Amitriptyline and magnesium sulfate reduces both opiate tolerance and withdrawal

[Jabberwocky]

https://journals.tbzmed.ac.ir/PHARM/Manuscript/PHARM-21-192.pdf

So this combo apparently reduces both tolerance and withdrawal symptoms from morphine in rats.

Very interesting.

 

[Xorkoth]

Very interesting indeed. It would be good to have a non-addictive method of making opiate withdrawal easier to get through. Also I wonder if tolerance reduction applies to the perma-tolerance that you get after abusing opiates heavily? Even when I took a 5 year break of absolutely no opiates, when I relapsed, my baseline tolerance was still way higher than it ever was before the abuse.

 

[4meSM]

the dosage used is very high Magnesium sulfate (20, 40 and 60 mg/kg,ip), Amitriptyline (5, 10 and 15 or 20 mg/kg,ip),
magnesium is NMDA antagonist and with that dosage NMDA receptors is significantly blocked, so there is no problem believing that magnesium will decrease tolerance and withdrawal, but you can use other NMDA antagonist with normal dosage

Yeah that's kinda what I thought. Plus they're giving them magnesium sulfate via injection (intraperitoneal). I don't think this translates very well to humans, but I could be wrong.
I'd rather take a more bioavailable form of magnesium though (like magnesium glycinate).

 

[Gaffy]

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[plumbus-nine]

Does magnesium work as a NMDA antagonist in humans too if you just take enough? So there should be a dose window where you'd get intoxicated/dissociated before hitting real toxicity? Any hints of this dose window? (Don't worry, I don't intend to try it anytime soon, atm memantine is good enough but I never got any results from magnesium..)

Interesting, but nothing new about amitriptyline. Even fluoxetine can potentiate morphine analgesia and possibly delay tolerance a bit (need to find the source again). Venlafaxine strongly interacts with opioids as I had to find out the hard way, one indeed feels less withdrawal from them but somehow taking opioid + venlafaxine together for some time reinforces dependency on the latter..