Comment · Mon, February 10, 2014
Amphetamine and dopamine receptors
Original post in this thread
GeneralStarkk · 14 points
Hello guys I've tried google and searching and I couldn't find anything. I take adderall, a lot. And I know that it can wear down your receptors over time and eventually make them stop functioning properly. Does any body know how much time it takes for them to regenerate? To keep things simple lets say that I take 60mg a day, for about 6 months. (I don't just a example.) how long would that take for my brain to get back to baseline? Thanks ahade of time.
What they were answering
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb
Tolerance is not the same thing as neuronal damage. Damage can cause tolerance, but tolerance does not necessarily mean damage.
Most amphetamine tolerance comes from immediate active gene expression, and the down-regulation that happens due to excess calcium influx into the neuron. This happens because amphetamine causes rises in extracellular glutamate, which binds to your NMDA receptors, opening them and allowing calcium to pass through. This is why it is suggested to take a good magnesium supplement every day, as that is the substance that blocks the NMDA channel. Then there are stronger NMDA receptor antagonists that you can use to slow and/or reverse tolerance. Memantine is the best one to use for long-term use, but DXM seems to work better for short-term tolerance breaks.
Then you get to the damage part. There are a number of different ways neurons can be damaged by amphetamine use. The first mechanism with calcium is one. If the calcium enters the cell in too high of concentrations, then the neuron can be damaged. The second is oxidative damage caused by reactive oxygen species. This happens due to amphetamine's reactive metabolites damaging dopamine neurons, or even dopamine itself being broken down by MAO to form hydrogen peroxide. To combat this, a nice antioxidant stack should be used. I would use a combination of Na-R-ALA, CoQ10, Vitamin A, Vitamin C, and resveratrol.
Now the reversal of tolerance depends on the cause. If your use was enough to cause neuronal damage, then it will take a while to recover. Taking supplements that increase BDNF, like lions mane mushrooms or noopept would be a good start. If it is normal tolerance from reasonable use, NMDA receptor antagonists are the best way to help reverse the tolerance. I would say a couple week break, paired with daily low-dose DXM would be the best route. Then use memantine every day with your amphetamine to slow the buildup of the tolerance to begin with. Everyone is different, so times are going to vary. One thing is for sure, you need time off to reduce tolerance.