While the federal government has resisted restoring cannabis to its place in the US Pharmacopeia, its own research studies acknowledge that the “use of cannabis for purposes of healing predates recorded history” and that it was included in “the fifteenth century BC Chinese Pharmacopeia, the Rh-Ya.” Ancient Egypt, India and Persia all made medical use of it more than 2,000 years ago. British herbalists in the seventeenth century noted its medicinal properties, but it did not become widely used in British medicine until the mid-nineteenth century. In 1890, Queen Victoria's personal physician, Sir Russell Reynolds, wrote in the first issue of The Lancet, "When pure and administered carefully, [it is] one of the most valuable medicines we possess."

William O’Shaughnessy, a British East India Company surgeon who studied its use while posted in India, expanded western understanding of its range of applications and championed its use upon his return to Britain in 1841 and election to the Royal Society, the scientific advisory body to the British government. Between 1840 and 1900, European and American medical journals published more than 100 articles on the therapeutic applications of cannabis, known then as Cannabis Indica or Indian hemp. Common indications for its use in the nineteenth century included “muscle spasms, menstrual cramps, rheumatism, and the convulsions of tetanus, rabies and epilepsy; it was also used to promote uterine contractions in childbirth, and as a sedative to induce sleep.” [House of Lords Select Committee on Science and Technology "Ninth Report: Cannabis," Nov. 11, 1998.]

The American Medical Association opposed the first federal law restricting legal access to cannabis with an article in its leading journal. Their representative, Dr. William C. Woodward, testified to Congress that "The American Medical Association knows of no evidence that marihuana is a dangerous drug," and that any prohibition "loses sight of the fact that future investigation may show that there are substantial medical uses for Cannabis."

The first state medical cannabis law was passed in 1996 by California voter initiative. Since then, 21 states and the District of Columbia have removed criminal penalties for their citizens who use cannabis on the advice of a physician and established means of distributing it. Ten of those states plus the District of Columbia established their medical cannabis laws through ballot initiative, while the legislatures in 11 others have enacted similar bills. As of January 2014, New York is poised to start a limited medical cannabis program under the Executive Order of Gov. Andrew Cuomo using federal supplies. Currently, nearly 40% of the U.S. population resides in a state that permits medical use, and medical cannabis legislation is introduced in more states every year.

Federal policy on medical cannabis is filled with contradictions. Cannabis was widely prescribed until the turn of the century, and an estimated one million Americans currently use it under medical supervision. Congress in 1970 classified cannabis is a Schedule I drug, defined as having no medicinal value and a high potential for abuse, yet its most psychoactive component, THC, is legally available as Marinol and is classified as Schedule III. The U.S. federal government also grows and provides free cannabis for a small number of patients today as part of an Investigational New Drug (IND) compassionate access research program created by court order in 1976. Though the program provided up to nine pounds of cannabis a year to these patients, and all reported being substantially helped by it, the application process was extremely complicated, and few physicians became involved. In the first twelve years, the government accepted only a handful of patients. But in 1989 the FDA was deluged with new applications from people living with AIDS, and 34 patients were approved within a year. In June 1991, the Public Health Service announced that the program would be suspended because it undercut the administration's opposition to the use of illegal drugs. The program was discontinued in March 1992 and the remaining patients had to sue the federal government on the basis of "medical necessity" to retain access to their medicine. Today, four surviving patients still receive medical cannabis from the federal government.

Despite this successful federal program, thousands of scientific articles, and dozens of successful clinical trials, as well as an unparalleled safety record, cannabis remains classified as a Schedule I substance. Healthcare advocates have tried to resolve this contradiction through legal and administrative channels. In 1972, a petition was submitted to reschedule cannabis in order to remove barriers to medical research and patient access. The DEA stalled hearings for 16 years, but after exhaustive hearings in 1988 their chief administrative law judge, Francis L. Young, ruled that, "Marijuana, in its natural form, is one of the safest therapeutically active substances known... It would be unreasonable, arbitrary and capricious for the DEA to continue to stand between those sufferers and the benefits of this substance." The DEA refused to implement this ruling based on a procedural technicality and continues to insist cannabis is a substance with no medical use. In 2009 the American Medical Association, the nation’s largest organization for physicians with a quarter million members, joined the chorus of professional medical groups calling on the federal government to reconsider the classification of cannabis and urging comprehensive clinical trials.

Public opinion is strongly in favor of ending the prohibition of medical cannabis and has been for some time, with every national poll conducted over the past two decades showing a substantial majority in support. An ABC News/Washington Post poll in October 2010 found that 81% of Americans say doctors “should be allowed to prescribe marijuana for medical purposes.” In 2004, the 35 million-member American Association of Retired Persons (AARP) released a national poll of older Americans showing 72% of seniors agreed that “adults should be allowed to legally use marijuana for medical purposes if a physician recommends it.” Every national poll for more than a decade has found similar super-majorities of support.

The refusal of the federal government to act on this widespread public support has meant that advocates have had to turn to the states for action. Currently, laws that effectively remove state-level criminal penalties for growing and/or possessing medical cannabis are in place in Alaska, Arizona, California, Colorado, Connecticut, Delaware, Hawaii, Illinois, Maine, Maryland, Massachusetts, Michigan, Montana, Nevada, New Hampshire, New Jersey, New Mexico, Oregon, Rhode Island, Vermont, Washington, and the District of Columbia. Maryland has reduced the criminal penalty for medical use to a maximum $100 fine. Thirty-six states have symbolic medical cannabis laws (laws that support medical cannabis but do not provide patients with legal protection under state law).

On August 29, 2013, the U.S. Department of Justice issued new guidance to federal prosecutors, telling them medical cannabis dispensaries should no longer automatically be considered targets for prosecution. The memo from Deputy Attorney General James M. Cole to all U.S. Attorneys reverses previous federal policy on prosecuting medical cannabis providers and businesses. The new guidance says state and local officials can avoid federal interference in their medical cannabis programs if they “'implement strong and effective regulatory and enforcement systems” that reflect eight federal enforcement priorities.

The memo does not change federal law, nor does it preclude prosecution of any individual or business, as the U.S. Attorneys’ offices are autonomous, and federal prosecutors make independent decisions about which cases to pursue.