Can Drugs Target the Gut Without Fogging the Brain?

After gallbladder surgery, Daniel's post-meal bloating has been "extremely hard to treat." The standard approach—low-dose tricyclic antidepressants like amitriptyline—works but leaves him impaired the next day. The core problem: these drugs were designed to cross the blood-brain barrier, so they can't selectively calm the gut. This episode explores the science of visceral hypersensitivity, why the gut and brain share the same wiring, and what's actually in the drug pipeline—from peripherally restricted mu-opioid antagonists to CB2 agonists and TRP channel modulators. We break down why olorinab stalled, how tenapanor works locally, and whether receptor subtype selectivity can solve the problem without requiring full gut restriction.