Vaping and the Brain: Effects of Electronic Cigarettes and E-Liquid Substances

E-cigarettes (ECs), also known as vape pens, e-cigars, vaping devices, e-hookahs, mods, vapes, tank systems, electronic nicotine delivery systems (ENDS), and puff bars (fourth-generation ECs), are battery-operated electronic devices used to inhale a heat-generated aerosol from an e-liquid source (2, 5, 11). E-liquids contain basic ingredients, including water, propylene glycol, glycerol, optional nicotine (available at various concentrations), and flavoring agents (e.g., chocolate, cotton candy, and green apple) (4). E-liquids in disposable puff bars contain over 120 different substances, including cytotoxic chemicals (2). Refill solutions, e-liquid cartridges, and emission vapors (i.e., aerosol mix of small particles in the air) contain many other substances and hazardous chemicals, including solvents, volatile organic compounds (e.g., benzene and formaldehyde), acrolein, acids, and synthetic coolants (2, 4, 8, 11–14). ECs can also be used to deliver marijuana. Using ECs is commonly known as “vaping” (15) (Figure 1).

ECs have several components, including a cartridge or “pod,” where the liquid solution containing nicotine, flavoring substances, and other chemicals is vaporized upon activation of an electronic heating element in the device that is triggered by inhalation (5). The heating element is powered by a rechargeable lithium battery (15). The consumer can choose the nicotine concentration of the e-liquid that is loaded into the EC cartridge (5) (Figure 1). The technology of pod mods allows manufacturers to combine acid mixtures and other dangerous chemicals with nicotine salts or crystals to elevate the nicotine concentrations of their products (2, 3). This design allows delivery of higher drug doses via relatively inconspicuous devices with reduced electrical power that closely resemble electronic USB drives (2, 3, 16, 17). Popular pods contain approximately 59.2–66.7 mg/mL of nicotine, which is comparable to one pack of 20 conventional cigarettes (3, 15, 18). Once the cartridge or pod is installed in the EC device, the user then inhales the vaporized products of the e-liquid into the lungs, and the residues are exhaled into the air (5, 15).

It has been suggested, incorrectly, that ECs are less harmful than conventional cigarettes (19). ECs are promoted as containing fewer chemicals, having lower levels of carcinogens, and producing fewer toxic agents than conventional cigarettes (19, 20). However, they are not emission-free devices, and their aerosol emissions are not harmless (5, 6, 11, 20). Bystanders to exhaled vaping fumes can be exposed to toxic aerosols and carcinogenic agents (e.g., acrolein, benzene, diacetyl, and formaldehyde) through second-hand or third-hand exposure (6, 11, 21). Elements from second-hand EC vapor increase particulate matter in the air, which can be harmful and lead to preclinical forms of cardiovascular, pulmonary, and other diseases (6, 7, 11, 22, 23). Third-hand exposure (through residual chemicals left on surfaces, skin, hair, and clothing following vaping) plays a role in the overall exposure of children to nicotine and a variety of toxicants (24, 25).

Vaping causes serious damage throughout the human body, including organs in the cardiovascular, central nervous, immunological, and respiratory systems. This damage is primarily due to the deleterious effects of toxic compounds that exacerbate oxidative stress responses and inflammatory reactions, causing endothelial dysfunction, cellular senescence, and subsequent disease sequelae (2, 6–10) (Figure 2). The nicotine and nonnicotinic agents in ECs, including hazardous neurotoxic elements (i.e., aluminum, arsenic, chromium, cadmium, copper, lead, manganese, nickel, tin, and zinc) and other by-products, pose serious threats to the brain (8, 13, 26, 27). To date, only a few studies have investigated the effects of these compounds on neurological function, mostly in animal models (8, 28).

According to the Centers for Disease Control and Prevention, ECs “have the potential to benefit adults who smoke and who are not pregnant if used as a complete substitute for regular cigarettes and other smoked tobacco products” (29). However, use of ECs may increase the risk of future cigarette smoking among adolescents and young adults (30). The use of any form of tobacco product (smoked, smokeless, or electronic) by youths is considered unsafe (15). The U.S. Surgeon General has concluded that exposure to nicotine during adolescence can cause addiction and impair the developing adolescent brain (11).

The use of ECs has skyrocketed among U.S. adolescents and young adults since 2014 (31, 32). In 2018, usage increased 77.8% over the previous year, the largest surge of youth tobacco consumption ever recorded by the Centers for Disease Control and Prevention (33). Most adolescents and young adult users do not know that ECs may contain higher concentrations of nicotine than conventional cigarettes (15, 34). Similar trends have been reported among youth in countries outside the United States (35–38). However, the United States dominates the global vaping market. By 2022, over 2.6 million young Americans reported current use of ECs (39). Global market research reports indicated that ECs generated $22.45 billion in U.S. dollars in 2022 and a compounded annual growth of 30.6% was projected from 2023 to 2030 (40).

The increased popularity and use of ECs seems to be linked (in part) to novelty and the alluring flavors of various e-liquid options (41). The flavoring chemicals and additives of ECs are largely unregulated (8, 14, 21). In 2020, the Food and Drug Administration enacted a ban on flavored EC pods in an effort to reduce accelerated use among young consumers (42). A technicality in the ban, which did not include “disposable products” (i.e., puffs ECs), has allowed young consumers and suppliers to keep these devices in high demand (2, 43, 44). At present, several thousand flavoring options and hundreds of brands are available (14, 26). However, the explosion in EC use also suggests that users may be experiencing dependency to both smoking and vaping (12, 45).