Could Metformin Prevent Opioid Tolerance?

Metformin inhibits mTOR signalling pathway which helps with its anti-cancer properties. Blocking mTOR also seems to reduce tolerance. Tolerance can be seen  in tissue lines by elevated nitrite levels. Metformin prevent nitrite elevation with both methadone and morphine.

I don’t know why actually studies in diabetics on metformin re opioids have not been done but implications from basic science suggests it might be helpful in preventing tolerance,

J Cell Physiol. 2018 Aug 26. doi: 10.1002/jcp.27125. [Epub ahead of print]
In vitro evaluation of effects of metformin on morphine and methadone tolerance
through mammalian target of rapamycin signaling pathway.
Shirooie S et al
https://www.ncbi.nlm.nih.gov/pubmed/30146703

It is mind numbing to go over all the tables but what I got out ot it included:

• signs of tolerance at much less with methadone
• metformin pre-treatment prevented tissue nitrite elevations that are signs of opioid tolerance

Comment – Metformin also has some mood stabilizing effect that might help subjects with mood issues. (in my old painmuse.org blog). These same people are more likely to develop excessive needs for opioids so perhaps these subjects should be offered the drug.

Diabetics that are just on metformin live 5 years longer than “normal” people and telomeres of metformin subjects are longer. It has also anti-cancer properties. I take it for that reason even though I am not diabetic.  I think there could be a place for using it with opioids – it often helps constipation which could be useful in those on opioids.