Polymorphisms in the mu-opioid receptor gene may potentially alter the clinical effects of opioid analgesics. A common mu-opioid receptor polymorphism occurring at an allelic frequency of 12% decreases the potency of opioid analgesics in humans. Interestingly, in carriers of this mutation, it appears to be possible to reach analgesia by increasing the opioid dose but side effects appear to occur less often despite the higher opioid dose. This suggests a broadened therapeutic range of the opioids. Other mutations of the mu-opioid receptor, for example three mutations within the third intracellular loop of the receptor, impair receptor signaling, but they are too rare to greatly affect pain therapy or have not yet been investigated in the context of pain therapy.