Analgesia and abuse potential: an accidental association or a common substrate?

The fact that centrally acting analgesics have abuse potential commensurate with their analgesic activity raises the question of whether these effects are related. The abuse potential of drugs depends on their ability to produce reinforcing effects, which are mediated by a neural system that includes the ventral tegmental dopamine cells and their connections with the ventral striatum. Morphine and amphetamine are both powerful analgesics and have high abuse potential. Their analgesic and reinforcing effects are mediated by similar receptors, similar sites of action, and overlapping neural substrates. These coincidences suggest that reinforcers may produce analgesia by transforming the aversive affective state evoked by pain into a more positive affective state. The implications of this hypothesis and its relation to other known mechanisms of analgesia are discussed. The hypothesis predicts that drugs with reinforcing effects should produce analgesia. A survey of drugs acting through 21 classes of receptors reveals that in 13 classes there is evidence for both analgesic and reinforcing effects that are approximately equipotent. The GABA(A) agonists were found to be the only drugs with confirmed abuse potential that lack analgesic activity. The interpretation of this and several other anomalous cases is discussed.