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THE MEDICINAL USES OF COCA AND MARIJUANA
AND THE HYPOCRISY OF WESTERN
MEDICINE
Category: Neurochemistry
Term Paper Code: 86
Return
Back To Main Medical Reports Page
The Medicinal Uses of Coca and Marijuana and the Hypocrisy of Western Drug
Policy.
Sergio Hernández
13194679
Molecular and Cell Biology 165
May 6, 1999
Keywords: Benzodiazepine Cannabinoid, Cannabis, Cocaine
Abstract:
The scientific basis for the medicinal use of coca and marijuana has until
recently been anecdotal and lacking in scientific research, but recent findings
may undermine the often hypocritical governmental opposition to the use of these
valuable medications. Coca has been shown to cure a variety of maladies by both
indigenous doctors and Western doctors, such as Dr. Andrew Weil. A proposed
neurological mechanism suggests that the body uses two different
neurotransmitter pathways, depending on the concentration of cocaine present.
Low doses of cocaine administered over a long period, such as in coca use, would
activate the norepinephrine pathway. High doses of cocaine, as in purified
cocaine, would stimulate the dopamine pathways, associated with addiction. This
mechanism allows for a comparison between cocaine and caffeine, a legal though
highly addictive drug and provides a chemical distinction between coca and
cocaine. Marijuana's medicinal use has been given credibility by the discovery
of a cannabinoid receptor and an endogenous cannabinoid, anandamide. New
research suggests that cannabinoids may play significant roles in the pain
pathways, interacting with the opiate receptor. Marijuana has also been found to
bind the benzodiazepine receptor, implying that it could be used to treat
anxiety disorders, rather than highly addictive, toxic benzodiazepines. A recent
report by the National Institute of Medicine supports the use of marijuana for
AIDS wasting, anxiety disorder, nausea, and pain relief, and dispels the belief
that marijuana is a "gateway" drug. Denying valuable medications, such
as coca and marijuana for political reasons while allowing and advocating the
use of addictive, dangerous medications, like benzodiazepines, for financial,
opportunistic purposes is a clear sign of the hypocrisy of Western drug
policies.
Over the past few years, the United States and the rest of the Western World
have witnessed a burgeoning of herbal and natural medicine, which much of the
medical establishment has berated and the Western governments have ignored. The
herbal medicine revolution's first battle began almost thirty years ago and the
medications involved in the battle have faced considerable fire from both
medical and governmental institutions. The plants, coca and marijuana
(cannabis), have both been stigmatized and associated with moral debasement
since their international ban with the Single Convention on Narcotic Drugs in
1961 and their definitive United States ban in 1970 with the passage of the
Controlled Substances Act. Both substances have been intertwined with human
history and used medicinally for thousands of years and they continue to be
used, despite vigorous restrictive efforts. Traditionally only historical use
and patient observation supported the medicinal value of both plants, but recent
research has provided evidence that gives a biochemical basis for the curative
properties of the plants. This paper will examine data supporting the medicinal
use of these plants, the attempts of Western governments to ignore credible
data, and the hypocrisy inherent in Western drug policy, the United States in
particular, with regard to medicinal compounds.
Coca
There is archeological evidence suggesting that Erythroxylon coca has been
cultivated and used medicinally since 3000 BC (Plowman 1979), making it one of
the first cultivated plants. Coca is used to refer to the species Erythroxylum
of the Erythroxylaceae family. The Erythroxylum genus contains about 250 species
found in South America. Coca is a sacred plant of many indigenous peoples in
South America and until recently, has served as a medicinal and dietary staple.
It is known medicinally "as the gran remedio - the great remedy- for
ailments as diverse as toothache and altitude sickness (Weil 1995)." As
nutritional supplements, "coca leaves contain several alkaloids, essential
oils, and relatively high amounts of vitamins and minerals (Plowman 1979)."
As is well known, coca also contains small amounts of the alkaloid cocaine
(0.50er leaf on average (Weil1981)). Cocaine was isolated as the "active
component" of coca in 1860, the first step towards the dishonoring of the
coca plant and those which depend upon it. The isolation of cocaine at first
seemed ideal. It eliminated the problem of developing different forms of
administering coca and the need to consume large amounts of coca. Cocaine
concentrated coca's well-known anesthetic and stimulant properties into an
easily administrated powder. This was the problem. Cocaine, in every possible
way, violated the natural safety net against abuse, addiction, and adverse
effects.
The differences between coca and cocaine administration present the first
problem. Traditionally, South American Indians have chewed coca leaves. There is
a significant amount of variation in the preparation of coca, but the principles
are the same. The coca leaves are mixed with an alkaline substance, such as
lime, and formed into a quid that is tucked into the side of the mouth and
allowed to mix with the saliva. After about 45 minutes, the leaves are
discarded. In some tribes, such as the Cubeos of Río Cudayorí in the Vaupés
territory of south eastern Colombia, the leaves are toasted, mixed with ashes
from Cecropia sclerophylla, a common jungle tree, to provide alkalinity, and
crushed into a fine powder. The powder is placed in the mouth, formed into a
quid, and allowed to dissolve over time. The addition of an alkaline substance
facilitates the entry of cocaine into the blood by increasing the pH of the
mouth. (Since cocaine is a base, a basic environment prevents it from obtaining
a charge, promoting its diffusion across blood vessels.)
The mastication of coca leaves results in a numbing of the mouth and "a
warm satisfying feeling in the stomach and a subtle sensation of energy through
the body, accompanied by a brightening of mood (Weil 1995)." The chewing of
coca orally administers a very low concentration of cocaine, over a long period
of time. Conversely, purified cocaine is usually insufflated, injected, or
smoked (in the crack form), resulting in the delivery of high cocaine
concentrations in a matter of seconds. As Dr. Andrew Weil points out,
"Users of illicit cocaine dose themselves intranasally or intravenously
with material that may be 600ure. Chewers of coca leaf use material containing
an average of 0.5ocaine by a route of administration that causes a gradual
increase in blood levels over the better part of an hour (Weil 1981)." It
is quite clear that purified cocaine bypasses a mechanism that prevents abuse.
Cocaine's easy, highly concentrated, fast acting forms of delivery dramatically
increase its potential for abuse and addiction.
The acute degree of addiction in the Western World has caused many Westerners to
associate the problems of cocaine addiction with the source of cocaine, namely
the coca shrub. Many have also claimed, probably over a drink or a smoke, that
South American Indians that use coca daily are addicted. Nothing could be
further from the truth. As noted by Richard Evans Schultes, "It is
noticeable that the Indians who use the largest amount of coca powder...seem to
be the healthiest and most robust Indians of the Colombian Amazon (Schultes
1990)." Dr. Weil reports the following:
I have lived among coca using of the Andes and the Amazon basin in Colombia and
Peru and have not seen any signs of physical deterioration attributable to the
leaf. I have never seen an instance of coca toxicity. Nor have I observed
physiological or psychological dependence on coca. Even life-long chewers seem
able to get the effect they want from the same dose over time; there is no
development of tolerance and certainly no withdrawal syndrome upon sudden
discontinuance of use (Weil 1981).
The belief that coca is as addictive and dangerous as cocaine is clearly
misguided and has unfortunately undermined the use of coca for medicinal
purposes.
The scientific basis for the medicinal use of coca is well founded in first hand
observation. "I have observed the relief of symptoms of indigestion, acute
gastritis, peptic ulcer, gastroenteritis, ulcerative colitis, and chronic
constipation (Weil 1981)." How coca performs its curative effects is not
well understood. In his paper, The therapeutic value of coca in contemporary
medicine, Dr. Andrew Weil presents several mechanisms to explain the actions of
coca. He states that the alkaloids, cocaine included, "belong to the
tropane series and may exert some atropinic effects on smooth muscles and glands
(Weil 1981)." This might serve as the basis for coca's ability to treat
maladies of the gastrointestinal tract. The atropinic effects would calm the
smooth muscles of the GI tract, alleviate cramping and pain. "It is likely
that one pathological mechanism underlying many gastrointestinal disorders is a
vicious cycle of feedback between the stomach or intestine and the
CNS...interruption of this cycle with a safe topical anesthetic might allow the
musculature to assume normal tone and function (Weil 1981)," states Weil.
Coca's action may have a neurological basis as well. Dr. Fernando Cabieses,
director of the Neurological Institute of Lima and President of the National
Institute of Traditional Medicine in Peru, presents a very interesting
neurological mechanism for coca. He suggests:
...that two different systems of neurotransmitters are involved in the
behavioral patterns [seen] around the habitual consumption of coca and cocaine.
Low doses of cocaine entering the brain slowly, may activate only the
norepinephrine system, producing alertness and dissipating fatigue. Higher
doses, taken in ways that cause rapid rises in concentration of the drug in the
blood and brain, may in addition the dopamine system, producing the intense,
short-lived euphoria that cocaine users seek (Weil 1995).
This theory is very interesting, not only because it suggests that the same
chemical can stimulate one pathway more than the other, solely because of
varying concentration, but more so because it shows that habitual coca use does
not stimulate the dopaminergic pathways associated with addiction. Furthermore,
this proposed pathway would allow for a comparison between cocaine and caffeine.
Both are alkaloid stimulants that have been purified as the active ingredients
in certain plants and both could potentially cause addiction and dependence. It
is easy to scoff at the idea of being addicted to caffeine, but many
(unknowingly addicted) people do not know that pure caffeine could be snorted or
inject much the same way that cocaine can and that it could cause overdose and
death. Death from caffeine overdoses are not common, partly because caffeine is
not typically used in the same way as cocaine and is not as potent. Caffeine is
commonly consumed in tea, coffee, or soft drinks, used for its mild stimulant
effect. In fact, the use of caffeine in the Western World sounds a great deal
like the use of coca in South America. Both are naturally occurring compounds
that can be consumed in beverages for their mild stimulant effects. Furthermore,
coca appears to be much less benign than caffeine because withdrawal symptoms
are rarely witnessed, whereas headaches, irritability, and constipation often
result within less than 24 hours after caffeine cessation. It is possible that
caffeine operates in a pathway similar to the proposed pathways for coca and
caffeine. Common caffeine usage may only stimulate norepinephrine pathways and
could potentially stimulate dopaminergic pathways, causing the euphoria
associated with cocaine. Coca and caffeine could thus be viewed as similar
drugs, with the difference that one is legal and the other is a target in the
war on drugs. In addition, the persecuted drug, coca, may offer more by
providing both a stimulant effect and a plethora of medicinal value, whereas the
legal, accepted drug, caffeine, provides only stimulation at the cost of
potential addiction. Unfortunately, coca will remain persecuted as long as the
Western World and its pseudo-leader, the United States maintain their ignorance.
The United States and the US-influenced United Nations have continually tried to
eradicate coca cultivation. The UN placement of coca on Schedule One of the
Single Convention of Narcotic Drugs of 1961
"prohibited international commerce in the leaves (except for shipments
destined for flavoring Coca-Cola(tm)) and envisioned total eradication of coca
within twenty-five years...Through the nineteen-sixties and seventies, many
attempts were made to limit coca production, encourage Indians to substitute
other crops, and destroy coca field with herbicides (usually supplied by
Washington) (Weil 1995)."
Perhaps the South Americans were encouraged to plant coffee or tea, or maybe
tobacco. Fortunately, many South American Indians and coca users have banned
together and slowed Western efforts, but eradication efforts are still underway.
Marijuana
The drug marijuana consists of the leaves and flower buds of the Cannabis plant,
of which there are two types (possibly three): Cannabis sativa and Cannabis
indica (maybe Cannabis ruderlaris). Much like coca, cannabis has been cultivated
and used for thousands of years. Cannabis, again like coca, is a plant of sacred
and medicinal stature. Medicinally cannabis has been used as an analgesic, an
anti-inflammatory, a sedative-hypnotic, an appetite stimulant, a muscle
relaxant, an antiemetic, and an anticonvulsant. For several decades, scientists
have known that the active components of marijuana are a class of molecules
called the cannabinoids. The cannabinoid (9-tetrahydrocannabinol (THC) has been
identified as the "active ingredient" in marijuana, but it is almost
certain that THC alone is not responsible for marijuana's medicinal effects. In
1990, a breakthrough was made in marijuana research with the discovery and
characterization of the cannabinoid receptor in the brain (Matsuda et al 1990).
Two receptors have been discovered thus far and have been named cannabinoid
receptor one and cannabinoid receptor two (CB-1 and CB-2). The discovery of the
cannabinoid receptor urged scientists to seek out an endogenous cannabinoid that
bound to the receptor. In 1992, scientists identified an endogenous cannabinoid,
anandamide (Devane et al 1992). The discovery of the cannabinoid receptor and
anandamide has allowed scientists to begin investigating the neurochemical and
biochemical basis for the medicinal properties of marijuana, but the legal
status of marijuana has interfered with research and medicinal use.
Although marijuana has been illegal in the United States since its placement in
Schedule 1 of the Controlled Substances Act of 1970, it is currently the subject
of many debates in regards to its medicinal use. Drugs in Schedule 1 of the
Controlled Substances Act are regarded by the United States Food and Drug
Administration (FDA) to have no known medicinal value and cannot be investigated
by researchers without extensive government review and approval. The reason for
marijuana's placement in Schedule 1 was clearly an action of politics and not of
science. Marijuana's popularity among the United States' counter-culture and
anti-Vietnam protestors in the 1960s and 70s is probably the main reason for its
placement in Schedule 1.
The medical utility of marijuana has resurfaced tremendously over the last
decade. Many cancer patients reeling from pain and nausea (from intense
chemotherapy) have turned to marijuana for amelioration. HIV-positive patients,
also suffering from nausea and a desire not to eat because of their medication
sometimes use marijuana to increase hunger and prevent wasting, a condition that
takes many lives among HIV patients. Several states have proposed legislation
that makes distribution, purchase, and consumption of marijuana for medicinal
usage legal. California and Arizona have passed such legislation, but the
Federal government has prevented the implementation of these voter-approved
documents and arrested both buyers and vendors of medicinal marijuana. In
January 1997, Gen. Barry McCaffrey, director of the Office of National Drug
Control Policy, commissioned a report to assess the "cruel hoax" of
medical marijuana or "Cheech and Chong" medicine as he called it (Dreyfuss
1999). The report by the National Institute of Medicine (IOM), released in March
1999 has caused many heads to turn and may finally cause the United States to
review its policies on medicinal marijuana.
IOM's report makes several conclusions and recommendations, such as: "Cannabinoids
likely have a natural role in pain modulation, control of movement, and
memory" and "The accumulated data indicate a potential therapeutic
value for cannabinoid drugs, particularly for symptoms such as pain relief,
control of nausea and vomiting and appetite stimulation (Benson and Watson
1999)." The study supported "that cannabinoids would be moderately
well suited for particular conditions, such as chemotherapy-induced nausea and
vomiting and AIDS wasting (Benson and Watson 1999)." The IOM's report gave
the US government and Barry McCaffrey little to cheer about. Although the report
ascertains that both tolerance and withdrawal may develop from marijuana use, it
states that withdrawal symptoms "appear to be mild compared to opiates or
benzodiazepines, such as diazepam (Valium(r)) (Benson and Watson 1999)." In
addition, the long held belief that marijuana is a "gateway" drug, a
drug that introduces user to more dangerous, addictive drugs, was dismissed by
the study: "But because underage smoking and alcohol use typically precede
marijuana use, marijuana is not the most common, and is rarely the first,
"gateway" to illicit drug use (Benson and Watson 1999)." The
IOM's report does acknowledge that there is a considerable risk of developing
cancer from prolonged smoking of marijuana and recommend research into
developing alternative methods of administering the cannabinoids in marijuana.
Yet the researchers state: "Until a nonsmoked, rapid-onset cannabinoid drug
delivery system becomes available, we acknowledge that there is no clear
alternative for people suffering from chronic conditions that might be relieved
by smoking marijuana, such as pain or AIDS wasting (Benson and Watson
1999)."
In light of the conclusions made by the IOM, many skeptics might wonder if there
are additional experiments to back up the claims made in the report. In fact,
many interesting discoveries are being made. The discovery of an endogenous
cannabinoid, anandamide, (mentioned earlier in this paper) caused many
scientists to ask: What is the role anandamide in the body? Furthermore, what do
cannabinoids do in the body? If we have receptors and endogenous cannabinoids,
then cannabinoids must perform some function in our bodies. Current research is
showing that cannabinoids may play a large role in pain. It has been determined
that cannabinoid type 1 (CB1) receptors are found in pain-processing areas of
the brain and spinal cord and it is believed that endogenous cannabinoids, such
as anandamide, may regulate pain transmission (Calignano et al 1998). It has
also been shown that "anandamide attenuates the pain behaviour produced by
chemical damage to cutaneous tissue by interacting with CB1-like receptors
located outside the CNS (Calignano et al 1998)." Researchers additionally
found that cannabinoids stimulate an opioid receptor (the (1 opioid receptor) in
the limbic system (the brain region containing part of the cerebellum and the
hypothalamus) (Tanda, Pontieri, and Chiara 1997). It is becoming increasingly
clear that the use of marijuana for the treatment of pain has a well-founded
biochemical basis, but what about the use of marijuana in the treatment of
neurological movement disorders and anxiety, as suggested by the IOM report.
Movement disorders typically occur as a result of abnormalities in the basal
ganglia and its connections through the thalamus to the cortical motor areas; a
disruption along any point along the pathway results in a movement disorder.
These disruptions can be genetic or result from drug use. A type of movement
disorder known as dystonia, which includes the horribly debilitating
Huntington's disease, has been considered for cannabinoid treatment. Although
research is limited because marijuana's Schedule 1 classification prevents it
from being studied in humans, an open trial study was conducted using
cannabidiol (the cannabinoid with the second highest concentration following THC
in marijuana) on dystonic patients. The study, "suggested modest
dose-related improvements in the five dystonic patients studied (Benson and
Watson 1999)." Cannabinoids have also been found to decrease dystonia in
mutant dystonic hamsters (Benson and Watson 1999). Cannabinoids have also been
considered for the treatment of Parkinson's disease. Parkinson's results from
the death of dopamine-producing (dopaminergic) cells in the substantia nigra
region of the brain and this in turn results in an increase inhibition of the
motor thalamus, the region of the brain responsible for initiating movement. It
is believed that cannabinoids may help ease Parkinson's symptoms by inhibiting
the pathway between the substantia nigra and the motor thalamus, thereby
decreasing the inhibition of the motor thalamus. The use of cannabinoids to
treat Parkinson's is still theoretical and requires substantial research.
Neurological conditions such as dystonia have been found to worsen with stress
and anxiety, creating a vicious cycle. For instance, a dystonic patient trying
to get out of someone else's way in a café may become nervous about having to
perform a coordinated movement quickly. The patient's nervousness would increase
the symptoms and cause the individual to become even more nervous. Conditions
such as dystonia that increase with anxiety have been particularly considered
for cannabinoid treatment because cannabinoids have been found to decrease
anxiety. Research has confirmed the long held belief that marijuana decreases
anxiety. In a clinical study consisting of 50 healthy, chronic marijuana users
and 50 matched controls, the marijuana users scored much lower on Taylor's
Manifest Anxiety Scale (TMA) (Sethi et al 1986). Clinical studies such as this
one, led researchers to inquire if cannabinoids were interacting with
benzodiazepine receptors. Benzodiazepines, such as diazepam (Valium(r)) and
alprazolam (Xanax(r)), are a class of molecules, known as sedative-hypnotics,
which are used in the treatment of anxiety and several behavioral disorders.
Studies where performed, wherein cannabis treated rats were tested for anxiety
with foot-shock induced aggression. The rats scored high on the test, suggesting
that cannabis had decreased the anxiety and aggressive behavior in the rats. The
rats were then tested after being given a benzodiazepine receptor antagonist,
which binds to the receptor and prevents binding of other molecules. The
increased tolerance for foot-shock induced aggression was blocked by the
antagonist. This suggests that cannabis was interacting with the benzodiazepine
receptor (Sethi et al 1986).
The findings that THC binds to the benzodiazepine receptor imply that marijuana
may be useful in the treatment of conditions that are now treated by
benzodiazepines, such as anxiety disorders. For many benzodiazepine users, the
prospect of a different method of treatment may be welcome because of the many
adverse effects caused by benzodiazepines. This class of compounds have many
unpleasant side-effects: "sedation, loss of coordination, aggravation of
glaucoma, confusion, nausea, vomiting, decreased reflexes, trembling, delusions,
muscle weakness, among others (WWW1)." There is a significant degree of
dependence and withdrawal symptoms that can develop to therapeutic doses.
"Discontinuation is associated with increased anxiety and agitation,
decreased sleep, high arousal and agitation, and in extreme cases, seizures.
There may also be flu-like symptoms, dysphoria, unsteadiness, and in extreme
cases (but rarely), hallucinations and psychosis (Salzman 1998)." Marijuana
withdrawal is not as potent: "Withdrawal symptoms can be observed in
animals, but appear to be mild compared to opiates or benzodiazepines, such as
diazepam (Valium(r)) (Benson and Watson 1999)."
Considering the dangers involved with benzodiazepines it is surprising that they
are in Schedule IV of the Controlled Substances Act, suggesting that the drugs
do not have much potential for addiction or abuse. It appears many physicians
and the US government believe that benzodiazepines are benign therapeutic drugs
and "although some patients may continue to take benzodiazepines to avoid
discontinuation symptoms, this is not evidence of 'addiction' (Salzman
1998)." Although benzodiazepine dependence may not be an addiction in the
strict sense of the term, it is quite ignorant to disregard the need of some
patients to continue benzodiazepine use in order to prevent withdrawal symptoms,
even though they would like to stop taking the medication. One could argue that
heroin addicts, for instance, continue to take heroin, although they would like
to stop, in order to "avoid discontinuation symptoms." The placement
of benzodiazepines in Schedule IV trivializes the powerful nature of these
drugs, especially when a drug like marijuana with far fewer side effects and
many more medicinal applications remains improperly categorized in Schedule I.
The Schedule IV of categorization benzodiazepines emphasizes the political
nature of the Controlled Substances Act. Tremendously lucrative and politically
resourceful pharmaceutical corporations manufacture benzodiazepines. Merck
Pharmaceuticals had a 14ales increase in 1998 with an annual gross of $26.9
billion and a net income of $5.25 billion. The mere suggestion of placing
benzodiazepines in a more restricted category would meet immense opposition from
the companies that produce them, the doctors that prescribe them, and the
primarily upper class citizens that consume them (a prescription of 30,
1milligram pills of Xanax(r) costs $37.65). It would be no surprise that if
marijuana were ever demoted, it would be on the condition that only the US
government or certain pharmaceutical companies could grow and sell the plant,
rather than allowing small private businesses. Marijuana, like coca, faces the
hypocrisy of United States, and therefore Western, drug law. It is incredulous
that natural medications of such importance remain prohibited, while more toxic,
dangerous drugs, both with medicinal properties (benzodiazepines) and without
(alcohol, tobacco) are readily available.
The status of marijuana and coca in the United States and their inaccessibility
for medicinal use is in a sense a violation of patients' rights and the ideals
of medicine. The government's continual hindrance of research and their
disregard for conclusive data supporting the medicinal use of these drugs is
unconscionable. Coca's curative powers have been harnessed by indigenous peoples
for thousands of years and witnessed by physicians of Western medicine. Yet,
coca has been shunned as a medication by Western medicine because it is the
natural source of cocaine, a compound that would have probably not been
detrimental had it not been isolated in the West. Western drug policies, in
particular the United States', have denied millions of people a potentially
useful medication because of its association with cocaine, a product of the
West, while allowing the legality of highly addictive drugs with known health
hazards and no medicinal effects, such as alcohol and tobacco. The continual
prohibition of the medicinal use of marijuana in light of voter approved
propositions, substantial and credible cannabinoid research demonstrating
marijuana's usefulness, and the support of a government commissioned study on
marijuana medicinal use, reflect the ignorance of the United States and the
West. Recent research showing marijuana's usefulness in neurological disorders,
anxiety disorders, and pain, in addition to its use in preventing nausea and
AIDS wasting, are too resounding to be ignored. Current treatments for anxiety
disorders, such as benzodiazepines, result in a overabundance of dangerous and
uncomfortable side effects, side effects which for the most part would not be
present as a result of marijuana use. Furthermore, the dependence and withdrawal
symptoms for marijuana are not as powerful as with benzodiazepines (Benson and
Watson 1999). Rather than administer or even consider less toxic, more effective
medication, such as coca and marijuana, Western medicine continues to prescribe
drugs with side effects that sometimes outweigh the cure, while Western
governments continue to ignore research and stubbornly deny the medical utility
of coca and marijuana. Until Western governments remove their blinders and allow
the use of these medications, the illness of hypocrisy will persist in Western
medicine.
Hernández
References
Benson, J.A., Watson, S.J. "Marijuana as Medicine: Assessing the Science
Base." Institute of
Medicine, Division of Neuroscience and Behavioral Health. Available online at
http://www.nap.edu (1999).
Calignano et al. "Control of pain initiation by endogenous cannabinoids."
Nature 394(6690) (16
Jul. 1998): 277-81.
Devane, W.A. et al. "Isolation and Structure of a Brain Constituent that
Binds to the Cannabinoid
Receptor." Science 258 (18 Dec. 1992): 1946-1949.
Dreyfuss, R. "Another Victory for Medical Marijuana." Rolling Stone
Issue 812 (13 May 1999):
32-33, 105.
Matsuda, L.A. et al. "Structure of a Cannabinoid Receptor and Functional
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