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Today in many Asian countries but especially in Pakistan, India and Bangladesh there is an excessive use of paan by men and women alike. Some people eat more then five paans a day. Despite the fact that all know that it is dangerous for health – since it causes cancer to the throat and mouth – it is still excessively used.

What is the active substance in paan that makes people addicted, despite the health risks?

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The traditional mixture of paan is a combination of products or substances.

Paan is most often prepared by using the betel nut (or Arcea nut), from the plant Areca catechu, chopped up and rolled into a portion using the leaves of the plant Piper betele, a plant from the pepper family. This can be further "enhanced" by adding tobacco, lime or any number of flavour or extraction amplifiers.

The main psychoactive ingredient of this preparation – of only betel nut and betel pepper leaf – then comes from the alkaloids found in the betel nut.

The strongest effects are found in the alkaloid arecoline. Its structure is similar to nicotine and it also acts similarly on acetylcholine receptors, which are found throughout the whole body. But arecoline is different in its actions compared to nicotine:

Arecoline is the primary active ingredient responsible for the central nervous system effects of the areca nut. Arecoline has been compared to nicotine; however, nicotine acts primarily on the nicotinic acetylcholine receptor. Arecoline is known to be a partial agonist of muscarinic acetylcholine M1, M2, M3 receptors and M4, which is believed to be the primary cause of its parasympathetic effects (such as pupillary constriction, bronchial constriction, etc.).

That means when used as a stimulant this combination is lends its spectrum of effects less to tobacco smoke but a bit more to the fly agaric side, while ebing substance wise very similar to nicotine in its addictiveness.

Using this stimulant habitually is indeed not advised. Not even advocates of "natural remedies" find much use for this:

Betel nut has been suggested as a treatment for many conditions. However, there is not enough scientific evidence to support the use of betel nut for any medical condition. Although betel nut is chewed recreationally, chewing or ingesting betel nut may cause many serious adverse effects, including cancer, effects on the heart and death. Betel nut should be avoided in pregnant or breast-feeding women and in children. Consult a health care professional immediately if you have any side effects.
Intellihealth, (Natural Standard and Harvard Medical School: Betel Nut (Areca catechu)

The leaf of the betel pepper has some effects on its own:

The medicinal components are primarily associated with the nut and betel quid. The nuts contain at least 9 structurally related pyridine alkaloids, including arecoline, arecaidine, arecaine, arecolidine, guvacine, isoguvacine, guvacoline, and coniine. However, the most common is the parasympathetic stimulant alkaloid arecoline. The total alkaloid content can reach 0.45%.
The methyl esters of arecoline and guvacoline are hydrolyzed in the presence of alkali to the respective acids, arecaidine and guvacine. The hydrolysis is catalyzed by lime, which is added to the quid. Arecoline most likely is present in the nut as a salt of tannic acid, and the lime facilitates the release of the base from the salt.
Components of the betel quid, most likely from P. betel and not betel nuts, contain about 1% of a volatile oil, chalbetol, chavicol, cadinene, allylpyrocatechol, and safrole.

CNS Effects Clinical data
Studies evaluating the effects of betel nut chewing suggest that a variety of the chemical compounds found in areca may exert activity. Arecoline demonstrates parasympathomimetic action on muscarinic and nicotinic receptors; arecaidine and guvacine act as gamma-aminobutyric acid uptake inhibitors, while phenolic compounds in the leaf stimulate the release of catecholamines. Electroencephalograph changes have been observed, with alpha and beta wave activity increased and theta decreased. Increases in plasma noradrenaline and adrenaline have been observed among betel nut chewers.

In 65 patients with schizophrenia, a decrease in positive symptoms as measured by the Positive and Negative Syndrome Scale was observed among men who were high-consumption betel nut chewers (more than 7.5 whole betel nuts/day). No significant relationships existed between betel chewing and positive or negative symptoms among women. The muscarinic cholinomimetic action of the alkaloids may be responsible for this effect, but a mechanism of action has not been determined.

Cardiovascular effects
Animal data Betel nuts contain a tannin with angiotensin-converting enzyme inhibitory activity in vitro. The activity of this tannin was shown to be comparable with captopril in an older experiment in rats.

Clinical data An acute cardiovascular response (hypertension and increased cardiac rate) to betel nut occurs in new chewers, but abates with chronic use. A review of this data and further study suggests this effect has a genetic dependency. A clinical application for this effect is unlikely considering the increased risk of cardiovascular disease associated with areca nut consumption.
drugs.com: Betel Nut

Also compare to: NS Chu: "Neurological aspects of areca and betel chewing", Addict Biol. 2002 Jan; Vol 7, No 1, p 111–4.

Adding to the purely biological aspects of paan chewing are some others factors that are affecting the addictiveness:

Medicinal Properties, Sign of Beauty, Availability at ceremonies, Cultural identifier, Peer pressure, Social acceptance
Kelle L Murphy &Thaddeus A Herzog: "Sociocultural Factors that Affect Chewing Behaviors among Betel Nut Chewers and Ex-Chewers on Guam", Hawaii J Med Public Health. 2015 Dec; 74(12): 406–411.

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