Smoking Cessation
Sonya Collins
E-cigarettes have eclipsed cigarettes in their popularity among youth and young adults. In 2024, nearly 8% of high school students reported having vaped in the last 30 days. In 2023, one in four young adults aged 18 to 25 years had reached for an e-cigarette in the last month.
Most of these young people are vaping nicotine, and over half to three-quarters of them have never smoked cigarettes. They represent a new demographic of understudied nicotine users, and according to Eden Evins, MD, founding director for the Center for Addiction Medicine at Massachusetts General Hospital in Boston, they are desperate to quit.
“They’re indignant that they’re having cravings,” Evins said. “They can’t sit at their desk or in the library without having cravings. It’s usurping the independence of these emerging adults who have just gained their independence. They felt it wasn’t what they’d bargained for.”
In a recent randomized controlled clinical trial, led by Edins and published on April 23, 2025, in JAMA, varenicline plus behavioral counseling was five to 10 times more effective than placebo plus counseling or a quit line alone in helping young never-smokers quit vaping.
Varenicline in youth never-smokers
The three-group randomized trial enrolled 261 young people in Massachusetts aged 16 to 25 years who vaped nicotine 5 or more days per week, who were interested in quitting, had no history of regular tobacco smoking, showed nicotine dependence based on the E-cigarette Dependence Inventory and had a saliva cotinine level over 30 ng/mL.
Enrollees in the pharmacotherapy arm received 12 weeks of varenicline titrated to 1 mg twice daily over 7 days or identical-appearing placebo plus 12 weekly 20-minute behavioral counseling sessions with a lay counselor trained in cognitive behavioral therapy for youth vaping cessation. Youth in the control arm were referred to TIQ—This is Quitting—a text-based quit line for vaping sponsored by Truth Initiative.
During the last 3 weeks of treatment, 51% of the volunteers in the varenicline group had continuously abstained from vaping compared with 14% of those in the placebo group. At 6 months’ postintervention, 28% of those who’d received varenicline were still nicotine-free compared to 7% of those in the placebo group.
Over the course of the study, participants in the varenicline group rated the severity of their cravings and nicotine withdrawal lower on average than their peers in the placebo group. They also reported lower levels of distress. Adherence was better among varenicline users as well. They took 72% of the doses, while those in the placebo group took 65% of the doses.
A generation desperate to quit
This is the first trial of varenicline in people who vape only. Based on enrollment patterns for the trial, this group has been extremely eager to free themselves from the stronghold that nicotine has on them.
Trial organizers placed ads on buses and rapid transit trains to overwhelming interest. “We had to slow down recruitment three times so we could handle the volume of calls,” Evins said, “which says to me that there’s huge demand for this. They can’t get treatment anywhere. There really is no treatment.”
The enthusiasm of those who vape to join the trial speaks to the highly addictive nature of nicotine. More than a third of people who try nicotine become addicted to it. That’s more than alcohol, cocaine, and marijuana, and the same as heroin, Evins said.
“Hopefully, this study will influence the practice of primary care doctors, pediatricians, or pharmacists who are doing nicotine cessation,” Evins said. “Smoking is now concentrated to a very small population, but vaping is almost normative. It’s a different population, and hopefully it’ll be easier to help them quit.” ■