Assuming that Rapamune (sirolimus aka rapamycin) does turn out to be beneficial for a number of people, I don't think there's much chance that this means mTORC1 is actually over-activated in ME/CFS. I'm definitely sticking with it being under-activated/inhibited.
A couple of explanations for why rapamycin might be working are:
1. Perhaps under-activation of mTORC1 in ME/CFS is actually a beneficial adaptation of the body in its attempt to deal with the disease and further inhibition of mTORC1 by rapamycin is helping achieve this goal.
2. Perhaps there is some non-mTORC1 related beneficial effect that rapamycin has that outweighs the seemingly negative effect of inhibition of mTORC1.
Regarding #1, a
mouse study found that rapamycin was able to protect cardiac function in a sepsis model by
further reducing mTORC1 activity that had already been reduced upon pathological exposure to lipopolysacharride (LPS). (Not sure if it's just a coincidence here that ME/CFS has been found to closely resemble SIRS/sepsis at the mRNA gene expression level.)
Regarding #2, even though rapamycin inhibits the mTORC1 enzyme complex it actually
increases the activity of the upstream Akt regulator enzyme. (The above mouse study also notes this as well.) This is pretty remarkable because most other substances that might inhibit mTORC1 will usually inhibit Akt too (e.g., metformin). So this might be a key aspect to the beneficial effect of rapamycin, assuming it is actually helping.
Lastly, I notice that both Mary Adelman (in the original post) and also
@XenForo previously found that low dose naltrexone (LDN) is helpful for them. So it's possible that rapamycin may only work for that subgroup of patients. LDN is very toxic to me but I'm very curious how I'd respond to rapamycin. (Note that naltrexone inhibits both mTORC1 and Akt.)
My experience with Berberine is clearly very positive though. I've been taking it for about 3 weeks now and have worked my way up to 500mg a day. I feel dramatically better!! 
