Before the Christian Era

Cannabis sativa (cannabis) is among the earliest plants cultivated by man. The first evidence of the use of cannabis was found in China around 4000 B.C., where fibers obtained from the cannabis stems were used to manufacture ropes, textiles and even paper.

The use of cannabis as a medicine was first recorded in the world's oldest pharmacopoeia, the Shennong Bencao Jing, which was compiled in the first century. Based on oral traditions passed down from the time of the mythical emperor Shen-Nung (who lived circa 2700 BCE), indications for the use of cannabis included: rheumatic pain, intestinal constipation, disorders of the female reproductive system, malaria, and other maladies. Hua Tuo, the founder of Chinese surgery, used a compound of the plant, taken with wine, to anesthetize patients during surgical operations.

In India, the medical and religious use of cannabis probably began around 1000 BCE. The plant was used for innumerous functions: as an analgesic (neuralgia, headache, toothache), anticonvulsant (epilepsy, tetanus, rabies), hypnotic, tranquilizer (anxiety, mania, hysteria), anesthetic, anti-inflammatory (rheumatism and other inflammatory diseases), antibiotic (topical use on skin infections, erysipelas, tuberculosis), antiparasite (internal and external worms), antispasmodic (colic, diarrhea), digestive, appetite stimulant, diuretic, aphrodisiac or anaphrodisiac, antitussive and expectorant (bronchitis, asthma).

In Europe, historical and archeological evidence suggests the presence of cannabis before the Christian era. It seems the plant was brought to the continent by Scythian invaders, who originated from central Asia. In the year 450 BCE, Herodotus described a Scythian funeral ceremony and stated that they inhaled burning cannabis seed vapor for both ritualistic and euphoric purposes. That description was later confirmed by archeologists who found charred cannabis seeds in Scythian tombs in Siberia and Germany.

Begining of the Christian Era to the 18th Century

During this period, the medical use of cannabis remained widespread in India, migrating gradually to the Middle East and Africa. In Arabia, well-known physicians mentioned cannabis in their medical compendiums, like Avicena's The Canon of Medicne. In the year 1000 AD, eight Muslim texts mention the use of cannabis as a diuretic, digestive, anti-flatulent, "to clean the brain," and to soothe pain of the ears. 

Cannabis was known in Africa since at least the 15th century. It was likely introduced by Arab traders who were somehow connected to India. This is evidenced by the similarity of the terms used for preparing the plant in Africa and India. In both countries, the plant was used for snake bite, to facilitate childbirth, malaria, fever, blood poisoning, anthrax, asthma, and dysentery.

In the Americas, the use of cannabis likely originated in South America. In the 16th century, the plant's seeds reached Brazil via African slaves, especially those from Angola. In fact, most synonyms for cannabis in Brazil (maconha, diamba, liamba, and others) have their origin in the Angolan language. There are reports of the use of cannabis in that region's popular religious rituals, especially the Catimbó, a cult ritual for African deities that used the plant for magical practices and healing. The use of cannabis for toothaches and menstrual cramps were also noted during this era.

In Europe, cannabis was cultivated exclusively for fiber. Muslims introduced the manufacture of paper from cannabis in 1150, first in Spain and then in Italy. Cannabis descriptions are found in botannical books during this period which clearly define the differences between male and female plants. References to the medical use of cannabis in Europe are scarce. Europeans may have known about the plant's medical use in the Middle East and Africa, but they appear to have confused it with opium.

Western Medicine in the 19th and 20th Centuries

There are reports from the early 19th century about the use of cannabis by European physicians, especially regarding the use of the seeds or in homeopathic applications. But the true introduction of cannabis to Western medicine occurred in earnest in the mid-19th century through the works of William B. O'Shaughnessy, an Irish physician, and Jacques-Joseph Moreau, a French psychiatrist.

O'Shaughnessy served in India with the British for several years and made his first contact with cannabis use in that country. He studied the literature on the plant, described many popular preparations, evaluated its toxicity in animals and, later, he tested its effects on patients with different pathologies.

Moreau used cannabis with a different purpose. He was an assistant physician at the Charenton Asylum, near Paris, and a common therapeutic practice at the time was to accompany psychiatric patients on long trips to exotic and distant countries. During those trips, Moreau observed that the use of hashish (cannabis resin) was very common among Arabs, and he was impressed with the substance's surprising effects. When he returned to Paris, Moreau decided to perform systematic experiments with different cannabis preparations, first on himself and later on his students.

O'Shaughnessy's and Moreau's contributions had a great impact on Western medicine, especially because of the scarcity of therapeutic options for infectious diseases like rabies, cholera, and tetanus. The medical use of the drug spread from England and France, eventually reaching all of Europe and then North America. In 1860, the first clinical conference about cannabis took place in the United States, organized by the Ohio State Medical Society.

In the second half of the 19th century, over 100 scientific articles were published in Europe and the United States about the therapeutic value of cannabis. The peak of the medical use of cannabis in Western medicine occurred in the late 19th/early 20th centuries. Various laboratories marketed cannabis extracts or tinctures, such as Merck (Germany), Burroughs-Wellcome (England), Bristol-Meyers Squibb (United States), Parke-Davis (United States), and Eli Lilly (United States).

Decline and Rediscovery

In the first decades of the 20th century, medical use of cannabis significantly decreased in the west. This likely occurred because of the difficulty to obtain replicable effects, due to the varying efficacy of different samples of the plant and relatively unsophisticated laboratories of the time. Cannabinoids had not yet been isolated and so cannabis was used in tinctures or extracts whose strength varied due to origin, age, and mode of preparation. In addition, new medications appeared at the end of the 19th century with known efficacy for the treatment of the main indications of cannabis. Vaccines were developed for various infectious diseases; effective analgesics such as aspirin appeared; and hypodermic syringes allowed the injectable use of morphine. As a narcotic and sedative, cannabis was rivaled by substances such as chloral hydrate, paraldehyde, and barbiturates.

Finally, legal restrictions began to limit the medical use and lab use of cannabis. As the result of a campaign by the Federal Bureau of Narcotics, the Marihuana Tax Act was passed in 1937. Under the laws it imposed, anyone using the plant was required to register and pay a tax of one dollar an ounce (28.35g) for medical purposes, and one hundred dollars an ounce for any other use. The non-payment of this tax, however, resulted in a $2,000 dollar fine and/or five years imprisonment. This law created difficulties for the use of the plant due to the excessive paperwork and the risk of severe punishment and it circumvented a decision of the Supreme Court which gave the states the right to control commercial transactions. In practice, the Marihuana Tax Act meant cannabis use was banned in the whole American territory. Cannabis was removed from the American pharmacopoeia in 1941.

In 1964, the chemical structure of D9-THC was identified by Yechiel Gaoni and Raphael Mechoulam, which contributed to a renewed interest in and a proliferation of studies about the active constituents of cannabis. This improved knowledge of its chemical composition (which made it possible to obtain its pure constituents) contributed to a significant increase in scientific interest for cannabis, as of 1965. The boost in cannabis consumption in the mid-1960s intensified its social importance alongside this increased research, and the number of publications about cannabis reached their peak in the early 1970s. A Brazilian research group, led by Elisaldo Carlini, had a great contribution to this research, especially in regards to the interactions of D9-THC with other cannabinoids. As a result of this research, Carlini has been advocating for the realignment of public policies concerning cannabis control. After the mid-1970s, the number of cannabis studies started a decline that lasted for nearly two decades.

The scientific interest in cannabis was renewed in the early 1990s with the discovery of specific receptors for cannabinoids in the nervous system, and the subsequent isolation of anandamide, an endogenous cannabinoid. These two significant discoveries kicked off a renewed interested in cannabis research, which has only increased as new beneficial properties of the plant continue to be discovered. 

Scientific interest in cannabis is growing, as researchers study its therapeutic effects using more accurate scientific methods and testing than ever before. The therapeutic efficacy of D9-THC is being studied and tested worldwide for conditions such as: epilepsy, insomnia, vomit, spasms, pain, glaucoma, asthma, Tourette's Syndrome, and others. Among the therapeutic indications of D9-THC, the following efficacies are considered close to being proven: anti-emetic, appetite stimulant, analgesic, and in symptoms of multiple sclerosis. Other cannabinoids are also under investigation, such as cannabidiol (CBD), which has strong emerging evidence for therapeutic effects for epilepsy, insomnia, anxiety, inflammation, brain damage (as a neuroprotector), psychoses, and others serious health issues. 

At the beginning of 2005, a multinational pharmaceutical laboratory received approval to market a medication containing D9-THC and CBD for the relief of neuropathic pain in patients with multiple sclerosis. As of mid-2013, the drug has been approved for use in Ireland, Italy, UK, Spain, Germany, Denmark, the Czech Republic, Sweden, New Zealand and Canada.

Thus, a new cycle begins for the use of cannabis derivatives as medication, this time more consistently than in the past. The structures of chemical compounds derived from cannabis are now known, the mechanisms of their action in the nervous system are being elucidated with the discovery of the endogenous cannabinoid system, and treatment effectiveness and safety are being scientifically proven.