The present study investigated the potential efficacy of buspirone for treating marijuana dependence. Participants received either buspirone (maximum 60mg/day) (n=23) or matching placebo (n=27) for 12 weeks, each in conjunction with motivational interviewing. In the modified intention-to-treat analysis, the percentage of negative UDS results in the buspirone-treatment group was 18 percentage points higher than the placebo-treatment group (95% CI: -2% to 37%, p=0.071). On self-report, participants receiving buspirone reported not using marijuana 45.2% of days and participants receiving placebo reported not using 51.4% of days (p=0.55). An analysis of participants that completed the 12-week trial showed a significant difference in the percentage negative UDS (95% CI: 7-63%, p=0.014) and a trend for participants randomized to the buspirone-treatment group who completed treatment to achieve the first negative UDS result sooner than those participants treated with placebo (p=0.054). Further study with buspirone in this population may be warranted; however, strategies to enhance study retention and improve outcome measurement should be considered in future trials.