Hey – great questions that go fair beyond the pseudo-scientific conjecture I have seen here, so I commend you for that. I’ll try to address the questions linearly:
You’re absolutely right about curcumin and piperine as being 5ARI’s. While their potencies as inhibitors are comparatively weak (especially in comparison to pharma-grade drugs like fin which work in the nM range as opposed to herbs/polyphenols that are generally inhibitors in the uM and mM range-- so orders of magnitude different), I would but a moratorium on using these supplements as you’re ultimately going for a recovery while using as few exogenous (and pricey) compounds as possible. A fairly comprehensive list can be found here (though I would also add quercetin to it): https://en.wikipedia.org/wiki/List_of_5α-reductase_inhibitors
I’ve checked nearly as many of them in my CSF as is possible (some are unstable intermediates that degrade quickly or there are simply not laboratories that have the testing capabilities for some of these neuro-steroids), and I tested most other in serum tests as many can reliably portend CSF levels (though in a pathological state this is not a hard-and-fast rule). In CSF, I tested: Allopregnanolone, Isopregnanolone, Aldosterone, Androstenedione, 5α-Androstanedione,Testosterone. I felt this gave a good gauge of both precursor steroid production as well as 5-Alpha reduced steroid output in my CNS.
I also did several panels of all iterations of these steroids in serum and even in urine metabolites. Long story short, all my levels were entirely within acceptable ranges (though established ranges for CSF neurosteroid concentrations are notoriously hard to establish). This was manifestly confusing as all my symptoms seemed to reflect poor ALLO concentration. That’s when I found this paper, which was really an inflection point in my recovery:
The result was a CSF assay mRNA transcription factors for GABA(a) regulation, which were woefully downregulated. At least in my case, it wasn’t dysfunctional 5AR reduction that was the problem, but rather a pathological reaction to acute and drastic upregulation of ALLO when I quit Finasteride.
- I’m now really only using a small amount of Bacopa (two does of 300mg @ 24% extract twice daily and fasting daily). I also drink coffee but not for therapeutic benefit–mostly just because I really like it. I have a fair amount of knowledge about GABA(a) and GABA(b) regulation and cell surface expression, and I can share that in a more granular way if you want. For the time being, Bacopa is a good option per this collection of studies that demonstrate consist upregulation of δ subunit-containing GABAA receptors in various brain regions:
I want to comment that I’ve seen the fairly erroneous idea floated that Bacopa is a potent 5ARI; this is patently untrue and these ideas represent the nadir of collective pseudo-scientist delusion that I really dislike about this site. The truth is that a minor component of Bacopa is Beta-Sitosterol which is a 5ARI (but is only .12% to .01% of Bacopa by weight depending on the sample under HPLC analysis), and even then this 5ARI is orders of magnitudes weaker than many other common inhibitors like zinc and vitamin b3.
I would be careful with any other adaptogens that have any activity at GABA(a) or GABA(b) receptors both as agonists or as PAM. As the above novel ALLO tolerance study delineates, potnet tolerance to PAM’s is a strong possibility and might just further exacerbate your problems. I would do a deep dive on Examine.com with respect to the mechanisms of action for any substance you are considering putting in your body.
That’s a very intelligent question, and I don’t have an answer for you. It seems to me that even in the use of an antagonist the upregulation would only be transient and dose-dependent w/ antagonist use. This would be problematic as you’d be experiencing the full gamut of negative side effects from increased neuronal depolarization (and subsequently heightened excitability). You could try it and see how you respond (just don’t use Zn as it’s a 5ARI). In a roundabout way, caffeine is a GABA receptor antagonist, so this may also be a route to pursue.