Smokers with schizophrenia spectrum disorders have high rates of morbidity and mortality from smoking-related diseases compared with the general population and current options for smoking cessation in this vulnerable group are unsatisfactory. Considering that most people with schizophrenia spectrum disorders continue smoking, it is urgent to consider alternative and more efficient interventions to reduce or prevent their morbidity and mortality. Switching to combustion-free technologies for nicotine delivery (I.e. e-cigarettes) could be a pragmatic and much less harmful alternative to tobacco smoking with the possibility of significant health gains. Emerging research is suggesting that ECs may be useful for smoking cessation and relapse prevention in people with schizophrenia spectrum disorders. In particular, a study conducted with JUUL e-cigarette with 5% nicotine strength showed that this product had sufficient nicotine delivery and product appeal to determine high success rates in heavy smokers with schizophrenia spectrum disorders. In consideration of these preliminary findings, we hypothesized that switching smokers with a schizophrenia spectrum disorder diagnosis to JUUL e-cigarette with 5% nicotine strength could result in higher success rates compared to JUUL e-cigarette with 1.7% nicotine strength. Recent work indicates that nicotine PK of the JUUL e-cigarette with 5% nicotine strength (a device that utilizes a nicotine salt formulation) approximates the nicotine delivery of combustible cigarettes and that the 5% nicotine strength product is far more efficient in delivering nicotine compared to the sister product with 1.7% nicotine strength. Both products are identical in their appearance, making them suitable for a double-blind study design.