199 Background: Dronabinol, a pharmaceutical tetrahydrocannabinol (THC), capsule is approved for anorexia associated with weight loss in patients with AIDS and for cancer chemotherapy-induced nausea/vomiting in patients with inadequate response to conventional antiemetic therapy. Food effects on absorption and bioavailability of a new dronabinol oral solution was compared with marketed capsules. Methods: In an open-label, single-dose, 3-period crossover study, healthy volunteers were randomized to receive dronabinol oral solution 4.25 mg (fed) or dronabinol capsule 5 mg (fed or fasted), after a 7-day washout period. Doses were administered under a fasted (overnight) or fed state (high-fat/calorie meal 30 minutes pre-dose). Plasma pharmacokinetics was evaluated for dronabinol and the major metabolite, 11-OH-Δ9-THC. Results: Pharmacokinetic data of 54 volunteers were analyzed. In the fed state, initial dronabinol absorption was rapid with oral solution versus capsules (mean Tlag, 0.15 vs 2.02 h), and 100% and 15% of volunteers receiving oral solution and capsules, respectively, had detectable plasma dronabinol levels 30 minutes post-dose. Inter-individual variability in plasma dronabinol concentrations during early absorption was less with oral dronabinol solution (%CV: 82.79%, 83.94%, and 90.68%) versus capsules (%CV: 318.54%, 250.33%, and 182.01%) observed at 0.5, 1, and 2 h, respectively, after dosing. Food increased mean AUC0-t similarly for dronabinol oral solution and capsules, versus capsules with fasting, increasing exposure to oral solution and capsules 2.1- to 2.4-fold. Mean Tmax was similarly delayed for dronabinol oral solution (7.7 h) and capsules (5.6 h) with food relative to fasting (1.7 h). On the basis of 11-OH-Δ9-THC plasma levels, AUC0-t up to 48 h postdose and AUC0-inf were found to be similar for the oral solution and capsules under fed conditions. Conclusions: An appreciable food effect was observed for dronabinol oral solution and capsules. Dronabinol oral solution may offer therapeutic benefit to patients given its rapid absorption and lower inter-individual variability compared with dronabinol capsules. Clinical trial information: NCT01448772.