Under the Federal Controlled Substances Act of 1970, cannabis is classified as a schedule one substance. Schedule one substances are defined as currently having no accepted medical use in the USA and having a high potential for abuse. Cannabis is the name of the genus to which the plant belongs. Three species names for Cannabis are indica, sativa, and ruderlaris. The preparation made from the stems, buds, and leaves of Cannabis is known as marijuana. Cannabis' psychoactive effects are caused by potent psychotoxins, which are present throughout its various forms (i.e. marijuana). The most well known of these psychotoxins, which is also it's primary psychoactive component, is delta-9-tetrahydrocannibinol (THC). There are many forms of THC; at least eighty derivatives have been synthesized and studied pharmacologically. The effects of THC range from euphoria and relaxation to anxiousness. From the various studies that have been done on marijuana, there has emerged evidence for marijuana having positive medical effects on people. Throughout history, cannabis has been a plant that has been used for medicinal purposes all over the world. By classifying marijuana under schedule one, is the government failing to acknowledge the many therapeutic advantages of marijuana? This paper will discuss the historical and current uses of marijuana and come to a conclusion on whether or not the beneficial effects of marijuana are conclusive enough for it to be used medicinally.

The chemistry behind THC remained a mystery until 1942, when H.J. Wollner and his co-workers first isolated and identified a natural tetrahydrocannabinol. In the mid to late 1940's, synthetic forms of THC began to appear under the trade names synhexyl, pyrahexyl, and parahexyl. THC is a highly lipid soluble molecule which is found throughout the male and female parts of the cannabis plant. The highest concentration of THC is present in the sticky resin that is produced by the flowering portion of the female plant. The THC content of marijuana varies depending on the section of the plant that is used. The presence of THC and THC metabolites remain in the body and can be detected in the urine for many days after use.

In 1990, the serendipitous discovery of the cannabinoid receptor was revealed at the National Institute of Mental Health (NIMH). Today, although much progress has been made in molecular biology with regards to cannabinoids and cannabinoid receptors (CB1, CB2, CB1A), there is still much to be discovered. CB1 receptors are mainly found in specific areas of the brain, spinal cord, and peripheral nervous system. Within these areas, high density binding occurs in the cerebellum, basal ganglia, hippocampus and cerebral cortex, while low density binding occurs in the brainstem. CB2 receptors are found mainly in the immune system on the spleen, tonsils, B cells, minocytes, natural killer cells, T4 cells, and T8 cells. All cannabinoid receptors belong to the superfamily of G-protein coupled plasma membrane receptors. Currently, a number of carefully directed laboratory studies are under way to explore the mechanisms behind cannabinoids and its receptors to explore their roles in the positive and negative effects (short and long term) of using marijuana. In 1992, a paper in Science was published revealing the discovery of an endogenous ligand for the cannabinoid receptor. William Devane and Raphael Mechoulam of the Hebrew University discovered the endogenous ligand, which was later named anandamide. Long before any research was ever done on marijuana, people used it all over the world for a variety of reasons.

The oldest record of medicinal use of marijuana comes from Chinese texts, around 5000 years ago. Its exact origins are still unknown but most experts hypothesize that it originated from somewhere in Central Asia, north of the Himalayan Mountains. The Latin term cannabis had a Greek origin (kannabis) whereas the English word hemp is derived from Middle English hempe and the earlier Old English form henep or haenep. The term marijuana may have arisen from the Portuguese marihuango or the Mexican-Spanish mariguana, both of which mean "intoxicant." Marijuana is a term that indicates a preparation made from the flowering or fruiting tops of the cannabis plant from which the resin has not been extracted. The use of the term cannabis is international, yet its products and the plant itself can be called many different names. The synonyms, excluding the street names, are almost legion and vary from country to country. For example, Central Africans refer to cannabis as mata, kwane, M bhanze, or dagga while Indians commonly refer to it as charas, bhang, ganja, or hashish.

Central Asiatic nomads may have been the agents for cultural dispersion of the hemp plant throughout Asia. Warlike equestrian pastoralists inhabiting Scythia, a large ancient region in southeastern Europe and Asia used the hemp plant for textiles and intoxication. Herodotus, a famous Greek historian, stated that the "Scythian passion was inhaling the smoke of burning hemp plants." This was done by burning portions of the plant in metal censers beneath small tent structures that enclosed the vapors, which were then inhaled for ritualistic and euphoric purposes. Later it was discovered by Russian archaeologists that hemp fibers were used by the Scythians for certain types of clothing's.

After 1700 B.C., nomads possessing use and knowledge of hemp migrated out of central Asia. Ancient Iranian literature implies that the hemp plant was used as an oil source. However, hemp's most significant use in southwest Asia, Egypt, the Mediterranean region, and Africa was for intoxicating purposes. The Assyrians in ancient Mesopotamia used hemp for fibers, incense, cultivation of sesame and flax for essential fats, and most notably, for drug sources.

In the Mediterranean region, there is strong evidence that hemp intoxication was a popular social practice. In the first century of the Christian era, Dioscordes, a physician, wrote a book on medicinal herbs. He was unaware of the "dioecious nature of the hemp plant and therefore listed a separate species for both the female (Kannabis Emeros) and the male (Kannabis Agria)." He indicated that for females, cannabis could be used for strong rope, relieving earaches, and inducing menstrual flow. For the male, on the other hand, cannabis could be used for muscular ailments. Claudius Galen (130-193 A.D.), a renowned scholar and author, reported that hemp was a commonly consumed substance on the Italian Peninsula. It was noted that it caused dry mouth but if taken in excess, produced sluggishness (torpor). It was often customary to offer guests hemp seeds as a promoter of hilarity. Marijuana was used to some extent for ecstatic purposes and had limited drug use in the northerly regions of central and Western Europe.

In the Chinese culture, one of the early medicinal uses of hemp was for "absent-mindedness." Shen Nung, the "father of husbandry," who probably lived some time between 3494 and 2657 B.C. experimented with cannabis for its drug potential. In his pharmacological book, he wrote that hemp should be prescribed for "female weakness, gout, rheumatism, malaria, beriberi, constipation, and absent-mindedness."

In India, there is evidence of migrating tribes being the first to introduce hemp into the region. The earliest synonym for hemp in ancient India was bhanga. In old Indian folk songs, "ganga or bhanga was the invariable drink of heroes before performing great feats of heroism." The traditional hemp intoxication was a means of stimulating confidence, bravery, and success. In the XV Fargard of the Vendidad, a compilation of religious laws and myths, hemp is referred to as a substance that stimulates abortions. In the Din Yast, a devotional treatise dedicated to the goddess Kista, hemp is referred to as being used for inducing euphoric feelings and righteous actions. Despite of all the evidence supporting marijuana's historical use for medicinal purposes, there is still much to be learned about its risks and benefits.

On March 17, 1999, the US Institute of Medicine (IOM) said that smoking marijuana has benefits for the terminally ill. They suggested that studies begin on producing inhalation devices to provide a safe alternative to the harmful effects of smoking. The study concluded that cannabinoids can be useful in treating pain, nausea and appetite loss caused by advanced cancer and AIDS. D-tetrahydrocannabinol (THC) also acts as a sedative and reduces anxiety, which in itself may have therapeutic effects. The results of the studies done by IOM also stated that there was no evidence for marijuana being a "gateway" to harder drugs, or that it is addictive.

Recently it was discovered that THC mimics the lipid molecule anandamide, both of which bind to the same cannabinoid receptors, CB1 and CB2, in the body. Anandamide, an endogenous cannabimimetic eicosanoid, is a member of the a family of fatty acid ethanolamides. Danielle Piomelli (University of California at Irvine) and his colleagues have recently uncovered one of anandamide's endogenous roles. When the nerve terminal releases anandamide, it inhibits other nerve cells that trigger physical action. This inhibition occurs by blocking the action of the brain neurotransmitter dopamine. David W. Self, of the Yale University School of Medicine, says that "these findings promise to propel anandamide from candidate status to bona fide neurotransmitter and may also open the door to novel treatments for diseases that involve dysfunction of dopamine signaling." Studies done on the striatum region of the brain in mice showed that by blocking anandamide release and increasing dopamine release via stimulation make the mice more hyperactive than if anandamide had not been blocked at all. The striatum is densely seeded with both dopamine and anandamide receptors. From these studies, it can be concluded that anandamide acts as a dopamine "brake. There is some evidence that boosting anandamidelike activity by administering THC alleviates symptoms of Tourette's syndrome, although this research is still in its preliminary stages.

The US National Institute of Health (NIH) and the British Medical Association released reports in 1997 on the potential therapeutic uses of cannabis and cannabinoids. Each one of the reports concluded that cannabinoids may be potentially useful as analgesics, antispasmodics, anti-emetics, appetite stimulants, and in treatment of epilepsy and glaucoma. Much of the evidence is from small controlled trials of oral dronabinol or nabilone. Although much evidence was gathered from these trials, doubt still lingers due to the difference between oral THC and smoked cannabis products. CB1 binding in the substantia gelatinosa could mediate analgesia while the high CB1 density in the basal ganglia could be the basis of antispasmodic effects of CB1 agonists. CB2 receptors so far are known to mainly appear on immune cells, especially on B cells. Activation of these receptors by cannabinoid agonists may cause the alleged immunosuppressant effect of cannabis. However, THC is unlikely to have a substantial effect at this receptor due to its low affinity for the CB2 receptor. More studies done with CB2 agonists and antagonists need to be done to help further see the effects of activating the CB2 receptor.

In the case of Multiple Sclerosis (MS), marijuana seems to bring relief to sufferers like no other painkillers can. Multiple Sclerosis is a debilitating disease that causes damage to the brain and destruction of the protective fatty coating around nerve cells. Subsequently, sufferers of MS tend to experience burning sensations in the limbs, particularly at night. Conventional analgesics can do little to ease this pain. Sufferers say that smoking a joint before bedtime can be the difference between getting sleeping at night and staying awake due to the pain. Sufferers of MS also experience spasms as a result of nerve damage. Marijuana has shown to help control the incidence of spasms in MS sufferers, epilepsy sufferers, and those who have suffered spinal cord injuries. Although there have not been many studies done on this aspect of therapeutic marijuana, the studies that have been done so far suggest that the sufferers may be right.

One of the first therapeutic uses of marijuana in the modern era has been its effects in suppressing nausea suffered by anti-cancer chemotherapy patients. The controversy in this case is whether or not marijuana needs to be smoked in order to achieve the full benefits. Unlike THC capsules or other legal nausea suppressors, smoking marijuana in the joint form allows the patients to have control over the dosage. This also allows patients to feel as though they have some sense of control over their bodies while suffering from cancer, a life-threatening illness that they have no control over.

Another well-known effect of marijuana is its ability to increase appetite. This could be helpful for anyone who has a decreased appetite due to an illness, especially those with AIDS and cancer patients who are undergoing chemotherapy. Smoking marijuana seems to be a more effective method to increase appetite than ingesting the THC capsule due to the poor absorption of the capsule in the digestive tract. Cost of treatment plays a role in marijuana use because the alternative to smoking marijuana to increase appetite is taking human growth hormone (GH) supplements. Although GH supplements have another benefit in that they also increases lean mass muscle in emaciated AIDS patients, treatment with these supplements cost an average of $36,000 a year. On the other hand a one year's treatment with medicinal marijuana would cost the AIDS patient around $500. Another alternative that was approved by the FDA is the use of Marinol. Marinol is a drug that contains the active ingredient of marijuana, THC. The problem with Marinol is that it doesn't always work as well as smoking marijuana. It is difficult to take just the right dosage of Marinol. If too little is taken, the effects can not be felt but if too much is ingested, then Marinol acts as a sedative. More conclusive studies need to be conducted on the relationship between marijuana and appetite in order to weigh the risks and benefits.

On a lighter note that relates to increased appetite is the recent discovery of chemicals found in chocolate that seem to target the same brain receptor system that is targeted by marijuana. One of the chemicals discovered has turned out to be anandamide. "Chocoholics" claim that not only is it the taste that makes them crave chocolate, it is the sensation of "feeling good' after eating chocolate that also plays a big part in the craving. Unlike THC, chocolate's chemicals turn on only a few circumscribed regions in the brain. A 130-pound person would have to eat about 25 pounds of chocolate to obtain a noticeable 'buzz.' Therefore, it is unlikely that one could eat so much chocolate as to experience a high. Yet, chocolate craving is a real physiological phenomena. The exact details of the mechanism by which this occurs is not yet understood. It is hypothesized that the chemicals in chocolate "intensify the sensory properties of chocolate." Or it could be that they elevate the mood directly. This could help explain why people tend to eat a vast amount of chocolate during physiological times of stress. In the long run, this discovery could lead to a new type of treatment for depression.

A negative aspect of increased anandamide activity was recently shown by studies done by scientists at the University at Buffalo in New York. It has been known for thirty years that very heavy marijuana smoking has drastic effects on sperm production within the testis. The study showed that human sperm contains receptors for cannabinoids. For the first time, a study showed that cannabinoids can affect three key fertilization processes: 1) Prevention of sperm binding to the egg cover, or zona, 2) Regulation of very active sperm swimming patterns, called hyperactivation, and 3) Inhibition of the acrosomal reaction, the normal release of the sperm enzymes that enable sperm to penetrate the egg. These new findings suggest that the anandamides and THC in marijuana smoke may affect sperm functions required for fertilization in the female reproductive tract. In thirty trials done by Schuel, Burkman, and colleagues, results showed that after six hours, sperm exposed to THC or AM-356 (a synthetic equivalent of the natural anandamide) had a 67% reduction in premature acrosome reactions. Motility studies showed that higher levels of AM-356 inhibited hyperactive swimming while lower concentrations actually stimulated hyperactivation. These results suggest that fluctuations in anandamide concentration levels within the oviduct may regulate sperm swimming patterns and subsequently affect the timing of the sperm meeting the egg.

Roger Pertwee, President of the International Cannabinoid Research Society, has conducted studies that have focused on CB1 activity and memory loss. Short-term memory loss has long since been a known effect of cannabis use. The effect of memory loss occurs at the hippocampus. The binding of THC to the CB1 receptors on the hippocampus fits with the ability of cannabis to affect short-term memory. In vitro work has shown that CB1 agonist can prevent long-term potentiation. In a study using a synthetic CB1 antagonist, SR141716A, improved memory in rats was observed. This finding raises the possibility that SR141716A could be used for improving memory in those aging and for those with cognitive disorders, supporting the theory that THC induces short-term memory loss.

The use of medicinal marijuana for treatment of glaucoma has had mixed results. Although most patients will tell you that marijuana helps their glaucoma, studies have revealed conflicting conclusions. A study by Keith Green, of the Department of Ophthamology at the Medical College of Georgia, was conducted to see the clinical effects, including toxicological effects, of marijuana and it's many constituent components on the eye and the remainder of the body. The conclusions derived from this study yielded mixed results. In the case of glaucoma, it is widely accepted that the elevated intraocular pressure (IOP) that causes damage to the optic nerve is greatly reduced in 60 to 65 percent of users when marijuana is smoked. That is why until 1991, America's Food and Drug Administration (FDA) permitted ophthamologists to prescribe marijuana to patients for whom all other treatments had failed. However, more recent research shows that the continued use of marijuana at the high dose that is required to control glaucomatous pressure would lead to substantial systemic toxic effects (i.e. increased risk of lung cancer). Concurrently, new glaucoma drugs have been produced. These drugs act at different biological pathways to help reduce the IOP. Yet, no approved drug so far actually makes the eyes' drainage system more efficient than marijuana. In order to circumvent the systemic toxic effects, Keith Green says that "development of drugs based on the cannabinoid molecule or its agonists for use as topical or oral antiglaucoma medications seems to be worthy of further pursuit."

A common theme that has been echoed in many of the studies or reviews of studies that have been done is that more research is needed in order for one to come to a clear conclusion about the therapeutic effects of marijuana. For groups who are interested in therapeutic uses, they advocate for proper trials of individual cannabinoids for specific disorders to be performed. Yet, regardless of whether all of the current research is conclusive or not, it has been noted throughout history that people feel relief and obtain pleasure from marijuana. One would find it difficult to discover another drug that has as many benefits as marijuana. In the past, records have shown that people smoked marijuana for its euphoric effects, painkilling quality, and for religious purposes. History has shown that the effects of marijuana can be beneficial. Yet, in the present day, due to advances in research and research techniques, skeptics are not so quick to call marijuana beneficial.

The risks of abuse versus therapeutic benefits is the main issue behind the debate of legalizing marijuana. Results obtained from studies that deem marijuana as a "gateway drug," a drug that leads to the consumption of other illicit drugs, have so far proven inconclusive. Studies have shown that there are more benefits to smoking marijuana than there are risks. The results of these studies should be interpreted with caution because most of them produced mixed results. However, for those who use marijuana as a last resort to treat their pain, they should have the option of having access to it via legal channels. Whether physiological evidence supports use or not, those people who use marijuana to sooth illness obviously feel better by using it. If marijuana use is psychological, then so be it. The bottom line is that marijuana use for therapeutic purposes should feel effective to those who are using it. From the hundreds of studies done over the years, scientists and the general public have a general notion of what the short and long term effects are. If one is willing to take the risk and use marijuana to help them cope with their illness, then it is their choice to do so. There is an obvious necessity for more research to be done. Science is headed in the right direction by developing new drugs that mimic the effects of marijuana and by continuing its quest to learn more about it. Until drugs are developed that work as well as smoking marijuana, there should be no doubt that this wonder drug should be allowed for medicinal use. History has dictated that there definitely is a role for marijuana in society. Science has shown that there are more positives than negatives in smoking marijuana. Up to this point in time, all of the evidence presented so far has made it clear that when it comes to the issue of marijuana for therapeutic use, the benefits outweigh the risks.

















References

1. Ziegler, Jan. Up in Smoke (medical use of marijuana). Hospitals and Health Networks v71, n12 (June 20, 1997)

2. Conant, Marcus. This is smart medicine: a doctor argues that marijuana can ease patients' suffering in ways nothing else can. Newsweek v129, n5 (Feb. 3, 1997)

3. Bloomquist, E.R. Marijuana Glencoe Press 1968

4. Buckley, William F., Jr. Marijuana Myths/Marijuana Facts. National Review v49, n23 (Dec. 8, 1997):63

5. Kalb, Claudia. No Green Light Yet: A long awaited report supports medical marijuana. So now what? Newsweek v133, n13 (March 29, 1999)

6. Marijuana-like Compounds May Alter Human Fertility. Impotence and Male Health Weekly Plus (Dec 28, 1998): NA

7. Travis, J. Marijuana reveals brain role. (tetrahydrocannabinol combines to same brain receptors as lipid molecule anandamide). Science News v155, n14 (April 3, 1999):215

8. Ault, Alicia. Institute of Medicine says marijuana has benefits. Lancet V353, n9158 (March 27, 1999):1077

9. Green, Keith. Marijuana Smoking vs Cannabinoids for Glaucoma Therapy. Jama v281, n5 (Feb 3, 1999):402k

10. Morris, Kelly. The cannabis remedy-wonder worker or evil weed? Lancet v350, n9094 (Dec 20, 1997):1828

11. Merlin, Mark David. Man and Marijuana: Some Aspects of Their Ancient Relationship. Associated University Presses, Inc. (1972)