Ketamine Research In A New Light

A pharmacology + meta-science post prompted by a Nature study finding ketamine's antidepressant effect comes from a metabolite (hydroxynorketamine, an AMPA agonist), not its NMDA antagonism. Scott uses this as a natural experiment on the replication crisis: given a whole field believed NMDA→depression and that was wrong, did researchers virtuously flag inconsistencies or tinker to confirm the paradigm? Examining the review literature, he finds a mixed-but-mostly-OK picture (reviews did admit other NMDA antagonists don't work) — EXCEPT where conflicts of interest exist (the rapastinel case, industry-affiliated authors more accepting of ambiguous positives). Concludes: trust the psych literature 'a lot, except in cases of conflicts of interest.'

Quality 65 · Strong. 65 — low Strong. A thoughtful pharmacology + self-correction-test post with a genuinely useful meta-point (the field mostly self-corrects, but COI is the failure mode), though in-the-weeds and preliminary (the metabolite finding wasn't fully confirmed). Firm low-Strong.

Claude’s paradigm shift 48 · Moderate. 48 — Moderate. The self-correction-test framing + the COI caveat is a useful, mildly generative angle.

Real-world impact 2 · Minor. 2 — minor/within-blog. Niche psychiatry/meta-science; no material reach.