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Substances for upregulating dopamine receptors


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#1 mycotheologist

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Posted 11 July 2012 - 10:01 AM


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.

#2 MrHappy

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Posted 11 July 2012 - 01:16 PM

Uridine.
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#3 mycotheologist

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Posted 11 July 2012 - 01:29 PM

I just read some interesting things about uridine, thanks a lot. This forum is a goldmine of novel information. Every compound somoene suggests turns out to have all sorts of additional benefits.

#4 hooter

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Posted 11 July 2012 - 03:53 PM

Tianeptine is BOSS !!! Second best ADHD medication next to dexedrine, but it's not harmful at all! On the contrary, look it up!
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#5 protoject

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Posted 11 July 2012 - 04:03 PM

CDP choline actually upregulates dopamine receptors. I'd recommend low dose CDP choline for an extended period.
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#6 kevinseven11

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Posted 11 July 2012 - 04:43 PM

Up regulating natural dopamine production is just the same as up regulating receptors.
Nicotine and thc long term upregulates dopamine production

Edited by kevinseven11, 11 July 2012 - 04:44 PM.

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#7 uglybuddy6

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Posted 11 July 2012 - 04:59 PM

Sulbutiamine upregulates the dopamine receptors if i remember correctly
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#8 nowayout

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Posted 11 July 2012 - 06:05 PM

CDP choline actually upregulates dopamine receptors. I'd recommend low dose CDP choline for an extended period.


What would you consider low dose, and do you find that it elevates libido (given that it is dopaminergic)?

Edited by viveutvivas, 11 July 2012 - 06:08 PM.


#9 protoject

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Posted 11 July 2012 - 08:35 PM

CDP choline actually upregulates dopamine receptors. I'd recommend low dose CDP choline for an extended period.


What would you consider low dose, and do you find that it elevates libido (given that it is dopaminergic)?


Yes it did elevate libido for me. The effects are definitely more pronounced as you continue taking it. Most people would say the regular low dose is 250 mg. The majority of people have no problems with that kind of dose, but for me I get changes in blood pressure and insomnia eventually. [but I used to megadose like 2 g a day, so maybe I caused a sensitivity in myself to it].. so for me personally I use like 25-50 mg a day when I do use it.. didn't notice a problem then.. but for you I am sure 250 mg is fine. As far as I know from when I researched it the half life is like 50 hrs so it should build up in your body.

#10 mycotheologist

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Posted 12 July 2012 - 08:34 PM

Thanks for the info, this will give me loads of things to experiment with. I like the sounds of tianeptine. After 6 months, my dopamine receptors should have significantly recovered but I'll still have the same problem I had before starting the dexedrine so I'll need a new solution. I have a comparitavely vast amount of knowledge now so I don't think that'll be an issue :). I'll definitely give tianeptine a try. I have a bottle of sulbutiamine left, I didn't know it upregulated dopamine. It gives me headaches so I stopped using it. Maybe I just need to lower the dosage though.

#11 What'sAllThisThen

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Posted 13 July 2012 - 01:26 AM

Tianeptine is BOSS !!! Second best ADHD medication next to dexedrine, but it's not harmful at all! On the contrary, look it up!


At all? Look up Tianeptine withdrawal and I don't think everyone would agree. I'd be a little more cautious about switching one dependency for another OP.
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#12 Algernoot

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Posted 14 July 2012 - 06:32 PM

CDP choline actually upregulates dopamine receptors. I'd recommend low dose CDP choline for an extended period.


Interesting! I'd like to read more on that if you have any sources to share. Would the upregulation effect also be present in other cholinergic supplements, or in dietary choline (i.e. my hard-boiled egg habit)?

#13 nowayout

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Posted 14 July 2012 - 06:47 PM

CDP choline actually upregulates dopamine receptors. I'd recommend low dose CDP choline for an extended period.


Interesting! I'd like to read more on that if you have any sources to share. Would the upregulation effect also be present in other cholinergic supplements, or in dietary choline (i.e. my hard-boiled egg habit)?


Wikipedia states this and has a source for it.
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#14 Algernoot

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Posted 14 July 2012 - 07:46 PM

CDP choline actually upregulates dopamine receptors. I'd recommend low dose CDP choline for an extended period.


Interesting! I'd like to read more on that if you have any sources to share. Would the upregulation effect also be present in other cholinergic supplements, or in dietary choline (i.e. my hard-boiled egg habit)?


Wikipedia states this and has a source for it.


Thanks, just found it and skimmed the source article (here). The question that remains for me is if there would be any meaningful difference if the mice initially had reduced dopamine receptor densities from pharmacological effects (Dexedrine as the OP wrote, or Adderall in my case). In the source article, the reduced densities in the mice occurred through normal aging. Still, it's definitely promising (and enough for me to continue taking my Citicholine today).

#15 medievil

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Posted 14 July 2012 - 08:01 PM

Memantine and DXM have a immense ammount of anecdotes behind them and also nmda antagonists have been shown in rodents to upregulate DA.

#16 tritium

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Posted 15 July 2012 - 03:44 AM

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.

I was on Adderall for several months. I quit because it caused significant hair loss, completely destroyed my social life, caused insomnia, and generally made me too stressed out.

How did you manage to quit after such a long period and how long did it take for you to return to somewhat normal? I have tried to quit several times, but always relapsed around days 16-18 after feeling absolutely terrible. Most recently I have only taken 1/4 of a 5mg tablet one day and still feel the effects about 1 week after this dose. But after that it is all downhill.

Currently I am taking CDP choline, noopept, activated B6 and just today added nicotine lozenges.

#17 Raza

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Posted 15 July 2012 - 01:49 PM

Inositol increases D2 receptor density.

Up regulating natural dopamine production is just the same as up regulating receptors.
Nicotine and thc long term upregulates dopamine production

It is not the same. If you upregulate production, receptors will downregulate to compensate. You might get a net gain when you reach the new equilibrium, but it's not a sure thing like upregulating receptors through external mechanisms is.

Uridine.

Do you remember the study for this? I thought it only increased neurites and dentrites.

#18 medievil

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Posted 16 July 2012 - 10:57 PM

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.

I was on Adderall for several months. I quit because it caused significant hair loss, completely destroyed my social life, caused insomnia, and generally made me too stressed out.

How did you manage to quit after such a long period and how long did it take for you to return to somewhat normal? I have tried to quit several times, but always relapsed around days 16-18 after feeling absolutely terrible. Most recently I have only taken 1/4 of a 5mg tablet one day and still feel the effects about 1 week after this dose. But after that it is all downhill.

Currently I am taking CDP choline, noopept, activated B6 and just today added nicotine lozenges.

Weird, amp only causes withdrawals for 2 days or something in the past, its not a real physically addictive substance.
Have you tried dxm or memantine?

#19 Algernoot

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Posted 17 July 2012 - 12:38 AM

I was on Adderall for several months. I quit because it caused significant hair loss, completely destroyed my social life, caused insomnia, and generally made me too stressed out.

How did you manage to quit after such a long period and how long did it take for you to return to somewhat normal? I have tried to quit several times, but always relapsed around days 16-18 after feeling absolutely terrible. Most recently I have only taken 1/4 of a 5mg tablet one day and still feel the effects about 1 week after this dose. But after that it is all downhill.

Currently I am taking CDP choline, noopept, activated B6 and just today added nicotine lozenges.

Weird, amp only causes withdrawals for 2 days or something in the past, its not a real physically addictive substance.
Have you tried dxm or memantine?


I disagree. There is the potential for downregulation of dopamine receptors from longterm use. In that case, it will take longer than 2 days to completely recover.

#20 medievil

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Posted 17 July 2012 - 10:38 AM

Well, id agree.

I think nmda antagonists are the best way to recover tough, they have a ton of anecdotes behind them.

#21 hooter

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Posted 17 July 2012 - 12:36 PM

Tianeptine is BOSS !!! Second best ADHD medication next to dexedrine, but it's not harmful at all! On the contrary, look it up!


At all? Look up Tianeptine withdrawal and I don't think everyone would agree. I'd be a little more cautious about switching one dependency for another OP.


I don't have to look up anything because I've been taking it on and off for YEARS and the withdrawal lasts about a day or two and is completely overblown and exaggerated... It's even been shown to help people get off opiates / stimulants.

After chronic use (and I've taken 12.5 x 5 instead of 12.5 x 3 as recommended) the only withdrawal is some mild akathisia, a little tension and maybe problems sleeping. Nothing you couldn't alleviate with a valerian root tea or something simple like that...

But suit yourself. :)

Edited by hooter, 17 July 2012 - 12:38 PM.

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#22 golden1

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Posted 17 July 2012 - 01:49 PM

^ For you those are the effects of stopping, for everyone else they could be different(obviously) and are, as I've read w/d reports from people on it with much worse effects than you describe.

For helping amphetamine w/d:

CDP-choline certainly works, in some strong way, especially if taken over time(250mg a day, yes sounds about right). I've had it change my sense of wellbeing from shit to feeling perfectly balanced and well, over I'd guess about a month.. but it has immediate effects for me if taken once too.

Deprenyl is also good for after you quit anything that raises dopamine, it is like a more immediate cdp-choline effect. I only needed 1mg, which made a noticable difference for 5+days by which I was over most of the problems(it helps most with restlessness tied to general discomfort and lack of reward + the possible depressive effects of activities lacking reward you are used to... not as much as a help for energy, but if you take caffeine with it, it will help possibly recover with less distress. I would recommend just one 1mg dose or 2 maybe a week apart.. mainly just to help with the initial sharp withdrawal, you don't want to get more withdrawal when you stop taking deprenyl... hah.

Piracetam + caffeine is also helpful and actually.. for me, with cdp-choline, pretty similar to amphetamine except less focusing/motivating for tasks you don't want to do. Too bad caffeine will get you w/d too, but I mean it's never going to be THAT bad, and you can just... taper off caffeine? I don't know, maybe save this for when you need more energy.

Edited by golden1, 17 July 2012 - 02:07 PM.


#23 tritium

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Posted 18 July 2012 - 01:31 AM

Weird, amp only causes withdrawals for 2 days or something in the past, its not a real physically addictive substance.
Have you tried dxm or memantine?

I have tried both dxm and memantine. Although they help me relax and become more social, they seem to make concentration worse for me and maybe make me feel a bit dumb. I probably wouldn't take them when I need to study, only when I want to go out and be social.

#24 mycotheologist

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Posted 18 July 2012 - 04:21 PM

I was on Adderall for several months. I quit because it caused significant hair loss, completely destroyed my social life, caused insomnia, and generally made me too stressed out.

How did you manage to quit after such a long period and how long did it take for you to return to somewhat normal? I have tried to quit several times, but always relapsed around days 16-18 after feeling absolutely terrible. Most recently I have only taken 1/4 of a 5mg tablet one day and still feel the effects about 1 week after this dose. But after that it is all downhill.

Currently I am taking CDP choline, noopept, activated B6 and just today added nicotine lozenges.

I just stopped taking them. I experienced absolutely no acute withdrawal symptoms. I felt fine after stopping them. During the 2 years I was on them, I would often take breaks of a week or more (i.e. if I ran out before my next refill) and I was fine. My daily dosage was 45mg which is pretty high. Thats strange that you feel terrible after quitting, with me, and a lot of people who I've heard from, when they quit they just have low motivation, sleep alot and eat alot. I did read one or two reports by people claiming to have horrible withdrawals after quitting dexedrine though so maybe its different for different people.

You say you took 5mg of adderall and felt the effects for a week. Do you mean you actually felt like you were on the drug for a week, or that the withdrawal symptoms were gone for a week? 5mg is nothing. By the sounds of it, you are hardly physically dependant at all. Maybe there are other factors causing you to feel bad. Could be depression. I recommend trying selegiline. Its an MAOI thats prescribed as an antidepressant but its also prescribed to treat Parkinsons disease (meaning it will remedy the symptoms caused by dopamine downregulation). Read up on it:
https://en.wikipedia...wiki/Selegiline
as you can see, it has a very similar structure to amphetamine and from what I read on the wiki page, the guy who discovered it, his intention was to actually come up with a drug that combines the beneficial effects of amphetamine with the beneficial effects of an MAOI. its the first thing i want to try once I recover from this GABAergic withdrawal (I used dexedrine to study for my Christmas exams and experimented with GHB, phenibut and benzos to counteract the insomnia and eventually ended up addicted to them) I have at the moment. I should mention that I was on a high dose of ritalin for a year prior to the dexedrine so that means theres even more dopamine downregulation for me to recover from. My last dexedrine prescription was before Christmas, and I still have a good bit of it leftover (gonna use it for the 2 exams I got deferred until the end of the summer) so I'm pretty sure my brain has done a serious amount of upregulating during that time period. I'm just determined to make a full recovery as rapidly as possible. For all I know, I may have already fully recovered. I don't actually feel that much drowsier now than before I started taking the ritalin and dexedrine.

EDIT: I recommended selegiline but thats only for treating the symptoms, it won't speed up the dopamine upregulation process. For that, the first thing I'm gonna try are NMDA antagonists, like people above have suggested. Memantine looks promising to me. Magnesium is also a partial NMDA antagonist so I've started taking baths with epsom salts like ScienceGuy recommended. I had my appendix removed when I was 15 and while doctors claim that the appendix serves no function in modern man, I believe this to be untrue. I've had digestion problems ever since I had it removed and I suspect I don't absorb nutrients as well as people who have their appendix. From what I read, appendix is like an incubator for many different strains of bacteria and since its connected to the large intestine, its possible that it plays a role in digestion. My experience backs that theory up. I find the idea of absorbing the substance through the skin while bathing in a solution of it pretty cool :)

Edited by mycotheologist, 18 July 2012 - 05:12 PM.


#25 mycotheologist

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Posted 18 July 2012 - 05:34 PM

I have tried both dxm and memantine. Although they help me relax and become more social, they seem to make concentration worse for me and maybe make me feel a bit dumb. I probably wouldn't take them when I need to study, only when I want to go out and be social.

The purpose of taking NMDA antagonists is to recover though, not to remedy the symptoms. If you have a task that requires concentration, then you wanna take a substance to remedy the symptoms. I'd opt for selegiline, although I haven't tried it yet so I can't say for sure whether it helps or not. I recommend trying rhodiola rosea. I've taken that during breaks from dexedrine and I was highly impressed by it. It elevates my mood and increases my energy. It has mild MAOI properties and increases endorphins.

#26 tritium

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Posted 19 July 2012 - 01:21 AM

You say you took 5mg of adderall and felt the effects for a week. Do you mean you actually felt like you were on the drug for a week, or that the withdrawal symptoms were gone for a week? 5mg is nothing. By the sounds of it, you are hardly physically dependant at all. Maybe there are other factors causing you to feel bad. Could be depression. I recommend trying selegiline. Its an MAOI thats prescribed as an antidepressant but its also prescribed to treat Parkinsons disease (meaning it will remedy the symptoms caused by dopamine downregulation).

After I take one tablet, it feels like I am still on the drug when I don't take it the next days, up to about a week. Maybe I am a slow metabolizer?

It could be actually that I have returned to my 'normal', but I don't really like what I am like 'normal' compared to what I am on Adderall. Paradoxically, I don't like the side effects it gives me, much like a love/hate relationship. When I am off, everything is slower, I have little confidence, and am less social. It could be depression and it must be really messing with my brain's reward system.

What dosage of memantine would you reccomend? I have some 5mg tablets but can always split them.

Edited by tritium, 19 July 2012 - 01:31 AM.


#27 tritium

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Posted 19 July 2012 - 01:58 AM

Just took a fourth of a 5mg tablet on Monday. Felt good that day, Tuesday, and this morning, but now I'm getting really lethargic/depressed and can't concentrate on anything...

#28 golden1

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Posted 19 July 2012 - 02:21 AM

Sorry for off topic, but is there way to get memantine w/o prescription in the US? Or is it not sold like deprenyl overseas and such?




edit: thanks

Edited by golden1, 19 July 2012 - 02:30 AM.


#29 tritium

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Posted 19 July 2012 - 02:28 AM

Sorry for off topic, but is there way to get memantine w/o prescription in the US? Or is it not sold like deprenyl overseas and such?

You need a prescription to get it in the US, unless you order it online from overseas, then you don't need a prescription. Last time I purchased it from alldaychemist, but they posted some fraudulant charges on my credit card and their credit card system wasn't working last time I tried. Good thing I have a really dumb phsychiatrist that will prescribe almost anything I suggest!

Edited by tritium, 19 July 2012 - 02:29 AM.

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#30 tritium

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Posted 19 July 2012 - 11:56 PM

I tried some Emsam (Selegiline Transdermal) today and it seems to have solved the issues I've had after stopping Adderall so far. Thanks for the suggestion. The only concern that I have is the possibility of additional downregulation. Since Selegiline inhibits the breakdown of dopamine and allowing more to be available in the brain, wouldn't this lead to downregulation?




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