Smoking is still the leading cause of preventable death in the U.S. Doctors may soon have new tools to help people quit

James Davis, MD, has worked with thousands of patients who have struggled with tobacco addiction. Many of them have been able to quit alcohol, methamphetamines, cocaine, and even opioids, but they are unable to quit smoking cigarettes.

"Tobacco addiction is an incredibly difficult addiction for people to overcome," says Davis, the medical director for the Duke Center for Smoking Cessation at Duke University School of Medicine in Durham, North Carolina. "For people who smoke, their lives are full of smoking triggers. As they go about their daily routine, they may encounter a smoking trigger every 10 to 15 minutes."

In 1965, 42% of U.S. adults smoked cigarettes, but as of 2022 that percentage had fallen to 11.6%, according to the Centers for Disease Control and Prevention (CDC).

Even so, smoking remains the leading cause of preventable death in the United States. CDC data show that smoking causes more than 480,000 deaths annually, with an estimated 41,000 deaths from secondhand smoke exposure, and it can reduce a person's life expectancy by 10 years.

It also creates a significant economic burden. In 2018, smoking had an estimated economic impact of $600 billion, including more than $240 billion in health care spending.

The negative impacts of smoking are widely known, and CDC surveys have shown that most smokers want to quit.

So, why is it so hard to finally put an end to smoking?

"There are certain genes that make it harder to quit smoking, and all sorts of social and psychological factors," says Jamie Hartmann-Boyce, PhD, a smoking cessation researcher and assistant professor of health policy and management at the University of Massachusetts Amherst School of Public Health and Health Sciences. "I wish that people knew that smoking is still a problem. Smoking rates have absolutely gone down, but they've not gone down evenly. … Some populations bear a disproportionate burden."

People with less than a high school diploma, those with low incomes, and those who experience mental illness are among the groups statistically more likely to smoke, according to CDC data.

In 2022, 67.7% of current smokers reported wanting to quit, and 53.3% said they had tried to quit in the past year, but only 8.8% of adults who smoked quit successfully.

In an October 2024 article for the Annals of Internal Medicine, the U.S. Food and Drug Administration (FDA) and the National Institutes of Health (NIH) called for engagement from clinicians, academic medicine researchers, public health workers, and industry stakeholders to advance innovative approaches to smoking cessation.

The FDA has approved several products and medications to aid in smoking cessation, but less than 40% of smokers who tried to quit in 2022 used evidence-based treatments.

That's why experts are calling for a twofold approach: further engaging smokers to use existing therapies and, at the same time, pushing for new and innovative treatments for the future.

"Twenty years ago the goal was essentially a [nicotine] patch and a pep talk," Davis says. "Now the goal has changed. We recognize that most people who are smoking want to quit and are making multiple attempts to quit. As providers, the direction we need to go is to provide more effective treatment. This includes more sophisticated use of medications and more intensive and more individualized behavioral treatment."

Resources for smoking cessation:

• Quitline: 800-784-8669
• CDC "Tips from Former Smokers"
• CDC's Clinical Cessation Tools

Working with biology

The main reason tobacco is so addictive is because it contains nicotine, a chemical found in the tobacco plant that triggers the release of endorphins and dopamine (the "feel-good" hormone) in the brain. Nicotine itself, like caffeine, has only a few negative side effects apart from a detrimental impact on developing fetuses and adolescent brains. But smoking is a highly engineered and efficient way to deliver its effects, and cigarettes contain thousands of other chemicals to improve flavor and enhance nicotine absorption, according to the NIH. Because of its quick impact on dopamine levels, it's easy for the brain to build up a tolerance, requiring higher and higher doses to create the same effect.

The impact of smoking on the body is almost all-encompassing. It damages blood vessels, increasing the risk for stroke, heart disease, and heart attack; it can reduce bone density and slow the healing of fractures; it impairs the immune system and increases inflammation; it increases the risk of gum disease; it can decrease fertility in men and women; it accelerates the aging process of the skin; it increases the risk for more than a dozen cancers; and it is the most common cause of lung diseases.

Because of how detrimental smoking is to the body, quitting at any age can have positive effects, says Hartmann-Boyce.

"A lot of people have to try to quit a lot of different ways," she says. "It's also worth noting that no matter how old you are, [quitting is] still going to benefit your health. Depending on how long you've been smoking, some of the damage may already have been done, but even if you've been smoking for decades, quitting will benefit your health almost immediately." The FDA reports that carbon monoxide levels, which can displace oxygen to vital organs, can drop back to normal in as soon as 12 hours after not smoking.

One method for helping with smoking cessation is nicotine-replacement therapy (NRT), which helps wean the dependence on nicotine without the harmful effects of smoking. The FDA has approved over-the-counter and prescription NRT in various forms, including a skin patch, gum, lozenges, nasal spray, and an inhaler. Studies have found that use of an NRT can improve a person's chance of quitting by 50 to 60%.

The CDC defines quitting as being abstinent from smoking for at least six months. Hartmann-Boyce says it's not unusual for people to relapse, even after abstaining for years, and cessation often takes multiple attempts.

The FDA has also approved two non-nicotine prescription medications to help with cessation: varenicline tartrate (known by the brand name Chantix) and bupropion hydrochloride (an antidepressant). Varenicline works by binding to dopamine receptors and blocking the positive effects of nicotine, thus reducing the pleasure and cravings of smoking.

While varenicline is effective, it can also come with side effects, including nausea, insomnia, and mood changes, Davis explains. He is hopeful that cytisinicline, a plant-derived medication that's currently used in some European countries and is now going through the FDA approval process, could be even more helpful.

"We are expecting that cytisinicline will have similar treatment effects as varenicline has - making smoking less satisfying - but will be much better tolerated, "Davis says. "That's going to be very exciting."

E-cigarettes: Harm reduction or swapping addictions?

One area that remains controversial among smoking cessation experts is the use of e-cigarettes, or vaping, as a method for quitting.

A Cochrane review of 88 studies published in January 2024 concluded that the evidence supports the use of e-cigarettes with nicotine as an effective tool for smoking cessation, translating to about four additional quitters per 100 smokers, when compared with traditional nicotine-replacement therapies.

"Addiction is not simply chemical. It's linked to social cues," says Hartmann-Boyce, who was the senior author on the review. "The reason we think [e-cigarettes] may be more effective is precisely because of the behavioral and psychosocial aspects."

But some experts worry that not enough is known about the harmful effects of e-cigarette usage to recommend it as a smoking replacement.

The aerosols used in e-cigarettes are known to contain cancer-causing chemicals, heavy metals, and tiny particles that can be harmful to the lungs, according to the CDC. There are no e-cigarettes approved by the FDA for cessation.

Furthermore, the use of commercially available e-cigarettes without medical or clinical trial supervision could have different effects on tobacco cessation than what is seen in clinical trials. Participants in clinical trials are encouraged to completely switch from cigarettes to e-cigarettes to minimize dual use, which has been shown to be harmful and may make it harder to quit tobacco use, says Maya Vijayaraghavan, MD, a professor in the Department of Medicine at the University of California San Francisco (UCSF) School of Medicine and the director of the UCSF Smoking Cessation Leadership Center.

"We don't know the safety profile and long-term health effects of e-cigarettes," she says. "It makes me hesitant to say I'd recommend buying an e-cigarette as a cessation aid now."

Instead, she recommends that people try FDA-approved aids first. If they want to try e-cigarettes for cessation, then she recommends completely switching to e-cigarettes and setting an e-cigarette cessation date to minimize prolonged use of e-cigarettes.

Another concern about e-cigarettes is their potential to entice nonsmokers, particularly adolescents, into addiction. There's evidence that nicotine can harm brain development in young people, and nearly 90% of current smokers started smoking before age 18.

But public health efforts and the FDA's crackdown on manufacturers and retailers selling illegal e-cigarettes seem to be working, as teen use of e-cigarettes hit a 10-year low in 2024, the Associated Press reported.

While emphasizing that e-cigarettes are not harmless for nonsmokers, the FDA and NIH recognize they could be a form of harm reduction and have called for more clinical trials into the safety and effectiveness of e-cigarettes as an aid in smoking cessation.

"Most experts now agree that e-cigarettes are less harmful than cigarettes," Davis says. "But cigarettes kill half the people who smoke them. It's a little like saying that e-cigarettes are less harmful than being hit in the head by a bowling ball - it's not saying much. Whenever possible, we want to help patients get off all forms of nicotine, e-cigarettes included."

An adaptive approach

The FDA and NIH have also called for more research into the repurposing of existing medications for smoking cessation. For example, some studies suggest that GLP-1 receptor agonists, which are currently prescribed for diabetes and weight loss (under the brand names Ozempic and Wegovy, respectively), have some effectiveness in aiding in smoking cessation. The agencies have also encouraged researchers to explore various endpoints, including reduction of smoking that may lead to future cessation.

In the meantime, evidence suggests that the most effective way to quit smoking is through a combination of medication and behavioral counseling.

Davis hopes to take the efforts a step further with an approach called adaptive pharmacotherapy - when a clinician checks in with their patient and then makes adjustments to the patient's medications based on a patient's response. "That's what doctors and medical providers do with everything, but smoking cessation hasn't been that way," he says. He led a clinical trial that found that adaptive pharmacotherapy, combined with behavioral counseling, improved chances of cessation compared with standard medication treatment.

Vijayaraghavan also emphasizes the need for cessation strategies to be tailored to the patient. Her research focuses on smoking cessation among populations that have disparately high smoking rates, including people experiencing homelessness, substance use disorders, and mental health conditions. Other groups that have disproportionately high smoking rates are those experiencing incarceration; American Indians and Alaska Natives; African Americans; and people who identify as LGBTQ.

For many of these people, there are barriers to accessing medication and counseling to help with cessation. And for some of these populations, culturally tailored approaches may be necessary. This calls for a more proactive public health approach, she says - for example, working with community pharmacies to deliver NRT and other cessation medications to homeless shelters. Other methods include engaging peer support, providing contingency management (offering incentives for cessation behaviors), working with patients over longer periods, and integrating approaches that address stress and overall wellbeing.

Researchers at the University of Wisconsin-Madison's Center for Tobacco Research and Intervention piloted an effort in 2017-2020 to reach out to patients of a hospital system who were known to be smokers based on their electronic health records. Tobacco-cessation outreach specialists made repeated calls to smokers to help connect them with evidence-based resources and encourage them to set a quit date. This proactive approach reached people who are less likely to receive cessation counseling and increased participation in quitting efforts among African American and Hispanic patients, according to the researchers. The study, which included six clinics in Madison, Wisconsin, and involved about 7,000 people, found that quit rates more than doubled, from 2.1% to 4.4%, in 15 months with the program.

Regardless of a patient's life circumstances, evidence suggests health care providers can play a major role in successful smoking cessation. The 2020 U.S. surgeon general's report on smoking cessation offers interventions that health care providers can use to build smoking cessation counseling into routine interactions with patients, whether in a primary care setting or during hospitalization.

"Health care professionals play a critical role in helping people to stop using tobacco products. They can provide trusted advice, connection to treatment, and encouragement," says Brenna VanFrank, MD, MSPH, senior medical officer in the CDC's Office on Smoking and Health. "Stopping tobacco use is hard, and it can take several tries before [there is] long-term success, but every quit attempt is another step closer to being tobacco-free. Health care professionals can support each step of that journey."

For Vijayaraghavan, making the time to counsel patients on cessation - even if it takes years for them to succeed - is what makes her work meaningful.

"It's one of the most important things we can do for our patients," she says. "It's immensely rewarding."