Opioids such as morphine are still the most effective analgesics for many types of pain. However, clinical utility of opioids is limited because long-term use leads to analgesic tolerance, such that higher concentrations of opioids are needed to achieve the same analgesic effect. This is problematic since tolerance to the life-threatening respiratory depressive effects of opioids develops slower than to the analgesic effects of opioids. Thus, opioid tolerance increases risk for overdose and death.