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MARIJUANA CANNABIS AS A MEDICINE
Category: Neurochemistry
Term Paper Code: 584
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ABSTRACT
Marijuana, scientifically known as Cannabis sativa or Cannabis indica , is the most widely used illicit drug in the United States. Much evidence supports the fact that it may possess properties that could warrant its usefulness in the medical field. For example, it has been used in the treatment of nausea, glaucoma, and migraines among other things.
On the other hand, many of its useful effects are accompanied with side affects such as disorientation and hallucinations. Very little studies have been done concerning the beneficial and malignant effects of marijuana despite its ubiquitous nature in American society. This paper combines many of the tested treatments of marijuana with reported side effects in order to test the validity of the drug as a medicine.
Since the passage of the Controlled Substance Act in 1970, marijuana has been considered a Schedule I drug. This means that it fits the following criteria: 1) has a high potential for abuse, 2) has no currently accepted medical use, and 3) lacks safety even under medical supervision (Boire 1993). No one can grow the plant, possess it or any mix or preparation, or absorb it in any way. Many argue in favor of the drug saying that it has no ill effects, and that it, in fact, harbors medicinal properties. Proposition 215 amended California state law to allow people to grow or possess marijuana for medical use when recommended by a physician. The physician may diagnose that a patient may benefit from its use in the treatment of cancer, anorexia, AIDS, chronic pain, spasticity, glaucoma, arthritis, migraine, or any other illness for which marijuana provides relief. Unfortunately, studies on the effects of marijuana are scarce so its useful purposes are highly debatable. Whether or not medical marijuana deserves to be legal shall be further examined here.
"Marijuana" is just one particular term for the hemp plant classified as Cannabis sativa or Cannabis indica. Linnaeus gave its name and classification in 1753 and for hundreds of years it has been used as an intoxicant or an herbal remedy. Cannabis is easily distinguishable by its leaf which is often long, has serrated edges and grows in groups of five, resembling the fingers of the hand. It is made up of about 480 substances. The active ingredient in cannabis is known as delta-9-tetrahydrocannabinol (delta-9-THC, mostly referred to simply as THC). However, the plant’s chemistry goes far beyond just THC. A whole family of drugs, called cannabinoids, are found exclusively in cannabis and may contribute to the behavioral effects of the plant. Over 60 cannabinoids have been identified, but the most common one is THC. The twist here is that the active ingredient and the amount of active ingredient appear to depend on the preparation and the route of administration of the marijuana. Cannabis is sometimes ingested orally, but usually it is smoked and inhaled. Studies have shown that burning changes many of the cannabinoids, perhaps creating new ones with increased potencies. In addition, when inactive cannabidiol (a cannabinoid) is burned, it gets converted into delta-9-THC (McKim 1991). More cannabinoids are also created during digestion when marijuana is taken orally and also during metabolism, but their effects are not fully known.
The entire cannabis plant contains THC, but there are certain parts that are more potent than others. Flowering buds of female plants have the highest THC content, hence the term "buds" for marijuana. Male plants do contain THC, but not in the same quantity as the female plants so most commercial growers selectively grow all females. Buds are usually smoked in a pipe, water pipe, or in cigarette papers (joints), but they are also sometimes baked into cookies, brownies, or some other baked goods to be eaten. When the dried resin from the top of the female plant is harvested, it is known as hashish. Hashish can be smoked alone, with tobacco or marijuana, or it can be baked like the other parts of the plant. Purified hashish is called hash oil and is prepared by boiling hashish in alcohol (or other solvent), filtering out the residue, and evaporating the alcohol (McKim 1991). This is much more potent than hashish and can be vaporized and inhaled or dropped onto paper (like tobacco paper) and smoked.
The intake of marijuana can have several different effects. It may give the user a feeling of euphoria, increased laughter or happiness, and a relaxed passive mood. Short-term memory may be impaired, attention span may be decreased, and senses may be distracted. Many users also lose track of time, experience paranoia and anxiety, and have hallucinations. Their eyes may become bloodshot because of the dilation of blood vessels in the eye whites. Pupils do not become dilated, however, which was previously believed. Accurate measurements of pupil diameter after smoking marijuana have actually shown that there is a slight decrease in pupil size, but the change cannot be seen without precise instruments (McKim 1991). Eyelids frequently droop, giving users a distinguishing look about them that other people can often detect. In addition, marijuana can cause a sensation of having a dry mouth accompanied by an increased appetite known as the "munchies". These are all superficial effects that marijuana has on smokers. On a molecular level, the drug’s actions are not so simple.
Depending on how marijuana is administered, it is either absorbed by the lungs or by the intestine, and then makes its way into the bloodstream. THC is highly lipophilic or fat-soluble and may be stored in fat tissue. For this reason, tests for cannabis in the body may detect its presence for over a month (Schlaadt et al. 1982). Metabolites are then excreted in urine and feces. Some cannabinoids accumulate in the fat of cells and are released over a period of days (Schlaadt et al. 1982). As soon as the cannabinoids enter the body is when metabolism of them begins. Some of the metabolism takes place in the lungs or intestines, but most takes place in the liver. The delta-9-THC first gets converted to 11-hydroxy-delta-9-THC and then to other metabolites. Most of the metabolites are not as lipid-soluble as THC but are more easily excreted (McKim 1991).
So what effect do these cannabinoids have on neurons that makes users feel "high"? The old hypothesis relies on the fact that THC is highly lipophilic so it probably perturbs the neural membrane. This disturbance could alter the cell surface membrane’s selective permeability, allowing an increase in intracellular sodium that could result in the disruption of assembly and the orientation of cytoskeletal elements, as well as alter many functions (Friedman et al. 1993). In 1990 the old hypothesis was put to rest when the discovery of a cannabinoid receptor was made. The NIMH receptor specific for binding cannabinoids was found throughout the mammalian brain and is a G protein coupled receptor (Presti 1999). Although THC is not produced by mammalian bodies, the receptor has a high affinity for THC. Several areas in the brain have a high binding density for the receptor such as the cerebellum and the basal ganglia. These parts of the brain are associated with movement and the perception of time. The hippocampus which plays a role in memory has high binding density as well as the cortex which is responsible for perception and reasoning.
On the other hand, the cannabinoid receptor has a low binding density for THC in the brain stem. All vital biological functions are coordinated by the brain stem so the use of marijuana does not extensively impair the systems imperative for survival. Therefore, there are no problems with marijuana overdose being lethal and there have been no reported instances of deaths caused by marijuana.
Cannabinoids also have a number of effects on neurotransmitters. For example, THC causes the release of seratonin from storage in the synapse (McKim 1991). It also elevates levels of acetylcholine and inhibits the synthesis of prostoglandins (McKim 1991). The cannabinoids have been shown to have an influence on levels of GABA and cyclic AMP as well, but the effects that this has on the psychological perspective and on behavior has not been extensively studied (McKim 1991).
Despite the relatively little amount of scientific study done for marijuana, it has many characteristics that suggest that it could be an important medicinal drug. THC may act as an antiemetic, or a drug that prevents nausea and vomiting. It has been used to treat the sickness from chemotherapy for cancer patients, but no patterns of efficiency have been found for THC with regards to different types of tumors or chemotherapy (Voth et al. 1997). In addition, several safe and effective drugs other than cannabinoids are available for chemotherapy nausea that do not exhibit the side effects of THC. One study showed that 810f patients being treated with THC experienced negative side effects (Voth et al. 1997). Of these patients, 90f them reported hallucinations, distortions of reality, and mental depression (Voth et al. 1997). Although THC can be effective in treating nausea produced by chemotherapy, it is often associated with intoxication.
In relation to people suffering from acquired immunodeficiency syndrome (AIDS) and severe cancer-related anorexia, THC may be helpful through its appetite stimulating effects. In a study, 2.5 mg of oral THC administered two times a day effectively stimulated appetite in patients with AIDS (Voth et al. 1997). Although muscle mass or total body fat was not considered, patients maintained or even increased weight slightly. There is no doubt that marijuana often increases the appetite, but whether or not the accompanying intoxication makes it unfit to be used as medication remains to be seen.
Intractable hiccups is also a complication of many AIDS patients. The condition usually stems from an esophageal disease. A patient with a disease known as esophageal candidosis had surgery and was treated with midazolam and dexamethsone. The next day he developed intractable hiccups. Several different drug treatments as well as the removal of a hair from the tympanic membrane had no permanent effects on the hiccups. Eight days into the persistent hiccups, the patient, having never smoked marijuana before, smoked marijuana, and his hiccups stopped (Gilson et al. 1998). The next day they came back so the patient again smoked marijuana whereupon the hiccups immediately ceased and did not recur (Gilson et al. 1998). The drugs midazolam and dexamethsone, given to the patient during surgery, probably caused the hiccups, but did marijuana stop them? "Because intractable hiccups is an uncommon condition, it is unlikely that the use of marijuana will ever be tested in a controlled clinical trial" (Gilson et al. 1998).
Another treatment that marijuana may be useful for is glaucoma. Glaucoma is a condition where pressure in the eyes is too high. Many cannabinoids have been shown to reduce the pressure of the fluid in the eyeball. Cannabinol, nabilone, THC, and delta-8-tetrahydrocannabinol have all been found to reduce pressure whereas cannabidiol does not (Voth et al.1997). Unfortunately, in order to reduce intraocular pressure, patients must remain under the influence of the cannabinoid almost continuously. No evidence has been found that indicate that pure THC or crude marijuana affects or prevents the underlying disease, despite the fact that it relieves pressure and may be helpful treating the disease.
At least in humans, marijuana causes drowsiness and increases sleeping time. Therefore, it may be useful in treating insomnia. Sleeping patterns definitely change during marijuana use, but the effects are not completely understood. At low doses, some studies do not find any effect at all (McKim 1991). At higher doses, it may interfere with sleep resulting in insomnia and depression of total REM sleep along with total eye movement activity during REM (Tart et al. 1970). Habitual smokers of marijuana may have difficulty getting to sleep. However, the sleep is not of poor quality, or accompanied by nightmares or frequent wakening. Perhaps marijuana would be most helpful in situations where insomnia is not a regular occurrence, but on infrequent occasions at mild doses. That way drowsiness would be induced without severe disturbance of the sleep schedule.
Some people report that marijuana is useful in treating multiple sclerosis, spasticity and other movement disorders. A recent study showed that in 112 multiple sclerosis patients who were treated with marijuana to relieve symptoms, 700f them said that marijuana reduced spasticity, chronic pain of extremities, paresthesias, numbness, trigeminal neuralgia, tremor, and reactive depression and anxiety (Smith 1998). Another study showed that smoked marijuana did not improve tremor symptoms in five patients suffering from idiopathic parkinsonism (Smith 1998). Much evidence suggests that cannabinoids have anticonvulsant effects against partial seizures, but results from human experimentation are mixed. One case reports that smoked marijuana may exacerbate epilepsy while another says that it improves seizure control (Smith 1998). Information and experimentation on these movement disorders is very limited and unclear. THC or other cannabinols have not been tested against the standard antispastic medications, but should especially be considered for those who exhibit negative responses to the standard oral medication.
Analgesic effects of THC and smoking marijuana have been studied to a small degree. An endogenous cannabinoid that serves as a ligand has been found for the THC receptor in humans. This ligand is known as anandamide and may play a role in regulating the threshold for pain. A recent study indicates that a high affinity cannabinoid agonist relieves pain behavior effectively in a rat model of neuropathic pain (Smith 1998). There are also reports of pain relief by smoking marijuana from headache, menstrual cramps, and abdominal pain (Smith 1998).
With regards to asthma, cannabinoids can dilate bronchioles to loosen constriction on air passageways. This effect, however is a short-term relief of asthmatic symptoms. In the long run, cannabinoids contain particulates and irritating terpenes that can actually cause bronchospasms. Lungs that are continually exposed to marijuana smoke exhibit changes as serious as, and perhaps even more serious than those found in tissues of cigarette smokers (Schlaadt et al. 1986). The practice of consuming large quantities of marijuana with deep inhalations as well as holding the smoke in may contribute to problems that might not occur when used in smaller quantities on a less frequent basis. Again, it is uncertain whether the beneficial effects of the drug support its use in the medical field despite the associated side effects.
Short-term adverse effects, besides the ones already mentioned, are numerous. One of the most common is anxiety or a panicked feeling. This is most common in elderly people, and occurs much less frequently in children. Psychosis has also been reported from marijuana usage. Incidences exist where patients have been admitted into psychiatric hospitals and test positive for marijuana use. However, a study of 10000 psychiatric hospital admissions argues that little evidence shows that a psychotic disorder can arise in a previously non-psychotic (Gurley et al. 1998). Cannabinoids may cause drug interactions deduced by their ability to decrease gut motility, decrease stomach acidity, and increase activity of the cytochrome P450 system (Gurley et al. 1998). Therefore, medical marijuana users should be very cautious of mixing it with other medications. Marijuana can be a source of infections and has been documented to be contaminated with many fungal species that may cause pulmonary and systemic infections (Gurley et al. 1998). A Salmonella outbreak was attributed to marijuana that was heavily contaminated with animal feces. Similarly, a hepatitis B outbreak in U.S. military personnel in Europe was linked to marijuana use (Gurley et al. 1998). Because marijuana impairs perception, focus, coordination, reaction time and time perception, it has been acknowledged as a serious risk for automobile accidents as well. Adolescents who drove after smoking marijuana at least six times a month were 2.4 times more likely to be involved in an accident (Gurley et al. 1998). The short-term effects of marijuana are indeed numerous, but obviously are not enough to deter people from indulging in its use.
Long-term adverse effects carry more serious consequences, but many people choose not to dwell on the long term. Using marijuana corresponds to the impairment of fetal growth and with a decreased length of gestation (Gurley et al. 1998). Developmental delays of the fetus also show up in pregnant women who use marijuana, but they have not been shown to be solely responsible. On the topic of lung damage that was addressed previously, marijuana contains more tar than cigarettes and, since most marijuana joints don’t contain filters, more of the particulates and carcinogens are inhaled. Thus, the potential for cancer and other lung diseases may be relatively high. Gynecomastia, the development of breast tissue in males, has also been cited as an adverse effect of marijuana. The condition is sensitive to changes in the ratio of estrogens to androgens which is thought to be altered by stimulation of the cytochrome P450 enzyme system by cannabis (Gurley et al. 1998). A frequently mentioned concern among smokers is that it might cause infertility, but this belief remains unconfirmed. Immunologic studies have, however, been used to show that cannabis acts as an immunosuppressant (Schlaadt et al. 1986). By inhibiting the body’s ability to respond to disease, it leaves the body more open to infections. The long-term effects of marijuana certainly seem more menacing than the short-term effects, but still don’t dampen the fact that marijuana is the most frequently used illicit drug in the United States.
Should marijuana be considered for medical use? The fact that the drug may produce dependence makes it difficult to choose between its therapeutic uses and its potentially dangerous properties. Also, burning and inhaling a drug deviates from the normal drug approval process which usually involves purified substances that can be manufactured and tested in a reproducible fashion (Smith 1998). Despite its possible therapeutic uses, it may be best suited as an alternative medicine if it does not provide any better of a response than an accepted drug. On the other hand, smoking allows a patient to regulate his or her dosages according to his or her own needs. Therefore, the self administration of the drug would be relatively easy. The benefits of marijuana are almost always countered by some negative effect so patients may be reluctant to use the substance. Those that are not reluctant, however, might benefit greatly by its use. Without a doubt, the time and the effort dedicated to studying the effects of cannabinoids has not been enough to determine whether they should truly be removed from their classification as a Schedule I drug. Several other drugs with adverse effects are prescribed every day. Perhaps it has been determined that their therapeutic effects outweigh the adverse effects. If marijuana receives its deserved examination, it may not be long before it becomes accepted medicinally or even legalized.
References
Friedman, H., T.W. Klein and S. Spector, "Drugs of Abuse, Immunity, and AIDS". Advances in Experimental Medicine and Biology, v. 335, Plenum Press, New York; 1993, p. 69-119.
Gilson, I. and Mary Busalacchi, "Marijuana for intractable hiccups". The Lancet, v. 351; 1998, p. 267.
Gurley, J., R. Aranow and M. Katz, "Medicinal Marijuana: A Comprehensive Review". Journal of Psychoactive Drugs, v. 30, n. 2; 1998, p. 137-146.
McKim, W., Drugs and Behavior. Prentice-Hall Inc., New Jersey; 1991.
Mead, A., "Proposition 214". Journal of Psychoactive Drugs, v. 30, n. 2; 1998, p. 151-153.
Schlaadt, R. and P. Shannon, Drugs of Choice. Prentic-Hall Inc., New Jersey; 1986.
Smith, D. "Review of the AMA Report on Medical Marijuana". Journal of Psychoactive Drugs, v. 30, n. 2; 1998, p. 133-135.
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