A Meta-Narrative Review of Channelopathies and Cannabis: Mechanistic, Epidemiologic, and Forensic Insights into...

Although cannabinoids have proven therapeutic benefits, they are increasingly known for their capacity to disturb cardiac electrophysiology, particularly in individuals with hidden genetic issues such as channelopathies. This review consolidates molecular, clinical, epidemiological, and forensic findings linking cannabinoid exposure to arrhythmias and sudden cardiac death. It examines how phytocannabinoids, synthetic analogs, and endocannabinoids influence calcium and potassium currents through cannabinoid receptor-dependent and -independent pathways, affect autonomic regulation, and contribute to adverse conditions such as oxidative stress and inflammation in heart tissue. Genetic variants in key genes linked to SCD (SCN5A, KCNH2, KCNQ1, RYR2, and NOS1AP) can reduce repolarization reserve, transforming otherwise subclinical mutations into lethal substrates when combined with cannabinoid-induced electrical disruptions. Forensic research highlights the importance of comprehensive toxicological testing and postmortem genetic analysis in distinguishing between actual causes and incidental findings. There is an urgent need to re-evaluate the cardiovascular safety of cannabinoids, and this is underscored by the findings presented. The merging of molecular, clinical, and forensic evidence reveals that cannabinoid exposure-especially from high-potency synthetic analogs-can reveal latent channelopathies and precipitate fatal arrhythmias. Accordingly, this review advocates for a paradigm shift toward personalized risk stratification. If genetic screening is integrated with ECG surveillance and controlled cannabinoid dosing, risk assessment can be personalized. Ultimately, forensic and epidemiological data highlight the heart's vulnerability, emphasizing its role as a target of cannabinoid toxicity and as a crucial aspect of public health monitoring.