With the opioid epidemic reaching new heights in the USA, it has become critical to find suitable alternatives to opioids. Cannabis, an antinociceptive, is a strong contender to help patients reduce their opioid usage. A growing literature has been examining the complex effects cannabis has on pain relief and on opioid usage; whether it is a substitute for opioids or increases their use. This review explores the studies that compare cannabis-opioid interactions and presents some challenges of cannabis research and usage. The practical clinical pharmacology of cannabis as an analgesic, including the route of administration, safety and pharmacokinetics, are discussed to address the concerns, as well as possible solutions, of cannabis as a pain reliever.