Nicotine Effects and Abuse Potential of Electronic Cigarettes

Compared to cigarette smoke, electronic cigarettes emit fewer toxins and, as their usage is lower than smoking, they have a role in reducing tobacco harm. A key issue in public health is that new tobacco and nicotine products should not be more addictive than cigarettes. To assess their abuse potential, we identified two electronic cigarettes along with the traditional cigarette substitute therapy (nicotine inhaler).

In a randomized, controlled, open-label, crossover study, healthy adult smokers were asked to use different research products for five minutes during each of four study periods. Subjective effects were evaluated using questionnaires on product liking, overall intent to use again, craving for the product, and urge to smoke. Maximum plasma nicotine levels were highest with combustible tobacco (22.7 ng/mL) compared to THP (8.6 and 10.5 ng/mL) and NRT (2.3 ng/mL). Median T max was significantly longer for NRT (15.03 minutes) compared to combustible tobacco (4.05-6.03 minutes). Overall product liking and intent to use again were highest for combustible tobacco, followed by THP and then NRT. Combustible tobacco was more effective at reducing smoking urge compared to the other three products. Use of THP resulted in greater urge to smoke compared to NRT. These findings suggest that the potential for abuse of e-cigarettes lies between that of the participants' preferred brand of combustible tobacco and NRT.

Nicotine is a naturally occurring chemical in tobacco leaves that is transferred to cigarette smoke during the burning process, primarily responsible for the addictive properties of smoking. However, it is believed that nicotine does not have a significant impact on smoking-related illnesses, which is typically due to the inhalation of tobacco smoke containing thousands of chemicals and numerous toxic substances. When a smoker inhales cigarette smoke, nicotine quickly enters the bloodstream and is delivered throughout the body; in the brain, it activates nicotine receptors associated with emotions and relaxation, which, along with the sensory aspects of smoking, leads to pleasurable and beneficial effects for the smoker.

Nicotine replacement therapy (NRT) and other medicinal nicotine products aim to replace the nicotine provided by traditional cigarettes, helping individuals quit by reducing cravings, withdrawal symptoms, and emotional changes. However, generally speaking, the delivery of nicotine in NRT products is relatively slow, and the pharmacokinetics (PK) curve differs from smoking. The time to reach the maximum plasma nicotine concentration (Tmax) is often longer, and the characteristic of the maximum nicotine concentration (Cmax) is not the same as smoking. Therefore, smokers' nicotine levels or satisfaction with NRT products are different from when they smoke.

A recent review of over 100 trials has found that NRT (nicotine replacement therapy) can increase the success rate of smokers trying to quit by 50-60%. However, this does not work for all smokers, possibly due to slow efficacy and reduced sensory defects of nicotine compared to smoking, as well as the inability to replace the behavioral activity of smoking. It is worth noting that NRT is considered a medical product, while tobacco heating and other non-combustible products are still considered consumer products and not approved for smoking cessation. Therefore, it is important to supplement existing smoking cessation measures with strategies aimed at reducing or preventing harm to those who would otherwise continue smoking.

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