Tolerance Troubles

A curious pharmacology essay on the puzzle of drug tolerance — why it develops for some drugs but not others. Heroin builds tolerance; Adderall supposedly doesn't (but abusers' does — the 'receptors read the FDA labels' running joke). All three logical outcomes occur: effect persists (Adderall), fades (heroin), or overshoots to anti-effect (antipsychotics → tardive dyskinesia via dopamine supersensitivity; low-dose naltrexone for post-acute-withdrawal). Worse, different people land in different branches (benzodiazepines — stable forever for some, a spiral for others), and SSRIs show tachyphylaxis (suddenly stop working, then work again years later). The meta-point: psychiatry under-theorizes tolerance, the receptor-sensitivity hypothesis doesn't close off possibility-space, tolerance is bound up with (genetic) addiction, and the best drugs (Xanax, opiates) are the ones we avoid precisely because of it — a tolerance-free Xanax would be a holy grail.

Quality 73 · Strong. A rich, honestly puzzled, clinically grounded essay on a genuinely under-discussed topic, full of sharp observations (tardive dyskinesia as supersensitivity; PAWS + low-dose naltrexone; SSRI tachyphylaxis; the benzo heterogeneity) and a good meta-point about psychiatry's blind spot. Strong; appropriately inconclusive, which keeps it there.

Claude’s paradigm shift 54 · Moderate. The 'all three branches occur, and different people land in different ones' synthesis plus the 'psychiatry under-theorizes tolerance' framing are a fresh take on scattered clinical facts. Notable.

Real-world impact 2 · Minor. A within-discourse pharmacology essay; no material-world effect. Within-blog influence.