this compound? this could be becasue I'm exausted mentally today but heck this is why I need this


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## crayzyMed (Nov 2, 2006)

> I'm 61. I've been retired since '99. At this age, things are wearing out. I was having mild depression with melancholy. I had no dreams. I was sleepy, had no motivation, and lethargic. I was drinking coffee all morning. As we age, we loose mental sharpness and memory skills. I felt like I was mentally dead.
> 
> I began to use 100mg of 5-HTP about one hour before bed. The depression symptoms left within several days. I began dreaming again. I began to sing a little to myself during the day.
> 
> ...





> Well this morning I downed one 50mg pill and so far i have been slightly dissapointed...it's hard to describe what i'm feeling slight energy but also with the occassional yawn but i am noticing when typing this the words come out a little bit better but that could be placebo...who knows
> 
> Would it be bad to throw in 500mgs of DLPA in hope that it'll synergize with it?
> 
> I might post at the end of the day and give a full evaluation of it!


Source: Imminst and mind&muscle, those anecdotal reports are mostly regarding the use of trivastal as a smart drug tough and not as an anxiolytic.
There is more science supporting the use of pramipexole (look at the previous page) for depression and other stuff, however trivastal could theoretically be a better option since its not as sedating at the start of the treatment.


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## crayzyMed (Nov 2, 2006)

Guide 4 Dummies said:


> That's just me, but α2-adrenergic antagonism is a major turn off since α2-adrenergic agonists seem to be very effective for my ADHD. Mirtazapine, which is also α2-adrenergic antagonist, made my ADHD much worse.


Yeah, pramipexole would be a better option in the long run.


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## crayzyMed (Nov 2, 2006)

I'm making an overview of the possibilities we have for raising/antagonizing/upregulation dopamine. Once i'm done i'l ask one of the mods to move all my posts as the first page so we have a nice overview.

Comt inhibitors: tolcapone



> Open study of the catechol-O-methyltransferase
> inhibitor tolcapone in major depressive disorder
> by
> Fava M, Rosenbaum JF, Kolsky AR, Alpert JE, Nierenberg AA,
> ...





> Beneficial effects of co-administration of catechol-O-methyltransferase
> inhibitors and L-dihydroxyphenylalanine in rat models of depression
> by
> Mannisto PT, Lang A, Rauhala P, Vasar E.
> ...





> Tolcapone: a potential new antidepressant
> detected in a novel animal model of depression
> by
> Moreau JL, Borgulya J, Jenck F, Martin JR.
> ...


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## euphoria (Jan 21, 2009)

But isn't tolcapone hepatotoxic?


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## crayzyMed (Nov 2, 2006)

Yes, you seem to be right, Entacapone would be the better option then.

EDIT: Nvm it doesnt cross the brain barrier.


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## borbiusle (Sep 26, 2009)

That must explain why I constantly fantasize about being in positions of power & glory even though I'm somewhat of a social recluse. Nothing fires me up like a Rambo movie or some tale of vindication/vengeance (The Crow, Lucky Number Slevin, etc.). Seems like whenever I'm on some mild stim (a few cups of cofee, few cans of redbull), I temporarily become that confident/well-spoken/motivated individual I've always wanted to be.

Dammit, I refuse to accept a lower social-status when everything inside of me screams otherwise. Looking outside my own head for a second, I'm in great health, I get straight A's, I have a toned/muscular-body, my finances are in top-shape, I have a great job, I'd probably have a girlfriend(hell any good friends in general) if I could get myself to leave the damn house more often, yet I feel like ****. This does not add up to me.


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## Vini Vidi Vici (Jul 4, 2009)

borbiusle said:


> Looking outside my own head for a second, I'm in great health, I get straight A's, I have a toned/muscular-body, my finances are in top-shape, I have a great job, I'd probably have a girlfriend(hell any good friends in general) if I could get myself to leave the damn house more often, yet I feel like ****. This does not add up to me.


 I constantly do it to, i realized after a while, that my fantastical identity was actually more in depth and developed than my current (recluse) ever has been. When i watch a really good movie, its like it jump starts me and for a couple minutes, i feel inspired to be the person i really think i am/want to be...same with Energy drinks, for a couple minutes, its like, :boogie then i fizzle out again. ALL the pieces of a potentially exceptional existence are in place, i have every resource i could ever need, ....but everything just sits there, the months go by and im still the same pathetic person (sitting on the couch with my laptop) i was a year ago. Im glad u have a job/$/work out, u seem 2 got it all together except for the SA....it doesnt add up to me either :sus Every day that goes by, I get more frustrated, well I used to, but what can I get mad at? Myself...?


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## Vini Vidi Vici (Jul 4, 2009)

polythene said:


> I have zero dopamine in my brain.
> 
> My social status is execrable.


when Amphetamines work properly, I get this weird awesome feeling....I suddenly have stuff to say, I want to talk to people, Im not anxious. Its too good to be true.. Its So...foreign, its like, does everyone Im looking at in school, do they feel this way constantly? Is that why they talk to each other? I can't imagine it... Nevertheless, I've been trying relentlessly to get my Dopamine levels to stay up without fizzling out, I don't even know where all the Dopamine goes. It just goes somewhere, or something kills it....what though? I can't figure out what is killing my Dopamine.


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## Vini Vidi Vici (Jul 4, 2009)

euphoria said:


> But isn't tolcapone hepatotoxic?


Prolonged Social Anxiety and self-induced Isolation = Hepatotoxic.  Ya i just had 2 say that, unfortunately I can't actually support my statement, cuz Experience has taught me the consequences of ignoring (Negative effects/net results) usually are permanent, while the benefits are transient. but still. :blank


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## euphoria (Jan 21, 2009)

Vini Vidi Vici said:


> when Amphetamines work properly, I get this weird awesome feeling....I suddenly have stuff to say, I want to talk to people, Im not anxious. Its too good to be true.. Its So...foreign, its like, does everyone Im looking at in school, do they feel this way constantly? Is that why they talk to each other? I can't imagine it... Nevertheless, I've been trying relentlessly to get my Dopamine levels to stay up without fizzling out, I don't even know where all the Dopamine goes. It just goes somewhere, or something kills it....what though? I can't figure out what is killing my Dopamine.


Maybe you're not taking enough memantine? As crayzyMed said, it upregulates dopamine receptors.


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## Vini Vidi Vici (Jul 4, 2009)

euphoria said:


> Maybe you're not taking enough memantine? As crayzyMed said, it upregulates dopamine receptors.


Completely Agree, ..I just took a 4-day break from Dexedrine, and went up to 10mg/day Memantine. I was completely tolerant to the positive effects of Dexedrine, so I kinda knew i had to do something, Crazymed was telling me for the last month that Im gonna get tolerant, but I didn't listen to him (as usual, and I suffered for my Stupidity ). But the break wasn't nearly as hard as I thought it would be, of course my SA was horrible and I slept and ate everything. I took about 4mg of Dexedrine today, i didnt think it was working, but I guess it is because Im making multiple posts on SAS and talking to people, which must mean somethings working.

The best part tho, is that Memantine seems to make Amphetamine stronger over time (=Only if ive just recently increased my dose of Memantine) I think from a-7 nAChr upregulation or D2 or something, which is nice because its like reverse tolerance for me.


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## crayzyMed (Nov 2, 2006)

Yeah 5 mg definatly was too low of a dose.


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## Vini Vidi Vici (Jul 4, 2009)

5mg was good, (not enough though) it made the Amph work for 2 months, instead of only 2 weeks without Memantine. I think 10mg will be really nice. And I also think ill take 2 day breaks every week if possible, but only if I have enough Peanut butter to make Peanut butter sandwiches on the off Days, because I don't like eating other stuff just peanut butter sandwiches.


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## crayzyMed (Nov 2, 2006)

A few ppl report needing an evening dose for full tolerance prevention and atleast 30 or 40mg, 10mg could still be too low.
The window of effects can be shorter then the actual half life just as with amphetamine, thus needing twice doses a day.

Anyway go to 30mg as unther that dose it also isnt effective for depression. And i also wont expect 10mg to work wonders in the long run too, maybe 5 months instead of 2 months, you need high enough doses and a 1 or 2 day break a week. Especially the small breaks are important as some form of tolerance can allways build up wich those small breaks would help prevent.


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## crayzyMed (Nov 2, 2006)

Vini Vidi Vici said:


> Ya 5mg wasn't enough, but it still made the Amph work for 2 months, instead of only 2 weeks without Memantine. I think 10mg will be really nice. And I also think ill take 2 day breaks every week if possible, but only if I have enough Peanut butter to make Peanut butter sandwiches on the off Days, because I don't like eating other stuff just peanut butter sandwiches.


Peanut butter is horrible stuff, in Holland everyone eats that crap. Ugh not my stuff.


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## ThatWierdGuy (Feb 20, 2010)

People with Asperger's and Schizophrenia produce too much dopamine. They are famous for their awesome social skills. This why antipsychotics are prescribed to people with autism.

Too much of a good thing. Be careful with drugs.


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## Vini Vidi Vici (Jul 4, 2009)

crayzyMed said:


> Peanut butter is horrible stuff, in Holland everyone eats that crap. Ugh not my stuff.


oh i should have specified, JIF peanut butter. All the natural kinds are horrible, only the JIF and Peter Pan are good, i guess all the easy spreadable ones are good. i survive on peanut butter sandwiches, energy drinks, and graham crackers.


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## crayzyMed (Nov 2, 2006)

ThatWierdGuy said:


> People with Asperger's and Schizophrenia produce too much dopamine. They are famous for their awesome social skills.
> 
> Too much of a good thing. Be careful with drugs.


Too much isnt a good thing and too low isnt a good thing either, so those wich are deficient need to work on increasing dopamine, making it normal and not increasing it too too high levels.


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## Vini Vidi Vici (Jul 4, 2009)

Ive been taking a combo of Parnate+Memantine+Dexedrine, (along with Energy drinks and Nicotine gum) for about 3 months now. I wanted to make a small update 4 anyone who is interested.....I have Severe Depression, OCD, and Social Anxiety/Phobia....Of all the Meds and Med combos Ive tried, no single or Combined meds have worked as well as this combination. I currently take 20mg Parnate/day, 15-30mg Dexedrine/day, and 10mg Memantine/day. I recently just raised the Memantine from 5mg to 10mg, since 5mg was helping prevent tolerance to Dexedrine's positive effects, but only prevented tolerance for 2 months (which is still Awesome!!). I take short 1-5 day breaks every once in a while, usually only when i raise the dose of Memantine, Ive only taken 2 5-day breaks since starting the Meds in early December. 

My Depression is reduced about 30-40 % without Dexedrine, but with Dexedrine, my Depression is reduced by at least 60% usually. Social Anxiety is reduced by about 20% without Dexedrine... and reduced by at least 50% with Dexedrine+Energy Drinks. OCD is sometimes helped and sometimes made worse depending on circumstances/environment....Nicotine gum usually reduces OCD significantly. 

This Med combo is Extremely effective at raising Dopamine levels consistently/long-term.....I have severe Depression, and Even that is almost obliterated with my meds. If somebody with only SA, and without depression, took this Combo, It would most likely do something awesomely amazing.  Of course, the specific meds are extremely hard 2 get, its taken me 3-4 years to get them, after going through all the other stuff. But its not impossible by any means....1 call/appointment with one Psychopharmacologist= All the meds at 1 time from one Doctor. 

If anybody lives In/near/within 500 miles of Minneapolis, Minnesota, the Psychopharmacologist (in Minneapolis) I'm seeing is the BEST and most knowledgeable P-doc I have ever seen/had/known....Hes insane. :boogie


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## crayzyMed (Nov 2, 2006)

Interesting study on ropinirole, it also weakly agonizes the opiate system so this one may be better then pramipexole for us.



> Anxiolytic profile of ropinirole in the rat,
> mouse and common marmoset
> by
> Rogers DC, Costall B, Domeney AM, Gerrard PA,
> ...


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## Vini Vidi Vici (Jul 4, 2009)

I got ropinirole last summer from one of my P-docs last summer, It seemed to help a little bit with concentration even after taking it only 2 times, It improved my mood and enjoyment of stuff a little bit i think, might have been placebo effect, ya. Requip = a pretty sounding name, it just sounds awesome for some reasons, to me at least. Not as awesome as "Dexedrine" but yeah:roll


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## crayzyMed (Nov 2, 2006)

Variations in the dopamine D2 gene predict extraverted personality.



> Neurosci Lett. 2010 Jan 14;468(3):234-7. Epub 2009 Nov 6.
> Variation in DRD2 dopamine gene predicts Extraverted personality.
> Smillie LD, Cooper AJ, Proitsi P, Powell JF, Pickering AD.
> 
> ...


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## podizzle (Nov 11, 2003)

cant wait for my nano pills that can manipulate my genes. i want root administrator access on this body right now i feel like i have user access only. Extraversion On! Access denied.


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## euphoria (Jan 21, 2009)

podizzle said:


> i want root administrator access on this body right now i feel like i have user access only. Extraversion On! Access denied.


sudo extroversion -enable


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## bahnhof (Jun 13, 2010)

interesting
does chronic use of SSRI influence these receptors. as in... _"SSRI-treatment decreases Social Status"_


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## lionheart (Jun 16, 2010)

when you take a ssri and fill up your serotonine, the dopamine goes down i thaught? because my libido is not so great now and dopamine levels are needed for that, im socially a lot more talkative and better with higher serotonine and automatically less dopamine, so im not sure if this article is accurate.


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## bahnhof (Jun 13, 2010)

SSRI is offcourse prescibed for a whole range of conditions but i think its mainly focus is on treating depression (eg making people not take _action_ to suicide) therefore some _"sideeffects" _like weakness, amotivation, apathy occur. I think the cases with parkinsonism after ssri-treatment also is due to some dopamine funciton.

As in following.





also here
http://www.biopsychiatry.com/akathisia-ssris.htm


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## Ehsan (Mar 21, 2009)

*Dopamine D2 Receptors in the Nucleus Accumbens Are Important for Social Attachment in Female Prairie Voles*


> *Dopamine D2 Receptors in the Nucleus Accumbens Are Important for Social Attachment in Female Prairie Voles (Microtus ochrogaster)*
> The prairie vole (Microtus ochrogaster), a monogamous rodent that forms long-lasting pair bonds, has proven useful for the neurobiological study of social attachment. In the laboratory, pair bonds can be assessed by testing for a partner preference, a choice test in which pair-bonded voles regularly prefer their partner to a conspecific stranger. Studies reported here investigate the role of dopamine D2-like receptors (i.e., D2, D3, and D4 receptors) in the nucleus accumbens (NAcc) for the formation of a partner preference in female voles. Mating facilitated partner preference formation and associated with an approximately 50% increase in extracellular dopamine in the NAcc. Microinjection of the D2 antagonist ticlopride into the NAcc (but not the prelimbic cortex) blocked the formation of a partner preference in mating voles, whereas the D2 agonist quinpirole facilitated formation of a partner preference in the absence of mating. Taken together, these results suggest that D2-like receptors in the NAcc are important for the mediation of social attachments in female voles.


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## Klonii (May 10, 2010)

Would combining tyrosine with bupropion do anything? At the very least it would actually be attainable as opposed to a lot of what is discussed in this thread.

Also, I've read that bupropion is far inferior to name brand wellbutrin. I am considering going on wellbutrin with my klonopin, are most of you of the opinion that wellbutrin is useless for SA?

thanks-


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## crayzyMed (Nov 2, 2006)

Wellbutrin is just a fancy NRI... Not much dopaminergic about it (enough dopaminergic action to sell it as a dopaminergic, but not enough to feel it if you know what i mean...)


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## jim_morrison (Aug 17, 2008)

crayzyMed said:


> Wellbutrin is just a fancy NRI... Not much dopaminergic about it (enough dopaminergic action to sell it as a dopaminergic, but not enough to feel it if you know what i mean...)


+1 Yeah wellbutrins actual blockade of dopamine reuptake transporters is weak at best. I think that the majority of it's dopaminergic activity is the result of it's NRI properties, so basically increased dopamine activity concentrated in the prefrontal cortex.


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## Ehsan (Mar 21, 2009)

*Dopamine deficiency*

*Dopamine deficiency signs/symptoms:*


Reduced ability to feel pleasure
Flat, bored, apathetic and low enthusiasm
Depressed
Low drive and motivation
Difficulty getting through a task even when interesting
Procrastinator/little urgency
Difficulty paying attention and concentrating
Slowed thinking and/or slow to learn new ideas
Crave uppers (e.g. caffeine/nicotine/diet soft drinks)
Use these to improve energy/motivation/mood

Prone to addictions (e.g. alcohol)/addictive personality
Shy/introvert
Low libido or impotence
Mentally fatigued easily and physically fatigued easily
Sleep too much and trouble getting out of bed
Put on weight easily
Family history of alcoholism/ADD/ADHD
 Dopamine levels may be low due to a combination of genetic and acquired reasons. Dopamine can be raised effectively using either nutrient based therapies or medications. Dopamine is synthesized form the amino acid tyrosine.

*Factors which reduce dopamine levels:*


Chronic stress
Inadequate sleep
Hypothyroidism
Lead, arsenic and cadmium exposure
Under-methylation
Tyrosine (precursor) deficiency
Magnesium, iron, zinc & vitamins B3/B6/C/D deficiency
Excess copper levels
Genetic dopamine receptor abnormalities
Chronic opioid, alcohol & marijuana use
Adrenal insufficiency
Glutathione deficiency
Parkinson's Disease
Influenza
Estrogen deficiency
Human growth hormone deficiency


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## Bigbird (Feb 25, 2010)

I suffer from all of those symptoms except for putting on weight easily.


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## podizzle (Nov 11, 2003)

new way to get your dopamine up: crack open a can of whoop ***

http://www.physorg.com/news119535403.html


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## Ehsan (Mar 21, 2009)

*Dopamine system genes not linked to social phobia.*



> *Dopamine system genes not linked to social phobia.*
> 
> AbstractSocial phobia, particularly in its generalized form, has a genetic component in its etiology as suggested by positive twin studies and child temperament studies of social anxiety. Observations from functional imaging research suggest that dopamine function may be abnormal in the brains of patients with social phobia. Our investigation examined polymorphisms in the dopamine D2, D3 and D4 receptor genes, plus the dopamine transporter gene in a sample consisting of 17 multiplex social phobia families. We employed both parametric and non-parametric methods to test for linkage. Linkage was excluded for all loci under the broad diagnostic category. In the medium diagnostic category, the D3 receptor gene showed non-significant positive LOD scores (LOD = 0.62). We are able to clearly exclude a major effect for each of the four dopamine gene markers under the broad diagnosis of social phobia. Additional studies of dopamine system genes will be necessary to define clearly their role in social phobia.


==================================================================


> * Sequence Variation in the Primate Dopamine Transporter Gene and Its Relationship to Social Dominance*
> 
> Dopaminergic activity differs between socially dominant and subordinate monkeys, and in humans, it correlates significantly with extraversion, a trait analogous to social dominance in monkeys. Furthermore, concentrations of monoamine metabolites within the cerebrospinal fluid are highly heritable. Dopaminergic activity is modulated by the dopamine transporter (DAT), and the gene encoding this transporter is therefore an excellent candidate for studies aiming to identify variants of functional or evolutionary significance. However, the majority of such research has focused exclusively on the human homologue and its most common polymorphism, a functional variable number tandem repeat in the 3' untranslated region. Cross-species comparisons provide valuable insights into genome evolution, speciation, and selection mechanisms and may highlight sites of evolutionary significance. To date, however, no comprehensive studies of the DAT gene have been performed simultaneously on multiple primate species. We therefore characterized sequence variation and extent of linkage disequilibrium (LD) across the DAT genes of cynomolgus macaques (_Macaca fascicularis_), rhesus macaques (_Macaca_ _mulatta_), and humans. We identified 2 potentially functional variants, which are associated with social rank in cynomolgus monkeys and which correspond to a putative transcription factor-binding site. Although highly conserved across mammals, the DAT gene differs significantly between humans and macaques in levels of sequence variation and LD structure, with the monkeys displaying up to 3 times more sequence variability and significantly less LD than humans. This suggests that the DAT gene has followed different evolutionary trajectories during primate speciation.


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## ElRey (Apr 9, 2010)

I've seen that dopamine deficiency list of symptoms before and I definitely fit a lot but not all those signs. And I've also seen a list of serotonin deficiency symptoms and some of the signs seem very similar to dopamines. Can anyone list key differences between the two? It's confusing trying to determine if there's a serotonin or dopamine problem. Maybe both, maybe neither, it's pretty confusing.


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## GnR (Sep 25, 2009)

I have almost all of those deficiency symptoms. No wonder Ritalin and Adderall make me feel better.


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## 1L45TTRI (Feb 10, 2010)

Has this thread died.... Any updates?


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## crayzyMed (Nov 2, 2006)

1L45TTRI said:


> Has this thread died.... Any updates?


There was a new thread going on dopaminergics:
http://www.socialanxietysupport.com...promosing-treatment-for-social-anxiety-99183/

Altough dopamine agonists have kinda fallen out of favor with the 2 ppl that tried them getting severe apathy and anhedonia on them, making MAOI's and stimulants the only 2 good options to raise dopamine.


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## 1L45TTRI (Feb 10, 2010)

Cheerz crayzymed


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