Nicotine and the young brain

WHAT IS NICOTINE?

Nicotine is highly addictive and found in cigarettes, e-cigarettes, and other tobacco products. When users inhale or otherwise use nicotine-containing products, the addictive drug makes its way quickly to the brain where it drives the release of dopamine, a chemical that signals pleasure and keeps users addicted to nicotine. In young people, 5 mg of nicotine a day is enough to establish a nicotine addiction – about the amount of nicotine in one-quarter of an e-cigarette pod.

Tobacco products have traditionally contained nicotine that is extracted from tobacco leaves. Recently, more products are claiming to contain synthetic nicotine that was created in a lab. Newer methods of making synthetic nicotine can produce and isolate the more potent version of nicotine found in tobacco leaves at lower costs, leading to a surplus of new nicotine-containing products like Puff Bar and oral nicotine Bidi Pouches that claim to be “tobacco-free” even though they still contain the addictive chemical nicotine.

HOW DOES NICOTINE AFFECT YOUNG BRAINS?

Nicotine is harmful to developing brains and its use during adolescence can disrupt the formation of brain circuits that control attention, learning, and susceptibility to addiction. Research has shown early age of smoking and pleasurable initial experiences are correlated with daily use and lifetime nicotine dependence. Here’s what we know about how nicotine exposure in its many forms can adversely affect adolescents:

• Exposure to nicotine among youth is particularly dangerous since it affects key brain receptors, making young people more susceptible to nicotine addiction.
• Studies have shown that young people who have never smoked previously and began using e-cigarettes are more likely to smoke cigarettes in the future. One study found that nicotine naïve youth and young adults who had ever used e-cigarettes had seven times higher odds of becoming smokers one year later compared with those who had never vaped.
• Vaping is significantly associated with higher levels of ADHD symptoms, based on a 2019 study of college students.
• Studies have shown that vaping nicotine can intensify symptoms of depression and anxiety and increase stress levels. Current e-cigarette users have double the odds of also having a diagnosis of depression compared to those who have never vaped, according to a 2019 cross-sectional study, published in JAMA, of nearly 30,000 current e-cigarette users. Frequent vaping is tied to even higher odds (2.4X) of having a diagnosis of depression compared to never users. (See our report “Colliding Crises: Youth Mental Health and Nicotine Use” for more details.)
• Nicotine use — whether through smoking or vaping — can increase stress levels. (See our report on “Nicotine Use and Stress” and the myth of nicotine as a stress-reliever.

HOW IS NICOTINE REGULATED IN THE U.S.?

The FDA regulates all nicotine products. Products containing tobacco or nicotine, regardless of its source (either tobacco-derived or synthetic), must be authorized by the Center for Tobacco Products. Cessation products such as nicotine replacement therapies (NRT) that are expressly for cessation or otherwise make therapeutic claims must be authorized by the Center for Drug Evaluation and Research approval process for safety and effectiveness.

Until recently, many e-cigarette makers used synthetic nicotine to try to skirt regulation by the FDA. For example, Puff Bar, a top vape brand among youth, was told by the FDA in July 2020 to stop selling their flavored, tobacco-derived e-cigarette products. In March 2021, the company returned to the market claiming their product had been reformulated with synthetic “tobacco-free nicotine.” A new law granting FDA authority over synthetic nicotine products has since gone into effect. The new law ensures that any nicotine-containing product, regardless of the nicotine’s origin, is regulated in a consistent way, and closes the loophole that e-cigarette manufacturers were exploiting to keep addictive, youth-appealing nicotine products on the market.

More research is needed on the health effects of synthetic nicotine.

IS THERE A CAP ON NICOTINE LEVELS?

There is no limit on nicotine levels in the U.S. in e-cigarettes or cigarettes. Popular e-cigarettes contain increasing levels of nicotine and many times match or exceed nicotine levels in cigarettes. A 2019 study found that the average nicotine concentration in e-cigarettes more than doubled from 2.1% in 2013 to 4.34% in 2018. Puff Bar, an e-cigarette brand popular with young people, can have nicotine levels as high as 5%, more than double the highest nicotine concentration allowed in the European Union, the United Kingdom, and Canada — 2%. When the flavored e-cigarette JUUL debuted, it came in concentrations of 5% (or 59 mg/ml) nicotine, with its pods containing 20 cigarettes worth of nicotine. Other e-cigarette competitors claim to have 6-7% nicotine.

The amount of nicotine delivered by tobacco products depends on other factors in addition to nicotine levels, such as the use of nicotine salts, other ingredients, and device features like voltage:

• Modern e-cigarettes rely on nicotine salts to ensure that they deliver a high level of nicotine that can be inhaled more easily and with less irritation than the free-base nicotine that has traditionally been used in tobacco products, including e-cigarettes. Puff Bar, JUUL, Vuse and most other popular e-cigarette brands use nicotine salts.
• The maker of JUUL claims its nicotine salt formulation increases the rate and amount of nicotine delivered into the blood, compared with other formulations. The company has claimed the product delivers nicotine up to 2.7 times faster than other e-cigarettes.
• Increasing efficiency in nicotine delivery isn’t limited to e-cigarettes. Tobacco manufacturers adjusted their cigarette design so that the nicotine delivered to smokers increased by 14.5% between 1999 and 2011.

Higher nicotine levels are important because they contribute to greater nicotine addiction. Young people who vaped fruit-, menthol-, and mint-flavored e-cigarettes with higher nicotine concentrations had greater nicotine dependence compared to those who used e-cigarettes with lower nicotine levels, according to a Truth Initiative study published in Substance Use and Misuse. In the Preamble to the propsed rule, FDA presented evidence that the interaction of menthol and nicotine in the brain enhances nicotine addiction, particularly among young people, resulting in increased nicotine dependence and making it more difficult for users to stop using such products.

QUITTING NICOTINE

Tapping into supports like medication and counseling to help quit smoking can triple a smoker’s chance of quitting. Nicotine replacement therapy (NRT) aims to replace nicotine from cigarettes in smokers who are attempting to quit and suffering from nicotine withdrawal symptoms. The FDA has approved NRT gum, inhalers, lozenges, nasal sprays, and patches, as well as the medications varenicline (Chantix) and bupropion for use in quitting tobacco. These medications have been demonstrated to improve quit rates by 50 to 70%.

There are substantial research gaps in proving the effectiveness of e-cigarettes as quit smoking aids. The 2020 Surgeon General’s Report on smoking cessation found that there is “inadequate evidence” to conclude that e-cigarettes increase smoking cessation. Similarly, the 2018 National Academies report found limited evidence on the effectiveness of e-cigarettes to promote quitting. E-cigarettes are also not approved as quit aids by the FDA or the U.S. Preventative Service Task Force. A 2019 study by the U.K. National Health Service and published in the New England Journal of Medicine did find, however, that e-cigarettes may help adults quit, if they have the right support. A group assigned to e-cigarettes as a combustible tobacco replacement were more likely to remain abstinent one year later compared with a group using nicotine replacement products (18% vs. 9.9%). However, a majority of e-cigarette users were still using e-cigarettes at the one-year follow-up. Study participants were actively seeking to quit smoking and received at least four weeks of behavioral support. No similar study has replicated these results in the U.S.

More research is needed to determine whether e-cigarettes are appropriate for tobacco cessation. [See “E-cigarettes: Facts, Stats, and Regulations” and “What you need to know to quit smoking” for more information.]

RESOURCES FOR QUITTING

Truth Initiative has resources for young people and adults to support quitting nicotine.