|
morrowasted
Worldwide Stepper


Registered: 10/30/09
Posts: 31,378
Loc: House of Mirrors
Last seen: 10 days, 9 hours
|
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)
|
cannabinated


Registered: 01/03/13
Posts: 14,743
Loc: Outside
|
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
|
morrowasted
Worldwide Stepper


Registered: 10/30/09
Posts: 31,378
Loc: House of Mirrors
Last seen: 10 days, 9 hours
|
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
|
Loaded Shaman
Psychophysiologist



Registered: 03/02/15
Posts: 8,006
Loc: Now O'Clock
Last seen: 1 month, 15 days
|
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
|
cannabinated


Registered: 01/03/13
Posts: 14,743
Loc: Outside
|
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) |
|
|
|
cannabinated


Registered: 01/03/13
Posts: 14,743
Loc: Outside
|
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.
|
gopher
Coffee Bean Extraordinaire



Registered: 11/22/17
Posts: 13,160
Loc: Canada
Last seen: 5 hours, 3 minutes
|
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
-------------------- For most of the normies out there, an operating system is just a bootloader for Google Chrome. Since Disney has obtained tremendous value from the public domain, knows how important the public domain is, and is firmly determined to never contribute anything to it. My pronouns are He and Him, and my adjectives are Fat and Jazzy
|
mndfreeze 
Shroomery Secret Service




Registered: 04/22/02
Posts: 20,529
Loc: PuppetMasterFlash
Last seen: 12 hours, 47 minutes
|
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]
-------------------- Nothing says love like grannies prolapsed anus! quote]Urb said: I know... Its fucked up... Ill fix it minyana..[/quote]
|
cannabinated


Registered: 01/03/13
Posts: 14,743
Loc: Outside
|
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
|
cannabinated


Registered: 01/03/13
Posts: 14,743
Loc: Outside
|
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.
|
cannabinated


Registered: 01/03/13
Posts: 14,743
Loc: Outside
|
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
|
nooneman


Registered: 04/24/09
Posts: 14,593
Loc: Utah
|
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.
|
openmind
curious


Registered: 08/03/07
Posts: 13,876
|
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 .
-OM
.
--------------------
|
|