Endogenous opioids have been repeatedly shown to be involved in the cognitive inhibition of pain. Mindfulness meditation, a practice premised on directing nonjudgmental attention to arising sensory events, reduces pain by engaging mechanisms supporting the cognitive control of pain. However, it was unknown if mindfulness-meditation-based analgesia is mediated by opioids, an important consideration for using meditation to treat chronic pain. To address this question, we examined pain reports during meditation in response to noxious heat and administration of the opioid antagonist naloxone and placebo saline. The results demonstrate that meditation-based pain relief does not require endogenous opioids. Therefore, the treatment of chronic pain may be more effective with meditation due to a lack of cross-tolerance with opiate-based medications.