Comment · Fri, December 27, 2013 · Ceretropic
"Glucose Is Not Willpower Fuel"
What they were answering
3AlarmLampscooter · 2 points
Well more specifically, dopamine is (check out that awesome talk on dopamine posted a few days ago, the footage of dopamine deficient mice being so apathetic that they won't eat is fascinating).
The only real problem is amphetamine is also a dopaminergic neurotoxin, so you really need to stack it with other drugs to potentiate it (thus keeping the doses lower) and counter its side effects for maximum sustainability. There's a big debate on this over at longecity right now. And a much more science-heavy thread on bluelight a while ago.
Edit: Also IMO 2-FMA > Vyvanse > Dexedrine > Adderall as functional amphetamines go. I think there are some even better ones out there waiting to be discovered with all the new drug design technology that's hit the market in the last decade. There honestly has been a huge paucity of amphetamine research as stims, there is really no counterpart to Shulgin and Nichols for stimulant research (Chatterjee when he was at Cephalon, sort of... but he was on modafinil derivatives, at least one of which we're working on at longecity).
I'd be especially interested in trying to develop an amphetamine derivative with high metabolic stability that acts as both a dopamine…
u/MisterYouAreSoDumb · Ceretropic
The issue is the inhibition of VMAT-2 caused by amphetamine. This makes the increased dopamine levels more susceptible to MAO inside the neuron, creating hydrogen peroxide. You can attack this in two ways. One, you can use selegiline to inhibit MAO, and slow/prevent the conversion. Or you can use a strong antioxidant that passes the blood brain barrier to scavenge the ROS as they are created. I personally like combining Na-R-ALA with ALCAR to accomplish this. Then you can add in CoQ10 and creatine to help support ATP production, and ensure the ion pumps have the energy needed to regulate the neuron, and add in a bioavailable magnesium supplement to help prevent excitotoxicity. You can even add in memantine to protect the NMDA channels even further, and slow tolerance buildup.
Or you can go with something that increases dopamine without inhibiting VMAT-2, like methylphenidate. Even though some studies have shown that long-term methylphenidate usage does lead to dopamine system damage, it is much less than what is caused by amphetamine. Adding in potent antioxidants like Na-R-ALA, and ALCAR for mitochondrial support, can help mitigate that risk even further.