Cannabinoid therapeutics in the 21st century: from molecular mechanisms to equitable clinical integration

Cannabis sativa has a long history in ethnomedicine, but advances in molecular biology and regulatory shifts have reignited global interest in its therapeutic potential. Cannabinoid research in the 21st century spans molecular pharmacology, clinical applications, and public health integration. This study provides a comprehensive synthesis of the current state of knowledge. This narrative review synthesizes evidence from Scopus, PubMed, and Google Scholar using Medical Subject Headings-based search strategies. Only articles published in English were included, without restrictions on publication year; however, greater emphasis was placed on recent studies to ensure currency, while seminal and historically important publications were included where necessary to provide foundational context. Relevant studies were thematically analyzed and summarized under predefined headings. Major phytocannabinoids have been identified, with Δ9-tetrahydrocannabinol, cannabidiol, and cannabigerol as key therapeutic candidates. Preclinical studies have shown neuroprotective, anti-inflammatory, analgesic, immunomodulatory, and anticancer effects, but clinical translation remains limited by variability, dosing challenges, and inconsistent reproducibility. These effects are mediated through the endocannabinoid system and related receptor networks. Emerging evidence suggests that epigenetic regulation and precision medicine approaches may enhance individualized cannabinoid therapy. However, safety concerns, including cognitive and psychiatric effects, drug interactions, and dependence, require robust pharmacovigilance. Fragmented regulatory frameworks continue to hinder research and equitable access, underscoring the need for standardized formulations, clinician training, and equity-focused integration into health systems. Cannabinoid therapeutics represent a rapidly evolving field with promise in multiple medical domains. Future progress hinges on harmonizing regulations, expanding clinical evidence, and integrating precision medicine, equity, and public health principles to maximize therapeutic benefits while minimizing risks.