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Dysphoric
10-03-2010, 05:01
What methods are there to up-regulate dopamine? I know L-Tyrosine is one, but any others? And how long would it take to notice up-regulation by tyrosine? I couldn't really find much on the web.

Dysphoric
10-03-2010, 06:13
You're using the wrong terminology. Supplementing L-tyrosine would actually downregulate dopamine receptors via tolerance as it would increase their activation. Overall the net effect would be enhanced dopaminergic activity though of course.

Anyway, there are numerous different kinds of drugs that can increase dopamine levels in the brain. They include dopamine reuptake inhibitors/releasing agents like methylphenidate, cocaine, and amphetamine, dopamine agonists like pramipexole and ropinirole, enzyme inhibitors like MAOIs (phenelzine, tranylcypromine, selegiline, etc) and COMT inhibitors (entacapone, tolcapone), and of course dopamine precursors like L-tyrosine as well as L-phenylalanine and levodopa.

I guess I am using the wrong terminology, but what I'm asking is, how to have more dopamine for future use. Like lets say i have 10,000 units (Or whatever) How can I get it up to say 30,000? I'm asking cause I take Desoxyn(Methamphetamine) now and it not only works as a DA agonist, it also works like a reuptake-inhibiter, thus resulting in downregulation. Which I think makes you more Desensitized(Right terminology)? I just want to know how to get more dopamine ready for use....

Dysphoric
10-03-2010, 06:31
Actually methamphetamine's not a [direct] dopamine agonist or really a reuptake inhibitor (except technically a weak one) -- it's a releasing agent -- but I'll spare you anymore technicalities than that. Okay, one more and that's it -- downregulation and desensitization are synonymous. And yes anything that increases activity at dopamine receptors (including L-tyrosine and methamphetamine) will downregulate/desensitize them to some extent as well.

Anyway, dopamine precursors would work very well for your intention as they'd provide much more dopamine for methamphetamine to release. You'll want to be careful with them though.. a combination of amphetamine and high dose L-phenylalanine sent me into full-blown psychosis once.


I already know not to take the two together. I've been taking about 1gm of Tyrosine a day, and I don't notice a difference. Is there any ways of measuring precisely how much dopamine 500mg's of Tyrosine actually creates? I've been taking DextroAmphetamine prior to Desoxyn for about a year. Lets say I want to achieve sensitizing myself again, just how much Tyrosine would I need? I just want to get my dopamine levels to normal so I can possibly have an experience similar to what I had in the first 6 or so months. BTW, I only take my meds twice a week so, I have a lot of off time to possibly replenish dopamine...

Dysphoric
10-03-2010, 06:42
L-Tyrosine isn't going to 'sensitize' your dopamine receptors, it's just going to produce even more tolerance in the long run. In any case, if you want stronger effects, I'd suggest either increasing your doses of either L-tyrosine or methamphetamine (or both) or taking a break from them and letting your receptors go back to normal. 1-2 weeks should be plenty of time.

I was always under the impression that L-Tyrosine helped dopamine replenish not make it worse. I'm so fucking confused... Sources please...

Dysphoric
10-03-2010, 07:39
It'll only really 'replenish' your dopamine if you were deficient to begin with. If you take it with excess dopamine activity already going on (as you are with methamphetamine) it'll just result in more tolerance as your body tries even harder to maintain normal levels of dopamine. You'll notice some significantly enhanced dopaminergic effects at first sure but it'll only be a matter of time before tolerance starts to rear its ugly head again and the effects are diminished.

Like I said already I suggest you take a break. Or you could also try augmenting with an anti-tolerance drug like memantine. I've been hearing some really good anecdotes of it blocking stimulant tolerance lately.

As for sources.. this is relatively basic pharmacology knowledge, hence I'm not going to bother.

Yeah, and how would one go about getting Memantine? It's not prescribed for tolerance reduction:p. I already know about that one to, but like I said HTF would I go about getting my hands on it?

seep
10-03-2010, 08:12
Memantine is beaucoup expensive. The older diamondoid is much cheaper (can't remember its name now; sounds like amanita)

MeDieViL
10-03-2010, 13:54
Dopamine upregulation:

NMDA antagonists
Forskolin
Tofisopam
Inositol

Raising dopamine:

LDOPA
Mucuna pruriens

Jamshyd
10-03-2010, 16:04
I guess I am using the wrong terminology, but what I'm asking is, how to have more dopamine for future use. Like lets say i have 10,000 units (Or whatever) How can I get it up to say 30,000? I'm asking cause I take Desoxyn(Methamphetamine) now and it not only works as a DA agonist, it also works like a reuptake-inhibiter, thus resulting in downregulation. Which I think makes you more Desensitized(Right terminology)? I just want to know how to get more dopamine ready for use....

It just doesn't work like that.

a. The idea that more [insert favourite transmitter here] = happiness/whatever is simply incorrect.
b. You do not have a DA "bank". When they teach you that dopamine is made and "stored" in cells, they are giving you the wrong impression that you can somehow deplete and replenish some kind of DA "safe".
c. As excessive DA is just as bad as deficient DA, your body will in and of itself work out the balance one way or another, eg. lowering tyrosine uptake and conversion, or downregulating receptors and transporters...etc., before finally collapsing if you keep pushing it.

The cream of it all is this: Methamphetamine is a poison with some positive short-term effects. This is not opinion, it is fact. There is simply no sustainable way to keep taking Meth, doctor-prescribed or not, without suffering at the end. .

Since I assume you will ignore what I say above, all I can tell you is make sure you at least take a good vitamin supplement with extra supplementation of Magnesium and Zinc.

lenses
10-03-2010, 17:54
I think the OP wants to make his dopamine receptors more sensitive. I understand what you mean...

-lenses

pofacedhoe
10-03-2010, 21:45
The cream of it all is this: Methamphetamine is a poison with some positive short-term effects. This is not opinion, it is fact. There is simply no sustainable way to keep taking Meth, doctor-prescribed or not, without suffering at the end. .

Since I assume you will ignore what I say above, all I can tell you is make sure you at least take a good vitamin supplement with extra supplementation of Magnesium and Zinc.

basically meth will leave you burnt out, if you do it twice a week as per your dextroamphetamine you will feel far more burnt out on your days off than you currently do. its plays with serotonin levels and once you start doing stims that mess with serotonin the comedowns are far more severe and harder to handle (i did a lot of mephedrone and mdma and they made my emotions more unstable for long periods of time afterwards).

i am assuming that your current amphetamine use is within the guidelines of what is prescribed:)

if you have been using amphetamine and expecting strong euphoric effects after six months even using it only two days out of seven then that is not going to last long term and meth wont bring that initial euphoria back (for any significant length of time)

lenses
10-03-2010, 23:33
I have read a few pubmed articles talking about 5HT receptor upregulation from use of SSRI'S... would the same happen with DRI's?

I also know some sort of DAT receptor upregulation (I guess it could also be called a rebound reaction) from sudden discontinuation of antipsychotics...

Just throwing that out there.

-lenses

/navarone/
11-03-2010, 01:46
Memantine, LOL it's more expensive than top quality cocaine.

Maybe an inverse agonists? Or antagonist depending on the dopamine receptor.
Some receptors downregulate even with antagonists.

MeDieViL
11-03-2010, 01:51
Memantine is cheap, atleast if you know where to look...

Hugs & Drugs
12-03-2010, 02:58
i have also been thinking along the same lines as the OP
i have been concerned with overall dopamine levels and stimulant tolerance

is there a way to basically, revert your dopamine levels to before one used stimulants?
therefore re-sensitising them
or abolishing tolerance? (which seems to be a bitch in the case of stimulants)
much like naltrexone does for opiate tolerance...

correct me if im wrong, my knowledge is more on the basic side
:)

p.s. is a tolerance lowering drug basically memantine?
if so, i would be quite interested in purchasing some, or at least finding out more on it...

MeDieViL
12-03-2010, 02:59
I few trips on DXM maybe.

Hugs & Drugs
12-03-2010, 03:02
"I few trips on DXM maybe."

please extend on that?
are you trying to say DXM would lower stimulant tolerance?

MikeHawk
12-03-2010, 03:09
I'm assuming it's due to NMDA agonism from DXM?

MeDieViL
12-03-2010, 03:27
NMDA antagonists upregulate dopamine receptors in the striatum, however memantine is known to only prevent tolerance from going up and not actually reversing tolerance, so i assume you need to be tripping for active upregulation.

Hugs & Drugs
12-03-2010, 06:00
haha i find that pretty ironic
having to get tripping on one drug to decrease tolerance in another

like MikeHawk said - is this due to is NMDA agonism?
i wonder if one would have to be actively tripping to experience this reversible tolerance
or merely a large therapeutic dose?

/navarone/
13-03-2010, 00:34
IIRC haloperidol has some potent dopamine upregulating properties due to it's very potent antidopaminergic properties.

Dysphoric
13-03-2010, 03:07
NMDA antagonists upregulate dopamine receptors in the striatum, however memantine is known to only prevent tolerance from going up and not actually reversing tolerance, so i assume you need to be tripping for active upregulation.


Well, I'm fucked then... I can't stand tripping, cause of Anxiety... :p

From what it seems, there is no such thing as literal tolerance, it just seems as if your dopamine or whatever that certain drug targets gets desensitized, thus feeling weaker. Am I correct? So, in order to re-experience the initial high you have to Up-regulate dopamine like no ones business... If this is true, then this shouldn't be to hard to accomplish if there are up-regulating drugs...

ebola?
13-03-2010, 03:14
The cream of it all is this: Methamphetamine is a poison with some positive short-term effects. This is not opinion, it is fact. There is simply no sustainable way to keep taking Meth, doctor-prescribed or not, without suffering at the end. .

except with exceeding rarity and moderation.

MeDieViL
14-03-2010, 14:15
haha i find that pretty ironic
having to get tripping on one drug to decrease tolerance in another

like MikeHawk said - is this due to is NMDA agonism?
i wonder if one would have to be actively tripping to experience this reversible tolerance
or merely a large therapeutic dose?

I dont know youll have to experiment, i know someone that got hes amp tolerance back by taking therapeutic doses of DXM with it.

Nagelfar
27-03-2010, 06:06
2β-Propanoyl-3β-(4-tolyl)-tropane. (a.k.a. WF-11) (http://en.wikipedia.org/wiki/2%CE%B2-Propanoyl-3%CE%B2-(4-tolyl)-tropane)

"...WF-11 has been shown to produce a uniform downregulation of tyrosine hydroxylase protein and activity gene expression with a regimen of use..."

source: Willard M. Freeman, George J. Yohrling, James B. Daunais, Lynda Gioia, Stephanie L. Hart, Linda J. Porrino, Huw M. L. Davies and Kent E. Vran (2000). "ScienceDirect - Drug and Alcohol Dependence : A cocaine analog, 2β-propanoyl-3β-(4-tolyl)-tropane (PTT), reduces tyrosine hydroxylase in the mesolimbic dopamine pathway". Drug and Alcohol Dependence 61 (1): 1521. doi:10.1016/S0376-8716(00)00119-8. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T63-41JM8RB-3&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=9dfa759f0130f9a4f404c4732edd1741. Retrieved 2008-01-11.

/navarone/
27-03-2010, 08:49
NMDA antagonism?

Well then..lets all get fucked up on Ketamine!! Woopeedooh!

MyDoorsAreOpen
28-03-2010, 19:14
I just took 150mg of DXM yesterday (a high first plateau dose for someone of my weight and habitus), and this morning, my reward circuitry finally feels back to normal, after months of dabbling in Mucuna pruriens, L-tyrosine, and occasional Adderall. All of these "dopamine boosters" left me with overall less motivation than ever before. I'd like to steer clear of all of them for some time.

The dopamine system demonstrates much homeostatic resilience, meaning that among other things, it will resist, long term, any pharmacological attempts to jack it up, mostly by downregulating receptors. This also means it eventually recovers from most insults.

DrugsDrugs
18-01-2012, 19:28
In order to find drugs/mechanisms to enhance the function of a certain neurotransmitter, you first must (thoroughly) understand the changes that will take place in your brain as a result of altering your natural state of being. Your brain is very plastic (it changes based on stimuli) and it will respond to any condition that you decide to impose outside of its natural physiological boundaries (which are specific for each person).

The concept of desensitization due to drug use can be made simple as follows. Dopamine binds to dopamine receptors in the post synaptic neuron and do their magic. If you increase the levels of dopamine in the synapse, there are a few physiological changes that will take place.

1. The number of receptors in the post synaptic neuron are going to decrease.
2. The amount of re-uptake transporter increases
3. Enzyme degradation of dopamine in the synapse increases.
4. Production of dopamine is slowed or halted, depending on the severity of the drug use (frequency and dose)
5. Number of synapses between the pre and the post synaptic neuron decrease.

These physiological changes are happening simultaneously. Research does not show the extant to which each condition is responsible for desensitization, but some or all maybe responsible (really depends on the person).

Adding a drug to enhance the effects is going to create homeostatic imbalance. Thus, adding more drugs to your repertoire is not very effective way of dealing with this issue. Just lay off of the meds for a bit.
You need to consult your psychiatrist and get a recommendation for a clinical psychologist that will also help you understand/deal with your conditions better (with or without drugs).

Good Luck!

DrugsDrugs
18-01-2012, 19:31
You can increase dopamine like no body's business, but remember, your brain is going to respond to an increase in dopamine by further reducing the impact of dopamine. You will need higher and higher amounts of dopamine to receive baseline effect. Your best bet is using slow acting stimulants in low dose. Extended release at lower doses are more effective than the short term high rush drugs.

Morpheus19
19-01-2012, 00:44
What's about a mao-b inhibitor like deprenyl? Doesn't it have a somewhat good cost-benefit ration in terms of having more dopamine available your brain?

ebola?
19-01-2012, 03:13
Your body will eventually upregulate production of mao (and will downregulate dopamine receptors more more quickly than that).

Renz Envy
20-01-2012, 03:35
If dopamine levels return to baseline eventually post methamphetamine use, then what causes permanent damage and how can one avoid this?

Nagelfar
20-01-2012, 04:02
If dopamine levels return to baseline eventually post methamphetamine use, then what causes permanent damage and how can one avoid this?

From my knowledge, neurotoxicity in general is even more than permanent psychological disorders based upon neurological fluctuations or life-long re-calibrations of functioning due to habituation that may cause such conditions as anhedonia.

True neurotoxicity has to do with some process of damaging cell destruction, usually more than simple activation of programmed cell death; but it might be as well if malignant (someone may be able to allude to more orthodoxy on this issue than I).

As far as I know with methamphetamine, it damages neurons at certain levels of concentration. Other comparable dopamine releasing agents have properties which make them less prone to be neurotoxic in this manner, but still display all the downregulation and dopaminergic stress that methamp does.

Renz Envy
20-01-2012, 04:21
Therefore would redosing multiply damage done?

(By multiply, I mean greatly increase the detrimental effects in comparison to someone waiting a day or two before use.)

I do not doubt that methamphetamine is highly dangerous and can cause the burn-out effect quickly in users, I have met many that delved into seeking its use for pleasure.

I wonder why it would be prescribed if heavy neurotoxic effects are inevitable even with moderated use.

Another version of my question:
[If someone were to use xxmg of methamphetamine many times for 7 days before they finally hit a block,

then would they suffer worse or the same effects as someone that uses xxmg the same amount of times over a longer span of time (let's say 3-4 months.)]

Nagelfar
20-01-2012, 04:58
I wonder why it would be prescribed if heavy neurotoxic effects are inevitable even with moderated use.

Well now that's arguable. Notice I said at "certain concentrations". There are however safer alternatives that have basically the same exact mode of action and duration so I wonder myself why the establishment uses desoxyn and such. Most likely due to convention and how easy it is to produce.

Renz Envy
20-01-2012, 05:17
Well now that's arguable. Notice I said at "certain concentrations". There are however safer alternatives that have basically the same exact mode of action and duration so I wonder myself why the establishment uses desoxyn and such. Most likely due to convention and how easy it is to produce.

I suppose phenmetrazine would be a better alternative.

Amu
20-01-2012, 07:18
No, heavy neurotoxic effects are NOT obvious at moderate doses, they are not even obvious at high doses (though I do concur they occur at high doses):

http://www.bluelight.ru/vb/threads/603295-Is-Cognitive-Functioning-Impaired-in-Methamphetamine-Users-A-Critical-Review.

Nagelfar
21-01-2012, 07:22
I suppose phenmetrazine would be a better alternative.

A lot of classes of dopamine releasers outside of the amphetamine structural type are superior in terms of having less neurotoxicity. 2-Aminoindane for example is one. 4-Methylaminorex, an oxazoline, even has a longer duration of action than methamphetamine and is considered less neurotoxic than the amphetamine class.

bluedolphin
21-01-2012, 22:38
A lot of classes of dopamine releasers outside of the amphetamine structural type are superior in terms of having less neurotoxicity. 2-Aminoindane for example is one. 4-Methylaminorex, an oxazoline, even has a longer duration of action than methamphetamine and is considered less neurotoxic than the amphetamine class.

In my experience 4-MAR doesn't last quite as long as methamphetamine. YMMV. Actually they are really close but Meth leaves the body feeling cracked out for longer, where 4-MAR is a smoother come down, so it seems like you reach something very close to baseline a bit sooner.

YMMV. Depending on dose, purity, and MOA as well.

ebola?
22-01-2012, 03:41
2-Aminoindane for example is one.

Is the activity of 2-aminoindane even known? I haven't been able to find anything on it...

ebola

/navarone/
22-01-2012, 14:35
What about a diet extra rich in magnesium and zink, would that at least help?

Also methoxetamine is a heavy NMDA antagonist But it is also a strong DRI profile...how would that behave on your dopamine receptors?

Ow, almost forgot.....Amantadane is a much much cheaper alternative to memantine and it's used for a variety of conditions including parkinsons and alzhaimer.

Nagelfar
22-01-2012, 21:46
Is the activity of 2-aminoindane even known? I haven't been able to find anything on it...

ebola

I suppose I mean the aminoindane class, though 2-aminoindane substitutes for amphetamine in rats, apparently, according to what I was quickly able to pull for a reference out of Wiki: Oberlender R, Nichols DE. (1991). "Structural variation and (+)-amphetamine-like discriminative stimulus properties."

Dysphoric
22-01-2012, 22:27
Someone revived my old ass thread?

Dysphoric
22-01-2012, 22:37
A lot of classes of dopamine releasers outside of the amphetamine structural type are superior in terms of having less neurotoxicity. 2-Aminoindane for example is one. 4-Methylaminorex, an oxazoline, even has a longer duration of action than methamphetamine and is considered less neurotoxic than the amphetamine class.

Yeah, I really don't understand why they don't have other stimulants available. As you were saying they are far less nuerotoxic and seem to be as effective if not better, I'm mainly referring to 4-Methylaminorex. Any reasons?

Amu
23-01-2012, 02:15
Yeah, I really don't understand why they don't have other stimulants available. As you were saying they are far less nuerotoxic and seem to be as effective if not better, I'm mainly referring to 4-Methylaminorex. Any reasons?

Because there are no patents available for the Pharm companies to make the moolah

Nagelfar
23-01-2012, 06:42
In my experience 4-MAR doesn't last quite as long as methamphetamine. YMMV. Actually they are really close but Meth leaves the body feeling cracked out for longer, where 4-MAR is a smoother come down, so it seems like you reach something very close to baseline a bit sooner.

YMMV. Depending on dose, purity, and MOA as well.

90% of methamphetamine is excreted unmetabolized so it stands to reason that if 4-MAR was more often excreted entirely unmetabolized that very little subjective difference would be noticed as to duration. Due to simply the time it takes for the body to excrete any given compound.