Smoking Cessation

Evidence-based pharmacotherapy and support for helping patients quit tobacco and nicotine

Key Points

• Tobacco use is the single most preventable cause of cancer — quitting at any age lowers cancer risk and improves outcomes, even after a cancer diagnosis.
• First-line pharmacotherapy has three pillars: nicotine replacement therapy (NRT), varenicline, and bupropion SR. Combining medication with behavioral support roughly doubles quit rates.
• Combination NRT — a long-acting patch for baseline cravings plus a fast-acting form (gum, lozenge, inhaler, or nasal spray) for breakthrough urges — outperforms any single NRT product.
• Varenicline is the most effective single agent; the FDA removed its neuropsychiatric boxed warning in 2016 after the EAGLES trial.
• Bupropion SR is the preferred option for patients with comorbid depression or concern about post-quit weight gain, but must be avoided in those with seizure or eating-disorder risk.
• Cytisinicline, an investigational partial nicotinic agonist already used for decades in Europe, could soon become the first novel-mechanism cessation drug in the U.S. in ~20 years, with a designation for vaping cessation.

Why Cessation Is Oncology's Highest-Value Intervention

Tobacco smoking causes about a third of all cancer deaths and is causally linked to at least 12 cancer types, including lung, head and neck, bladder, pancreatic, esophageal, and cervical cancer. Quitting is not only preventive — for patients already diagnosed with cancer, continued smoking worsens treatment tolerance, increases complications and second primary cancers, and shortens survival, while quitting improves outcomes. Cessation counseling therefore belongs in every oncology encounter, not just primary care. Nicotine dependence is a chronic, relapsing condition driven by α4β2 nicotinic…

Nicotine Replacement Therapies (NRTs)

NRTs ease the physical withdrawal symptoms of quitting by delivering controlled, therapeutic doses of Nicotine without the tar, carbon monoxide, and carcinogens of combustible tobacco. They come in over-the-counter (OTC) and prescription forms and are best understood by how quickly they act. The transdermal patch provides a steady, baseline nicotine level all day to curb chronic background cravings, while the faster forms — gum, lozenge, oral inhaler, and nasal spray — are used on demand to rescue acute breakthrough urges. The single most important practical point is that combining a…

Non-Nicotine Prescription Medications

Two oral, non-nicotine tablets act directly on central nervous system receptors to modify the addiction pathway. Varenicline (formerly branded Chantix, now generic) is a selective partial agonist at the α4β2 nicotinic acetylcholine receptors. It stimulates a mild release of dopamine to minimize withdrawal and cravings, while binding tightly enough to block inhaled nicotine from attaching to the same receptors — so if a patient slips and smokes, the usual rewarding sensation of the cigarette is effectively neutralized. It is the most effective single agent and can be combined with a nicotine…

Pipeline Spotlight: Cytisinicline

Cytisinicline (cytisine) is an investigational plant-derived alkaloid that shares a nearly identical mechanism with varenicline as a partial nicotinic receptor agonist, and it has been used for smoking cessation in Europe for decades. The drug recently completed large-scale Phase 3 U.S. trials — the ORCA-2 and ORCA-3 studies — demonstrating significantly higher continuous abstinence rates than placebo alongside a favorable gastrointestinal tolerability profile. Following a June 2026 FDA Complete Response Letter that cited third-party manufacturing facility issues rather than any clinical…

Behavioral Support, Programs & Advocacy

Medication works best alongside structured behavioral support. Free, evidence-based programs are widely available — from 12-step peer fellowships and the American Lung Association's Freedom From Smoking® program to digital communities and the national quitline network (1-800-QUIT-NOW), many of which also distribute free nicotine replacement therapy. National foundations fund the research, prevention campaigns, and policy work that underpin these services. Use the links below to connect patients with cessation support groups and to explore the foundations leading tobacco control and prevention.