Phytocannabinoids in neurologic, neuropsychiatric, inflammatory, pain, cardiometabolic, hepatic, renal, and neoplastic disorders: Pharmacology, clinical evidence, and translational perspectives

Phytocannabinoids are pharmacologically diverse constituents of Cannabis sativa whose actions go beyond canonical cannabinoid receptors. Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are best characterized, while cannabigerol, cannabidivarin, tetrahydrocannabivarin, cannabichromene, cannabinol, and related compounds are emerging candidates. This review integrates molecular pharmacology, pharmacokinetics, safety, and therapeutic evidence across neurologic, neuropsychiatric, inflammatory, pain, cardiovascular and metabolic, hepatic, renal, and neoplastic disorders. The strongest evidence supports pharmaceutical-grade oral CBD as adjunctive therapy for seizures associated with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex, and standardized THC-CBD formulations for selected patients with multiple sclerosis-associated spasticity. Emerging clinical signals in schizophrenia, pain, fibromyalgia, sleep disturbance, substance-use disorders, dermatologic conditions, sickle cell disease, and other symptom-focused indications support continued development. However, efficacy remains compound-, formulation-, exposure-, and indication-specific. In oncology, supportive-care applications must remain distinct from tumor-directed treatment, for which clinical efficacy has not been established. Preclinical studies show coherent effects on neuronal excitability, glial and immune activation, endothelial dysfunction, oxidative and nitrative stress, mitochondrial injury, fibrosis, and regulated cell death. These findings support further investigation in neurodegeneration, ischemia-reperfusion injury, diabetic cardiovascular disease, immune-mediated disorders, hepatic and renal injury, and selected cancers. Translation is constrained by product heterogeneity, variable exposure, uncertain target engagement, model differences, drug interactions, and underpowered trials. Standardized products, exposure-informed dosing, pharmacodynamic biomarkers, responder-enriched designs, and indication-specific randomized studies can address these barriers. Phytocannabinoids therefore represent a promising therapeutic platform whose potential will be best realized by matching defined compounds and formulations to biologically coherent diseases, mechanisms, treatment windows, and patient populations.