@Hip have you investigated nigella sativa during your many trials?
Funnily enough, 15 years ago, when my health problems first began (with severe IBS and its associated anxiety symptoms), black seed oil was one of the first supplements that I tried. Not because black seed oil is good for IBS, but simply because I happened to be walking past a shop in London which was advertising: "
Black seed oil: a remedy for all diseases except death — the prophet Mohammed".
Always amused by hyperbole, I bought some there and then. It did not really help my IBS much, though it slightly reduced my anxiety levels.
One of the main pharmacodynamic effects of black seed oil is its
NF-κB inhibition. That can be useful. For example, when I was experimenting with supplements to decrease my very high anxiety levels (anxiety which I believe may be due to brain inflammation), I discovered that supplements or drugs that potently inhibited NF-κB helped to reduce the anxiety.
This is probably because NF-κB inhibition can reduce inflammation, which in turn I think will reduce anxiety, if neuroinflammation is the cause of your anxiety.
NF-κB
has been found to be more activated in ME/CFS, which in turn may induce more inflammatory cytokines.
Black seed oil is not the only NF-κB inhibitor supplement, though, there are many others. Some of more potent ones are: curcumin, alpha lipoic acid, grape seed extract and ashwagandha (Withania somnifera).
And if you want a really potent NF-κB inhibitor, then consider the drug sulfasalazine. I found that strong NF-κB inhibition noticeably reduce my anxiety levels, so I was taking sulfasalazine for a while for that purpose, and it worked reasonably well. Though eventually I switched to taking a cocktail of several NF-κB inhibitor supplements, which were almost as effective.
After I later discovered the potent anti-anxiety effects of N-acetyl-glucosamine (NAG), I then mostly dropped the NF-κB inhibition strategy, as NAG and a few other added supplements were sufficient to keep my anxiety in check.
Selfhacked has a page on NF-κB inhibition:
How To Inhibit NF-kB: The Key To Health And Master Control of Inflammation - Selfhacked
Note that black seed oil is also a
histone deacetylase (HDAC) inhibitor, so that is another action it has in the body.