DARK Classics in Chemical Neuroscience: Arecoline.

Arecoline is a naturally occurring psychoactive alkaloid from areca (betel) nuts of the areca palm (Areca catechu) endemic to South and Southeast Asia. A partial agonist of nicotinic and muscarinic acetylcholine receptors, arecoline evokes multiple effects on the central nervous system (CNS), including stimulation, alertness, elation and anxiolysis. Like nicotine, arecoline also evokes addiction and withdrawal symptoms (upon discontinuation). The abuse of areca nuts is widespread, with over 600 million users globally. The importance of arecoline is further supported by its being the world's forth most commonly used human psychoactive substance (after alcohol, nicotine and caffeine). Here, we discuss neuropharmacology, pharmacokinetics and metabolism of arecoline, as well as social and historical aspects of its use and abuse. Paralleling clinical findings, we also evaluate its effects in animal models and outline future clinical and preclinical CNS research in this field.