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Substances for upregulating dopamine receptors


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#91 Psionic

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Posted 19 September 2012 - 09:13 PM

@welp:

Why would cdp choline be counter productive with uridine?


Actually, the effect is exactly the same as CDP, only more pronounced, as CDP breaks down into uridine and choline. Uridine is an earlier part of the CDP-choline pathway. It also inhibits NMDA activity, but increases AMPA.


but I found the effect from each quite different

#92 MrHappy

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Posted 19 September 2012 - 09:29 PM

@welp:

Why would cdp choline be counter productive with uridine?


Actually, the effect is exactly the same as CDP, only more pronounced, as CDP breaks down into uridine and choline. Uridine is an earlier part of the CDP-choline pathway. It also inhibits NMDA activity, but increases AMPA.


but I found the effect from each quite different

I'm curious - in what way? I take both uridine and currently CDP-choline, as a choline source. My experience has been that it behaves like uridine, but about 1/8th the dose.

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#93 Psionic

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Posted 19 September 2012 - 09:43 PM

happened only once when I took 1g of CDP-choline in the morning and another 1g about 4 hours later, I got headache and severe nervousness (which was probably caused by combination with too much caffeine or dark chocolate which I should quit), with 500mg its probably very comparable to uridine. I have been on CDP for about a month and can definitely recognize its positives, will try to regularly add uridine at night too

I also wonder if theres same need to supplement with cofactors to CDP-choline, because I started to got difficulty to concentrate on uridine alone @200mg taken during the day

Edited by Psionic, 19 September 2012 - 09:48 PM.


#94 golden1

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Posted 21 September 2012 - 03:26 PM

I love CDP-choline.. just saying 250-500mg twice a day

#95 Mikael

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Posted 21 September 2012 - 04:17 PM

would alpha-gpc do the same as cdp-choline?

#96 noopeptisgood

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Posted 22 September 2012 - 08:14 PM

What about sulbutiamine? It increases density of D1 receptors according to this study (retrieved from wikipedia) : http://www.ncbi.nlm....pubmed/10996447
However acute administration seems to be counterproductive.
Also phenylpiracetam is also said to upregulate massively dopamine.

That's upregulation of receptors due to desensitized receptors.

#97 mike23

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Posted 09 November 2012 - 02:09 PM

does the iboga work ?


I was on dexedrine for 2 years (my psychiatrist prescribed it for ADHD but the real reason I took it was to counteract lethargy, possibly caused by depression) and quit about 6 months ago. I quit for a number of reasons so there will probably be a fair bit of downregulation of dopamine receptors to recover from. Are there any supplements I can take to upregulate dopamine receptors? I'd say iboga probably works wonders for that but I dont want to jump head first into an intense, 24 hour psychedelic experience just yet. Also, can you recommend some substances to counteract the lethargy and lack of motivation that comes with dopamine downregulation? I tried rhosiola rosea and I was very impressed by how it improves my mood and remedies the drowsiness but it doesn't increase my motivation to read and learn things at all. I've tried modafinil but it dulls my mood and decreases my motivation. Gives me headaches too.



#98 mike23

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Posted 09 November 2012 - 02:19 PM

i think I have completely de senstitized dopamine receptors.

I cannot feel anything while having sex anymore, no matter what i do. I was taking abilify 15 mg per day for about 8 months every day in year 2010. and I stopped taking it due to the sexual problem. I have stopped taking it, a long time ago, about 2 years now, and for the last 2 years no feeling is possible,. it seems to be permanent problem.

Maybe it is the dopamine receptors, and I need something to re sensitize them ?



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What about sulbutiamine? It increases density of D1 receptors according to this study (retrieved from wikipedia) : http://www.ncbi.nlm....pubmed/10996447
However acute administration seems to be counterproductive.
Also phenylpiracetam is also said to upregulate massively dopamine.

That's upregulation of receptors due to desensitized receptors.



#99 noopeptisgood

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Posted 09 November 2012 - 04:49 PM

Perhaps that's the problem. If so, I think an NMDA antagonist or uridine focused regimen would be apposite.

If it makes you feel better, I haven't had a pleasurable orgasm since the 8th grade. I masturbated with a small object up my ass, had an uncomfortable orgasm, and I've had shitty orgasms ever since. And I don't suffer from sever dopaminergic dysfunction, so I don't know what it could be.

Edited by noopeptisgood, 09 November 2012 - 04:49 PM.


#100 mike23

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Posted 10 November 2012 - 04:25 AM

I have always been very good with sex. No problem with masturbating and good with a girl in bed. I've been pretty lucky also. I always had a great time, it was unbelievable, anything I wanted to do was possible, for as long as I could go. Many hours sometimes, like 4 hours, and the next day also. I never would have throught that I would have a sexual problem.

This abilify medication is horrible. I was never on any medications when I was younger. Just recently , in the year 2010, this abilifty thing, caused this problem, and now nothing works at all.

thanks for writing/posting on here, I hope you find something that helps you.

I just started on this web forum. I came from another web forum I was on, and a friend of mine there refferred me to here cause he said they talk about dopamine specifically more, on here.

thank you
talk to you later

#101 mike23

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Posted 10 November 2012 - 04:35 AM

ok, what is a NMDA Antagonist / what is Uridine Focused regimen ?


thanks
mike


Perhaps that's the problem. If so, I think an NMDA antagonist or uridine focused regimen would be apposite.

If it makes you feel better, I haven't had a pleasurable orgasm since the 8th grade. I masturbated with a small object up my ass, had an uncomfortable orgasm, and I've had shitty orgasms ever since. And I don't suffer from sever dopaminergic dysfunction, so I don't know what it could be.



#102 noopeptisgood

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Posted 10 November 2012 - 06:05 AM

NMDA antagonists can upregulate D2 receptors. http://www.ncbi.nlm..../pubmed/1382178
Uridine is getting a lot of interest on the board for its potential to increase dopamine receptor density. http://www.longecity...ne-uridine-dha/

I don't take uridine, but I do take CDP-choline which is a uridine source. It has also been shown to increase dopamine receptor density, but that's speculated to be due to the uridine effect.

#103 stablemind

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Posted 10 November 2012 - 06:22 AM

CDP is some powerful stuff. Make sure you start low, even half a pill may be enough. It effectively crosses the BBB.

@welp:

Why would cdp choline be counter productive with uridine?


Actually, the effect is exactly the same as CDP, only more pronounced, as CDP breaks down into uridine and choline. Uridine is an earlier part of the CDP-choline pathway. It also inhibits NMDA activity, but increases AMPA.


but I found the effect from each quite different

I'm curious - in what way? I take both uridine and currently CDP-choline, as a choline source. My experience has been that it behaves like uridine, but about 1/8th the dose.



I actually had a different experience with CDP Choline. I may be feeling and benefiting from the cholinergic aspect of it as well though since I had a greater antidepressant response when pairing it together with Uridine than with Uridine alone. This may be why ALCAR also works on me.

Edited by stablemind, 10 November 2012 - 06:23 AM.


#104 noopeptisgood

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Posted 10 November 2012 - 05:16 PM

I too respond well to cholinergics. CDP-choline works great for me! Along with the choline I appreciate the psychostimulant/anti-depressant effect. I combine it with fish oil in hopes of getting the benefits that Mr. Happy has. I don't know if it's increasing my dopamine receptor density, but I do feel good. I also agree that CDP-choline is very potent. I take about ~200mg which still seems excessive.

#105 the_apollo

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Posted 13 January 2013 - 05:18 PM

There is a lot of supplements to take to upregulate D2 receptors, but what about D1 and D3 to 5 ?
Is there anything (beside Sulbutiamine for D1) that upregulate Dopamine receptors?

#106 kevinseven11

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Posted 13 January 2013 - 08:38 PM

THC and nicotine Raise dopamine long term. Why did you guys down vote me on the first page?
http://www.ncbi.nlm....pubmed/21820648
http://www.ncbi.nlm....pubmed/12494400
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#107 mycotheologist

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Posted 10 March 2013 - 01:08 AM

According to that article, nicotine only upregulates D3 receptors. I don't know what the function of D3 receptors is so I don't know whether thats a desirable thing or not.

i think I have completely de senstitized dopamine receptors.

I cannot feel anything while having sex anymore, no matter what i do. I was taking abilify 15 mg per day for about 8 months every day in year 2010. and I stopped taking it due to the sexual problem. I have stopped taking it, a long time ago, about 2 years now, and for the last 2 years no feeling is possible,. it seems to be permanent problem.


Is your sex drive gone too? I have the same issue (complete numbness) and I also have little or no sex drive anymore. If I take dexedrine, it all comes back full force.

does the iboga work ?

There is evidence to suggest that iboga does work for dopamine downregulation. Like opioid addictions, plenty of people have been cured of cocaine and amphetamine addictions with iboga. An iboga flood (a high dose which produces the full psychedelic/visionary effects) is not something to be taken lightly though, one has to do a great deal of research and make sure they're ready for it. I haven't done it yet myself. You can also microdose with iboga but it seems to boost serotonin which is counterproductive if your trying to raise your dopamine levels.

Edited by mycotheologist, 10 March 2013 - 01:25 AM.


#108 mycotheologist

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Posted 10 March 2013 - 04:10 AM

All I want to add here, is be really, really cautious with Iboga. It's not something to be taken lightly. I had an insanely bad trip on that stuff due to my own neglegence. I too thought, hell I'll just microdose. But I was impatient and took waaaay too much. I thought I was dying and my heart was beating extremely arythmnic and slow, and I had all kinds of scary visuals. I'll spare you the details. I mean I had many benefit's from Iboga, I also saw and felt wonderous things. But I was unguided and it turned out to be the scariest thing I've ever done. I lost my mind and gained it again, but I haven't been the same since. I'm not trying to be discouraging, I'm just saying that it should not be done without proper guidance.

Besides that I wish you the best of luck!

How much did you take? The most I've done so far is 8g (which was spread out over about 10 hours) but it wasn't a very psychedelic experience, I was just extremely relaxed and euphoric. It effects everyone differently from what I hear. The way to experiment with it is to increase your dose in small increments every 2 hours. That way there are no scary surprises. IMO this is how it should be done with all psychedelic substances.

#109 mycotheologist

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Posted 27 March 2013 - 01:12 PM

I was looking into acupunctures effects on the dopaminergic system there and came across a few articles:

https://www.scienced...304394005012231

Many studies have shown that acupuncture can contribute to the biochemical balance in the central nervous system and maintenance or recovery of homeostasis. It is well known that chronic administration of ethanol may produce depletion or sensitization of extracellular dopamine levels in the nucleus accumbens. The present study was designed to investigate the effects of acupuncture on chronic ethanol-induced changes in extracellular dopamine levels in the nucleus accumbens shell (using in vivo microdialysis in unanesthetized rats). Male Sprague–Dawley rats were treated with 3 g/kg/day of ethanol (20%, w/v) or saline by intraperitoneal injection for 21 days. Following 72 h of ethanol withdrawal, acupuncture was applied at bilateral Shenmen (HT7) points for 1 min. Different group of rats using the same paradigm of ethanol treatment were acupunctured at the same points after the systemic ethanol challenge (3 g/kg, i.p.). Acupuncture at the specific acupoint HT7, but not at control points (PC6 or tail) significantly prevented both a decrease of extracellular dopamine levels in the nucleus accumbens during ethanol withdrawal and an increase in accumbal dopamine levels induced by the ethanol challenge. These results provided strong evidence that stimulation of the specific acupoint HT7 helps to normalize the release of dopamine in the mesolimbic system following chronic ethanol treatment.



http://www.plosone.o...al.pone.0027566

Parkinson's disease (PD) is caused by the selective loss of dopaminergic neurons in the substantia nigra (SN) and the depletion of striatal dopamine (DA). Acupuncture, as an alternative therapy for PD, has beneficial effects in both PD patients and PD animal models, although the underlying mechanisms therein remain uncertain. The present study investigated whether acupuncture treatment affected dopamine neurotransmission in a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri​dine(MPTP). We found that acupuncture treatment at acupoint GB34 improved motor function with accompanying dopaminergic neuron protection against MPTP but did not restore striatal dopamine depletion. Instead, acupuncture treatment increased dopamine release that in turn, may lead to the enhancement of dopamine availability in the synaptic cleft. Moreover, acupuncture treatment mitigated MPTP-induced abnormal postsynaptic changes, suggesting that acupuncture treatment may increase postsynaptic dopamine neurotransmission and facilitate the normalization of basal ganglia activity. These results suggest that the acupuncture-induced enhancement of synaptic dopamine availability may play a critical role in motor function improvement against MPTP.


Interesting stuff. I'm gonna go to an acupuncturist and get them to apply the needle to the HT7 point and see if that alleviates some of these protracted amphetamine withdrawal symptoms that I have.
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#110 renfr

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Posted 27 March 2013 - 10:51 PM

Yohimbine may upregulate D2
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#111 Peak Noots

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Posted 18 February 2014 - 05:57 PM

How about THP? It is a dopamine antagonist that doubles as a sleep aid. I am not sure, but as a dopamine antagonist it should up regulate dopamine receptors during its use at night. Here is a post, please scroll down to the THP section http://peaknootropic...pic-sleep-stack
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#112 Sciencyst

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Posted 19 February 2014 - 02:49 AM

Tetrahydropalmatine (THP) would indeed be your best bet.
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#113 celebes

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Posted 19 February 2014 - 03:17 AM

How about THP? It is a dopamine antagonist that doubles as a sleep aid.

Tetrahydropalmatine (THP) would indeed be your best bet.


Where to buy?

#114 Peak Noots

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Posted 19 February 2014 - 01:42 PM

celebes,

I got >99% pure THP in synthetic form from a trusted chemical supplier. I take 200-250mg THP for sleep in regular DL form however if you cannot find it in pure or the more potent "L" form, just type "corydalis extract" into google and find a powerful herbal form of 40x or higher. It should do the trick

Edited by Peak Nootropics, 19 February 2014 - 01:58 PM.


#115 Peak Noots

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Posted 19 February 2014 - 01:49 PM

actually, better of trying "buy tetrahydropalmatine"

#116 celebes

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Posted 19 February 2014 - 07:55 PM

Ordered L-THP at Heavenly Products. Improving sleep would be enough for me. Is there any data showing it to upregulate DA receptors? Antipsychotics actually cause downregulation.

#117 Peak Noots

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Posted 19 February 2014 - 10:06 PM

Dopamine agonists cause down regulation so it is only common sense that an antagonist would up regulate but I cannot find anything on dopamine up regulation. I would assume it is not that easy and there are probably more complicated mechanisms at play. It does not appear that dopamine antagonists reduce amphetamine tolerance but can certainly block the effects. Very interesting.

Edited by Peak Nootropics, 19 February 2014 - 10:07 PM.


#118 chemicalambrosia

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Posted 22 February 2014 - 05:50 PM

Ordered L-THP at Heavenly Products. Improving sleep would be enough for me. Is there any data showing it to upregulate DA receptors? Antipsychotics actually cause downregulation.


Please let us know if you find it effective for sleep.

#119 Sciencyst

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Posted 22 February 2014 - 08:26 PM

Phenylpiracetam;

We studied the effects of administration of the new nootropic drug phenotropil (N-carbamoylmethyl-4-phenyl-2-pyrrolidone) at a dose of 100 mg/kg on the quantitative characteristics of dopamine (DA), serotonin (5-HT), glutamate (NMDA), GABA-A (BDZ), and acetylcholine (nACh) receptors in rats using the conditioned passive avoidance task (PAT) under normal conditions and during scopolamine-induced amnesia ex vivo. We found that the cholinolytic drug scopolamine induced a substantial increase in the density (B max) of n-choline receptors in the cortex (by 99% as compared to the control) and NMDA receptors in the hippocampus (by 93%). A single administration of phenotropil (100mg/kg, intraperitoneally) abolished the effect of scopolamine and decreased the number of nACh and NMDA receptors by 46% and 14%, respectively. Phenotropil also abolished the effect of scopolamine on the benzodiazepine receptors and dopamine D1 receptors. Scopolamine decreased the density of D1 receptors by 20% and BDZ receptors by 17%, whereas phenotropil increased the density of receptors by 16% and 25%, respectively. Phenotropil considerably increased the density of dopamine D2 and D3 receptors by 29% and 62%, respectively. Scopolamine also increased the density of D3 receptors by 44% as compared to the control. We did not find any changes in the binding characteristics of 5-HT2 receptors during scopolamine-induced amnesia or during phenotropil treatment. These results demonstrate the role of these receptors in the development of scopolamine-induced amnesia and in neurochemical mechanisms of the anti-amnestic effects of phenotropil.

http://link.springer...819712411020048

I actually just ordered some after seeing this study..

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#120 downregulated

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Posted 22 February 2014 - 10:56 PM

I'd say my dopamine receptors are quite upregulated by antipsychotic drug olanzapine. When I don't take the drug for a day or two I get quite electric and get the shivers, goosebumps and it feels like I'm on amphetamine... Very goal oriented and feeling very light, a bit too stimulated and speedy. So I ususally take the pill to bring me down a bit. I'd like to downregulate my receptors though. Funny you want to upregulate dopamine... Dopamine is a hell of a drug :)
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