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The origins of U.S. drug prohibition lie in the early 20th century. Prior to 1906, there was no drug regulation in the United States and crimes such as drug dealing and drug possession did not exist. The first regulation came with the 1906 Pure Food and Drug Act, which required labeling of ingredients. Passed in the wake of public disgust over Upton Sinclair's slaughterhouse exposé The Jungle, the law also required patent medicine and similar nostrums to disclose their ingredients, which often included a healthy dose of morphine or cocaine. The Harrison Act in 1914 banned the distribution of opiates and cocaine and began the prohibition of drugs as a national policy. Although the act had a clause allowing doctors' use in their practices, in 1917 this was interpreted to not allow heroin maintenance to patients.

The Marijuana Tax Act of 1937 was passed with little fanfare. Many legislators were unsure exactly what marijuana was, and there was minimal debate leading up to the floor vote. Sociologist Howard Becker attributed this law to the moral entrepreneur-ship of Harry Anslinger, the long-standing head of the Federal Bureau of Narcotics, who promoted marijuana as a threat to public safety and luridly linked the drug with Mexican immigration into the Southwest. (The Federal Bureau of Narcotics was the precursor to the Drug Enforcement Administration.)

Early drug laws did not have a major impact on the criminal justice system because of the limited use of some drugs (marijuana) and the medical acceptability of others (cocaine, morphine). The significance of early drug laws lies in the vast expansion of incarceration and the criminal justice system during the 1990s, driven in part by the addition of mandatory minimum sentencing for drug offenses. Resistance to drug laws now focuses mainly on the criminal justice system and the cost and scope of the war on drugs.

During the 1960s and 1970s, marijuana use diffused through the population, greatly increasing the number of people who had tried the drug. As well-educated, middle-class people used marijuana, sentiments toward decriminalization became increasingly favorable. Jerome Himmelstein's analysis of news reports found that descriptions of the physical effects of marijuana changed as the reference group of users changed—marijuana was no longer associated with violence and addiction, but passivity and dependence instead. As drug law affected more middle-class young people, support for drug law reform grew among civil society and politicians concerned about a seemingly unrealistic legal regime of prohibition. The American Bar Association and the American Nurses Association passed resolutions in favor of decriminalization. The New York State Congress of Parents and Teachers Associations passed a similar resolution in 1976.

The possibility of reform seemed to be at its peak in 1977 when President Jimmy Carter spoke to Congress with the message that penalties against drug use should not be more damaging to an individual than the use of the drug itself;he tied this explicitly to the laws against the possession of marijuana in private for personal use. Carter's statement had precedent in earlier reports and official statements. President Nixon commissioned a study of marijuana law and policy in the United States, headed by Raymond Shafer, Republican ex-governor of Pennsylvania. Published in 1972 with the title Marihuana: Signal of Misunderstanding, the Shafer commission concluded the criminalization of possession of marijuana for personal use was socially self-defeating and, in the overall scheme of things, did not rank high in ranking of social concerns in the United States. The study recommended de-emphasizing marijuana as a problem.

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