• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

Overactive Dopaminergic System

overactive dopamine anxiety depression downregulation upregulation serotonin numb brain fog

  • Please log in to reply
26 replies to this topic

#1 xeon

  • Guest
  • 153 posts
  • 20
  • Location:USA

Posted 18 May 2013 - 08:40 AM


This question popped up today and seems very interesting.

Is it possible to have a [natural or stress-induced] over-active Dopamine system which ends up mimicking symptoms of lowered Dopamine?

The reason I ask is because I can't tell if my Dopamine system is under-active or overactive. I experience racing thoughts a lot, and I tend to obsess, over-think and stay anxious for long periods of time. But sometimes I have terrible brain fog and fatigue. I am also depressed. It caused me to wonder if it's possible for the Dopamine system to overwork itself, possibly due to lowered Serotonin, and end up downregulating Dopamine receptors... which would then cause symptoms of lowered Dopamine? If this is the case, shouldn't things that enhance Serotonin (Bacopa, Inositol, SSRI's, etc.) cause an initial spike of lethargy/demotivation > then D receptors upregulate and then cause and overall balance?

If this is the case, that could potentially explain why any stimulant only works for me for a very short amount of time and I have a horrible crash afterwards even if it's a mild one like caffeine or ginseng.

Thoughts?

#2 darksanity

  • Guest
  • 47 posts
  • 3
  • Location:Vancouver, BC

Posted 18 May 2013 - 08:52 AM

Lol it's a lot more complex than that. There's what 5 different receptors for dopamine? Their function probably differ depending on their location in the brain (i.e. the D2 receptor in the amygdala doesn't do the same thing as the D2 receptor in the nucleus accumbens). Then you have to take into account the glutamatergic system, not to mention the myriad of hormones, peptides, trace amines, other obscure receptors, etc.

You can't simplify mental states down to a few neurotransmitters... Your brain is an insanely complex system with complex feedback mechanisms. Every new thing neuroscientists discover seems to simply show just how little we truly understand (kind of like with the Universe).

Pointing to a single neurotransmitter as a cause of mental states is good for marketing (*cough* SSRIs), but in practice it just doesn't work like that.

Edited by darksanity, 18 May 2013 - 08:59 AM.


sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#3 xeon

  • Topic Starter
  • Guest
  • 153 posts
  • 20
  • Location:USA

Posted 18 May 2013 - 09:45 AM

Lol it's a lot more complex than that. There's what 5 different receptors for dopamine? Their function probably differ depending on their location in the brain (i.e. the D2 receptor in the amygdala doesn't do the same thing as the D2 receptor in the nucleus accumbens). Then you have to take into account the glutamatergic system, not to mention the myriad of hormones, peptides, trace amines, other obscure receptors, etc.

You can't simplify mental states down to a few neurotransmitters... Your brain is an insanely complex system with complex feedback mechanisms. Every new thing neuroscientists discover seems to simply show just how little we truly understand (kind of like with the Universe).

Pointing to a single neurotransmitter as a cause of mental states is good for marketing (*cough* SSRIs), but in practice it just doesn't work like that.


I understand what you say to be true, but it is known that certain neurotransmitters can be manipulated to get certain types of behavioral effects (clearly, if you read the reviews of nootropics here on LC and any scientific studies).... I'm not trying to oversimplify here, but I am pretty sure the scenario I described is possible and could be a potential starting point for treatment in anxiety.

I'm not trying to simplify a "mental state"; I'm trying to understand certain aspects of mental states to a degree that it can be manipulated to live a better life.

#4 renfr

  • Guest
  • 1,059 posts
  • 72
  • Location:France

Posted 18 May 2013 - 10:03 AM

Too much dopamine can also lead to anxiety and brain fog, it's not really about downregulation but more about a proper balance between neurotransmitters concentrations and quantity of receptors.
I also have that kind of anxiety that comes out of nowhere.
Interestingly exercise doesn't intensify it but calms it down.
Magnesium oftenly provides a certain relief against these symptoms, I started taking a lot of magnesium and I also removed most of my calcium food sources (such as milk) and it provides a great relief.
Look at your diet and see if there's a certain food or supplement that causes such anxiety.
Coffee for instance is highly anxiogenic and maybe you can balance that excess dopamine with some serotonin.


#5 xeon

  • Topic Starter
  • Guest
  • 153 posts
  • 20
  • Location:USA

Posted 18 May 2013 - 10:23 AM

Too much dopamine can also lead to anxiety and brain fog, it's not really about downregulation but more about a proper balance between neurotransmitters concentrations and quantity of receptors.
I also have that kind of anxiety that comes out of nowhere.
Interestingly exercise doesn't intensify it but calms it down.
Magnesium oftenly provides a certain relief against these symptoms, I started taking a lot of magnesium and I also removed most of my calcium food sources (such as milk) and it provides a great relief.
Look at your diet and see if there's a certain food or supplement that causes such anxiety.
Coffee for instance is highly anxiogenic and maybe you can balance that excess dopamine with some serotonin.


I've checked everything and I cannot pinpoint a certain cause of anxiety aside from excessive stimulation. I don't drink caffeine or take stimulants, but when I do (before I quit drinking caffeine) I would feel better until it wears off and then the anxiety becomes really bad. Even getting really excited about stuff in general causes an immediate letdown followed with anxiety and feelings of depression. A very noticeable pattern. I'm hoping some serotonin enhancement will do the trick.

#6 cATsE

  • Guest
  • 56 posts
  • 10
  • Location:Europe

Posted 18 May 2013 - 12:51 PM

I would strongly advice to first have your adrenals checked, before you start 'treating' yourself any further with dopamine up/down regulators. Your own hormone system, when out of whack, can do some pretty strange things to your brain/mind. Just saying..

#7 xeon

  • Topic Starter
  • Guest
  • 153 posts
  • 20
  • Location:USA

Posted 18 May 2013 - 07:44 PM

I would strongly advice to first have your adrenals checked, before you start 'treating' yourself any further with dopamine up/down regulators. Your own hormone system, when out of whack, can do some pretty strange things to your brain/mind. Just saying..


How exactly would I go about getting my adrenals checked? I have no idea what to say to a doctor.. "Hey, can you check my adrenal glands? I feel tired but also anxious." Lol

#8 darksanity

  • Guest
  • 47 posts
  • 3
  • Location:Vancouver, BC

Posted 19 May 2013 - 02:16 AM

I'm not trying to simplify a "mental state"; I'm trying to understand certain aspects of mental states to a degree that it can be manipulated to live a better life.

Yes I understand, I think we all are trying to do the same here lol. Sometimes I do wonder though whether any attempt to 'control' our neurochemistry is futile (at least with the few crude drugs and methods we currently have). I mean, sure you can manipulate your neurochemistry on a short-term basis.. but in the long-run, homeostasis is a bitch.

Truth be told I have similar issues (like a lot of people here). I just don't think so much about it anymore and gave up trying to 'fix it'. Just thinking about it is enough to make one anxious lol (OCD-like).

Anyway checking your adrenals is a good idea. What drugs/supplements are you taking (if any) ?

Edited by darksanity, 19 May 2013 - 02:23 AM.

  • like x 1

#9 xeon

  • Topic Starter
  • Guest
  • 153 posts
  • 20
  • Location:USA

Posted 19 May 2013 - 03:40 AM

I'm not trying to simplify a "mental state"; I'm trying to understand certain aspects of mental states to a degree that it can be manipulated to live a better life.

Yes I understand, I think we all are trying to do the same here lol. Sometimes I do wonder though whether any attempt to 'control' our neurochemistry is futile (at least with the few crude drugs and methods we currently have). I mean, sure you can manipulate your neurochemistry on a short-term basis.. but in the long-run, homeostasis is a bitch.

Truth be told I have similar issues (like a lot of people here). I just don't think so much about it anymore and gave up trying to 'fix it'. Just thinking about it is enough to make one anxious lol (OCD-like).

Anyway checking your adrenals is a good idea. What drugs/supplements are you taking (if any) ?


Yeah homeostasis is a bitch. I don't even want to be "enhanced"... I just simply want to be back to my normal levels of energy/focus/mood again. I do get really OCD about it as well, lol. I would probably go get my adrenals checked if I knew that my doctor could do it accurately and give me useful information based on the results -- so I wouldn't be wasting a bunch of money. Would be sweet if there was a way to check them at home, heh.

I'm actually taking nothing and I haven't had caffeine in about a year (approximately). I have Bacopa but I'm kind of reluctant to take it since some people claim it makes them more foggy/tired/unmotivated and that's not too attractive to me.

#10 darksanity

  • Guest
  • 47 posts
  • 3
  • Location:Vancouver, BC

Posted 21 May 2013 - 06:00 AM

I'm actually taking nothing.

Nothing?? Not even a single supplement?? :|?

Wow so you're like a virgin.. you have lots of potential brother! :laugh:

...What have you tried so far?

#11 xeon

  • Topic Starter
  • Guest
  • 153 posts
  • 20
  • Location:USA

Posted 21 May 2013 - 06:19 AM

I'm actually taking nothing.

Nothing?? Not even a single supplement?? :|?

Wow so you're like a virgin.. you have lots of potential brother! :laugh:

...What have you tried so far?


Absolutely nothing. Lol.

I've tried:
L-Tryptophan - helps me to relax/sleep but doesn't help my depression.. actually makes me feel numb the day after I take it.
5-HTP - similar but more pronounced effect as L-Tryptophan
L-Tyrosine - Made me kind of panicky and have racing thoughts one time, tried it a couple other times with no noticeable effect
L-Phenylalanine - No noticable effect
DLPA - No noticeable effect
Rhodiola - Caused several anxiety and jitteryness even at very low doses, no "pleasurable" stimulation or antidepressant effect

I own but have yet to try:
Solgar Choline Bitartrate
Planetary Herbals Bacopa

Seems that everything Serotonin related either does nothing or numbs me out completely, and stimulating supplements cause agitation and anxiety to skyrocket if it does anything at all. Sometimes I think my brain is in an "avoidant" state rather than a "pleasure seeking" state.

#12 darksanity

  • Guest
  • 47 posts
  • 3
  • Location:Vancouver, BC

Posted 21 May 2013 - 07:08 AM

.

Edited by darksanity, 21 May 2013 - 07:17 AM.


#13 darksanity

  • Guest
  • 47 posts
  • 3
  • Location:Vancouver, BC

Posted 21 May 2013 - 07:16 AM

Seems that everything Serotonin related either does nothing or numbs me out completely, and stimulating supplements cause agitation and anxiety to skyrocket if it does anything at all. Sometimes I think my brain is in an "avoidant" state rather than a "pleasure seeking" state.

Try tianeptine. :-D I'm not a doctor though but if I was in the US and had to actually pay to merely see a doctor I would just order tianeptine hehe.

By the way that's just a random suggestion I'm not responsible if you try to commit suicide on it or something lol.

IME it's one of the best compounds relatively available out there. But there's always people that react in odd ways to everything.

At least do some research on it. ;)

#14 brainslugged

  • Guest
  • 305 posts
  • 39
  • Location:Georgia, US
  • NO

Posted 21 May 2013 - 08:39 AM

Serotonin and dopamine are horribly confusing when it comes to symptoms and hypo/hyper activity.

Wikipedia says (although with citation needed, lol) "Serotonin inhibits the fleeing reaction in subordinates, but enhances it in socially dominant or isolated individuals." and (with citation) "The effect of 5-HT1 receptors predominates in subordinate animals, while 5-HT2 receptors predominates in dominants [and presumably in isolated individuals as well]". So, increased serotonin activity is not nessesscarily anxiliotic. It largely depends on the environment and other factors (which I would imagine is more complex in humans than simple dominance/isolation).

I would say that your reactions to the supplements you listed are fairly normal.

Higher serotonin has been known for making people feel number, and Rhodiola isn't all that great in my opinion (when it works for me, it also increases anxiety, and I react really well to other stims).

I think you should try supplementing with choline and see how that goes. If the choline bitartrate does nothing, don't give up on choline. Bitartrate is the least bioavailable form of choline, so you may want to try something like CDP choline or Alpha-GPC. Choline's effects seem to be kinda opposing to dopamine from what I understand. Anti-cholinergics used to be used to help parkinsons patients, so it would logically follow that increasing choline may help with high dopamine, right?

Another thing, if you have access to a doctor, may be Mirtazapine. It is interesting and tolerated very well. In the binding profile list one the wiki, lower Ki values correspond to higher binding on those receptors, by the way (so an antagonist with a Ki of 1nM will be more potent than one with a Ki of 20nM). It seems like it may be helpful for you. It only increases serotonergic activity on specific receptors and it looks like it decreases dopamine activity on D4 primarily, the one that is the primary subtype [or at least one of the primary ones] indicated in ADHD (hypo in ADHD, so it may help with your overfocus. (however, remember that hyperfocus is also present in ADHD to a degree))

As cATsE said, adrenals are a big thing you should check too. You can go to a doctor and have blood tests for it. However, it may be difficult, depending on your doctor. Mine was really reluctant to test anything, really. She said that my insurance wouldn't cover it considering my age and lack of health complaints prior and that if I had complained about it in the past it would be easier to get coverage. So, really, it may be best to go ahead to the doctor and start complaining so that the problem is documented and thus will be justified to the insurance company. I would get blood tests on thyroid, adrenals, and sex hormones, any of the three that you can get covered. Thyroid is part of the basic tests, and while that doesnt seem to be the problem, it is still best to get it checked out.

In the US, you can still get ephedrine OTC in the form of Primatene tablets (for asthma if they ask). Try ephedrine and see how your react. If you don't want to do the kinda shady situation required to acquire it, try pseudoephedrine, about 120mg(instant release) for a good dose, but test it first at a lower dose to make sure you don't have bad cardio effects from it. They pretty much boost the adrenergic stuff(epinephrine and norepinephrine) so they may be helpful and it would be interesting to see how you react. Pseudoephedrine isn't going to be nearly as good as ephedrine for this purpose, but it will be a very very mild indicator, a better indicator if taken alongside piracetam.

Good luck. Don't know if I have been helpful, but I kinda forgot what my main point was, lol [time for bed].

Try tianeptine. :-D I'm not a doctor though but if I was in the US and had to actually pay to merely see a doctor I would just order tianeptine hehe.

Tianeptine is an incredibly interesting drug, one that I would really like to try to see how I react to.

However, I don't know if it would be especially useful in his situation if he is correct that excess dopamine is the problem considering that it seems like it increases dopamine activity. Still, whats the harm in trying it since it has such a good safety profile and seems to be available on the internet? Just watch out of the suicide thing.

#15 xeon

  • Topic Starter
  • Guest
  • 153 posts
  • 20
  • Location:USA

Posted 21 May 2013 - 08:54 PM

Thanks for the posts guys.

I will look into Tianeptine. Is there any way to order it from the US without a prescription? I know absolutely nothing about obtaining things that aren't OTC without seeing a doc.

Also about the norepinephrine thing, I've tried Strattera before. Forget to mention that. I took it a few times and every time it made me extremely anxious, sweaty, panicky, and WIDE awake for a really, really long time. It was terrible. I took it a couple times where the side effects were not so bad, but it just kept me awake for very long periods of time and didn't reduce anxiety/racing thoughts/anything relevant.

I've considered trying to get Mirtazapine as well, but haven't tried to yet. I'll take your advice and try my Choline and then maybe some CDP Choline if it doesn't help anything.

Another question: when I am sitting still, I have this uncontrollable urge to tap my feet or my hands all the time. I simply cannot sit still. I never really thought of it as a problem, but it never goes away. If I am awake and I'm doing anything sitting down I am always tapping my feet, legs, hands, whatever. And when I talk on the phone I have to pace back and forth repeatedly. It's very hard to concentrate if I'm not moving. I have to put all my effort in staying still in order to stop it. I used to not have this strange problem before... isn't it like "psychomotor agitation" or something like that? Is it a sign of anything?

#16 magniloquentc0unt

  • Guest
  • 299 posts
  • 13
  • Location:[xxx]

Posted 22 May 2013 - 11:19 AM

interesting. yes, it is not so simple. me myself, im always tired, unable to concentrate, bad memory, not motivated, would make one think somethings wrong with the dopamine.
but not: i dont have big appetite, im very libidinous, etc. I tried ritalin and it did not do SHIT... but i have had a perios with SSRIs back then and they seemed to do something..
  • like x 1

#17 xeon

  • Topic Starter
  • Guest
  • 153 posts
  • 20
  • Location:USA

Posted 23 May 2013 - 08:08 PM

interesting. yes, it is not so simple. me myself, im always tired, unable to concentrate, bad memory, not motivated, would make one think somethings wrong with the dopamine.
but not: i dont have big appetite, im very libidinous, etc. I tried ritalin and it did not do SHIT... but i have had a perios with SSRIs back then and they seemed to do something..


You're the first person I've seen to present a personal account of likely having excessive dopaminergic activity but symptoms of low dopamine. I really do think this is a valid situation people should look into before jumping into the "OMG I don't feel motivated and can't focus, I should get stimulants and increase Dopamine activity" bandwagon.

Thanks for posting this. Hopefully more people will look into this particular kind of imbalance if it exists.

#18 hullcrush

  • Guest
  • 83 posts
  • 4

Posted 25 May 2013 - 12:26 AM

In the context of getting your adrenals checked, plenty of sites exist where you don't need medical directive to get AM cortisol drawn. I run a website that does specifically allows access to this.

Briefly, you don't exhibit any common symptoms of effusive DA activity. That does not mean it's absent, you just might not have written it whether it be positive aspects of schizophrenia or hypersexuality/gambling. Moreover, mesolimbic DA pathway is easily pillaged if you'd like to decrease it, either via antagonism or reuptake of serotonin (lot of gaps in that reasoning). Current agents have almost no selectivity for DA in a long-term scenario whether it be through massive downregulation or unsustainable reuptake.

Your poor response to Strattera is not telling, and I mean that positively. Norepinephrine is extraordinarily easy to manipulate and as a psychoactive is almost absent therapeutic efficacy. Tianeptine is the essential forum drug, with lots of upside in theory and in practicality a shitload of unsuccessful treatment anecdotals coupled with clinical data that does not supersede those claims.

I'd try to block some aspects of NE before I mess with DA/5-HT. Plus, it's easy to reverse. Good luck.

#19 darksanity

  • Guest
  • 47 posts
  • 3
  • Location:Vancouver, BC

Posted 25 May 2013 - 06:47 AM

.

Edited by darksanity, 25 May 2013 - 06:57 AM.


#20 darksanity

  • Guest
  • 47 posts
  • 3
  • Location:Vancouver, BC

Posted 25 May 2013 - 06:57 AM

I will look into Tianeptine. Is there any way to order it from the US without a prescription? I know absolutely nothing about obtaining things that aren't OTC without seeing a doc.

I think you'd feel much better on tianeptine than any money wasted on a doctor's appointment (my opinion).. And you definitely can order it from the US without a prescription lol.

I've considered trying to get Mirtazapine as well, but haven't tried to yet. I'll take your advice and try my Choline and then maybe some CDP Choline if it doesn't help anything.

I don't see how extra choline will help you.. In fact it may hurt and make racing thoughts, anxiety, etc. worst.

Another question: when I am sitting still, I have this uncontrollable urge to tap my feet or my hands all the time. I simply cannot sit still. I never really thought of it as a problem, but it never goes away. If I am awake and I'm doing anything sitting down I am always tapping my feet, legs, hands, whatever. And when I talk on the phone I have to pace back and forth repeatedly. It's very hard to concentrate if I'm not moving. I have to put all my effort in staying still in order to stop it. I used to not have this strange problem before... isn't it like "psychomotor agitation" or something like that? Is it a sign of anything?

It's probably anxiety causing the agitation. I have the same problem to varying intensity depending on anxiety levels. In class, sitting drives me nuts, like a tension inside.

I don't think you have an "overactive" dopamine system.. If you did you'd be very impulsive, most likely addicted to something or many things, and with psychotic symptoms. Maybe "imbalanced" dopamine system would be a better way to see it (or even better an imbalanced glutamatergic system... dopamine is overrated lol).

#21 magniloquentc0unt

  • Guest
  • 299 posts
  • 13
  • Location:[xxx]

Posted 25 May 2013 - 08:05 AM

Btw i forgot ti mention that i actually have been on tianeptine for the past 5-6 weeks: its working so so.. Subtle... But no side effects

#22 magniloquentc0unt

  • Guest
  • 299 posts
  • 13
  • Location:[xxx]

Posted 25 May 2013 - 11:30 AM

I have been advised to try subultiamine from mAny people for my simptoms and am finally doing so in conjunction with tianeptine. Subultiamine supposedly increases da receptors count. I have no idea if its adviseable to injest both substances at the same time tho. Tought it was worth mentioning

#23 Sunwind

  • Guest
  • 103 posts
  • 11
  • Location:England

Posted 26 May 2013 - 09:33 AM

I have been advised to try subultiamine from mAny people for my simptoms and am finally doing so in conjunction with tianeptine. Subultiamine supposedly increases da receptors count. I have no idea if its adviseable to injest both substances at the same time tho. Tought it was worth mentioning


Strangely I feel like his and have this same problem described in the OP. I tried sulbutiamine and it just made me anxious and my heart race. also if you take it any time other than early-morning you will not sleep at all that night.

Edited by Sunwind, 26 May 2013 - 09:33 AM.


#24 magniloquentc0unt

  • Guest
  • 299 posts
  • 13
  • Location:[xxx]

Posted 26 May 2013 - 02:09 PM

I have taken subultiamine the last two days. I have to say i am extremely, extremely pleased. I have tried a lot of supplements, adaptogens, etc. this one is very subtle but is definitely there, its not harsh and it makes me more sociable, active, talkative, somehow relaxed. It is only the second time i took it and its together with tianeptine, but it has definitely done betterthan any ginseng, rhodiola, methylphenidate, modafinil. Ill have to try it long term and investigate its pharmacodynamics. Anyhow, one of my simptoms is hypersomnia: ive had no problem falling asleep in the evening but i experienced a sligh increase in difficulty falling asleep for my afternoon nap. Ill keep you updated

#25 magniloquentc0unt

  • Guest
  • 299 posts
  • 13
  • Location:[xxx]

Posted 28 May 2013 - 10:51 AM

Funny how the sulbutiamine has already lost its immediate effectiveness... wondering if it makes sense to take it long term
  • like x 1

#26 cATsE

  • Guest
  • 56 posts
  • 10
  • Location:Europe

Posted 28 May 2013 - 02:23 PM

Funny how the sulbutiamine has already lost its immediate effectiveness... wondering if it makes sense to take it long term

Try mulungu tea. For even stronger effect add some (very, very little!!!) wild lettuce extract. This will give you a deep, relaxed sleep, which is probably the best 'medicine' for strengthening/rebuilding the adrenals and thus make you more stress resistant.

Don't abuse it though, especially the wild lettuce, as it is poisonous in large amounts. What you want is the relaxing effect of the herb(s) (small dose), NOT the hallucinatory effect (large dose), which can be frightening, leading to even more stress, energy drain etc, etc.

Don't use it for months on end either, as tolerance will build eventually

sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#27 kurdishfella

  • Guest
  • 2,397 posts
  • -69
  • Location:russia
  • NO

Posted 19 July 2020 - 07:29 PM

I call them ''wandering leg'' they make multiple pointless movements they could have done in just one to do something even more further pointless just to get in the way of others and annoy them.but i think it causes a dopamine release that's why they do it. It's a form of akathisia in combination with ADHD.


Edited by kurdishfella, 19 July 2020 - 07:30 PM.






Also tagged with one or more of these keywords: overactive, dopamine, anxiety, depression, downregulation, upregulation, serotonin, numb, brain fog

1 user(s) are reading this topic

0 members, 1 guests, 0 anonymous users