Cannabinol

Cannabis sativa is a plant with a long and controversial history of use in food and medicine around the world. In this column I will examine this plant in cross cultural perspective as well as recent findings from clinical studies on its medical applications and interest among pharmaceutical companies. In particular, I will explore its applications in the management of pain, as occurs with fibromyalgia, MS and other related health conditions. This paper is the culmination of early research I performed for a natural products company. Much of this information is drawn from the excellent text by Conrad (1997) on this subject.

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Traditional Use

In traditional medicine (Conrad 1997) formulas containing hemp's seed or flowering tops were frequently recommended for difficult childbirth, menstrual cramps, rheumatism and convulsions, earaches, fevers, dysentery, epilepsy and insomnia, as well as to soothe nervous tension, stimulate appetite, and serve as an analgesic and aphrodesiac.

The oldest confirmed medical use of cannabis was in China in 3750 B.C.A philosopher farmer named Shen Nung produced the first reported pharmacopoeia, the Pen Ts'ao which listed hemp, ta ma, as a superior immortality elixir. The female plant was said to possess yin energy as opposed to the male plant's yang energy and was recommended for "female weakness," rheumatism, beri-beri, malaria, constipation, gout and absent-mindedness, among other ailments. Hempseed is discussed in the 16th century Chinese manuscript Pen T'sao Kang Mu of Li Shih-chen. He described the ability of the seed to increase chi, slow aging, enhance circulation, preventing stagnation of lymphatic fluid, increase flow of milk in nursing mothers and help paralysis. Li also claimed a shampoo of the seed would accelerate hair growth.

In the second century BC, Pliny the Elder prescribed hempseed for constipation, the herb for earaches, and root poultices to ease cramped joints, gout and burns. His contemporary, Galen, described how Romans would fry and consume the seed with desserts. With the collapse of the Roman Empire and the Dark Ages, the use and study of hemp was put on hold. The Inquisition banned use of the scientific method and herbal medicine in Europe in favor of the medieval Church, magic and witch-hunts.

Hemp was used in Ayurvedic medicine for the alleviation of migraine headaches and stomach spasms, as an analgesic, antispasmodic, to promote digestion, and to assist in the flow of urine. India is so heavily steeped in the cultural and spiritual use of resinous cannabis that its people won a cultural exception to the UN Single Convention Treaty on Narcotic Drugs. It allows them to continue to consume the plant, known as ganga. The Vedas are ancient writings that serve as the foundation of Hindu civilization. Ganga, like many other important medicinal plants, is said to have originated from the primordial nectar which arose during the churning of the oceans. Ganja is used by priests and yogis (to trigger meditation), devotees of Shiva and other gods (for ceremonies), people who perform hard physical labor and athletes such as the wrestlers called Chaubes (to relieve pain and fatigue), and people who are ill (to relieve their illness.) The female plant is acknowledged to contain the most potent medicinal effects.

Ganja is consumed as an ingredient in various foods, such as barfee, laddoo, sarabat (sweet drink), and a chewy green honey candy called ma'joun. Raw cannabis is chewed, sometimes along with the stimulant betel leaf. And finally, people smoke it through a chillum, a chimney-style pipe used by Sadhu monks. It is consumed in powdered form (curna), lumped into a bolus (modaka), pressed into a tablet (vatika), used as a tincture (leha and paka), boiled with milk (dugdhapaka) and boiled in water to produce a decoction (kvatha.)

Cannabis is seldom used alone but is combined with other medicines to reduce its natural psychotropic effects or broaden its therapeutic applications. It is considered appropriate for both healthy and ill people to consume cannabis in Ayurveda. Healthy people consume it as an aphrodisiac and rejuvenating agent. To reduce its psychotropic effects, a pinch of powdered calamus root is taken with honey in the morning and evening.

Rejuvenation therapies using cannabis usually involve mixing 500 grams of the powdered plant with 50g each of other medicinal herbs in a liter of milk with ghee and honey. Doses are 5 grams each. The catch is that one usually also has to live in a closed-up house for three years, be celibate, and eat only milk and rice. If one does this periodically one is said to be able to live free of disease or old-age for three hundred years.

During the European Renaissance, European explorers returned from Africa with reports of the use of hemp to treat malaria, blackwater fever, dysentary, blood poisoning, and anthrax.

Culpeper's classic pharmacopoia The Complete Herbal mentioned the use of cannabis to treat cough. In the early 19th century Europeans travelling in Africa and Asia further expanded our knowledge of the use of hemp. William B. O'Shaughnessy, the British East India Company surgeon in Calcutta, noted that it helped relieve the pain of rheumatism and calm convulsions of infants as well as the muscle spasms of tetanus and rabies. The United States Dispensatory first listed it in 1854. It noted that extracts have been found to produce sleep, allay spasm, relieve pain and calm nervousness. It was recommended for neuralgia, gout, tetanus, phobias, cholera, convulsions, spasticity, hysteria, mental depression, insanity and uterine hemorrhage. It was used in a number of pharmaceutical preparations including Eli Lilly's Dr. Brown Sedative Tablets, and products by Parke Davis and Squibb. In the early 20th century the hypodermic needle was invented. Since cannabinoids are fat soluble they cannot be dissolved in water or injected into the bloodstream easily. As a result, therapeutic use of cannabis began to decline.

Neurological Disorders

Unlike alcohol, some research suggests cannabinoids do not harm brain cells or nerve tissue. In fact, people have THC receptors in their brains, clustered in the cerebral cortex, the home of higher thinking, perception, emotions, and cognition, as well as the hippocampus, home of memory, cerebellum and striatum, associated with movement, and basal ganglia, associated with control and coordination.

The arrangement of these receptor sites indicates that THC analogs and antagonists might eventually be useful for symptoms of movement disorders like the tremors of Parkinson's disease and Huntington's chorea as well as Alzheimer's. Cannabis may ease neurological and muscle problems associated with diseases such as multiple sclerosis (MS) including cramps, spasticity and ataxia. Amputees who experience the phantom limb effect and spasticity caused by spinal cord injury may also be relieved. Cannabis is useful for pain control and is used by peasant farmers in Poland, Russia and Lithuania who inhale the vapors of smoldering seedling tops of hemp plants thrown onto hot stones.

Cannabis is useful for migraines and was taken with a tincture of yellow jasmine for this purpose before antipyrine and its cogeners were introduced. It combines an analgesic and anti-emetic and may help the patient sleep as well. Once an attack is underway, sleep in a dark room is the best solution. Some patients find that only a few puffs and a short nap completely control migraine attacks once the symptoms of flickering visuals begin.

Cannabis may be useful for depression since it moderates the manic mood swings experienced by manic depressives, including calming the manic rage. It also provides a distraction from traumatic or distressing life situations as noted among US troops in Vietnam. The US government has studied this effect in New Mexico using veterans suffering from Post-traumatic Stress Disorder. Symptoms include flashbacks and sudden fits of anger, anxiety, and depression. Gulf War veterans have reported similar benefits. Recent evidence suggests these troops were exposed to nerve gas.

One of the most consistent and marked symptoms of cannabis use is the sensation of prolonged time. In addition, a separation of the mental faculties occurs, during which one functions as both a participant and an observer. However, an advantage of cannabis over other mood-altering drugs is that the patient remains fully functional and in control. Cannabis smokers retain their mental faculties, personal responsibility and mental clarity. They remain aware of their physical pains and problems but also feel a sense of detachment that helps them keep things in proper perspective. This allows terminally ill patients to face their deaths with courage and dignity. The 19th century physician Williams O'Shaughnessy poetically described this effect as enabling the physician to "strew the path to the tomb with flowers."

Unfortunately, it's not easy to establish the cannabinoid profile of a given sample of herb. The process requires gas chromatography which is expensive. What we do know is that the biochemical pathway of the cannabinoids in the body is from olivetol to CBG (cannabinol), then to either CBC (cannabichromene) or CBD (cannabidiol), then to THC. The body performs this biochemistry by adding a hydroxyl group (hydrogen plus oxygen) to the molecule's terpene carbon. This occurs most readily in the liver and in digestion which may explain why eating the herb can cause much stronger effects.

The US government claims that THC is the only medically active drug in cannabis which justifies its acceptance of synthetic THC pills as a legal prescription drug while banning natural cannabis. The most important non-psychoactive compound in cannabis is CBD which occurs in greater concentrations in industrial hemp. Cannabidiol is a precursor in the organic pathway of the cannabinoids. It tends to maintain an inverse relationship with THC. Hence, industrial hemp is very low in THC but high in CBD. CBD acts as a chemical buffer to THC and suppresses its effects including increased pulse rate, time distortion and the anxiety response. CBD may be useful for convulsions, movement disorders and symptoms of Huntington's disease, as an anti-inflammatory (it is more effective than aspirin), aid for insomnia, and anti-psychotic. Many of these conditions respond well to natural cannabis but not to THC alone. The fatigue-inducing properties of marijuana leaf (high in CBD) in particular have made it a popular treatment for insomnia. Interestingly, cannabinoids are also found in chocolate which may contribute to the subjective feelings associated with eating chocolate.

Glaucoma

Cannabis flower can lower fluid pressure inside the eyeball itself which builds to high levels in diseases such as glaucoma (which accounts for 15% of blindness.) Regular use of the herb may help hold down the pressure and prevent this painful process. Cannabis drugs reduce IOP in animals as well as or better than conventional pharmaceutical drugs with fewer or no medical side effects. Orthodox medicine opens up drainage ducts, much like an engineer would, to lower ocular pressure using drugs or surgery. Cannabis works like nature to let the water spread out and be absorbed into marshes that suck the water down into an underground water table. Cannabis also dehydrates the eyes thereby reducing the volume of fluid that is trying to pass through them. Unlike currently legal drugs, cannabis does not cause damage to the liver or kidneys.

Resination (use of cannabis) causes bloodshot eyes. However, this is simply due to dilation of blood vessels which makes them more visible--not ruptures in blood vessels. No loss of objective visual acuity or perception of light brightness is caused by cannabis. In fact, increased sensitivity to light indicates improved night vision. Local fishermen who smoke cannabis or drink a beverage made of it have an increased ability to see in the dark, according to some anthropological studies.

Topical Applications

The flowers and leaves of the cannabis plant are a common topical folk remedy for the relief of swollen joints, inflammation, fever, infection, superficial injuries, burns, and rheumatism. In Mexico and Central America, cannabis leaves soaked in alcohol have traditionally been wrapped around aching, arthritic joints. The New English Dispensatory of 1764 recommends boiling cannabis roots in water and applying the paste to skin inflammations. The boiled root was also applied as a poultice to soothe joint pains and reduce inflammations.

The juicy resin pressed from the flowering industrial hemp plant with ripe seeds rich in CBD are very useful for burns, and as an antibiotic against bacterial infections that might invade a wound or the ear, nose, and throat. The extract was found to help control oral herpes and ulcerative gingivitis. Extracts of unripe cannabis tops demonstrate antibiotic activity against certain bacteria and fungi. CBD is effective against strains of staphylococcus that are resistant to penicillin and other antibiotics. In one study THC injected into tumors in the lungs of mice causes a 28 to 82% reduction in tumor size.

Juice of cannabis was used by the Roman physicians of the second century A.D., Pliny the Elder and Galen, as an analgesic for ear pains. In England the 1645 Compleat Herbal suggested using cannabis juice to eliminate earwigs. Culpeper's 1814 Complete Herbal agrees that the seeding flower can help expel worms in humans and other animals.

The Greek historian Herodotus described Scythians in 450 BC using hemp to purify and cleanse themselves which made their skin shining and clean. Today, a growing number of hempseed based personal hygiene products are on the market as soaps, shampoos, salves, cosmetics, and other skin and hair care items. Essential fatty acids are being researched to treat epidermal conditions such as psoriasis and eczema.

Eating Disorders

Cannabis causes the mouth to dry which increases appetite to moisten the palate. It is used clinically to treat people with anorexia nervosa, wasting caused by AIDS, tuberculosis, and cancer. It helps settle the stomach of people with motion sickness. Cannabis can control the nausea triggered by chemotherapy and radiation treatments. This may be caused by the resin's antispasmodic effect which suppresses the gag reflex and relaxes abdominal muscle spasms.

Cardiopulmonary Disorders

Smoking Cannabis introduces resin into the depths of the lungs where the drug is quickly absorbed across the alveolar membranes into the bloodstream. This avoids the liver and is a much more efficient way to introduce the drug into the body. Unlike tobacco smoke Cannabis appears to cause minimal damage to the lungs.

Cannabis speeds the heart rate by 10-40 beats per minute in response to THC doses of 2-70 mg. It also expands the blood vessels, improving blood flow throughout the vascular system which may lower blood pressure and help reduce stress. The breath rate is slowed as shown by studies of ascetics in India who used it for religious purposes. This may also reduce stress. A cooling of the body occurs, especially the extremities, explaining its historic use for fevers.

By dilating the bronchi and bronchioles (tiny air tubes in the lungs) and relaxing the bronchial muscles, cannabis can help control asthma. This increases exchange of gases in the lungs and total oxygen flow. A few puffs can bring fast relief to an asthma attack. The shallowness of breath, headaches, chest pains, and other symptoms of exposure to heavy smog might be alleviated by use of cannabis.

Cannabis is also an expectorant that helps the patient break up and expel phlegm and clear out congested air passages.

Reproductive Health

Cannabis has traditionally been used to control morning sickness, speed labor (by increasing uterine contractions), and wean children from breast-milk, in Africa, the Middle East, and Asia. It is also a sexual stimulant and dilates vasculature which increases blood supply to the reproductive organs causing erection in males and production of vaginal fluids in the female.

Nutrition

While the medicinally active compounds in hemp, the cannabinoids, require extraction in hot oil, alcohol tinctures, burning, or other techniques for use by the body, other components are available as nutrients with minimal processing. Hempseed is grown extensively in the former Soviet Union as a food and is consumed as an oatmeal. Drinking beverages made with boiled hempseed have been featured in the medical literature for millennia as a soothing remedy for coughs and throat irritations. Eating the seed lubricates the bowels and is a traditional treatment for constipation, diarrhea, and digestive problems.

Hemp is rich in linoleic acid (also called omega 6), a type of essential fatty acid, deficiency of which may cause infections, impaired wound healing, retarded growth, miscarriage, male sterility, skin eruptions, arthritic symptoms, behavioral disturbances, dehydration, liver or kidney degeneration, heart problems, poor blood circulation and hair loss. Hempseed is the highest in essential fatty acid of any plant, up to 81% of total oil volume. Raw hempseed oil is among the lowest in saturated fats, at just 8% of total oil volume.

Hempseed is also a good source of gamma-linolenic acid (GLA), a particularly rare oil that is so beneficial to human growth and development that it is a component in mother's milk. Before hempseed was available once again, Americans have been able to obtain GLA only by consuming borage, black currant, or evening primrose seed oils. The oil's optimum refrigerated shelf life is less than 2 months after the seed has been pressed or the sealed container opened. Rancidity is measured by the Peroxide Value or PV (how many by-products of oxidation have formed as milli-equivalents per kilogram). If an oil has a strong or bitter smell, use it topically only. This number should be less than 10 PV. Cold pressed oils are best for consumption as heating the oil destroys much of the nutritional value.

The seed can be ground or sprouted. One pound of seed will yield three pounds of sprouts. Even sterilized hempseed will sprout though it will not germinate and grow into a viable plant. Like soybean, hempseed extracts can be made into vegetable milk. The seed is rich in dietary fiber, carotene, vitamins B1, B2, B3, B6, C and E. About 35% of the seed is fatty acids. The seed also contains a complete protein. The protein in hemp is more digestible than soy protein due to edestin, a special type of protein. Steam sterilization slightly reduces digestibility of the protein.

Recent Research

Many companies and organizations are now actively researching uses of Cannabis for nutrition and pharmaceutical products. Below is a brief review of some of this research.

Dr. Donald Abrams at University of California at San Francisco (UCSF) in partnership with Charlotte, North Carolina-based Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit organization that supports research into psychedelic drugs and marijuana is studying marijuana, for flagging appetites and nausea as well as its safety with protease inhibitors. This teamwork has resulted in an application to the National Institute on Drug Abuse (NIDA) in Rockville, Md., to obtain marijuana in order to study its effects on people with HIV/AIDS. NIDA dragged its feet but finally granted Abrams a small $1 million grant. While Marinol is prescribed for nausea, many AIDS patients say they cannot keep the pills down and they are slower to take effect and to wear off than the smoked version. Abrams research has looked at patients' caloric intake, body weight and body composition (of fat and muscle), as well as the effects of marijuana and THC on protease inhibitor metabolism.

Alterna, a hair-care company that uses hemp seeds in products, granted researchers a $200,000 grant to study industrial hemp in Hawaii. While some states have moved to allow hemp growing, Hawaii is among the first to get a test project going. University of Hawaii plant geneticist David West who leads the research, notes that hemp seed oil contains essential fatty acids, protein and other vital elements, and serves as a base for skin- and hair-care products.

Cannabidiol has been found to work much like Enbel and Remicade, new drugs for rheumatoid arthritis, but unlike them can be taken orally according to researcher Dr. Marc Feldmann, a prominent arthritis researcher in London whose 2001 findings are described in the Proceedings of the National Academy of Sciences. Scientists gave laboratory mice injections of collagen, a connective-tissue protein that sparked an abnormal immune system attack on the mice's tissues and joints. Rheumatoid arthritis is characterized by such mistaken attacks by the body's own defense system, which leads to swelling, pain, inflammation and destruction of joints. The cannabidiol, purified from hashish, was injected into some rats and given orally to others, while control animals received a placebo. Researchers evaluated the drug's effect by measuring swelling, inflammation and joint stiffness in the animals. Some of the rodents' hind feet were removed so they could be studied for physical damage by the renegade immune system attack. Animals who got the drug had significantly fewer symptoms, and more of them escaped damage to their feet. Feldmann is a division chief at the Kennedy Institute of Rheumatology in London, the largest institution in the world studying rheumatic diseases and recently received a $500,000 prize from the Swedish Academy of Scientists for their showing that blocking TNF could help arthritis, which paved the way for drugs like Enbrel and Remicade. He notes that these drugs have to be injected by the patient or someone else twice a week, and that they are expensive with a year's treatment costing about $10,000. This makes cannabidiol a promising alternative. The only potential problem is that cannabidiol compound is only effective at a narrow range of doses. Feldmann credits Dr. Raffi Mechoulem in Israel for these discoveries, who he calls the "guru of cannabinoid chemistry."

Sativex is a whole plant medicinal cannabis extract containing tetranabinex (THC) and nabidiolex (cannabidiol--CBD) as its principal component and is administered by means of a spray into the mouth rather than smoked. It is indicated for the relief of symptoms of multiple sclerosis as well as treatment of severe neuropathy pain and was developed by GW Pharmaceuticals in March 2003. GW has also entered a licensing agreement with Bayer, which gives Bayer exclusive rights to market Sativex in the UK with the option to extend this to other countries around the world. Unfortunately US approval may take two or three years. Sativex is also undergoing phase III trials for the relief of neuropathic-related cancer pain. Between 10% and 30% of multiple sclerosis patients in Europe smoke cannabis to ease the pain and disabling symptoms of the disease according to estimates. GW Pharmaceuticals has increased production of cannabis at its greenhouses to 60 tons per year.

In Phase III placebo-controlled trials in 350 patients with multiple sclerosis, significantly more patients on Sativex experienced reduced neuropathic pain, spasticity, and sleep disturbances than placebos. Sativex can dull severe pain while allowing patients to perform daily activities. For more information see University of California's Center for Medicinal Cannabis Research (CMCR) http://cmcr.ucsd.edu/

Toxicity

Toxicologically, cannabis is fairly safe, having no practical lethal dose (IOM 1982). However, when smoking it is better to exhale it quickly as after a few seconds the ratio of beneficial to destructive compounds decreases.

Various studies have suggested that cannabis causes higher accident rates and infertility however they are often based on bias samples. For example, concerns over higher accident rates while using cannabis are due to faulty survey methods. A dramatic, recent increase in "emergency room mentions" of marijuana use was due to the fact that the hospital admission process was amended to ask patients if they ever used marijuana which led to a jump in reporting. Hemp has also been scape-goated for the dramatic, global decrease in human fertility in the last 50 years which may in fact, be caused by pesticides.

The psychoactive effects of even large doses of marijuana are milder and more easily controlled than those of LSD. THC even at large doses lacks the effects of physiological and mental stress found with the psychotomimetics. Tolerance does not occur to any significant extent with cannabis but occurs rapidly with psychotomimetics. In fact, frequent consumers of marijuana show reverse tolerance: they achieve a higher plasma level after a test dose and excrete the dose over a longer period than do infrequent consumers. Familiarity also leads to increased sensitivity and the use of lower dosages. The acute changes in brain wave patterns seen with LSD are absent and use of cannabis ends in sedation and sleep while restlessness occurs with true hallucinogens.

Likewise, in many ways THC is much safer than alcohol. Both cause a sedated phase at lower doses and an excited one at medium doses. However, in larger doses alcohol acts as a general anesthetic: depressing the central nervous system, and also slowing brain wave rhythms and decreasing mental and physical performance, but not altering sensory perceptions. Cannabis in contrast, affects perception but has little effect on brain waves. Marijuana leads to moderate overestimation of time while alcohol leads to extreme underestimation. Hunger and food consumption are increased by marijuana and decreased by alcohol. Alcoholic beverages must be ingested in grams rather than milligrams and they provide empty calories that can take the place of healthy food resulting in a loss of protein and vitamins and in some people, a thiamine deficiency that can lead to atrophy of the brain. Alcohol is also toxic to the liver, upper respiratory tracts, and brain.

Benign substances, as found in cannabis, are processed slowly in the body so it can use any possible nutritional or medicinal compounds. According to research this slow disposal process explains why it is impossible to become physically addicted to cannabis: the cannabinoids don't leave the system fast enough to cause severe withdrawal symptoms such as painful cravings. Cannabis is detectable for days in feces, months in the urine and years in the hair.

Since cerebral blood flow is large, the brain is a fatty organ, and cannabinoids are like a fatty compound in the body, THC is promptly absorbed into the lipids of the brain tissue. Some reach the liver where a portion is chemically rendered inert with each pass. Once cannabinoid levels drop below a certain concentration in the brain an osmotic exchange occurs in which the chemical flow reverses direction and moves THC from the brain back into the blood. The effects of the drug diminish in a few hours and metabolites are distributed throughout the body, accumulating primarily in adipose tissue at levels more than 20 times greater than in any other organ. The slow release of these stored inert substances results in the persistent appearance of THC metabolites in the urine for weeks after use of cannabis.

Cannabis has mild diuretic effects. As cannabis resin travels through the body it dries out the mucus passages, eyes, and palate. The fluid that accumulates flushes out the body by increasing the flow of urine which carries inert cannabinoid metabolites with it.

Good quality cannabis should have 4-10 percent THC. A single cigarette is enough for several doses at 5-10 mg THC each. At 4 percent THC, each one gram joint contains 40 mg. THC up to one half of which may be destroyed by heat or lost as smoke. Each dose lasts 2-4 hours if smoked and 4-8 hours if eaten. An oral dose is usually 0.5 to 1 gram. The LD50 of pure THC is one gram per 1000 grams of body weight. Thus a potential lethal dose of THC is several thousand times more than its effective medical dose. For alcohol, aspirin and other common nonprescription drugs the difference is only about twenty times.

Access

Unfortunately, despite the many medical benefits of Cannabis, it still remains illegal in the US. Patients have no choice but to break the law for medical necessity. I discuss the many regulatory aspects of Cannabis in depth on my website however, here I'll briefly point out some of the tactics currently in use for gaining access to life saving Cannabis.

First, Conrad notes that patients can sue government agencies for civil rights violations. Use of Cannabis for religious functions, as found in at least one Christian church for faith healing, is also legal and to deny church members use is to violate their civil rights. As an article of faith, medical use does not require scientific proof, being akin to the "laying on of hands" of other churches.

Buyers clubs spread the risk of buying or growing hemp among many people. One famous club was founded by Denis Peron in San Francisco in the wake of the AIDS epidemic after the federal IND program ended in 1991. The club occupied a five story building and had over 12,000 members. To join, patients needed a note from their doctor with a diagnosis of a serious health problem likely to be helped by Cannabis. City and county police refused to go after the club which was featured in many news reports.

And consumers searching for safe effective drugs for health problems are not the only groups interested in Cannabis for medicine. Authors of a recent article in the prestigious journal Lancet stated "the smoking of cannabis, even long term, is not harmful to health. Sooner or later politicians will have to stop running scared and address the evidence: cannabis per se is not a hazard to society but driving it further underground may well be." Even Merck pharmaceuticals has stated that "the chief opposition to the drug rests on a moral and political, not a toxicological foundation."

Further, the Journal of the American Medical Association recently stated that marijuana is medicinally useful, as well. In 1991 a Harvard team found 44% of specialists who responded to a survey privately recommended they smoke Cannabis to relieve chemotherapy side effects; 48% said they would like to prescribe it if was legal while 54% agreed it should be legal for doctors to prescribe.

In 1982 the Institute of Medicine reviewed the rumors of "new dangers" of marijuana and released a study that contradicted most of them. More detailed studies were undertaken in the 1970's and 1980's. The herb was found to be useful in migraine headache and to help reduce intra-ocular pressure thereby relieving the buildup of ocular fluids that characterize glaucoma. It was found to help stimulate appetite and was used in the treatment of wasting syndromes associated with AIDS, anorexia, and cancer. It was also found to help control nausea and vomiting associated with chemotherapy for cancer or AIDS.

Conclusions

Cannabis sativa is an extremely useful and politically charged plant that is today finally penetrating the pharmaceutical and healthcare industries of the US, despite being widely used throughout the world for important medicinal functions for millennia. In this article, I've outlined a number of the nutritional and medicinal properties and benefits of this plant as well as important pharmaceutical pipelines employing compounds derived from it. In particular, Cannabis appears to be very useful in the management of pain. It is only possible to hope that US regulatory agencies will stop stifling research on natural products such as Cannabis and allow their many benefits to be fully studied.

Appendix

Botany

The cannabinoids, the medical compounds in Cannabis, occupy tiny trichomes on the resin glands that line the calyxes, hairs, and bottoms of the upper leaves and flowers of the female Cannabis plant. Hemp is a member of the botanical order urticales which includes the hops plant (Humulus luphulus L.) used to make beer. It is usually placed in a distinct family called cannabacea although some prefer to assign it to moracea which includes the mulberry.

The plant's official scientific name is Cannabis sativa L. derived from the Greek kannabis and the Latin sativa, meaning "useful." This double name was first listed in AD 60 by Dioscorides and adopted by Carl Linnaeus for his 1753 compendium, Species Planatarum. A 1783 encyclopedia listed Cannabis indica as a separate species, named to honor India, the presumed homeland of this short, stocky, and high resinous variety.

When hemp grows in tightly crowded circumstances, as when farmed as a fiber crop, by season's end the mature plants have lost almost all their branches and foliage except near the very top. When given room to stretch its limbs, as when grown for seed or medicine, Cannabis produces many strong branches.

Immature seeds are pale green while mature seeds are dark gray to light brown and heavier. The stalks wrap one of nature's strongest and longest fibers. It can be fertilized using a combination of manure and rotation with nitrogen-fixing crops instead of chemical fertilizers.

Industrial hemp is low in the psychoactive chemicals called cannabinoids, especially tetrahydrocannabinol or THC, which are normally found primarily in the female flower. The competition for sunlight in industrial production directs energy away from producing resinous compounds and toward producing a taller, stalkier plant. Furthermore, industrial hemp is often harvested before the crop goes to flower and its resin flow becomes most potent. There is essentially no THC in the stalk, seeds or roots.

Climatic factors control production of resin and nutritional compounds. THC is lower in temperate climates and cultivated plants because it acts as an ultraviolet light shield and discourages insect pests. In contrast, the hotter temperatures, year-long equatorial light cycle of 12 hours of light and 12 hours of darkness, increase flowering and resin production. In temperate climates this pattern occurs only briefly around the spring equinox and fall equinox. As a result, European hemp remains primarily a food and fiber crop.

Cannabis is dioecious (has two separate flowers). The pollen-bearing, staminate, male flower is smaller, less-vigorous, and has a shorter life-span, serving primarily to pass on genetic material. Male plants die soon after their pollen is shed. The seed-producing, pistillate female flowers bloom on their own plants. Female plants remain green and vigorous for two months after pollination while the seeds develop.

If the flowers catch pollen and fertilize their ovaries, seed development becomes the major focus of plant activity. This diverts energy away from resin production (the medicinally active compound) so it is less desirable from a pharmacological standpoint. Cannabis grown for unseeded flower is called sinsemilla.

Good quality Cannabis will have a fresh, strong aroma (not moldy), rich green color, a springy texture with sticky glands, maximal buds with visible resin glands and few seeds or stems, and produces a white smoke, not black and sooty. It should be stored in a cool, dry place, in a sealed jar. The herb should be cured and dried to a moisture content of 10-15% to prevent growth of fungus.

Regulation

The history of Cannabis regulation reveals just how closely medicine is tied to culture and politics. A leading writer on this topic, Conrad (1997), notes that according to the Constitution, the federal government exists to defend the land and protect interstate commerce. Criminal law belongs to the states. The Bill of Rights was added to clarify this point on federal jurisdiction: leave the states alone. He notes that using this logic, drug prohibition is unconstitutional, as proved when Prohibition was repealed by the 21st Amendment.

Conrad notes this little stumbling block is why the "narcotics police" resorted to the smoke screen of a regulatory Marihuana Tax Act of 1937 to suppress Cannabis, which could be seen as the official start of the war on Cannabis. This act was created to boost logging and synthetic fiber industries by eliminating hemp from the market and was the legislation that ultimately banned almost all use of the hemp plant in the US. It originated with the post-prohibition Treasury Department and large corporations, such as Du Pont, that pushed for the legislation because of the huge potential profits. The Federal Bureau of Narcotics, left with little to do after Prohibition budget cuts, found hemp an easy target. The American Medical Association sent lobbyists to Congress to oppose the legislation but doctors who prescribed the plant or tried to study it were criminalized.

During the 1960's marijuana use among young protesters politicized the issue. In a case involving Timothy Leary, the US Supreme Court ruled the Marihuana Tax Act unconstitutional. Hope for cannabis policy reform came when the Kennedy Administration in 1961 refused to sign the UN Single Convention Treaty on Narcotic Drugs. The President himself was rumored to use Cannabis for his back pain. Then Kennedy was assassinated and Richard Nixon launched the Drug War, consolidating federal drug agencies into the DEA.

During the 1970's John Ingersoll, the first Director of the federal Drug Enforcement Administration (DEA) created a media blitz of anti-hemp "new studies" in 1972. Partnership for a Drug Free America (PDFA) continued this trend defaming members of society who used marijuana. One particularly erroneous study by Health forced monkeys to inhale immense amounts of Cannabis smoke through oxygen masks with no chance to breathe. The oxygen deprivation that resulted caused brain damage but Cannabis was blamed. This single study was the basis for the "your brain on drugs" campaign by PDFA. Interestingly, large amounts of tax-deductible money are contributed to PDFA by the alcohol, tobacco, and pharmaceutical drug industries which do create products that cause brain damage. When Congress implemented the Investigational New Drug program in the 1970's to provide cannabis for medicinal use, the DEA blocked individuals from enrolling in the program and kept the substance out of the hands of researchers.

Then in the 1980's Nancy Reagan added her "just say no" campaign for children's drug use. George Bush blasted US government supported Panamanian drug runner Manuel Noriega with tons of missiles as an example of the tough new US drug policy. Bill Clinton admitted that he opposed Vietnam and even tried Cannabis in college but quickly added that he "didn't inhale" and actually signed a bill in 1994 that set the death penalty for growing a tenth of an acre of Cannabis.

Conrad points out the ridiculous extremes the US Government has taken in the war against Cannabis. Hemp is one of the only plants to be listed in national emergency plans, have its own federal eradication program costing taxpayers about $48 billion per year, and generating $36 billion in the underground economy each year. Furthermore, domestic prison labor provides a cheap source of workers (paid 37 cents an hour.)

The principle of posse comitatus adopted after the Civil War forbids the military to enforce domestic law, yet the Pentagon has received more than $7 billion for counter-drug operations since the Bush administration overrode that provision in 1989. Rich contracts for exotic equipment are awarded to the same contractors who brought us Vietnam. The military now employs more than 8000 active duty and reserve personnel as professional drug warriors. In a defacto form of martial law, the Defense Department project Joint Task Force Six links the nation's domestic law enforcement forces with soldier, members of the Air Forces, Green Berets, Navy SEALs, and Marine reconnaissance patrols. In addition, police departments and federal agencies get billions of tax dollars from the government each year to creep around forests, look into backyards, fly overhead in planes and helicopters, and use satellite surveillance to spy on citizens, looking for hemp. Conrad goes so far as to state that just as slavery was the great injustice of 19th century America, the Drug War is the defining injustice of this century.

Today, drug testing is a major barrier to the hemp food industry. In 1996 an employee who had eaten a Seedy Sweety snack failed a drug test for marijuana. The candy is made of pressed hempseed. DEA is considering making hempseed snack bars illegal since they may occasionally trigger false positives.

And despite all the many medical benefits of the plant, the government has stated that it can never approve cannabis because it is such a complex substance (it contains 421 chemical compounds.) The FDA approval process is designed to handle molecules, not plants. The solution is not to put Cannabis through the new drug approval process but rather, recognize its historical use and grandfather it in as a traditional natural medicine and crop. Currently, the government considers Cannabis a schedule 1 drug which means it is considered to have a high potential for abuse, no currently accepted medical use in the US, and a lack of accepted safety of use for the drug.

Conrad points out that the UN and WHO don't have jurisdiction over domestic hemp commerce, so this is not an excuse for further limitations either. In fact the Single Convention notes that drug laws should not apply to industrial hemp, an ecological farm crop with no psychoactive properties. The European farm community actually subsidizes farmers for growing seed or fiber hemp.

Fortunately, federal and local governments are finally showing signs of renewed interest in Cannabis. Early government interest began during WWII when the federal government waved prohibition and purchased a million acres of seed and fiber hemp from American farmers--subsidizing the production of processing factories through the War Hemp Industries and producing the 1943 film Hemp for Victory.

The first industrial hemp bill was introduced into the New York legislature by Senator Joe Galiber in 1991. Delegates to the 1996 national convention of the American Farm Bureau Federation voted overwhelmingly in favor of research into domestic hemp development. Legislation authorizing research into restoring hemp was adopted by Vermont and Hawaii in 1996. Legislators in 37 states have endorsed medical marijuana. In Kentucky, actor Woody Harrelson (Cheers, The People vs. Larry Flynt) planted four industrial hempseeds into the soil of the Bluegrass State which was once the nation's largest producer of fiber hemp. Harrelson was arrested on the spot. He is challenging the law against nonpsychoactive seed lines and faces a year in prison for his political stand.

California decriminalized Cannabis in the 1970's and recently passed Proposition 215 supporting Cannabis reform. After the proposition passed, the California Medical Association announced plans to encourage the federal government to conduct controlled clinical studies of Cannabis for medicinal purposes. In 1996 Arizona voters passed Proposition 200--an even more sweeping bill that legalizes prescription and medical use of Cannabis and other controlled substances and replaces prison sentences for nonviolent drug possession with probation. Twenty states now have bills that allow patients to argue medical necessity if charged with Cannabis possession.

Environment

Hemp requires virtually no herbicides and pesticides to grow. In fact, it is so naturally resistant to pests it is used to make organic pest repellants. It will grow in almost any climate. Even the seed-cake left over from pressing is edible and provides an excellent source of animal feed, improving their health as well as human's. Wildlife consume hempseed, as well. By substituting hemp cultivation for mining, drilling and forestry, we can preserve our environment. Hemp is a sustainable resource that can renew itself as quickly as we consume it and grows back every year (it's a perennial).

It is also one of the most profitable agricultural crops to grow. It can be manufactured to produce food, clothing, housing, paper, energy and many other essential consumer goods. Henry Ford built a car using hemp in 1941 and Daimler Benz is creating one as well. Over 20 years hemp will produce four times as much pulp per acre as will forest land. Hempseed is used industrially for soap, paint, fuel and heating oil, precision engine lubricants, varnish, lacquer, sealants, and plastics. Historically, the domestic demand has almost always exceeded the supply produced by American farms so industry has relied on imports from China, Russia, and other lands. The US imported 116 million pounds of the seed in 1935 alone, much of which was used in paint, because it is such a good drying agent. Yields are 3-5 tons of stalk per acre including a ton of fiber for textiles and composites and a ton of cellulose for paper and construction material. Leftovers can be used for compost, fuel or plastics.

Hemp is a hardy, pest-resistant, soil-building plant that is excellent in crop rotation. Hemp is helpful for erosion control, reforestation, weed eradication, supporting wildlife habitat, and reducing air and water pollution. Hemp is grown as a green fertilizer to prepare the ground for the next crop since it squeezes out weeds and leaves the soil in excellent condition for the next crop. The strong roots anchor and aerate the soil to control erosion and mudslides and it is especially helpful in recently deforested areas. Its deep taproot allows it to survive droughts and is as cold-hardy as oats and other spring crops. The plants shed their leaves throughout the growing season, enriching the topsoil with organic matter.

The New World was legendary in Europe for its fertile soil, in part because, as Thomas Morton observed, hemp in New England grew twice as high as that in England. The timing of the American Revolution may have been due in part to a particularly abundant hemp harvest that was abundant enough to outfit the Continental army and navy, observed Thomas Paine. Thomas Jefferson urged farmers in 1791 to drop tobacco and return to hemp cultivation because it was easier on the soil. Hemp covered the wagons of the pioneers and powered the sailing ships that expanded the nation.

Over two-thirds of our original topsoil was lost between the beginning of European colonization and the late 1980's. Current loss of agricultural lands continues at the rate of over 5 billion tons per year; 85% results from croplands, pastures, range-lands, and forest-land being directly used for raising cattle and other livestock. Each ton of paper made from hemp saves twelve mature trees. Hemp and trees are both made of wood but because Cannabis is an annual plant it constructs a less durable organic structure than a tree requires to stand for decades or longer. Paper made from hemp requires much less of the acids and other toxic chemicals used to break trees down to pulp. Because the bast fiber of hemp is much longer than the wood fiber of trees, paper made with hemp can be recycled more than twice as many times as tree-pulp paper before losing its strength. Hemp can also be made into fiberboard, particle board, or variable density composite boards for all types of mold-making, construction, and commercial fabrication. Anything now made with paper can be made of hemp.

In the US alone, agricultural pollution including soil, fertilizer, and pesticide runoff accounts for more pollution than all municipal and industrial sources combined. Cotton, corn, sugar cane and tobacco receive the most chemical inputs and deplete the soil of nutrients most dramatically. About half of all agricultural chemicals are used on cotton. Yet an acre of land will produce two or three times as much hemp fiber as cotton. Livestock in the US produces 230,000 pounds of excrement each and every second, much of which ends up as water pollution. Fortunately, this is the best possible fertilizer for hemp. As raw material for pulp and paper, hemp can greatly reduce mills' use of sulfur-based acids used to break down tree cellulose, a major source of river contamination. This means less water pollution from the timber pulping process. Tree-free hemp paper can be made without dioxin-producing chlorine bleach, another toxin in our air and water. The EPA estimates that 99% of airborne dioxin emissions come from incineration of medical and municipal waste that contains chlorine. Much of this comes from papers and fabrics that have been bleached to create an impression of cleanliness and purity.

Chlorine is destroying the ozone layer which is increasing rates of skin cancer in humans and cataract blindness in wildlife in the Southern hemisphere. Fossil fuel burning produces carbon monoxide, a carcinogen, as well as sulfur dioxide and nitrous oxide, two components of acid rain. Biofuels do not contain sulfur or lead. Each crop of hemp produces as much oxygen while growing as it produces C[O.sub.2] if burned as fuel, creating a balanced cycle. Furthermore, not all of it can be burned as fuel (10% remains in the soil as roots and 30% as leaves that drop through the growing season) so up to a 40% gain in oxygen can be produced each season.

Hemp produces a larger amount of dry vegetable matter than almost any other rotational crop in temperate climates. During WW2, the head of the US War Hemp Industries Corporation oversaw the burning of hemp waste to power its own mills generating a huge energy surplus. Department of Energy estimates suggest that renewable energy plus conservation could produce a return on investment of almost 100 dollars for every dollar spent, through avoided oil imports and environmental damage.

The cumulative energy value used to produce one calorie of beef protein is 78 calories of fuel, while one calorie of soybean protein takes only two calories of fuel. If Americans reduced their intake of meat by just 10%, an estimated 100 million people could be adequately nourished using the land, water and energy freed from growing livestock feed. Feeding our livestock hempseed is a way to boost their immune systems and reduce abuse of antibiotics which may be creating global outbreaks of drug-resistant germs. Growing hemp can extract heavy metal contaminants into the fiber of the plant from the chemically degraded soil in damaged farm lands, so the lands can be used to grow food crops again. Hemp is unphased by ultraviolet radiation in contrast to other crops such as loblolly pine, used to make paper, and soy, used for food, which face up to a 50% loss in productivity. Cannabis merely increases the output of resinous cannabinoids that shield it. Hemp also increases its ratio of female to male plants to better survive ultraviolet radiation. Returning from plastics to natural fiber will also reduce the buildup of solid waste that fills our landfills. Plastic bags can be eliminated and replaced with hemp based bags, either reusable cloth or recyclable paper bags of tree-free hemp cellulose. Hemp cardboard packaging can be designed to replace most Styrofoam containers. Entrepreneurs and investors have created new companies and joined together to form the Hemp Industries Association (HIA) to protect their interests and the integrity of the trades.

Products

* Clothing: Hemp has one of nature's strongest and longest fibers and is made into many types of clothing including sandals, gloves, belts, watchbands, hats, shirts and pants. Hemp covered the wagons of the pioneers and powered the sailing ships that expanded the nation. An acre of land will produce two or three times as much hemp fiber as cotton.

* Paper: Each ton of paper made from hemp saves twelve mature trees. Paper made from hemp requires much less of the acids and other toxic chemicals used to break trees down to pulp. Because the bast fiber of hemp is much longer than the wood fiber of trees, paper made with hemp can be recycled more than twice as many times as tree-pulp paper before losing its strength.

* Luggage and bags: Plastic bags can be eliminated and replaced with hemp-based bags, either reusable cloth or recyclable paper bags of tree-free hemp cellulose. Wallets, carryons, purses and briefcases are just a sample of the wide variety of cloth hemp bags available.

* Bodycare products: Today, a growing number of hempseed based personal hygiene products are on the market as soaps, shampoos, salves, cosmetics, and other skin and hair care items. Essential fatty acids are being researched to treat epidermal conditions such as psoriasis and eczema.

* Nutraceuticals: Hempseed oil is rich in essential fatty acids and comes in capsules and liquids. The oil's optimum refrigerated shelf life is less than 2 months after the seed has been pressed or the sealed container opened. Cold pressed oils are best for consumption as heating the oil destroys much of the nutritional value.

* Foods: The seed is rich in dietary fiber, carotene, vitamins B1, B2, B3, B6, C and E. The seed also contains a complete protein. The protein in hemp is more digestible than soy protein due to edestin, a special type of protein. Types of foods available include nuts and beer.

Terminology

* Cannabindon (Red oil) is a concentrated liquid extract of Cannabis resin

* Indica (Afghani, Indica, stinky bud) is a short, dense plant with higher yield for indoor growing. Strong aroma, may cause fatigue.

* Industrial hemp (Bunk, dirtweed, ditchweed, hemp, rope, schwag) is a farm crop. Minimal THC in temperate zones but may be high in CBD.

* Leaf (Shake) has low concentration of THC and more CBD and other therapeutic compounds. Best for eating, not smoking.

* Marijuana (Bhang, bud, dagga, ganja, grass, green cookies, greenies, herb, kif, kind, ma'joun, Mary Jane, pot, reefer, smoke, tea, weed, etc.) consists of preparations from resinous Cannabis foliage with higher levels of active compounds, especially THC. Various seed lines are characterized by varying levels of cannabinoids. Many medical benefits.

* Resin (Charas, glands, hash, hashish, kif, polum (pollen), trichomes) are collected trichome glands in either loose or compacted form. High THC content.

* Resinous bud or flower (Bud, chronic, cola, green bud, herb, kind bud, sticky bud) has high THC content and ratio to CBD. Many medical benefits.

* Sativa (Columbian, Mexican, Thai) are taller, leggier plants. Bigger yield per plant outdoors. Sweet aroma and taste. Effect is more cerebral, less tiring.

* Seed (Hempseed) is the Cannabis fruit with many qualities of a grain: seed oils contain essential fatty acids, proteins, and globulin in a rigid hull. Both internal and topical medical applications. All varieties have similar characteristics and no THC.

* THC (Natural: tetrahydrocannabinol; Synthetic: dronabinol or Marinol) is a psychoactive compound that is responsible for many neurological and ocular benefits.

* Cannabidiol (CBD) provides medical benefits including relieving movement disorders and pain.

Bibliography

Abel, Ernest L., Marihuana: the First 12,000 Years. New York: Plenum Press, 1980

Bayer, R. and G. Oppenheimer, eds. Confronting Drug Policy Cambridge: Cambridge University Press, 1993

Conrad, Chris Hemp for Health: the Medicinal and Nutritional Uses of Cannabis Rochester, Vermont: Healing Arts Press, 1997

Grinspoon, L. and Bakalar, J.B. Marijuana, the Forbidden Medicine New Haven, CT: Yale University Press, 1993

Institute of Medicine, Marijuana and Health, Washington, D.C.: National Academy Press, 1982

Mechoulum, R. Cannabinoids as Therapeutic Agents, Boca Raton, FI: CRC Press, 1986

Nahas, C.G. and C. Latour, eds. Cannabis Physiopathology, Epidemiology, Detection. Boca Raton, FI: CRC Press, 1993

Van der Werf, Hayo Crop Physiology of Fibre Hemp. (Cannabis Sativa L.) Wageningen, the Netherlands: Wageningen Agricultural University, 1994.

by Tim Batchelder, BA

www.anthrocode.com * tim@anthrocode.com

About the Author

Tim Batchelder, BA, is a communications consultant to natural products and pharmaceutical companies and specializes in empowering consumers with innovative solutions to difficult health problems. Additional information on his services and research for this article can be found on his website www.anthrocode.com

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