Cigarette smoking remains the leading cause of preventable disease and death in the United States, killing more than 480,000 Americans each year and costing over $600 billion annually in healthcare expenditures and lost productivity, according to a statement released on Mar. 13. Despite these harms, most people who smoke and try to quit are unsuccessful. In 2022, about 53 percent of adult smokers in the United States reported making a quit attempt, but fewer than 9 percent succeeded.
The need for new solutions is pressing as current treatments like nicotine replacement therapy (NRT), varenicline, and bupropion combined with behavioral counseling produce long-term success rates of only about 20 to 30 percent under ideal conditions. With two-thirds of current smokers wanting to quit, there is significant demand for innovative alternatives.
Recent research at Johns Hopkins University has examined whether psilocybin—the psychoactive compound found in “magic mushrooms”—could help people stop smoking. In a pilot randomized clinical trial, one group received a single high dose of psilocybin while another was given standard nicotine patches; both groups also received cognitive behavioral therapy for 13 weeks. At six months, 40.5 percent of participants in the psilocybin group showed prolonged abstinence compared to just 10 percent in the nicotine patch group. The study had limitations such as a small sample size and limited demographic diversity, but the National Institutes of Health has funded a larger follow-up trial.
Other emerging treatments include cytisinicline—a plant-derived partial agonist used for decades in Eastern Europe—which showed promising results in recent trials; transcranial magnetic stimulation (TMS), which earned clearance from the U.S. Food and Drug Administration after demonstrating higher short-term quit rates; digital therapeutics that use virtual reality and mobile apps; and GLP-1 receptor agonists like semaglutide that may reduce cravings while addressing weight gain concerns.
There is also growing interest in reduced-risk products such as e-cigarettes, heated tobacco products, snus, and nicotine pouches as tools for those unable to quit using traditional methods. A recent Cochrane review found high-certainty evidence that nicotine e-cigarettes increase quit rates compared to NRT. Sweden became the first country in Europe to achieve “smoke-free” status by making lower-risk alternatives accessible and affordable—resulting in daily smoking rates below five percent and the lowest smoking-related mortality rate in the European Union.
While concerns remain about youth uptake and dual use of reduced-risk products, experts say these options may offer pragmatic pathways away from combustible cigarettes for those who have not succeeded with approved therapies. The report concludes that “every person who smokes and wants to quit deserves access to the full spectrum of evidence-based options,” emphasizing compassion and pragmatism over ideology.
