The human immunodeficiency virus (HIV) remains a major burden to the health care system and neuropathic pain is the most common neurological complication of HIV infection. Since current treatment strategies often lack satisfying pain relief, cannabinoids are discussed as a new option. We investigated cannabidivarin as treatment for HIV-associated neuropathic pain. We conducted a randomized, double-blind, placebo-controlled cross-over study. Patients underwent two successive treatment phases (4 weeks each) and were treated with cannabidivarin (400mg/d) or placebo in a randomized order. A 3-week wash-out phase was designed to eliminate potential carry-over effects. Patients were followed up for 3 weeks after the end of the second treatment phase. The primary endpoint was pain intensity on an 11-point numeric rating scale, recorded in a diary. Secondary endpoints were additional pain medication, pain characteristics and quality of life. We included 32 patients. The mean pain intensity under cannabidivarin was 0.62 points higher compared to placebo (p=0.16; 95% CI -0.27 to 1.51). Cannabidivarin did not influence the amount of additional pain medication, pain characteristics or quality of life. The incidence of adverse events was similar during both treatments. No suspected unexpected adverse reactions occurred during either treatment. Cannabidivarin was safe but failed to reduce neuropathic pain in HIV-patients. This may be explained by a lack of cannabinoid receptor activation, as indicated by preclinical experiments. Although a larger patient number might be desirable, we would not expect a change in the conclusions since the present differences are far from statistical significance. Therefore, we would currently not consider CBDV as a clinically meaningful treatment option for neuropathic pain.