Opioid tolerance: The clinical phenomenon of decreasing effect of opioids (pain relief, sedation, euphoria, etc.) or increasing need for higher doses to maintain the same effect with repeated use of opioids. The commonly recognized mechanism is the opioid receptor desensitization processes. However, allostatic opponent effect is considered the more clinically relevant mechanistic process. Tolerance achieved through increased pain relief from allostatic opponent adaptations are difficult to reverse with dose increase. Although tolerance and physiological dependence are considered separate phenomena, they intricately interwoven with each other and often progress together.