A prospective observational study assessed the effectiveness of adjuvant nabilone (Cesamet) therapy in managing pain and symptoms experienced by advanced cancer patients. The primary outcomes were the differences between treated and untreated patients at 30 days' follow-up, in Edmonton Symptom Assessment System (ESAS) pain scores, and in total morphine-sulfate-equivalent (MSE) use after adjusting for baseline discrepancies using the propensity-score method. Secondary outcomes included other ESAS parameters and frequency of other drug use. Data from 112 patients (47 treated, 65 untreated) met criteria for analyses.The propensity-adjusted pain scores and total MSE use in nabilone-treated patients were significantly lower than were those found in untreated patients (both P < 0.0001). Other ESAS parameters that improved significantly in patients receiving nabilone were nausea (P < 0.0001), anxiety (P = 0.0284) and overall distress (total ESAS score; P = 0.0208). The nabilone group showed borderline improvement in appetite (P = 0.0516). When compared with those not taking nabilone, patients using this cannabinoid had a lower rate of starting nonsteroidal anti-inflammatory agents, tricyclic antidepressants, gabapentin, dexamethasone, metoclopramide, and ondansetron and a greater tendency to discontinue these drugs.