Betel quid: New insights into an ancient addiction

The use of areca nuts (areca) in the form of betel quids constitutes the fourth most common addiction in the world, associated with high risk for oral disease and cancer. Areca is a complex natural product, making it difficult to identify specific components associated with the addictive and carcinogenic properties. It is commonly believed that the muscarinic agonist arecoline is at the core of the addiction. However, muscarinic receptor activation is not generally believed to support drug-taking behaviour. Subjective accounts of areca use include descriptions of both sedative and stimulatory effects, consistent with the presence of multiple psychoactive agents. We have previously reported partial agonism of alpha 4-containing nicotinic acetylcholine receptors by arecoline and subsequent inhibition of those receptors by whole areca broth. In the present study, we report the inhibition of nicotinic acetylcholine receptors and other types of neurotransmitter receptors with compounds of high molecular weight in areca and the ability of low molecular weight areca extract to activate GABA and glutamate receptors. We confirm the presence of a high concentration of GABA and glutamate in areca. Additionally, data also indicate the presence of a dopamine and serotonin transporter blocking activity in areca that could account for the reported stimulant and antidepressant activity. Our data suggest that toxic elements of high molecular weight may contribute to the oral health liability of betel quid use, while two distinct low molecular weight components may provide elements of reward, and the nicotinic activity of arecoline contributes to the physical dependence of addiction.

Automated summary

Betel quid use, involving the use of areca nuts, is the fourth most common addiction globally and is associated with increased risks of oral disease and cancer. Areca is a complex natural product, making it challenging to identify specific components responsible for addiction and carcinogenic properties. This study found that high molecular weight compounds in areca inhibit nicotinic acetylcholine receptors and other neurotransmitter receptors, while low molecular weight areca extract activates GABA and glutamate receptors. Additionally, areca contains dopamine and serotonin transporter blocking activity, which may explain its reported stimulant and antidepressant effects.