The resulting “broth” was then applied to frog egg cells (Xenopus oocytes) that had been genetically engineered to express human muscarinic acetylcholine receptors on their surface.

These cells function as biosensors for receptor activation: when a compound activates the receptors, the cells produce a measurable electrical signal.

The result: the arecoline released by intact areca nuts soaked in artificial saliva was sufficient to activate the human muscarinic receptors.

The dose was lower than what modern betel quid use produces — processing with lime significantly increases arecoline extraction — but it was pharmacologically active.

This experimental confirmation is what distinguishes the Sulawesi study from a purely correlational archaeological finding.