Pharmacology

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History of Therapeutic Cannabis PDF Print E-mail
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Books - Cannabis in Medical Practice
Written by Michael Aldrich   
Michael Aldrich, Ph.D., is a historian of cannabis in San Francisco, California.
 
On a February morning in 1994, the U.S. District Court of Appeals in Washington, D.C., with a panel of three law judges, issued a finding indicating that in their opinion cannabis has no medicinal value—none.
 
China: The World's Oldest Pharmacopoeia
 
Cannabis, called to ma ("great hemp"), was one of the staple crops of ancient China, valued not only for food, fiber, oil, and paper but also as a medicine. According to legend, the ancient Emperor Shen Nung, patron deity of agriculture (c. 2700 B.c.), had a transparent abdomen, which allowed him to see the effects of medicines passing through his body (Wallnofer and von Rottauscher 1965). After experimenting with more than one hundred herbs, he is credited with the discovery of ephedra, ginseng, and cannabis as therapeutic agents.
 
The world's oldest pharmacopoeia, the Shen-nung pen-ts'ao ching (compiled in the first or second century A.D. but based on oral traditions passed down from the time of Shen Nung), gives cannabis the name ma, an ideogram that shows two plants (male and female) under a drying shed with the sun beating down on top (Dewey 1913). The text shows that the Chinese understood its psychoactive properties: "ma fen [the fruits of hemp] ... if taken in excess will produce hallucinations [literally, "seeing devils"] ... over a long term, it makes one communicate with spirits and lightens one's body" (Li 1974,1975). Hua T'o, the founder of Chinese surgery (A.D. 110-207), used a "hemp boiling compound," taken with wine, to anesthetize patients during surgical operations (ibid.).
 
Later editions of Shen Nung's pharmacopoeia list more than 100 ailments treated with cannabis, including "female weakness, gout, rheumatism, malaria, beri-beri, boils, constipation, and absent-mindedness" (Camp 1936, 113). By the  tenth century A.D., the Cheng-lei pen-ts'ao summarized the therapeutic value of cannabis: "Mafen has a spicy taste; it is toxic; it is used for waste diseases and injuries; it clears blood and cools temperature; it relieves fluxes [diarrhea]; it undoes rheumatism; it discharges pus." (Li 1975, 56)
 
Other therapeutic uses of cannabis were preserved in the classic Pen ts'ao kang mu of Li Shih-Chen (A.D. 1578). Many of these uses—as an antiemetic, antibiotic, anthelmintic (treatment of parasites), to treat leprosy, and to stop hemorrhages—deserve modern investigation (Mechoulam 1986).
 
The historical use of cannabis for wasting diseases is one of its most common medical uses today in the age of AIDS. This is also emphasized in folk medicine throughout modern Asia. For example, in Thailand, "cannabis is frequently used to stimulate the appetite of sick people and make them sleep.... Its use to counteract diarrhea and dysentery is equally common" (Martin 1975, 72).
 
Ancient texts also refer to cannabis seed eaten as food. Even the Buddha himself, according to Chinese legend, existed for six years under the Bo Tree while awaiting enlightenment, eating only one cannabis seed each day (Abel 1980, 20). The nutritional and medical value of hemp seed and all the ancient economic uses of hemp are currently being reinvestigated (Rubin 1976; Herer 1990; Conrad 1993; Rosenthal 1994); see also chapters 16 and 17 of this book.
 
India
 
In India, the Atharva Veda (c. 1400 B.c.) mentions cannabis (bhang) as one of five sacred plants used for "freedom from distress" (11.6.15), and it also (8.8.3) ordains the practice of throwing hemp boughs into a fire during a magical rite "to overcome enemies" or evil forces (Aldrich 1977). As in China, where hemp stalks were used to strike the beds of sick people to drive out disease demons (Abel 1980), cannabis has been intimately associated with magical, medical, religious, and social customs in India for thousands of years (Hasan 1975; Aldrich 1977; Touw 1981; Morningstar 1985). Sushruta, the most renowned physician of ancient India, recommended it as an antiphlegmatic (drying mucous membranes and relieving congestion, or more broadly regulating the bodily humors). Sushruta also mentions vijaya (cannabis, or perhaps yellow myrobalan) as a remedy for catarrh accompanied by diarrhea and as an ingredient in a cure for fevers (Grierson 1894; Chopra and Chopra 1957). It has thousands of uses in traditional Ayurvedic medicine, is noted in medieval texts as a soporific (sleep medication) and an excitant, appetite stimulant and digestive aid, remedy for many ailments and conditions, analgesic, aphrodisiac, intoxicant and elixir vitae.
 
One of the most famous jokes in the literature of medical cannabis occurs in the Dhurtasamagama or "Rogues' Congress," an amusing if coarsely written farce from circa A.D. 1500 (Grierson 1894):
 
In the second act, two Shivaite mendicants come before an unjust judge, and demand a decision on a quarrel which they have about a nymph of the bazaar [prostitute]. The judge demands payment of a deposit before he will give any opinion. Not having any money, one of the holy men says, "Here is my ganja bag; let it be accepted as payment." The judge, taking it pompously, and then smelling it greedily, says, "Let me try what it is like" (takes a pinch). "Ah! I have just now got by the merest chance some ganja which is soporific and corrects derangements of the humours, which produces a healthy appetite, sharpens the wits, and acts like an aphrodisiac."
 
The Rajavallabha, a seventeenth century Ayurvedic text, says cannabis:
 
is acid, produces infatuation, and destroys leprosy. It creates vital energy, the mental powers, and internal heat; corrects irregularities of the phlegmatic humour; and is an elixir vitae. It was originally produced, like nectar, from the ocean by the churning with Mt. Mandara, and inasmuch as it gives victory in the three worlds, it, the delight of the king of the gods, is called vijaya, the victorious. This desire-fulfilling drug was obtained by men on earth, through desire for the welfare of all people. To those who regularly use it, it begets joy and destroys every anxiety [Grierson 1894].
 
The Indian Hemp Drugs Commission of 1893-1894 heard testimony from hundreds of native and Western doctors about its therapeutic uses in treatment of cramps, spasms, convulsions, headache, hysteria, neuralgia, sciatica, tetanus, hydrophobia, ague, cholera, dysentery, leprosy, brain fever, gonorrhea, hay fever, asthma, bronchitis, catarrh, tuberculosis, piles, flatulence, dyspepsia, diabetes, delirium tremens, and impotence; as a sedative and febrifuge (substance that reduces fever); as an analgesic for toothache, tooth extraction and many other acute or chronic pains; as an anesthetic for minor surgery including circumcision; as a diuretic, tonic, digestive, disinfectant, aphrodisiac, anaphrodisiac (substance used to decrease sexual desire), food supplement, appetite stimulant, energy-creator, cool refreshing drink to prevent malaria, cure insomnia, alleviate hunger, and ... for freedom from distress (Kaplan 1969; Mikuriya 1968). In sum, the commission concluded:
 
It is interesting to note that while the [hemp] drugs appear now to be frequently used for precisely the same purposes and in the same manner as was recommended centuries ago, many uses of these drugs by native doctors are in accord with their application in modern European therapeutics. Cannabis indica must be looked upon as one of the most important drugs of Indian materia medica [Kaplan 1969, 175].
 
For this reason, and because of its importance in religious and social life, the commission "unhesitatingly" gave "their verdict against such a violent measure as total prohibition in respect of any of the hemp drugs" (p. 287).
 
Ancient Middle East
 
Mechoulam (1986) provides the best summary of the literary evidence for medical use of cannabis in ancient Assyria, Egypt, and Judea. If the names of plants (azallu, qunnabu, and gan-zi-gun-nu) in Assyrian tablets of the seventh century B.C. are correctly translated as cannabis, the drug was used externally as a bandage and in salves for swellings and bruises, and internally for depression of spirits, impotence, "poison of all limbs" (arthritis?), kidney stones, for a "female ailment," and for the annulment of witchcraft. Similarly, if the hieroglyph "smsm.t." in the ancient medical papyri of Egypt indicates cannabis, it was used as incense, as an oral medication for "mothers and children" (in childbirth?), in enemas, in eye medications, and as an ointment in bandages. This may be its first mention in world literature as an eye medication.
 
Although Benet (1975) interpreted the Hebrew term kaneb-bosm in the Bible as cannabis, there was until recently no direct evidence of medicinal use of cannabis in ancient Judea. However, in 1992 the skeletal remains of a 14-year-old girl who apparently died while giving birth were discovered in a tomb near Jerusalem dating from the fourth century A.D. (Zias et al. 1993). Ashes in the skeleton's abdominal area were analyzed and were found to contain a cannabinoid, delta-6-tetrahydrocannabinol. The researchers concluded that cannabis was burned in a bowl and administered to the girl as an inhalant to facilitate the birth process. Another possibility is that a mixture of cannabis ashes and honey was used for labor pains, as described in the Greek Geoponica for ulcers in the lower back (Brunner 1973). Yet another possibility is that cannabis was burned in a purification rite after her death, as Herodotus describes for the Scythians, who had swept down through Palestine 630 B.C. (Mechoulam 1986; Benet 1975).
 
Central Asia: The Scythians
 
The earliest Greek mention of Kannabis is Herodotus's famous story of the funeral ceremonies of the Scythians in the Histories (c. 450 B.c.). After the death of a king, the Scythians made small head tents, crept inside, threw hemp seeds (or blooms) on red-hot stones in an urn, and "howled for joy" at the vapor (Aldrich 1972). This is the first ethnographic description of a cannabis smoking device in world literature that was later confirmed by modern archaeologists who found kettles containing charred hemp seeds in Scythian tombs in the Altai Mountains (Rudenko 1970) and in Germany (Reininger 1966).
 
In the same book Herodotus (I: 202) also describes the practice of inhabitants of islands in the Araxes river throwing an unidentified fruit on a fire and getting "drunk" by inhaling its fumes (Brunner 1973, 347). This brings to mind the passage in the Atharva Veda, noted above, where Vedic worshippers threw hemp into a fire to ward off evil forces. The ritual intoxicant use of cannabis to communicate with spirits (or ward off evil) is thus found in ancient China, India, Central Asia, and Europe before the Christian era, and this magical use seems to have preceded specific medical uses in each region. Indeed, "folk medicine" tends to preserve ancient rituals simply because many generations have found the rituals medically useful. For example, Benet (1975, 46) notes that "in Poland, Russia, and Lithuania, hemp was used to alleviate toothache by inhaling the vapor from hemp seeds thrown on hot stones," right up into the twentieth century.
 
It is quite possible that Scythian influence may have introduced ritual use of cannabis throughout the Middle East. Scythian cavalry were employed by Philip of Macedon and by Alexander the Great on his campaign across Persia to the Hindu Kush in 326 B.C. (Aldrich 1972). By and large, however, the early references to hemp in Greek and Roman literature are to its fiber and medical uses rather than its ceremonial uses (Brunner 1973).
 
Ancient Greece and Rome
 
Dioscorides, a doctor in Nero's army in the first century A.D., wrote that cannabis seeds, "when eaten in excess, diminish sexual potency. The juice of the fresh seed, dropped in the ear, is beneficial for earaches." He also described a wild cannabis (hemp mallow?) whose roots could assuage inflammations and disperse hard matter about the joints. Pliny the Elder (A.D. 23-79), in his Natural History (20.259), combined these two descriptions and wrote that cannabis seed makes the genitals impotent, and its juice drives worms and insects out of the ears, but "at the cost of a headache." It makes water coagulate, and the boiled root "eases cramped joints, gout and similar pains, and is applied raw to burns" (Brunner 1973). Pliny may have been the first in the world to note that cannabis is not very miscible in water.
 
Galen, the second century physician renowned for making compound drug preparations (still called galenicals), said that cannabis seed is hard to digest and causes headaches; but "cooked and consumed with dessert after dinner, it stimulates the appetite for drinking, and in excess sends a warm and toxic vapor to the head." He added that it "eliminates intestinal gas, and dehydrates [the user] to such a degree that if eaten in excess it quenches sexual potency. Some squeeze juice from the green seeds and use it as an analgesic for pains caused by ear-obstruction" (Brunner 1973, 350). Galen is the only classical author to describe the intoxicating properties of cannabis consumed orally, including appetite stimulation (or at least dry mouth).
 
In these references, medical properties are described for the sperma (seed) of the plant; in many cases the term sperma may also refer to the blossom, the whole top of the flower where cannabis resin is produced. Such descriptions were the basis of European knowledge of medicinal cannabis all through the Middle Ages and the Renaissance. An illustration in a Byzantine manuscript of Dioscorides (c. A.D. 512) is the first botanical illustration of the plant in Western literature. It depicts both male and female flowers on the same plant—a mistake often repeated in later herbals (Aldrich 1992).
 
Medieval Middle East
 
Reviewing the literature from the thirteenth through the sixteenth centuries, Rosenthal (1971) has produced the only modern scholarly work in English on the subject of hashish in medieval Muslim society. Muslim physicians translated Dioscorides and Galen, poets wrote lovely and often satirical poetry contrasting hashish and wine, and theologians debated whether hashish should be forbidden under Muslim law, since, unlike alcohol, it is not expressly forbidden in the Koran. According to the most conservative legalists, the punishment for using hashish as an intoxicant would be 40 to 80 lashes (which would cripple the recipient for life), but the "medical use, even if it leads to mental derangement, remains exempt" from such punishment. Az-Zarkashi, a fourteenth century scholar whose work gives the fullest information on this subject, speaks of "the permissibility of its use for medical purposes if it is established that it is beneficial. ... Thus, it has been stated that it dissolves flatulence and cleans up dandruff." Other medical uses of hashish mentioned in Muslim texts are as a diuretic, to clean the brain, to soothe pains of the ears, and to aid digestion (Rosenthal, 114-115, 126). In this legal distinction between the intoxicant and the medical uses of cannabis, medieval Muslim theologians were far ahead of present-day American law.
 
One of the earliest "case reports" of the value of cannabis in treatment of epilepsy is a story told by Ibn al-Badri (c. A.D. 1464) about a poet who visited the epileptic son of the caliph's chamberlain and gave him some hashish as a medication. "It cured him completely, but he became an addict who could not for a moment be without the drug" (Rosenthal 1971, 152). Mechoulam et al. (1976) also mention this story in their discussion of the anticonvulsant effect of cannabidiol derivatives, one of the most promising new studies of the medical cannabinoids. More recent reviews of the use of cannabis derivatives in epilepsy, seizures, dystonia, and other convulsive and neurological disorders may be found in Mechoulam et al. (1984), Consroe and Snider (1986), Randall (1991a) and in chapters 9 and 10 of this book. An interesting offshoot of the research is that cannabidiol is also being reinvestigated as an anxiolytic (Musty 1984)—which takes modern medicine back full circle to the Atharva Veda's "freedom from distress."
 
Muslims also introduced the art of making hemp paper into Europe, with the first paper mill established in Spain in A.D. 1150 and the second in Italy in 1276. Papermaking finally reached England in 1494. Much of the world's paper contained hemp fiber until the mid-nineteenth century, when sulfite tree pulp processing began to replace hemp paper (Conrad 1993), leading to worldwide deforestation and deterioration in the quality and longevity of books ever since.
 
Africa
 
Du Toit (1980) finds that cannabis has been smoked in Africa for at least six centuries, probably introduced by Arab traders down the east coast from Egypt and certainly having some connection to India as evidenced by the similarity of African and Hindi terms for the drug. Most accounts of native medical use come from white explorers and colonists of the nineteenth and twentieth centuries. The plant was used as a remedy for snake bite (Hottentots), to facilitate childbirth (Sotho), and among Africans of Rhodesia as a remedy for malaria, blackwater fever, blood poisoning, anthrax, and dysentery (Du Toit 1980, 58).
In addition, South African dagga (cannabis) was "famous in relieving the symptoms of asthma. This belief was shared by rural African farm workers and white farmers and many a pipe was shared between persons who suffered from this respiratory congestion" (Du Toit, 59).
 
Renaissance Europe
 
Europe during the Middle Ages did not have hashish and did not know much about the medical uses of the drug even though hemp had been cultivated throughout Europe since Roman times (Godwin 1967). Only one reference to hemp in Anglo-Saxon medicine has survived, that being haenap as an ingredient of a "holy salve" in the Lacnunga, a magico-medical recipe book of about the tenth century (Grattan and Singer 1952, 123). A few crusaders and Marco Polo told the tale of the assassins (eleventh to thirteenth centuries), without stating which drug was used in the potion that gave initiates a glimpse of paradise (Aldrich 1970). The Latin herbal of Rufinis (thirteenth century) mentions it as canape, and many subsequent herbals give crude illustrations of the plant along with its names in European languages. Fuchs's De Historia Stirpium (1542) describes the morphology and cultivation of Cannabis sativa and quotes Dioscorides, Galen, Pliny, and Simeon Sethi about its medical uses. Fuchs has the finest Renaissance illustration of cannabis, drawn from life but still displaying male and female flowers on the same plant (Aldrich 1992).
 
Parkinson, the king's herbalist (1640), summarized most of the herbalist uses of cannabis in treating dry cough, jaundice, fluxes (diarrhea), colic, gout, hard tumors, or knots of the joints, the "paines and shrinking of sinewes," burns or scalds, and to stay bleeding, and to kill worms. These are based on the classical sources with occasional local additions. For example, Parkinson says that a hemp decoction "powred into the holes of earthwormes, will draw them forth, and fishermen and anglers have used this feate to get wormes to bait their hookes" (Mechoulam 1986, 5).
 
Explorers and travelers in Africa, the Middle East, and especially India sent back reports of the use of hemp by natives, reports that were often superficial, always condescending, and usually confused hemp with opium (Aldrich 1970). An outstanding exception is Garcia da Orta's Colloquies on the Simples and Drugs of India (1563), in which a Portuguese physician, who grew cannabis in his own garden in Goa, consulted with native herbalists (as well as household servants), and gave a clear, scientific, and amusing account of bangue. He noted that it is quite distinct from opium, that unlike European hemp it is not used to make cords, and "the Indians eat either the seeds or the pounded leaves to assist or quiet the women. They also take it for another purpose, to give an appetite." (Da Orta 1563).
 
Rabelais (c. 1535), physician and author of Gargantua and Pantagruel, says that juice of the herb Pantagruelion (hemp),
 
kills every kind of vermin ... [and is] a prompt remedy for horses with colic and broken wind. Its root, boiled in water, softens hardened sinews, contracted joints, sclerotic gout, and gouty swellings. If you want to quickly heal a scald or burn, apply some Pantagruelion raw [Grinspoon 1971, 397].
 
Rabelais expands on his main source, Pliny, noting a veterinary use of hemp and specifying its antibiotic ("kills vermin") properties.
 
The antibiotic use was verified by Czech scientists in the 1950s in a remarkable series of experiments (Kabelik, Krejci, and Santavy 1960; Rubin 1976) that showed "hemp extract proved itself valuable often when all modern antibiotic measures, including Terramycin [and others] failed." The Czech researchers also confirmed the value of cannabis unguent or spray in the treatment of burns, and found, as Dioscorides had said almost 2,000 years earlier, cannabis extracts achieved "rapid success" in the treatment of otitis media—earache (Rubin 1976, 6-7).
 
Eighteenth Century: Botany and Bounties
 
European botany lagged behind Chinese knowledge of the two sexes of the plant by several thousand years. In most pre-Linnaean botanical authors, the longer-living bushier plant was called male and the other one female—which iA the opposite of the true situation in regard to cannabis, where the bushier pistillate plant is female (Steam 1974). Hemp cultivation manuals, such as that appended to Barrufaldi's book of hemp poetry (1741), showed pictures of both sexes but reversed. Linnaeus corrected this mistake when he classified the plant as Cannabis sativa in 1753, and a few years later he grew cannabis on his windowsill and showed incontrovertibly that cannabis is dioecious by separating the male (staminate) and female (pistillate) plants at various stages of development (Linnaeus 1760; Steam 1974). In 1783 the French naturalist Lamarck described Cannabis indica as a separate species based on a specimen collected in India, and botanists are still debating whether there are one, two, or three distinct species of this cultigen (Schultes et al. 1974).
 
From the sixteenth to the eighteenth centuries, military demand for cannabis (ship rigging and sails) and its widespread use for textiles and rope made all the royal houses of Europe command that their colonies grow hemp (Abel 1980; Conrad 1993). The Ludlow Library in San Francisco has originals of two of the most famous royal hemp edicts. In 1764 King George III offered American colonists a bounty of eight pounds sterling for every bale of raw hemp delivered to London, to which Ben Franklin's reply was, "We have not yet enough for our own consumption" (Abel 1980, 80). In 1788 the viceroy of Mexico ordered the mission at Monterey to plant hemp, thus starting hemp cultivation in California (Aldrich 1992).
 
So that the United States would not have to depend on England and Russia for hemp, George Washington tried, not very successfully, to grow hemp for seed at Mt. Vernon in the 1790s. And Thomas Jefferson invented a new type of hemp brake to mitigate the hard labor of extracting the bast fibers from hemp stalks (Conrad 1993, 304-305). Although African slaves may have known about cannabis intoxication, there is no evidence that the American plantation owners used it for intoxicating or medical purposes.
 
Nineteenth Century Europe: Cannabis Therapeutics
 
During Napoleon's disastrous expedition to Egypt in 1798, many of his troops discovered the pleasures of hashish, and his apothecary Rouyer wrote an article about the Egyptians' use of the drug in 1810 (O'Shaughnessy 1839). Interest in North African hashish and the assassins legend was the context in which the "Club des Haschichins" was founded in Paris in the 1840s, attracting the cream of French literary society (Aldrich 1970; Mickel 1969). One of its founders was Jacques Joseph Moreau de Tours, who began experimenting with the drug as a psychotomimetic (thinking cannabis intoxication might provide some insight into the genesis of mental illness) and as a possible treatment for fixed ideas in depressed patients (Moreau 1845). Although neither approach was successful, Moreau is justly regarded as the father of modern psychopharmacology.
 
It was not Moreau, however, but William B. O'Shaughnessy, a young Irish doctor serving the British Raj at the Medical College of Calcutta, who in 1839 introduced cannabis into Western medicine. By 1831 O'Shaughnessy had already discovered the modern fluid electrolyte treatment for cholera and would later be knighted by Queen Victoria for establishing the telegraph in India (Moon 1967).
 
After studying the literature on cannabis and conferring with contemporary Hindu and Mohammedan scholars, O'Shaughnessy tested the effects of various hemp preparations on animals, before attempting to use them to treat humans. Satisfied that the drug was reasonably safe, he administered preparations of cannabis extract to patients, and discovered that it had analgesic and sedative properties. O'Shaughnessy successfully relieved the pain of rheumatism and stilled the convulsions of an infant with this strange new drug. His most spectacular success came, however, when he quelled the wrenching muscle spasms of tetanus and rabies with the fragrant resin [Mikuriya, 1973].
 
He also gave cannabis tinctures to cholera victims during an epidemic and found that ten drops every half hour would usually stop the vomiting and diarrhea that make the disease fatal (O'Shaughnessy 1839). This seems to be the first mention in European clinical literature of cannabis as an antiemetic.
 
Any drug that demonstrated success in the treatment of the most wretched diseases of the nineteenth century—rabies, tetanus, cholera—would be hailed as a wonder drug; and that's what happened when O'Shaughnessy brought his research back to London along with specimens for the Royal Botanical Gardens. Between 1840 and 1900 more than 100 articles about the therapeutic value of cannabis were published in Europe and North America (Grinspoon 1971).
 
Mikuriya (1973) collected the key nineteenth and twentieth century documents and summarized them in Marijuana: Medical Papers, 1839-19 72. Other detailed accounts of cannabis therapy in the nineteenth century may be found in Mikuriya (1969), Grinspoon (1971), Snyder (1971), Carlson (1974), Cole (1976), Cohen and Stillman (1976), Abel (1980), and Mechoulam (1986). Mikuriya (1973) lists the following therapeutic applications of cannabis based on the literature:
 
1. Analgesic-hypnotic
2. Appetite stimulant
3. Antiepileptic and antispasmodic
4. Prophylactic and treatment of the neuralgias, including migraine
5. Antidepressant and tranquilizer
6. Antiasthmatic
7. Oxytocic (stimulates uterine contractions in childbirth)
8. Childbirth analgesic
9. Antitussive
10. Topical anesthetic
11. Withdrawal agent for opiate and alcohol addiction
12. Antibiotic
 
Queen Victoria's physician, Sir J. Russell Reynolds (1890), summed up 30 years of clinical experience with the drug finding it useful as a nocturnal sedative in senile insomnia and valuable in treating dysmenorrhea, neuralgias including tic douloureux and tabetic symptoms, migraine headache, and certain epileptoid or choreoid muscle spasms. He thought it less beneficial in asthma, alcoholic delirium and depressions, joint pains, or true epilepsy. He also advised doctors to start with very small doses of cannabis extracts and tinctures, gradually increasing the dose until relief is obtained; "with these precautions I have never met with any toxic effects" (Mikuriya, 1973, p. xviii).
 
Nineteenth—Twentieth Century America: Cannabis Therapeutics
 
Fitz Hugh Ludlow made a perceptive prediction in America's first drug book, The Hasheesh Eater (1857, 368): "Except as an antispasmodic in a very limited number of diseases, the cannabis is known and prized very little among our practitioners, and I am persuaded that its uses are far wider and more important than has yet been imagined." Ludlow also appended an article by an American physician, J.W. Palmer, which summarized O'Shaughnessy's work and recommended it to American doctors especially in hydrophobia and tetanus.
 
The first American clinical conference on medical marijuana was a meeting of the Ohio State Medical Society in 1860, which reported successful treatments of stomach pain, childbirth psychosis, chronic cough, gonorrhea, and marijuana's general usefulness as an analgesic for inflammatory or neuralgic pains (McMeens 1860). The Civil War edition of the U.S. Dispensatory (Wood and Bache 1868) devoted four pages to the medical properties of Extractum Cannabis, including its action as "a decided aphrodisiac, to increase the appetite, and occasionally to induce the cataleptic state ... to cause sleep, to allay spasm, to compose nervous inquietude, and to relieve pain." It was preferable to opium because it did not cause constipation, and it was recommended specifically for "neuralgia, gout, rheumatism, tetanus, hydrophobia, epidemic cholera, convulsions, chorea, hysteria, mental depression, delirium tremens, insanity, and uterine hemorrhage." The book also mentioned that Dr. Alexander Christison in Edinburgh had "found it to have the property of hastening and increasing the contractions of the uterus in delivery" based on clinical experiments to confirm its ancient use in childbirth.
 
Laboratories around the world experimented with different tinctures and extracts of cannabis, searching for a standard preparation with an established dose-response curve. Problems with the variable potency of such preparations led to the inclusion of cannabis itself—"the flowering tops of the female plant of C. sativa"—in medical practice. The U.S. Dispensatory of 1899 finally noticed that when ganja is cultivated in India, "The utmost care is taken to prevent fertilization, it being affirmed that a single male plant will spoil a whole field" (Wood, Remington, and Sadtler 1899). This forced American pharmaceutical companies to learn what is now called sinsemilla cultivation, removing male from female plants before seeds are set, and by 1918 it was shown that American-grown cannabis and its extracts were as fully reliable as those from India. By the 1930s both Eli Lilly and Parke-Davis were marketing cannabis extracts and tinctures that were uniformly effective at dose levels of 10 mg (Mikuriya and Aldrich 1988).
 
Amazingly little clinical work was done to investigate the smoking of cannabis for medical purposes. Walton (1938, 49) reports that in 1899 a researcher named Dixon experimented with powdered ganja and noted the ease with which patients titrated their own dose, with "little danger of taking an excess." He considered that smoking cannabis was "a satisfactory expedient in combating fatigue, headache and exhaustion, whereas the oral ingestion of cannabis results chiefly in a narcotic effect which may cause serious alarm."
 
This is very similar to the reports of present-day AIDS patients who much prefer smoking cannabis to taking Marinol pills (Randall 1991b, 99-112). So far the United States government has rejected a well-designed research project proposed by Dr. Donald Abrams and his colleagues at the University of California, San Francisco to compare the value of smoked marijuana to that of oral THC pills as a treatment for the wasting syndrome accompanying AIDS (Klinger 1995).
 
Straub (1931) also emphasized the self-regulation of dosage with smoking due to the rapid absorption of the smoke, leading to milder and shorter-acting effects. Walton (1938, 49) remarked that despite these recommendations, "the smoking of cannabis as a medicinal has been very limited," mainly to the anti-asthma cigarettes of Grimault & Company. Today the value of aerosol cannabis as a bronchodilator for asthma attacks is being investigated (Graham 1986). Robinson (1912) stated,
 
In medicinal doses cannabis is used as an aphrodisiac, for neuralgia, to quiet maniacs, for the cure of chronic alcoholism and morphine and chloral habits, for mental depression, hysteria, softening of the brain, nervous vomiting, for distressing cough, for St. Vitus' Dance, and for ... epileptic fits of the most appalling kind. It is used in spasm of the bladder, in migraine, and when the dreaded Bacillus tetanus makes the muscles rigid. It is a uterine tonic, and a remedy in the headaches and hemorrhages occurring at the final cessation of the menses. It has been pressed into the service of the diseases that mankind has named in honor of Venus [sexually transmitted diseases] ... [It] is sometimes useful in locomotor ataxia ... the intense itching of eczema ... as a hypnotic ... as a specific in hydrophobia ... Hemp enters into four galenicals; in chloral and bromine compound which is used as a sedative and hypnotic, in chloroform anodyne which is used in diarrhoea and cholera, in Brown Sequard's antineuralgic pills, and in corn collodions. Hemp is a constituent in the majority of corn remedies. Not many drugs are used for both the brain and the feet, but with cannabis we have this anomaly: a man may see visions by swallowing his corn-cure [30-32].
 
Robinson's little joke obscures an important point in the history of drug delivery systems, namely that cannabis corn plasters were among the first transdermal patches employed in medicine for timed release of water-insoluble drugs through the skin.
 
Sajous's Analytic Cyclopedia of Practical Medicine (1924) succinctly summarized early twentieth century cannabis therapy in three areas:
 
1. As a sedative or hypnotic in insomnia, senile insomnia, melancholia, mania, delirium tremens, chorea, tetanus, rabies, hay fever, bronchitis, pulmonary tuberculosis, coughs, paralysis agitans, exophthalmic goiter, spasm of the bladder, and gonorrhea.
 
2. As an analgesic in headaches, migraine, eye-strain, menopause, and brain tumors; tic douloureux, neuralgia, gastric ulcer, gastralgia (indigestion), tabes, multiple neuritis, and pain not due to lesions; in uterine disturbances, dysmenorrhea, subinvolution and chronic inflammatory states, menorrhagia and impending abortion, postpartum hemorrhage, acute rheumatism, eczema, senile pruritus, tingling, formication and numbness of gout, and for relief of dental pain.
 
3. Other uses to improve appetite and digestion, for the "pronounced anorexia following exhausting diseases," also in gastric neuroses, dyspepsia, diarrhea, dysentery, cholera, nephritis, hematuria, diabetes mellitus, cardiac palpitation, vertigo, sexual atony in the female, and impotence in the male.
 
Marihuana Tax Act, 1937-1969
 
While police waged campaigns against the "marihuana menace," medical use of cannabis preparations began to decline in the 1930s as they were gradually replaced by synthetic drugs. When the United States House of Representatives held hearings on the Marihuana Tax Act of 1937, Dr. W.C. Woodward of the American Medical Association (AMA) was the only witness who opposed the bill. The legislative activities committee of the AMA wrote to protest the impending legislation (Grinspoon 1971):
 
There is positively no evidence to indicate the abuse of cannabis as a medicinal agent or to show that its medicinal use is leading to the development of cannabis addiction. Cannabis at the present time is slightly used for medicinal purposes, but it would seem worthwhile to maintain its status as a medicinal agent.... There is a possibility that a restudy of the drug by modern means may show other advantages to be derived from its medicinal use [p. 226].
 
Against all medical advice, the Marihuana Tax Act was passed in 1937 and cannabis preparations were removed from the United States pharmacopoeia in 1941 (Bonnie and Whitebread 1974). As Walton (1938, 162) noted, "Sasman in 1937 listed 28 pharmaceuticals which contained Cannabis indica. Most of the manufacturers are now removing cannabis from such combinations since the 1937 federal restrictions make it inconvenient to use such formulae."
 
Only a few years later, the LaGuardia Committee took a clear-headed look at the marijuana "problem" in New York and found most of the police claims that it caused crime, violence, insanity and death were completely unsubstantiated. In regard to medical use, the LaGuardia Report said,
 
Marihuana possesses two qualities which suggest that it might have useful actions in man. The first is the typical euphoria-producing action which might be applicable in the treatment of various types of mental depression; the second is the rather unique property which results in stimulation of the appetite [1944, 147].
 
It is interesting that the committee did not shrink from commending euphoria itself as having therapeutic potential, and that it noted more than 50 years ago the greatest contemporary (1990s) use of cannabis as an appetite stimulant for patients with cancer or AIDS.
 
1970s-1990s: Rediscovering Medical Marijuana
 
In 1969, the United States Supreme Court ruled in the case of Timothy Leary that the Marihuana Tax Act could no longer be enforced because, had Dr. Leary tried to pay the tax on cannabis required by federal law, he would have broken Texas state law prohibiting possession of marijuana. This meant President Richard M. Nixon had to rewrite the federal drug laws in 1970, when marijuana was associated with war protesters and hippies, rather than with medical patients. The Controlled Substances Act of 1970 placed illicit drugs in one of five schedules, and the final decision about which schedule a drug was put in was made not by medical experts but by the Justice Department—the attorney general (John Mitchell) and the Bureau of Narcotics and Dangerous Drugs, later named the Drug Enforcement Administration (DEA). Cannabis and its derivatives were placed in Schedule I, for drugs with a high potential for abuse and no medical use (Baum 1996).
 
Ironically, two new medical uses were discovered shortly after the law was passed. The first was the ability of cannabis to reduce intraocular pressure (Hepler and Frank 1971; Hepler, Frank, and Petrus 1976; Roffman 1982; Colasanti 1986; Adler and Geller 1986), which suggested its use as a treatment for glaucoma. Robert Randall, a schoolteacher suffering from glaucoma who was arrested for using cannabis to keep from going blind, fought his case through the courts and finally in 1976 forced the federal government to provide him with cannabis for this purpose—the first legal marijuana smoker in the United States since 1937 (see the articles by Randall and West, in chapters 7 and 8 of this book).
 
The second discovery can be considered new because of a new context, the horrors of more than 40 kinds of chemotherapy used by contemporary doctors as treatment for cancer (Roffman 1982). The most frequent toxic side effect of chemotherapy is violent, uncontrollable nausea and vomiting that lasts for hours, and conventional antiemetics often do not help. Patients who smoked cannabis before chemotherapy, however, reported to their doctors that the illegal drug helped them enormously, stopping the vomiting and even making them hungry (Grinspoon and Bakalar 1995). This led to many clinical reports on the antiemetic effect of cannabis and the cannabinoids, starting with Sallan, Zinberg, and Frei (1975). Most of the research in this field has been summarized by Regelson et al. (1976), Roffman (1982), Levitt (1986), and Randall (1990) (see Dansak's review in chapter 5 of this book). The successful use of cannabis in cancer chemotherapy led to the marketing of an expensive synthetic tetrahydrocannabinol under the name Marinol and the rescheduling of this synthetic drug into Schedule II, though the plant and THC extracted from the natural source, remain in Schedule I.
 
The proven antiemetic value of cannabis also led to its use by many AIDS patients in the 1980s, both as an appetite stimulant against the AIDS wasting syndrome and as a remedy against the intense nausea often caused by the HIV's gradual takeover of the immune system and by the toxicity of AZT therapy. There are AIDS and cancer patients all over the country using cannabis for these purposes, regardless of the laws. Ironically, so many people with AIDS applied for admission to the federal "Compassionate Access" program for marijuana that in 1992 the United States Department of Health and Human Services shut down the only way for people to get this medicine legally (Randall 1991b). The use of Marinol in Schedule IT is allowed in AIDS wasting syndrome, but the plant itself is not (see Krampf's review in chapter 6 of this book).
 
In San Francisco, a major AIDS epicenter, voters in 1991 approved a local ballot proposition recommending that cannabis be restored to the list of approved medicines by nearly 80 percent, the largest popular vote for marijuana in world history. As a result, the San Francisco board of supervisors approved a resolution in 1992 recognizing the therapeutic value of cannabis in AIDS, glaucoma, cancer, spastic and convulsive diseases, for the control of chronic pain and any other healing purposes. The resolution stated that arresting patients for medical use of marijuana would be the lowest of police enforcement priorities as long as patients obtained a letter of diagnosis from their physician. As a result, Dennis Peron was able to establish the Cannabis Buyer's Club, along the lines of AIDS drug buyer's clubs, which allows more than 10,000 registered patients, mostly people with AIDS, cancer, and painful paraplegic or spastic conditions (see Petro's review in chapter 9), to use the drug therapeutically without fear of arrest (Rathbun and Peron 1993). Cannabis clubs have also sprung up in several other cities. Bills approving the medical use of marijuana have passed the California legislature three times and have been vetoed by Governor Pete Wilson. A statewide initiative (Proposition 215) allowing doctors to prescribe, and patients to use, cannabis without fear of arrest was passed (by 56 percent) on November 5, 1996, as did a similar initiative in Arizona, Proposition 200 (by 65 percent). They cannot be vetoed by the governor; whether they can supersede the federal Schedule I classification will be for the courts to decide.
 
The improper classification of cannabis in Schedule I was challenged in 1972 by the National Organization for Reform of Marijuana Laws (NORML). For decades NORML, the Alliance for Cannabis Therapeutics (ACT), and other groups have petitioned the courts for hearings on rescheduling medicinal marijuana. Finally hearings were held in 1986, with dozens of doctors, patients, and health experts testifying that marijuana should at least be placed in Schedule II, for drugs with medical use and some potential for abuse (Grinspoon and Bakalar 1995). Testimony from the hearings has been published in a series of five books written and compiled by Randall (1988-1991).
 
On September 6, 1988, the DEA's own administrative law judge, Francis L. Young, ruled that,
 
The evidence in this record clearly shows that marijuana has been accepted as capable of relieving the distress of great numbers of very ill people, and doing so with safety under medical supervision. It would be unreasonable, arbitrary and capricious for DEA to continue to stand between those sufferers and the benefits of this substance in this record.
 
The administrative-law judge recommends that the (DEA) Administrator conclude that the marijuana plant considered as a whole has a currently accepted medical use in treatment in the United States, that there is no lack of accepted safety for use of it under medical supervision and that it may lawfully be transferred from Schedule I to Schedule II. The judge recommends that the Administrator transfer marijuana from Schedule I to Schedule II [Young 1988].
 
That should have been the end of it. Medical experts had shown conclusively that there is an accepted medical use for cannabis in the United States, and the DEA's own judge had agreed that it should be placed in Schedule II, where it belongs according to the definitions in the law itself. Nonetheless, on December 29, 1989, DEA Administrator John Lawn ignored the recommendations and findings of fact and stated that the DEA would not allow the rescheduling.
 
And on a February morning in 1994, the U.S. District Court of Appeals in Washington, D.C., with a panel of three judges, issued a finding indicating that in its opinion cannabis has no medicinal value—none.
 
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