Provided are a pharmaceutical composition and a method for reducing, preventing, or delaying the development of a biological condition associated with administration of an opioid drug, in particular, tolerance to and/or physical dependence on an opioid drug. The pharmaceutical composition includes an opioid drug, a ceramide biosynthesis inhibitor and a pharmaceutically acceptable carrier. The method of treatment involves administration of an opioid drug and a ceramide biosynthesis inhibitor. Also provided are a method of screening for an agent that reduces, prevents or delays the development of tolerance to and/or physical dependence on an opioid drug as well as compositions comprising a dsRNA for inhibiting ceramide biosynthesis in a cell and a vector for expressing a shRNA for inhibiting ceramide biosynthesis in a cell.
