Regulation of opioid receptors by opioid antagonists: implications for rapid opioid detoxification

Opioid receptor antagonists have long been used in the diagnosis of opioid dependence and in the treatment of both opioid overdose and addiction. More recently they have been used in rapid opioid detoxification, a technique which has generated much ethical and scientific controversy. Because of this, the present review aims to integrate and summarize the current state of knowledge on adaptational changes to opioid systems as a result of antagonist administration. It is generally accepted that chronic treatment with an opioid antagonist results in opioid receptor upregulation. However, the mechanism(s) underlying this resultant opioid supersensitivity remain unresolved. In addition, there is not yet consensus regarding whether changes in opioid receptor number are directly responsible for the functional changes observed after chronic opioid antagonist treatment. Moreover, changes in opioid receptor number and sensitivity to opioid agonists and antagonists after chronic opioid antagonist treatment are dependent on dosing regimes as well as the kinetic properties of the antagonist itself. The role of these variables is appraised critically given the implication that an opioid antagonist can enhance functional responses. For example, such responses are an important consideration in the use of opioids because of possible adverse outcomes, such as overdose, after cessation of administration. Based on the literature discussed in this review it is concluded that caution is essential in the use of opioid antagonists for rapid opioid detoxification.