Cannabis Co-Use and Endocannabinoid System Modulation in Tobacco Use Disorder: A Translational Systematic Review and...

Area of Science:

• Neuroscience
• Pharmacology
• Public Health

Background:

• Tobacco use disorder (TUD) is a major cause of preventable death, with current treatments showing limited long-term success.
• Expanding cannabis legalization coincides with increased concurrent tobacco and cannabis use, raising questions about their interaction in cessation.
• The endocannabinoid system's (ECS) role in TUD and the impact of cannabis co-use on cessation outcomes require clarification.

Purpose of the Study:

• To systematically review and meta-analyze the impact of concurrent cannabis use on tobacco cessation.
• To evaluate the preclinical and clinical evidence for endocannabinoid system (ECS) modulation as a tobacco cessation strategy.

Main Methods:

• A translational systematic review and meta-analysis adhering to PRISMA 2020 guidelines.
• Searched major databases (MEDLINE, Embase, PsycInfo, Web of Science) for studies on cannabis co-use and cessation, cannabinoid modulators, and ECS-targeted interventions.
• Included observational, preclinical, and human experimental studies; meta-analysis performed on eligible data.

Main Results:

• Observational studies (N=229,630) indicated cannabis co-use is associated with a 35% reduction in odds of tobacco cessation (OR=0.65).
• Preclinical studies showed CB1 receptor antagonists reduced nicotine intake, while cannabidiol (CBD) decreased nicotine use and withdrawal symptoms.
• Clinical data suggest CBD reduced cigarette consumption by 40%, reversed cue-induced attentional bias, and alleviated withdrawal, unlike failed CB1 inverse agonists.

Conclusions:

• Naturalistic cannabis exposure negatively impacts tobacco cessation success.
• Targeted ECS modulation, specifically with CBD, demonstrates therapeutic potential for smoking cessation.
• CBD warrants further investigation in adequately powered clinical trials for TUD treatment.