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Offlinemorrowasted
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How to slow the rate of tolerance to drugs that act on dopamine * 1
    #26394590 - 12/21/19 07:59 PM (4 years, 1 month ago)

Pathology of tolerance development to d1 receptor activation in the nucleus accumbens:

↑Extracellular Dopamine -> D1 receptor agonism -> NMDA receptor activation -> ↑ Intracellular Ca2+ ion -> ↑Intracellular cAMP -> PKA activation -> ↑pCREB (CREB phosphorylation) -> ↑ΔFosB accumulation -> HDAC1 overexpression -> c-Fos downregulation.



As you can see, induction of c-Fos is NMDAr-dependent. This is the rationale behind the use of NMDA receptor antagonists for the attenuation of D1-mediated psychostimulant tolerance.

commonly available NMDAr antagonists used for this purpose include magnesium l-threonate, agmatine, ketamine, and memantine. DXM, PCP, and alcohol also do this but they're not good choices.

Agmatine is my personal favorite of these. I don't use it to prevent tolerance, though. It makes me feel increasingly focused over time. also great for lifting weights


Amphetamine and Dopamine-Induced Immediate Early Gene Expression in Striatal Neurons Depends on Postsynaptic NMDA Receptors and Calcium

Of course, the best way to avoid developing a tolerance to a substance is not to use it.


Edited by morrowasted (12/21/19 08:06 PM)


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Invisiblecannabinated
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: morrowasted]
    #26394671 - 12/21/19 09:23 PM (4 years, 1 month ago)

what about cannabis


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Offlinemorrowasted
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: cannabinated]
    #26394722 - 12/21/19 10:16 PM (4 years, 1 month ago)

Quote:

cannabinated said:
what about cannabis



This will reduce tolerance to the "reward" aspect of using cannabis, which still takes place via dopaminergic neurons in the nucleus accumbens. It won't reduce your tolerance to the other effects of CB receptor downregulation though, so if you quit you'll still get insomnia, anorexia, etc. But yeah, take 1000mg agmatine sulfate 3x a day for a couple of days and you'll very likely get a more "uplifting" high when you smoke, and not feel the compulsion to redose as frequently


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OfflineLoaded Shaman
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: morrowasted]
    #26394993 - 12/22/19 05:34 AM (4 years, 1 month ago)

Now this is interesting AF.


--------------------



"Real knowledge is to know the extent of one’s ignorance." — Confucius


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Invisiblecannabinated
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: morrowasted]
    #26395151 - 12/22/19 08:24 AM (4 years, 1 month ago)

:strokebeard:


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Invisiblecannabinated
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: cannabinated]
    #26395184 - 12/22/19 08:44 AM (4 years, 1 month ago)

im really intereseted in the CB receptor cause of its use of retrograde signalling and apparent lack of withdrawal effects. As well as reports of cannabis hypermesis syndrome.

It makes me think that it has way cool attenuation techniques. Plus the fact that the receptor is already involved in neuronal regulatory pathways.


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Offlinegopher
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: morrowasted]
    #26395317 - 12/22/19 10:12 AM (4 years, 1 month ago)

Quote:

morrowasted said:
But yeah, take 1000mg agmatine sulfate 3x a day for a couple of days and you'll very likely get a more "uplifting" high when you smoke,





I think thats one of he drugs they preach on r/kratom

another interesting thing I learned on r/kratom is white grapefruit juice is bad for kratom, people think its good cause it potentiates opiates, but with kratom it blocks the conversion of mitragynine into 7-Hydroxymitragynine, which is what really gets you high


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For most of the normies out there, an operating system is just a bootloader for Google Chrome.

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OfflinemndfreezeMDiscordReddit
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: morrowasted] * 1
    #26395478 - 12/22/19 11:44 AM (4 years, 1 month ago)

This is the nerd shit that makes me wish I was more focus'd in school. 

Agmatine looks interesting.

Opioid liability
Systemic agmatine can potentiate opioid analgesia and prevent tolerance to chronic morphine in laboratory rodents. Since then, cumulative evidence amply shows that agmatine inhibits opioid dependence and relapse in several animal species.[23]


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Nothing says love like grannies prolapsed anus!

quote]Urb said:
I know... Its fucked up... Ill fix it minyana..[/quote]


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Invisiblecannabinated
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: mndfreeze]
    #26395498 - 12/22/19 11:54 AM (4 years, 1 month ago)

The sad part about this is that its really simple but school doesnt wanna teach this stuff so corporations can get a drip feed of free stuff  from universities


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Invisiblecannabinated
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: cannabinated]
    #26395508 - 12/22/19 12:01 PM (4 years, 1 month ago)

chemistry and biology should be consolidated as a single class in highschool and there should be a year of highschool focused on genetics then kids can know this shit coming out

the simple chemistry stuff should be taught in 8th grade and they should consolidate physics into math.


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Invisiblecannabinated
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: cannabinated]
    #26395509 - 12/22/19 12:03 PM (4 years, 1 month ago)

which leaves all the time to focus on harder stuff in college

not that any of this matters


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Invisiblenooneman
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: morrowasted]
    #26395759 - 12/22/19 02:58 PM (4 years, 1 month ago)

Interesting. Possibly you could take 15mg DXM for a couple of days and see some effect if this is true. Still, its dependence on regularly using an NMDA antagonist is problematic. I would think this would most benefit serious regular stimulant users.

Now do LSD.


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Invisibleopenmind
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Re: How to slow the rate of tolerance to drugs that act on dopamine [Re: nooneman]
    #26395865 - 12/22/19 03:53 PM (4 years, 1 month ago)

Quote:

nooneman said:
Interesting. Possibly you could take 15mg DXM for a couple of days and see some effect if this is true. Still, its dependence on regularly using an NMDA antagonist is problematic. I would think this would most benefit serious regular stimulant users.

Now do LSD.





I've noticed that DXM lessens tolerance to opioids. (I took dosages around 150mg to 350mg)

DXM seemed to kinda "reset" me all together in ways. The day after my mind always felt more lucid, my mood was lifted, my cognition felt sharper, I was more social and outgoing, I was able to convey myself & translate my thoughts into verbal-language easier.

I never dabbled with it all that often and it's been years since I've taken any but I've been considering taking a small amount for those reasons specifically.




....because of this thread I'm also looking into agmatine :strokebeard: .






-OM

.


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