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Since e-cigarette technology emerged over two decades ago, nicotine vaping has presented a conundrum for public health. Commercial vaping devices are optimized to deliver nicotine in the most rewarding possible way, and by mixing it with flavors, it is possible to tailor its appeal to targeted consumers like youth, making transition from experimentation to escalation of use much more likely. There is evidence that initiation with vape products in adolescence can be a steppingstone to taking up smoking cigarettes and use of other drugs.¹

On the other hand, there is growing evidence that vaping does not present the worst health risks associated with combustible tobacco,² that it can facilitate smoking cessation, and that it is a safer alternative for smokers who can completely switch to these devices. While the US Preventive Services Task Force has determined that the evidence is currently insufficient to support recommending commercial e-cigarettes for smoking cessation,³ there is growing evidence from randomized controlled trials that electronic cigarettes are successful as smoking cessation aids, specifically when they are provided free as a therapeutic intervention.⁴ A Cochrane systematic review in 2024 suggested that nicotine e-cigarettes can help people stop smoking for at least six months and that they outperform nicotine replacement therapy (NRT).⁵ Switching from combustible cigarettes to e-cigarettes is also noted as an approach to reducing the harm associated with combusted tobacco use by the American Society of Addiction Medicine⁶ and the National Health Service of the UK recommends e-cigarettes as a quit aid.⁷

Although the FDA has authorized 39 e-cigarette devices to be sold and marketed as tobacco products to adults in the United States, no electronic cigarette has yet been approved as a smoking cessation therapeutic, and as of last year the FDA had received no applications seeking approval of such a product.⁸ Yet advancing the development of an FDA-approved e-cigarette for smoking cessation could more effectively harness their potential for reducing the public health burden associated with combustible tobacco. Bringing an e-cigarette therapeutic to market would provide assurance that they are safe and effective interventions. Having FDA approval could also facilitate reimbursement by health insurance payors, thus expanding access. Moreover, smoking cessation is such a high priority area for the FDA that applicants may be eligible for review under its expedited programs, making it a potentially attractive drug development pathway.⁹

Abstinence is currently the primary study endpoint accepted by the FDA in evaluating products for smoking cessation, and NIDA is funding research examining the impact of e-cigarettes on smoking cessation that could pave the way for their development and approval as therapeutics. Among them is a trial of e-cigarettes and heated tobacco products (which also produce less toxicants than cigarettes) versus medications like NRT in smokers who had previously failed to quit with traditional methods. NIDA is also funding several randomized clinical trials on the use of electronic cigarettes as quit aids for people in treatment for opioid use disorder and for people with other drug use disorders. Many people who are addicted to alcohol or other drugs also smoke cigarettes, and there is evidence that quitting smoking is associated with recovery from other substance use disorders.¹⁰

In addition to abstinence, reduced smoking may also be a valuable endpoint in smoking cessation trials if those reductions provide meaningful clinical benefits or increase the probability of eventual cessation. Additional research is needed to better understand how reduced smoking, including completely or partially switching to e-cigarettes, affects other health conditions, as well as how much of a reduction translates into health benefits. Such research could support the acceptance by FDA of reduced smoking or transition to e-cigarettes as an acceptable endpoint in smoking cessation clinical trials.

Since electronic cigarettes have only been commercially available since 2007, there are limited data on health impacts of their long-term use, and this is another area that merits investigation.¹¹ This is especially important if e-cigarettes are to be developed into therapeutics that people may use over the long-term. To that end, NIDA is funding research comparing the deposition, absorption, and accumulation of nicotine in the brain from e-cigarettes versus traditional cigarettes, as well as a study comparing nicotine and toxicant exposure and health biomarkers in people using a standard research e-cigarette versus people using both the electronic cigarette and traditional cigarettes. NIDA and other NIH Institutes are currently soliciting applications for projects that could contribute to tobacco regulatory science, including studies on the cardiovascular, pulmonary, neurodevelopmental and neuropsychiatric effects of e-cigarettes, their addictive potential, and their impact on tobacco product use behaviors.

Establishing safety and efficacy is central to the development of medications and other treatments. Few medications are without potential risks or harms at least for a subset of patients, but the dire outcomes of combustible tobacco use demand that we use everything in our toolkit to divert smokers to less harmful alternatives, if full cessation is unfeasible. Developing e-cigarettes as therapeutics could be one way to accomplish that.

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