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Cannabinoids: A Secret History

A tincture bottle of cannabis fluid extract produced by Parke, Davis pharmaceutical company, 1928.
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By Tom Geller

The history of cannabinoids starts with the use of cannabis as a fiber plant over 12,000 years ago. The plant was first specified in a medical context by the Chinese emperor Shen-Nung in 2700 BCE to treat “beri-beri, constipation, female weakness, gout, malaria, rheumatism and absentmindedness.' Wide-ranging recommendations for cannabis use continued in to appear in ancient sources until around the 2nd century CE, when Western-world documentation on its uses—as on many other scientific matters—disappeared. Even so, cannabis (also called hemp) continued to be cultivated in Europe and Asia as a fiber plant and ultimately became a central non-food crop of colonial and post-revolutionary America. Cannabis almost certainly found use as a drug everywhere that it grew with sufficient potency. George Washington, among others, is believed to have smoked hemp for entertainment and to relieve tooth pain.

In 1799 Napoleon Bonaparte’s army returned to France from an unsuccessful Egyptian military campaign, bringing with it three science-minded soldiers who carried new knowledge of the plant. Napoleon’s scientists were perhaps the first Western Europeans to study cannabinoids’ effects methodically; two of them, Silvestre de Sacy and P. C. Rouyer, published papers on cannabinoids in a French medical journal in 1809, touching off a new round of medical inquiry. The drug began to enjoy moderate popularity as an intoxicant and home remedy used in alcohol-based tinctures, poultices, and other forms.

Interest in cannabinoids surged in 1841 when the Irish doctor William Brooke O’Shaughnessy published a seminal article in the obscure journal Transactions of the Medical and Physical Society of Bengal. Although O’Shaughnessy’s choice of publication would seem to have limited his audience, his 49-page treatise nevertheless became an important reference for 19th-century scientists interested in cannabinoids’ effects. His report summarized cannabis use as both an intoxicant and a medical drug in Europe and around the world. Most important, he noted, “The extraordinary symptoms [found in the hemp of Turkey and India] depend on a resinous secretion with which it abounds and which seems totally absent in the European kind.' This resinous secretion is, of course, the plant part richest in cannabinoids.

From Cure-all to Social Ill

Sir William’s work (O’Shaughnessy was knighted in 1856) sparked interest in cannabinoids throughout the scientific community and the public at large. Two years later in Great Britain, John Clendenning studied cannabinoids as a clinical tool for treating chronic pain and alcohol withdrawal; in France, psychiatrist Jacques-Joseph Moreau’s 1845 book Du haschich et de l’aliénation mentale (Hashish and Mental Alienation) described mental effects of the drug; the British Medical Association’s president, Sir Robert Christison, recommended it for treating (among other things) tetanus and pain relief; and Sir John Russell Reynolds, personal physician to Queen Victoria, prescribed it for “female problems.”

Soon after it appeared in the U.S. Pharmacopoeia in 1850, cannabis was marketed in patent medicines, with some packages eventually carrying the Good Housekeeping Seal of Approval. As was typical of patent medicines, manufacturers claimed the drug could cure practically everything and included it in products as diverse as aphrodisiacs and foot powder. Many of these advertising claims were supported by mainstream medical studies such as the 1860 Report of the Ohio State Medical Committee on Cannabis Indica. Cannabis was also a standard ingredient in tinctures and generic compound drugs. Among the companies that produced cannabis-containing compounds were Abbott Laboratories; E. R. Squibb and Sons (now Bristol-Myers Squibb); Smith, Kline and Company (now GlaxoSmithKline); Eli Lilly; Sharp and Dohme (now Merck); and Parke, Davis.

But even in the mid-19th century the drug had its critics. Personal accounts described such uncomfortable side effects such as nausea, reduced productivity and concentration, and exhaustion. Cannabis’s image came under further attack in the 1880s when burgeoning temperance movements expanded their mandate from alcohol to other substances, encompassing all with warnings against intoxication in general. Media outlets reacted to this popular movement with sensational stories of alcohol, marijuana, and opium excess. A substantial number of these reports played on fears that cannabis use encouraged a foreign threat put forth by immigrants and racial and ethnic minorities. One sign of this change appeared in the 1910s, as the Spanish term marihuana started to supplant cannabis in reports of drug-related crime, while cannabis continued to be the term used for medical applications.

Growing suspicions regarding patent medicines added to the public’s doubts about cannabis’s medical legitimacy. The Pure Food and Drugs Act of 1906 did not target cannabis specifically but laid the path for future anticannabis regulations (see “How Chemists Pushed for Consumer Protection,” CH, Summer 2006, pp. 6–11). Next came the Harrison Narcotics Tax Act of 1914, which regulated and taxed opiates and cocaine—but, again, not cannabis. In 1920 sales of alcohol were prohibited by the 18th Amendment. Cannabis remained unregulated federally until 1937, ironically only four years after the 21st Amendment acknowledged the failure of alcohol prohibition.

The regulation that felled cannabis—the 1937 Marihuana Tax Act—effectively prohibited it by imposing regulations that were difficult or impossible to meet. On its face the act only required purchase of a $1 tax stamp by all who possessed, traded, or prescribed cannabis. But the devil was in its associated 60 pages of regulations, which detailed the application and maintenance process for obtaining the stamp. Doctors who wished to prescribe it had to give the Federal Bureau of Narcotics extensive information, including the names and addresses of patients, circumstances surrounding the prescriptions, and so on. Frequent reports and Treasury Department inspections were required, and errors were punishable by a fine of $2,000 (about $25,000 in today’s dollars), a five-year imprisonment, or both. As with the Harrison Act, the power to tax conveyed the power to destroy, and the Marihuana Tax Act’s restrictions—together with widely publicized arrests of doctors who failed to meet tax act requirements—effectively closed off legal channels for provision of the substance.

The chill affected researchers as well as clinicians. Medical journals published dozens of studies before the tax act but few after its enactment. As researcher Lester Grinspoon noted, “virtually no medical investigation of cannabis was conducted for many years” as a string of additional laws, including the 1951 Boggs Act and the 1970 Controlled Substances Act, further deterred research.

Today, American researchers who wish to obtain legal cannabis for scientific study must apply to the National Institute on Drug Abuse (NIDA), which maintains a government-funded, 1.5-acre marijuana farm in Oxford, Mississippi. Compared with street marijuana, however, the government’s plants are low in cannabinoid content, and some researchers have also complained of the institute’s slow and seemingly arbitrary decisions. In 1994 Donald Abrams, a professor of medicine at the University of California, San Francisco, proposed to study the effects of smoking cannabis on HIV-related weight loss, but his application was rejected by NIDA, even though it had been approved by the U.S. Food and Drug Administration. When he then resubmitted his proposal, this time emphasizing the drug’s potential negative effects, NIDA not only approved the study but also provided him with nearly a million dollars in funding. Another researcher, Lyle Craker of the University of Massachusetts–Amherst, applied to the Drug Enforcement Administration in 2001 for the right to grow cannabis for research purposes as a way of sidestepping these potency and access issues. For three years he heard nothing, until a federal court ordered the Drug Enforcement Administration to respond. They said no, so he sued them. That case is still under way.

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