Cannabinoids have been used for pain relief for centuries and recent studies have investigated their analgesic and anti-inflammatory mechanisms, as well as clinical efficacy, in treating chronic pain. We report an open-label study addressed to evaluate the effect and adverse events of orally administered Delta-9-tetrahydrocannabinol (Delta-9-THC) in 13 patients with chronic nonmalignant pain (CNMP) unresponsive to conventional pharmacotherapy. The effect of the treatment was assessed on an eight-item HRQoL questionnaire. Five out of 13 patients reported adequate response to the treatment while eight patients reported inadequate or no response. Seven patients did not experience any adverse events (AEs), six patients reported AEs, two of which discontinued the treatment. We conclude that oral THC may be a valuable therapeutic option for selected patients with CNMP that are unresponsive to previous treatments, though further research is warranted to characterize those patients.