Duncan is best known for his contributions in the field of drug abuse, which have often been highly controversial. In 1974, he and Edward Khantzian of Harvard Medical School, in separate publications, proposed what has come to be known as the self-medication hypothesis of addiction. Both authors proposed that addiction arose out of the use of drugs to medicate a preexisting disorder or problem. Duncan's version of the hypothesis is distinguished by its identification of addiction with negative reinforcement. Duncan argued that all of the characteristics commonly cited as typical of addiction, such as persistence in the face of negative consequences and high probability of relapse, are all common in any negatively reinforced behaviors.