Pavlovian Conditioning and Drug Overdose: When Tolerance Fails

There is a considerable amount of evidence that Pavlovian conditioning contributes to tolerance; Organisms learn to make responses that attenuate the effect of the drug in the presence of cues previously paired with the drug. The conditioning analysis is relevant to understanding seemingly enigmatic “failures” of tolerance that occur when a drug-experienced (and presumably drug-tolerant) individual suffers an “overdose.” There are several demonstrations that Pavlovian conditioning is relevant to understanding opiate (as well as barbiturate and alcohol) “overdose” deaths in laboratory studies with rats. There also are case-reports of human opiate “overdoses,” both in illicit users and in patients receiving medically prescribed morphine, that are consistent with the conditioning interpretation of drug overdose.