In the 17th century hemp was encouraged by the government in the production of rope, sails, and clothing; however, hemp use declined in the late eighteenth century. In the late nineteenth century, marijuana became a common ingredient in medicine and was openly sold at pharmacies.

The first significant instance of marijuana regulation appeared in District of Columbia in 1906. Regulations of marijuana, the word Indian Hemp is sometimes used, followed in Massachusetts in 1911; Maine, California, Texas, Wyoming and Indiana in 1913; New York City in 1914; Utah and Vermont in 1915; Colorado and Nevada in 1917. These laws were passed not due to any widespread use or concern about cannabis, but as regulatory initiatives to discourage future use.

The decision of the United States Congress to pass the 1937 "Marihuana Tax Act" was based on hearings, reports and in part on testimony derived from articles in newspapers owned by William Randolph Hearst, who had significant financial interests in the timber industry, which manufactured his newsprint.

Marijuana activtist Jack Herer has researched DuPont and in his 1985 book The Emperor Wears No Clothes, Herer concluded Dupont played a large role in the criminalization of cannabis. In 1938, DuPont patented the processes for creating plastics from coal and oil and a new process for creating paper from wood pulp. If hemp would have been largely exploited, Herer believes it would have likely been used to make paper and plastic (nylon), and may have hurt DuPonts profits. Andrew Mellon of the Mellon Bank was DuPont's chief financial backer and was also the Secretary of Treasury under the Hoover administration. Mellon appointed Harry J. Anslinger, who later became his nephew-in-law, as the head of the Bureau of Narcotics and Dangerous Drugs (FBNDD) and the Federal Bureau of Narcotics (FBN), where Mellon stayed until 1962.

In 1916, United States Department of Agriculture (USDA) chief scientists Jason L. Merrill and Lyster H. Dewe created paper made from hemp pulp, which they concluded was "favorable in comparison with those used with pulp wood in USDA Bulletin No. 404." Jack Herer, in the book "The Emperor Wears No Clothes" summarized the findings of Bulletin No. 404:

USDA Bulletin No. 404, reported that one acre of hemp, in annual rotation over a 20-year period, would produce as much pulp for paper as 4.1 acres of trees being cut down over the same 20-year period. This process would use only 1/4 to 1/7 as much polluting sulfur-based acid chemicals to break down the glue-like lignin that binds the fibers of the pulp, or even none at all using soda ash. The problem of dioxin contamination of rivers is avoided in the hemp paper making process, which does not need to use chlorine bleach (as the wood pulp paper making process requires) but instead safely substitutes hydrogen peroxide in the bleaching process. ... If the new (1916) hemp pulp paper process were legal today, it would soon replace about 70% of all wood pulp paper, including computer printout paper, corrugated boxes and paper bags.

Hemp was a relatively easy target because factories already had made large investments in equipment to handle cotton, wool, and linen, but there were relatively small investments in hemp production. Big technological improvements in the wood pulp industry was invented in the 1930s, for example the recovery boiler, and other improvements came later. So, there is a niche market for hemp paper, but the cost of hemp pulp is approximately six times that of wood pulp, There was also a misconception hemp had an intoxicating effect because it has the same active substance, THC, which is in potent marijuana strains; however, hemp only has minimal amount of THC when compared to recreational marijuana strains.

An alternative explanation for Anslingers opinion's about hemp is that he believed that a tax on marijuana could be easier to supervise if it included hemp and that he had reports from experiments with mechanical harvesting of hemp reporting that the machines was no success and reports about marijuana farms.

"The existence of the old 1934-1935 crop of harvested hemp on the fields of southern Minnesota is a menace to society in that it is being used by traffickers in marihuana as a source of supply "

"they were able to cut only a part of the Tribune Farm crop by machine, two thirds of it they did by hand with a sharp hand cuttertuff".

Argument for the alternative theory is that hemp was not an alternative as raw material in the new commercial products from DuPont, the nylon-bristled toothbrush (1938) followed more famously by women's nylons stockings (1940). Nylon was intended to be a synthetic replacement for silk not hemp.

In 1978, Robert Randall sued the federal government for arresting him for using marijuana to treat his glaucoma. The judge ruled Randall needed marijuana for medical purposes and required the Food and Drug Administration set up a program to grow marijuana on a farm at the University of Mississippi and to distribute 300 marijuana cigarettes a month to Randall. In 1992, George H. W. Bush discontinued the program after Randall tried to make AIDS patients eligible for the program. At the time, thirteen people were already enrolled and were allowed to continue receiving marijuana cigarettes; however, since 1992, six of the patients have died and currently the government only ships marijuana cigarettes to seven persons. Irvin Rosenfeld, who became eligible to receive marijuana from the program in 1982 to treat rare bone tumors, has urged the George W. Bush administration to reopen the program; however, he has been unsuccessful.

In 1996, California passed the Compassionate Use Act, which decriminalized medical marijuana by enacting laws that allow regulated marijuana consumption, possession, cultivation, and distribution for medicinal use; since then twelve states have enacted similar laws. As a result of the court rulings of United States v. Oakland Cannabis Buyers' Cooperative and Gonzales v. Raich, and the classification of marijuana as a Schedule I drug, the Federal government does not permit marijuana to be used medically; the DEA taken an active stance against medical marijuana and often raids marijuana dispensories.

In 1972, 1995, and 2002, petitions for marijuana rescheduling in the United States were filed to remove marijuana from the "Schedule I" category of tightly-restricted drugs that have no medical use, as the Controlled Substance Act allows the executive branch to decriminalize medical and recreational use of marijuana without any action by Congress depending on the findings of the Secretary of the United States Department of Health and Human Services on certain scientific and medical issues specified by the Act.

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