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Normalizing desensitized dopamine receptors

dopamine neurotransmitters

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#1 Baten

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Posted 03 August 2015 - 05:40 PM


Is there any way to speed up the process? All I can gather is that it can take many months, possibly years.

 

Exercise can help. Meditation can help. Sulbutiamine/phenylpiractam could help.

I'm exercising, meditating and have taken sulbu/phenyl for some time. I'm not noticing much of an improvement.

 

Dopamine related things like dominance, arousal, reward/ambition-like feelings: I seem to be in great lack of all of these.

 

I could kill to get my neurotransmitters back in balance. Any tips would be greatly appreciated.


Edited by Baten, 03 August 2015 - 05:41 PM.


#2 Deartothesun

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Posted 03 August 2015 - 08:27 PM

Fasting, Jiaogulan tea, stop using porn, Uridine... There are tons of things.



But be careful not to quickly assume that your issues are caused by reduced Dopamine... Those things can also be caused by depression. And that is just one example.


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#3 Construct

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Posted 03 August 2015 - 11:49 PM

 

Dopamine related things like dominance, arousal, reward/ambition-like feelings: I seem to be in great lack of all of these.

 

I could kill to get my neurotransmitters back in balance. Any tips would be greatly appreciated.

 

Neurotransmitter reductionism is a seductively simple concept, but it's almost never anywhere near accurate. Complex macro phenomena such as reward and ambition extend far beyond simplistic explanations of a single neurotransmitter system or receptor.

 

What you're describing sounds more like depression. You will probably have more luck in treating it as such, and that doesn't just mean medications or supplements.


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#4 Baten

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Posted 04 August 2015 - 06:02 AM

Thank you for the replies. Funny you both seem to suspect I could suffer from a depression. I wouldn't think that is the case, I feel just fine in that department, subjectively.



#5 registered

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Posted 06 August 2015 - 08:51 AM

well you are probably not

you have willpower to excercise and do meditation you have intiative and you are feeling good

depression for me is when you cant get out of bad to eat or to pee



#6 gamesguru

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Posted 06 August 2015 - 06:36 PM

So depression is where you pee in your bed and go without food for days?  Seems extreme.

 

A high percentage of patients with depression who seek treatment in a primary care setting report only physical symptoms, which can make depression very difficult to diagnose ... chronic joint pain, limb pain, back pain, gastrointestinal problems, tiredness, sleep disturbances, psychomotor activity changes, and appetite changes

http://www.ncbi.nlm....cles/PMC486942/

 

Quitting porn def helps.  Just relying on mental imagery and "a harem of imaginary brides" [girls you see in person I would hope], you'll go for 10-30 minutes twice a week instead of 2-3 minutes every day.  There were times with porn I lasted less than 60 seconds, anhedonic, felt worse after, didn't enjoy it, wondered why I was doing it.  Definitely feel more sexually balanced, less addicted.  I don't get urges as often now, and I don't act on them as often either.  Sometime I just lay in bed with an erection for up to half an hour thinking, OK, how am I going to get laid next, until the erection subsides.  Breaking the porn addiction and only masturbating to girls you've met in person does a lot to motivate a man and put him in the proper mindset to ask a girl on a date (something many of us are afraid to do, and years overdue on).

Consider loose tea, whether black or green or white it makes no difference: http://science.natur..._on_sexual.html

 

Exercise and a mostly plant-based, whole food diet will contribute to improvement.

 

Learning to meditate, or just to think or to daydream clearly and meaningfully will go a long way in increasing your awareness and sense of peace.

 

Certain anti-depressive supplements may be worth considering:

 

Antidepressant-like effects of curcumin in rat model of depression is associated with an increase in hippocampal BDNF (upregulates BDNF where we want it)
http://www.sciencedi...166432812006997

 

Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats
http://www.sciencedi...006899307012590

 

Chronic Administration of Bacopa Monniera Increases BDNF Protein and mRNA Expressions: A Study in Chronic Unpredictable Stress Induced Animal Model of Depression
http://www.ncbi.nlm....les/PMC4124189/

 

Bacopa extract displays strong serotonin receptor activity
http://www.thefreeli...ty.-a0139683595

 

Green tea polyphenols produce antidepressant-like effects
http://www.ncbi.nlm....pubmed/21964320

 

Antidepressant-like effects of tea polyphenols
http://www.ncbi.nlm....pubmed/23290936

 

Caffeine increases striatal D2/D3 receptor availability in the human brain
http://www.ncbi.nlm....les/PMC4462609/    [credit: http://www.longecity...gments-effect/]

 


Edited by gamesguru, 06 August 2015 - 06:44 PM.


#7 registered

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Posted 06 August 2015 - 08:16 PM

 

So depression is where you pee in your bed and go without food for days?  Seems extreme.

 

 

hmmm was that supposed to be funny

i told about extreme condition yes

clinical depression can get very extreme

but you should stop using term depression in colloquial sense

 

i suggests to you that you watch this TED talk by andrew solomon http://www.ted.com/t...secret_we_share

and not just to you

but to everyone who wants to have a glimpse into how it FEELS to have depression

 

what makes you say he have that psychiatric disorder

its very serious health problem

 

i dont know whats happening with OP

he simply hasnt provided us with enough info

whats his hedonic tone

does he enjoy those things he obviously have a willpower to do

why would his dopamine receptors would be desensitized at the first place

all he said is this "Dopamine related things like dominance, arousal, reward/ambition-like feelings: I seem to be in great lack of all of these."

no feelings of sorrow and guilt and hopelessness

no quarreling or irritability or anxiety

no problems with sleep like early awakenings

no change in appetite

no digestion problems

nothing

 

btw OP could provide us with some details about his condition

how old are you?

any stimulant abuse?

weed?


Edited by registered, 06 August 2015 - 08:18 PM.


#8 Baten

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Posted 06 August 2015 - 09:12 PM

i dont know whats happening with OP

 

 

 

he simply hasnt provided us with enough info

whats his hedonic tone

does he enjoy those things he obviously have a willpower to do

why would his dopamine receptors would be desensitized at the first place

all he said is this "Dopamine related things like dominance, arousal, reward/ambition-like feelings: I seem to be in great lack of all of these."

no feelings of sorrow and guilt and hopelessness

no quarreling or irritability or anxiety

no problems with sleep like early awakenings

no change in appetite

no digestion problems

nothing

 

btw OP could provide us with some details about his condition

how old are you?

any stimulant abuse?

weed?

 

 

I don't feel anedhonic, can still find joy in things. Willpower etc seems pretty OK. I've suffered from depression before but seem to be pretty far away from that state, all things considered.

 

I'm not entirely sure what's the cause. (Past) porn addiction could be a major factor, but I don't really know. Some believe in porn being terrible for you, others think that's a big overstatement.

 

I don't suffer from irritability or anxiety. I'm a sound sleeper, but I do wake early at all times: between 6 and 8 AM, generally around 7. Appetite seems normal although I am quite skinny and actually have a hard time gaining weight.

 

I'm 23. No drug/stimulant/weed abuse. Pretty healthy life, healthy diet and sports. Some depressive episodes years ago.

 

Symptoms: kind of lost my 'drive', things don't feel rewarding, hardly anything arouses me, drives me; sexually as well. I am pretty meek, passive.

 

I went to my physician and he did some blood tests just yesterday, there were some abnormal results:

 

Cortisol 17h 14.47 µg/dL (2.30 - 11.90)
LH 7.7 U/L (<10.0)
FSH 3.6 U/L (<12.4)
SHBG 63.2 nmol/L (18.3 - 54.1)
Testosteron total 494 (280 - 1100)
Testosteron free  6.28 ng/dL (6.00 - 18.00)

 

High cortisol, dramatically high SHBG. Have to schedule an appointment to talk about what this could mean.



#9 gamesguru

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Posted 07 August 2015 - 09:33 AM

clinical depression can get very extreme

but you should stop using term depression in colloquial sense

 

depression can be mild, moderate, or severe.

 

 

I do wake early at all times: between 6 and 8 AM, generally around 7.

 

i wake up at 330am sometimes,  that's a problem.

high cortisol and shbg = stress/anxiety

 

it's good you're following a healthy diet and exercising.  are you still using porn/jailbait/FB stalking/anything like that?  i'd recommend giving it up for a month and see if that improves things.

no one can give you a roadmap/blueprint of your body or know the exact cellular pathology (if any) underlying your disease state, you just have to try different supplements until you find something you feel works
 

 



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#10 Heinsbeans

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Posted 07 August 2015 - 01:09 PM

You're only 23, how did you manage to get tested for cortisol and testosterone? I've asked my doctor countless times that I want to get tested for testosterone and cortisol but they were very reluctant to do it and basically refused to let me do it since they told me that it's not related to my mental health issues and the likelyhood of low cortisol/testosterone is very unlikely for my age. My mental health issues are described here and here. I might go to a different hospital away from my current doctor to get my testosterone and cortisol checked as well since your results came back abormal which concerns me since I'm a similar age as you(24). I've already had a thyroid, diabetes, celiac, iron levels and full blood count tested(my full health report here). I just want to do testosterone and cortisol test just in case since I haven't had it before, but for some reason my doctors act very reluctant to do it.


Edited by Heinsbeans, 07 August 2015 - 02:08 PM.


#11 Flex

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Posted 07 August 2015 - 01:16 PM

look into tyrosine hydroxilase expression as well. there are some herbs mentioned here (see links below) like chinese foxglove aka rehmannia glutinosa or its main compound: catalpol

those effects could be also indirectly via GDNF upregulation.

 

Gdnf upregulation does afaik increase the expression of Dopamine D! and D2 receptors but too much would decrease it

see the first study of this post

 

GDNF pretreatment (1) reduced D1 and D2 receptors functional responses and D2 receptor gene expression in s. nigra of CBA mice; (2)

increased D1 and D2 receptor genes expression in n. accumbens of ASC mice and (3) improved spatial learning in ASC mice. GDNF enhanced depressive-like behavior both in CBA and ASC mice

http://www.longecity...ds/#entry706163

 

I´m not quite convinced about Your view of dopamine receptor upregulation.

 

Note, since I´m an amateur, I will use the term afaik quite often to prevent any wrong convictions/beliefs

 

There is afaik one which leads to more functional synapses but I dont know much about it.

 

Whereas Yours (e.g. sulbutiamine, coffeine) is the same as when Youre inhibiting (reversibly via e.g. clomipramine or seroquel) a receptor which leads to more density because its the next step after desentitation.

This can be easily reverted (after 1 or few days ?) by increasing the dopamine content via e.g. a mao inhibitor = seemingly nothing is achieved.

 

So You need something that increase the ( postsynaptic! not presynaptic) dopamine receptor expression and/or tyrosine hydroxilase, decrease mao- a or b and perhaps a modulation of darpp-32 (?) and so on.

 

uridine is good for synaptic building but it also increases the density via a decrease of dopamine. No reason to avoid any of them, they just wont do their supposed job.

 

atypical and older (trycyclic) antidepressants like tianeptine or amitriptyline could have such increasing properties and dont bear problematic risks like PSSD ( those 2 do actually decrease the D2 expression)

http://www.longecity...on-and-related/

 

I would stick with the OTC´s and the herbs, if You ask me

 

2nd Note I dont know Your mentality but dont throw anything just in. Some herbs shouldnt be mixed in high doses, it could be dangerous like bleeding and stuff.

 

I´m actually to lazy to post any references but You should actually allways either request some or research them on their own. otherwise could people tell You anything.

 

Here are some further links

http://www.longecity...esting-effects/

http://www.longecity...s-herbs-thread/

http://www.longecity...hen-substances/


Edited by Flex, 07 August 2015 - 01:54 PM.


#12 Baten

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Posted 07 August 2015 - 03:04 PM

You're only 23, how did you manage to get tested for cortisol and testosterone? I've asked my doctor countless times that I want to get tested for testosterone and cortisol but they were very reluctant to do it and basically refused to let me do it since they told me that it's not related to my mental health issues and the likelyhood of low cortisol/testosterone is very unlikely for my age. My mental health issues are described here and here. I might go to a different hospital away from my current doctor to get my testosterone and cortisol checked as well since your results came back abormal which concerns me since I'm a similar age as you(24). I've already had a thyroid, diabetes, celiac, iron levels and full blood count tested(my full health report here). I just want to do testosterone and cortisol test just in case since I haven't had it before, but for some reason my doctors act very reluctant to do it.

 

I visited two docs (our old physician has retired unfortunately). The first was very young and stiff and didn't want to help me at all, didn't feel comfortable with him in the first place. I told him I wanted bloods checks out of concern and for peace of mind, he told me there's little sense in doing that.

 

Doc two was older als more old-school, the kind that makes jokes, I like him. I told him I wanted thyroids checked since my brother and sister have problems with theirs and it could run in the family. Then I told him I had problems with libido/sex related, after which he requested hormones to be checked as well. As easy as that.

 

Visited him today as well and he prescribed me Proviron. Low dose to start and to see if there's changes, to be ramped up slowly as needed. Hope it helps somewhat but I don't really know. Honestly pretty surprised I'm being given T.

 

 

atypical and older (trycyclic) antidepressants like tianeptine or amitriptyline could have such increasing properties and dont bear problematic risks like PSSD ( those 2 do actually decrease the D2 expression)

http://www.longecity...on-and-related/

 

Thank you for the detailled post, Flex. A little confused about this bit, do you think that tianeptine or amitriptyline could help me?



#13 Flex

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Posted 08 August 2015 - 03:52 AM

looked into it and Yes, might be. So those which increase dopamine D3 receptors like tianpetine (but it decreases afaik D2) other which increase dopamine d2 expression like amitriptyline

 

Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments.

http://www.ncbi.nlm....pubmed/10889548

 

from what I´ve read is that more dopamine receptors (caused by expression, not upregulation via inhibition or a lack of dopamine) means a better transmission.

both D2 and D3 are antidepressive but D2 afaik pro motivational and D3 prohedonic

and afaik both are responsible for libido but I believe that D2 even more

 

However, it could be freely another cause like mentioned by others, like too low NMDA transmission, decrease of DAT (dopamine transporter) expression,

too much serotonine like in the case of PSSD and so on.

 

-> theaflavin seems to increase DAT as well as Vmat2 expression. Benzoate (E211) is also interresting btw

http://www.longecity...or/#entry686317

 

->

I would try a reversible mao inhibitor like rhodiola rosea (mao- A and B) and look how Youre responding.

the increase of serotonine caused by mao-a or noradrenaline by mao-a and b does also modulate the effects. So Youre not experiencing a pure dopamine elevation.

 

Heres a further example of cause and effect:

 

An-jun-ning, a traditional herbal formula, attenuates spontaneous withdrawal symptoms via modulation of the dopamine system in morphine-dependent rats

http://www.biomedcen...472-6882/14/308

 

So from my amateurish knowledge, I cant tell whether those antidepressants would decrease the effects form opioids on the D2 expression, compared to this mixture.

Could be that (one or the mixture of) those herbs revert the alteration through a different effect then just upregulating the gene expression. 

 

the ingredients that I´ve found through recherche are: clover, white peony, fumaric acid and corydalis yansuhuo.

Not sure if there are some missing, just couldnt find more.

Will post the references

 

 

Could You tell me how did it started or the cause ?

 

Further cautions: be carefull about dopamine agonists because of DAWS (chronic withdrawal symptoms), if Youre evetually getting the idea to try Dopamine agonists


Edited by Flex, 08 August 2015 - 03:56 AM.

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#14 Baten

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Posted 08 August 2015 - 09:12 PM

Both amitriptyline and Theaflavin seem pretty interesting. I'll be sure to give them a try. Thanks for the tips!



#15 insearchfor

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Posted 08 August 2015 - 09:19 PM

In order to produce enough feel good molecules you need good food.

What's your diet constiting of?

Try high tryptophan foods for some time with probiotics.

Phospatidyl serine is good for lowering glucocorticoids like cortisol and cortisone...

Try some relaxation techniques like isochronic tones or walks in the nature.

Sustain from rewarding stuff like sex and fast food so you don't have dopamine spikes.

Take your time to "reset" and fuel your batteries. You'll be fine.

 



#16 Baten

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Posted 08 August 2015 - 09:26 PM

Diet: varied, lots of veggies and protein, relatively low on carbs and fat. I eat meat, fish, cheese, nuts, ... No fast food and junk.

 

I have tried phosphatidyl serine at night before and will try it again once I can find some bulk supplier.

 

I already practice relaxation techniques but that's pretty recent.

 

Dopamine spikes might be hard to avoid what's with the internet and news feeds and stuff.

 

Time might be what I need most but I guess I'm too impatient to wait for my batteries to fuel, heh. But thanks for the reassurance.



#17 insearchfor

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Posted 08 August 2015 - 10:11 PM

You need carbs, believe me. Not simple sugars, but good carbs like those in brown rice, potatoes etc. And good fats. If you excersise, carbs are essential. Excercise is great to boost mood. Testosterone is made from cholesterol so get yourself some bacon, avoid trans fats and highly refined oils, other fats are good no need to avoid them. 15% proteins from your total calorie intake is sufficient. Otherwise your kidneys may suffer if there's too much protein to deal with.

Isochronic sounds are great.

Your free T is also low so boost your T with some good excercise and enough rest and you'll be back on track.

Good luck

 



#18 Baten

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Posted 08 August 2015 - 10:21 PM

I'm actually supplementing with oats every meal to gain some weight so I have more carbs than usual in my diet right now, as well as exercising 3 times a week at the least, boosting T in mind. "Testosterone is made from cholesterol so get yourself some bacon" didn't realize this. I do eat the occasional avocado, heh. I'll keep it in mind.



#19 Flex

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Posted 10 August 2015 - 12:18 AM

Look into the suggested Jiaogulan from Deartothesun

 

heres an interresting thread with the refrerences and some further stuff

 

17 Random Dopaminergic Supplements

http://www.longecity...ts/#entry630441



#20 illuminatus104

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Posted 10 August 2015 - 12:37 AM

Why did the Dr give you steroids?



#21 Baten

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Posted 10 August 2015 - 06:01 AM

Look into the suggested Jiaogulan from Deartothesun

 

Yeah, I ordered some quality Jiaogulan tea. There's also a supplement version but I'd think the tea would be better.

 

 

Why did the Dr give you steroids?

 

Proviron isn't a steroid per sé, it's DHT. The doc gave it to me to hopefully lower SHBG and up testosterone, free testosterone especially. Next labs will tell if it's working. Then again I'm not sure my problems are hormone-related, brain inbalance could be the more likely culprit. But it's worth a shot.



#22 Flex

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Posted 19 August 2015 - 08:28 PM

looked into it and Yes, might be. So those which increase dopamine D3 receptors like tianpetine (but it decreases afaik D2) other which increase dopamine d2 expression like amitriptyline

 

Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments.

http://www.ncbi.nlm....pubmed/10889548

 

from what I´ve read is that more dopamine receptors (caused by expression, not upregulation via inhibition or a lack of dopamine) means a better transmission.

both D2 and D3 are antidepressive but D2 afaik pro motivational and D3 prohedonic

and afaik both are responsible for libido but I believe that D2 even more

 

 

Have to revise this claim. Found this:

 

It is interesting, though, that in postmortem brains of suicide victims treated with antidepressants, the D2 receptor is higher in number but 'lower' in ligand affinity

Isotretinoin and psychopathology: a review

http://www.ncbi.nlm....les/PMC2637283/

 

Its funny how easily the dopamine system stems against any manipulations  but the Serotonine (like in the case of PSSD) does exactly the opposite and that in a manner, as easy as the former...


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#23 Flex

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Posted 24 August 2015 - 04:39 PM

I´ve read the thread

http://www.longecity...n-libido/page-3

 

what was actually the cause and what led You to the assumption that Your receptors are desensitized ?

 







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