Abstract Background People living with HIV (PWH) with undetectable HIV viral load still have an impaired health-related quality of life (HRQoL). Cannabidiol (CBD) is a non-intoxicating cannabis-derived cannabinoid that holds promise for the treatment of many ailments. In the present study, we tested whether oral CBD-rich medication could significantly improve PWH’s HRQoL. Methods Eighty participants with undetectable HIV viral load were randomized to either a placebo or full-spectrum CBD (1 mg/kg twice a day) arm for 12 weeks plus a 4-week follow-up period. HRQoL was assessed at baseline, week 12 and week 16 using the SF-36 questionnaire. Primary outcomes were physical and mental component...