Benzos for Amphetamine Toxicity

[Madrus]

Follow this train of thought here:

Amphetamines -> release dopamine -> lots of brain activity -> glutamate = activity -> too much glutamate = excitotoxicity
Benzodiazepines -> more GABA -> GABA helps stop glutamate activity -> reduce excitotoxicity.

So can I take a benzo with my amphetamine to reduce possible excitotoxicity? Is there any data out there supporting anything like this?

 

[AlphaMethylPhenyl]

Pretty doubtful. Amphetamine is more of a monoaminergic.

If indeed this did work, then the amount of amphetamines high that you nuke will correspond to nuking its toxicity.

 

[Nagelfar]

Perhaps instead of amphetamine, some sort of NMDAr modulation? Allosteric?

 

[serotonin2A]

The toxicity produced by amphetamine is not mediated by the mechanism you proposed. First, you can't treat brain activity as being exclusively excitatory; there are also inhibitory neurons, and high levels of excitatory brain activity tend to be balanced with high levels of inhibition -- otherwise you would get seizures. Second, amphetamines are thought to produce neurotoxicity due to hyperthermia and as a direct result of their pharmacological effects -- ie, increasing the concentration of dopamine in the cytoplasm of nerve terminals produces oxidative stress. Benzodiazepines would not necessarily do anything to help with the latter effect -- and there is some reason to think that benzodiazepines may disinhibit dopaminergic neurons, which could potentially exacerbate the toxicity.

 

[kleinerkiffer]

This is a great paper about amphetamine-induced toxicity https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955986/

 

[RedRum OG]

IMHO, neurochemistry aside, if you use meth/amps often enough to worry about neurotoxicity, you'll be doing benzos that often too. Benzos may not be neurotoxic, but that shit will destroy your brain. Serious, long-term benzo withdrawal will fuck your head just as bad a meth. Just a thought

 

[Seppi]

Amphetamine inhibits EAAT3; it does not inhibit EAAT1 or EAAT2. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159050/
Methamphetamine inhibits both EAAT1 and EAAT2. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418472/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103010/

EAAT2 is responsible for the vast majority of glutamate reuptake in the brain.

AFAIK, EAAT inhibition is the only pharmacodynamic mechanism of these drugs that directly affects glutamatergic neurotransmission.