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Antiepileptic drug; Cannabinoid; Epilepsy Fármaco antiepiléptico; Cannabinoide; Epilepsia Fàrmac antiepilèptic; Cannabinoide; Epilèpsia Objective: We assessed the efficacy, safety, and tolerability of cannabidivarin (CBDV) as add-on therapy in adults with inadequately controlled focal seizures. Materials and Methods: One hundred and sixty-two participants (CBDV n=81; placebo n=81) were enrolled. After a 4-week baseline, participants titrated from 400 to 800 mg CBDV twice daily (b.i.d.) (or placebo) over 2 weeks, followed by 6 weeks stable dosing (at 800 mg b.i.d.) and a 12-day taper period. The primary endpoint was the change from baseline in focal seizure frequency during the 8-week treatment period. Secondary endpoints included additional efficacy measures relating to seizures, physician- and participant-reported outcomes, change in the use of rescue medication, cognitive assessments, and safety. Results: Median baseline focal seizure frequencies were 17–18 per 28 days in both groups, and similar reductions in frequency were observed in the CBDV (40.5%) and placebo (37.7%) groups during the treatment period (treatment ratio [% reduction] CBDV/placebo: 0.95 [4.6]; confidence interval: 0.78–1.17 [−16.7 to 21.9]; p=0.648). There were no differences between the CBDV and placebo groups for any seizure subtype. There were no significant treatment differences between CBDV and placebo groups for any of the secondary efficacy outcome measures. Overall, 59 (72.8%) of participants in the CBDV group and 39 (48.1%) in the placebo group had ≥1 treatment-emergent adverse event (AE); the 3 most common were diarrhea, nausea, and somnolence. The incidence of serious AEs was low (3.7% in the CBDV group vs. 1.2% in the placebo group). There was little or no effect of CBDV on vital signs, physical examination, or electrocardiogram findings. Elevations in serum transaminases (alanine aminotransferase or aspartate aminotransferase) to levels >3×upper limit of normal occurred in three participants taking CBDV (two discontinued as a result) and one taking placebo; however, none met the criteria for potential Hy's Law cases. Conclusion: It is likely the 40.5% seizure reduction with CBDV represents an appropriate pharmacological response in this population with focal seizures. The placebo response was, however, high, which may reflect the participants' expectations of CBDV, and a treatment difference from placebo was not observed. CBDV was generally well tolerated. The trial was sponsored by GW Research Ltd.