UC Irvine

Cigarette smoking remains a leading cause of preventable disease and death worldwide. Due to the damaging effects of smoking, many users attempt to quit, but few are successful in the long-term. Thus, there is a critical need for novel therapeutic approaches. In these investigations, we sought to investigate whether cannabidiol (CBD) has the potential to be repurposed as a cessation therapeutic. In the first study, male and female C57BL/6J mice were trained to respond for intravenous nicotine infusions at either a low or moderate nicotine dose. Once stable responding was evidenced, mice were pretreated with CBD in a Latin square design. We found that both CBD produced significant changes in nicotine rewards earned and altered lever responding. In the second study, we examined mice behavioral responding for a grain-based food reward and found no significant effect of CBD on lever pressing behavior, thereby demonstrating the specificity of CBD in altering nicotine intake. In the third study, we investigated the potential effects of CBD in mitigating nicotine withdrawal symptoms, and we found that administration of CBD altered various aspects of nicotine withdrawal. Finally, we determined the efficacy of extended pretreatment of CBD over the course of peak bioavailability, mice were observed to produce significant changes in nicotine rewards earned. Together, these results indicate that modulation of cannabinoid signaling may be a viable therapeutic option for smoking cessation.