Just want to point out that a lot of ME people seem to get significant benefit from opioids. If you put 'opioid' in the site search box you will find numerous posts stating this, although there are indeed also people who react badly to them.
Yes, my weakness and greatest analytical strength is that I am a generalist. I have a tendency to generalize about things, like my characterization of opioids. At the same time, having a general knowledge of many parts of this, I think, allows me to see patterns that perhaps someone with intense specialization would never see. The increasing super-specialization of our medical/scientific community has its detriments; we need more RVK's, more unifiers, more people who look at things macroscopically. Unfortunately, the market is not supporting this. I talk to physicians most every day, and I find that the primary care specialist are among the best problem solvers because they see the whole problem, yet there are financial incentives to specialize. The specialists are disproportionately compensated, and this trend is worsening, at least here in the US.
One of the most interesting things to me is the chemical duality I see in nature, and opioids are a perfect example. Morphine is a plant alkaloid, and an amine, and like other alkaloids can provoke wildly different reactions in those with ME/CFS. The distinction between anti and pro-inflammatory substances can be hard to make. I think people have to ask, does a substances short term benefits exceed its long term effects. This can be highly subjective. Long term, something like morphine, which depletes glutathione and should have a negative net ROS consequence, among other things, would seem to do more harm than good, but if someone is hurting, well you do what you have to do. It's a shame that we have so little guidance in these matters, but our symptoms do seem to be the most reliable indicator we have.
The list of TLR4 agonist and antagonist, which includes Ampligen is a curious list with some patients tolerating one or the other, and not that much overlap. Actually, this biochemistry/immunology thing, which I am just learning, makes more sense when one looks at a chemicals as having necessary functions instead of being good or bad. An amine like histamine is not simply a yucky thing that makes us itch, it modulates an immune response. In the case of LPS, it binds to these molecules and is protective.
Whether or not someone does well with a TLR4 agonist or antagonist may have to do with ones sensitization and level exposure to LPS (I guess I'm not really a generalist since I am so fixated on LPS and there are obviously other plausible explanation) and thus the expression of ones immune system as a consequence of ones bacterial balance and capacity to render these substances inert. More importantly, though than any weak hypothesis from me, though is a question for those who are looking at ME/CFS: Why is there an intersection at TLR4, which is the signature for LPS?
