PFS claimed to rest on an overwhelming evidence base; PSSD mechanism still open and possibly multiple
u/drwillpowers
r/DrWillPowers2026-06-19T23:06:28Z
Dr Will Powers’ own statements and theorizing
Mentions treatments or doses — not guidance
Summary (paraphrased)
Replying to a community member's 3α-HSD oxidation-inhibition proposal — fluoxetine inhibiting allopregnanolone oxidation via RoDH-4 as the direct drug→metabolite-accumulation link — Powers contrasts the two syndromes: PFS, he says, rests on an overwhelming evidence base (his data plus crowdsourced genomes/labs), while PSSD's mechanism is still open and may not be one thing. One PSSD flavor could be PFS-like metabolic pile-up; his recent AI-assisted analysis, he says, keeps flagging a 5-HT2C effect putting "brakes on dopamine" signaling even with normal dopamine levels. He announces a hospital-funded IRB research study to formally prove the PFS work — "parallel construction," since his existing evidence-gathering wouldn't count in academic settings. He adds a timing argument: single-pill onsets must be neurotransmission-mediated (too fast for metabolic crush), while withdrawal or delayed onsets could be PFS-like pile-up.
Key points (paraphrased)
- PFS claimed to rest on an overwhelming evidence base; PSSD mechanism still open and possibly multiple.
- New PSSD hypothesis: 5-HT2C-mediated braking of dopamine signaling despite normal dopamine levels (AI-flagged).
- Hospital-funded IRB study announced to formally prove the PFS work — "parallel construction" for academic admissibility.
- Timing argument: single-pill onsets imply neurotransmission; delayed/withdrawal onsets allow pile-up mechanisms.
- Treatment philosophy: patients choose among educated options as a team; he denies experimenting on patients.
Why it’s in the corpus
Two major corpus items: the PSSD 5-HT2C/dopamine hypothesis (new) and the hospital IRB study announcement. It also captures his evidence hierarchy — crowdsourced proof vs. academically admissible proof — and the onset-timing differential diagnosis.
Context — the post Powers was replying toVerbatim third-party text, shown for context only — not Powers’ statement. Usernames removed.ShowHide
Powers' comment replies to [username removed], who proposed 3α-HSD oxidation inhibition (citing a fluoxetine/RoDH-4 paper) as the junction point causing metabolite accumulation and asked whether this matches the angle Powers is pursuing, in the "3α-HSD oxidation inhibition as the junction point" thread.
_Note: the export's permalink for this entry resolves to an unrelated comment; the curated comment was located by text match on its true thread (see backfill log)._
(Parent context recovered from the r.genit.al mirror on 2026-10-09; Powers' comment text itself is from John's user-provided export.)
Some fields on this page come from the release’s Markdown edition, which carries text the JSON edition omits.
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