Relief from chronic pain has been a common reason cited by patients for the medical use of cannabis.1-3 A two-stage open label single arm study (n=30) assessed a single ascending dose (SAD; Stage 1) and multiple ascending doses (MAD; Stage 2) of a standardised and purified mixture of Δ9-Tetrahydrocannabinol (Δ9-THC)/Cannabidiol (CBD) in a water-soluble nanoparticle oro-buccal spray formulation for the management of intractable pain in people with advanced cancer. On day 1 Stage I participants received 2.5 mg Δ9THC and 2.5 mg CBD (two sprays); escalating to 7.5 mg Δ9-THC and 7.5 mg CBD (six sprays) on day 2. In Stage II, participants administered daily Δ9-THC/CBD as one spray containing 1.25 mg Δ9-THC and 1.25 mg CBD; two sprays; or three sprays every four hours unless asleep. Δ9-THC and CBD were rapidly absorbed. As single and multiple doses were increased, maximum observed plasma concentrations (Cmax) of all analytes were proportional to dose. The bioavailability of Δ9-THC and CBD in this water-soluble nanoparticle formulation was approximately twice the bioavailability reported for a Δ9-THC/CBD spray that uses ethanol as the vehicle. The water-soluble cannabis-based medicine resulted in a higher bioavailability of Δ9-THC than CBD (bioavailability from 2.5 mg each of Δ9-THC and CBD was 2.8 ng/mL.h and 1.5 h.mg/mL, respectively). In a subgroup of participants diagnosed with breast and prostate cancer with bone metastases, the mean pain scores improvement from baseline was approximately 40% (unadjusted) and 33% adjusted for rescue medication use. For all patients the most commonly reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively and nausea and vomiting that affected 18 (72%) patients. The water-soluble cannabis-based medicine provided adequate bioavailability for Δ9-THC and CBD, appears safe and tolerable in people with cancer and uncontrolled pain with preliminary evidence of analgesic efficacy.