• Jason M White.
• Department of Clinical and Experimental Pharmacology, University of Adelaide, Adelaide, South Australia 5005, Australia. jason.white@adelaide.edu.au
• Addict Behav. 2004 Sep 1;29(7):1311-24.

AbstractOne consequence of repeated drug administration is the development of adaptations in the nervous system, sometimes termed 'drug-opposite' responses. During administration, the effects of the drug are diminished by these adaptations (tolerance), while cessation of drug use results in the emergence of these drug-opposite responses as the withdrawal syndrome. Recent evidence on pain responses challenges this simple notion of withdrawal and suggests that aversive drug-opposite states may play a more important role in drug dependence than previously thought. While opioids such as heroin produce analgesia, people with a history of opioid self-administration are hypersensitive to certain kinds of pain during the time they are under the influence of the analgesic drug. This suggests that in pain systems, the drug-opposite response exceeds the pain inhibiting effect of the drug itself. This hyperalgesia is evident in people with a history of heroin use and is not modified by methadone or buprenorphine treatment but is reduced by long-term abstinence from opioids. This same pattern of the drug-opposite response exceeding the drug effect may also occur for mood. While opioids cause elevation of mood, commonly described as euphoria and reduction of emotional distress, methadone maintenance participants show significant negative mood disturbance relative to controls. Thus, for pain and mood, the chronic opioid user under the influence of the drug does not experience an opioid effect diminished by tolerance but a state opposite to the effect of the drug. Increases in drug concentration arising from administration serve only to reduce the degree of pain and mood disturbance. These aversive pain and mood states may contribute to the motivation for continued drug use and the dysfunction associated with drug dependence.Copyright 2004 Elsevier Ltd.

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