Abstract
Public interest in cannabinoid medicines has outpaced the clinical pharmacology needed to judge product, dose and route. In the United States the only fully approved plant-derived cannabinoid is purified cannabidiol (CBD) oral solution (Epidiolex, United States; Epidyolex, EU), indicated for three rare epilepsies. Approval trials showed oral CBD can be titrated to effective concentrations, with a large food effect, established drug interactions and hepatic effects warranting scheduled monitoring. Preclinical work, including circuit-level studies, suggests anti-inflammatory effects on microglia and astrocytes at similar daily doses. This raises the possibility of testing CBD in unresolved chronic neuroinflammation, a glial-mediated driver of progression in early-onset dementias. Chronic neuroinflammation is failed resolution of an initial primary inflammatory response. Except where the blood-brain barrier is breached, it is largely independent of peripheral immunity. Single-target anti-inflammatories often fail for distinct reasons: many never reach adequate CNS concentrations; those that do may engage only one of many potentially redundant pathways; and suppression can block resolution as well as injury. Unlike Δ9-tetrahydrocannabinol (dronabinol), CBD is not an intoxicating CB1 agonist, but after systemic dosing it reaches the brain and can modulate inflammatory signaling through several systems. Evidence outside epilepsy is limited, partly because many small studies used uncharacterized products, unstandardized meals and no plasma concentrations. This narrative review is not a systematic survey. An interpretable next clinical trial needs one characterized CBD preparation, meal-standardized with oral dosing, pre-specified interaction and liver monitoring, a functional outcome that can change within months, and a co-signal such as blood GFAP.