History of Cannabinoids (Cannabis) Use For Pain

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 strings, ropes, textiles,and even paper.

The use of cannabis as a medicine by ancient Chinese was reported in the world's oldest pharmacopoeia, thepen-ts'ao ching which was compiled in the first century of this Era, but based on oral traditions passed down from the time of Emperor Shen-Nung, who lived during the years 2700 B.C. Indications for the use of cannabis included: rheumatic pain, intestinal constipation, disorders of the female reproductive system, malaria, and others. In the beginning of the Christian Era, Hua T'o, the founder of Chinese surgery (A.D. 110 – 207), 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 together around 1000 years B.C. The plant was used for innumerous functions, such as: 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 by Scythian invaders, who originated from Central Asian and reached close to the Mediterranean. In the year 450 B.C., Herodotus described a Scythian funeral ceremony, and stated that they inhaled the vapors obtained from burning cannabis seeds with 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

In this period, the medical use of cannabis remained very intense in India and was then spread to the Middle East and Africa. In Arabia, well-known physicians mentioned cannabis in their medical compendiums, as Avicena, in the year 1000 A.D. 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. In 1464, Ibn al-Badri reported that the epileptic son of the caliph's chamberlain was treated with the plant's resin, and stated: it (cannabis) cured him completely, but he became an addict who could not for a moment be without the drug'.

Cannabis was known in Africa at least since the 15th century and possibly 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 Africa, 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 probably began in South America. In the 16th century, the plant's seeds reached Brazil; brought by African slaves, especially those from Angola, and its use was considerably common among Blacks in the Northeastern rural area. 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', which includes cult to African deities and presumes the value of the plant for magical practice and treatment of diseases. In the rural environment, there are reports of the use of cannabis for toothache and menstrual cramps.

In Europe, during this period, cannabis was cultivated exclusively for fibers. Muslims introduced the manufacture ofpaper from cannabis, in 1150, first in Spain then in Italy. Cannabis descriptions are found in many books about plants written in this period, which clearly state, since the mid 18th century, the distinction between male and female plants (previously described in a Chinese ideogram in the beginning of the Christian Era). References to the medical use of cannabis are scarce. Europeans may have known about the plant's medical use in the Middle East and Africa, but they confused it with opium.

Western Medicine in the 19th and 20th Centuries

There are some reports, from the early 19th century, about the use of cannabis by European physicians, especially regarding the use of the seeds or homeopathic medications. However, the effective introduction of cannabis in Western medicine occurred in the midst 19th century through the works of Willian B. O'Shaughnessy, an Irish physician, and by the book by 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 effect 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 in long trips to exotic and distant countries. During those trips he observed that the use of hashish (cannabis resin) was very common among Arabs, and he was impressed with the substance's surprising effects. In Paris, around 1840, Moreau decided to experiment, systematically, different cannabis preparations; first on himself and later on his students.

O'Shaughnessy and Moreau's contributions had a great impact on Western medicine, especially due to the scarcity of therapeutic options for infectious diseases such as rabies, cholera, and tetanus. The medical use of the drug spread from England and France reaching all Europe and then North America. In 1860, the first clinical conference about cannabis took place in America, 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 climax of the medical use of cannabis by Western medicine occurred in the late 19th and early 20th century. 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, the Western medical use of cannabis significantly decreased. This may have occurred, among other factors, because of the difficulty to obtain replicable effects, due to the extreme varying efficacy of different samples of the plant. At that time, the active principle of cannabis had not yet been isolated and the drug was used in the form of tinctures or extracts whose power was dependent on different factors, such as origin, age, and mode of preparation.8 In addition, various 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, such as tetanus; effective analgesics such as aspirin appeared , and hypodermic syringes allowed the injectable use of morphine; and, as a narcotic and sedative, cannabis was rivaled by substances such as chloral hydrate, paraldehyde, and barbiturates.

Finally, many legal restrictions limited the medical use and experimentation of cannabis. In the United States, as the result of a campaign of the Federal Bureau of Narcotics, the Marihuana Tax Act law was passed in 1937. Under this Act, anyone using the plant was required to register and pay a tax of a dollar an ounce (28.35 g), for medical purposes, and 100 dollars an ounce for any other use. Despite the low value for medical use, the non-payment of this tax, however, resulted in a 2.000 dollar fine and/or 5 years imprisonment. This law brought difficulties for the use of the plant due to the excessive paperwork and the risk of severe punishment. When cannabis transaction regulations, including prescriptions, were transferred to the tribute area, this law circumvented a decision of the Supreme Court which gave the States the right to control commercial transactions and, in practice, meant banning the use of cannabis 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 Gaoni and Mechoulam, which contributed to a proliferation of studies about the active constituents of cannabis

The startling boost in cannabis consumption, which intensified its social importance, along with the better 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 number of publications about cannabisreached their peak in the early 1970's. In this period, a Brazilian research group, led by Carlini, had a great contribution, especially about the interactions of D9-THC with other cannabinoids. Since then, Carlini has been developing efforts for the realignment of public policies concerning cannabis control. After the middle of 1970's, the number of publications started to slowly decline during the following two decades. The interest in studies about cannabis was renewed in the early 1990's, with the description and cloning of specific receptors for the cannabinoids in the nervous system and the subsequent isolation of anandamide, an endogenous cannabinoid. Afterwards, the number of publications about cannabis has been continuously growing, attesting the great interest in research involving the herb.

With the growth of scientific interest for cannabis, its therapeutic effects are being once again studied, this time using more accurate scientific methods. There are studies, in different phases, about the therapeutic effects of D9-THC in conditions such as: epilepsy, insomnia, vomits, spasms, pain, glaucoma, asthma, inappetence, Tourette syndrome, and others. Among the therapeutic indications of D9-THC the following are considered close to being proven: anti-emetic, stimulant of appetite, analgesic, and in symptoms of Multiple Sclerosis. Other cannabinoids are also under investigation, such as Canabidiol (CBD), which has evidence for therapeutic effects in epilepsy, insomnia, anxiety, inflammations, brain damage (as a neuroprotector), psychoses, and others.However, cannabis products must be used cautiously since some studies suggest that early-onset cannabis use can induce cognitive deficits and apparently acts as a risk factor for the onset of psychosis among vulnerable youths.

At the beginning of 2005, a multinational pharmaceutical laboratory received the approval in Canada, and is pleading authorization in the United Kingdom and the European Union, to market a medication containing D9-THC and CBD for the relief of neuropathic pain in patients with multiple sclerosis.

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 an endogenous cannabinoid system, and treatment effectiveness and safety are being scientifically proven.