Upregulating dopamine?

[Dysphoric]

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...

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?]

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]

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]

2β-Propanoyl-3β-(4-tolyl)-tropane. (a.k.a. WF-11)

"...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): 15–21. doi:10.1016/S0376-8716(00)00119-8. http://www.sciencedirect.com/scienc...serid=10&md5=9dfa759f0130f9a4f404c4732edd1741. Retrieved 2008-01-11.

 

[/navarone/]

NMDA antagonism?

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

 

[MyDoorsAreOpen]

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]

Up-regulating neurotransmitters!

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]

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.

 

[ebola?]

Your body will eventually upregulate production of mao (and will downregulate dopamine receptors more more quickly than that).

 

[Renz Envy]

If dopamine levels return to baseline eventually post methamphetamine use, then what causes permanent damage and how can one avoid this?

 

[Nagelfar]

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]

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]

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]

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]

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/...ed-in-Methamphetamine-Users-A-Critical-Review.

 

[Nagelfar]

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]

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?]

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/]

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]

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."