Marijuana News

Medicinal uses for cannabis date back to 2737 B.C., when the Chinese

emperor and pharmacologist Shen Neng prescribed the drug for gout,

malaria, beriberi, rheumatism, and memory problems. News of the medication

spread throughout the world. The drug helped reduce symptoms

in India, Africa, Greece, and Rome. Many authors assert that medical

marijuana treatments would not have reached other countries unless they

had meaningful efficacy. Dr. William O’Shaughnessy introduced the

medication to Europe in the 1830s. By the early 1900s, some of the most

prominent drug companies in Europe and America marketed cannabis

extracts as cures for a variety of symptoms, including headache, nausea,

cramps, and muscle spasms. Tinctures of cannabis may have had problems

because of inconsistent potency, but they were often as good or

better than other medications available for the same symptoms (Abel,

1980).

In the United States, the Marijuana Tax Act of 1937 discouraged medical

(and recreational) use by requiring an expensive tax stamp and extensive

paperwork. By 1942, against the recommendation of the American

Medical Association, the U.S. Pharmacopoeia removed marijuana

from its list of medications. This move eliminated research on the medical

efficacy of the drug in this era, but recreational use increased. Users

eventually noticed an impact on physical symptoms. Clinical lore about

these medicinal effects spread. In 1970, the Comprehensive Drug Abuse

Prevention and Control Act separated substances based on perceptions

of their medical utility and liability for abuse. The act placed marijuana

in Schedule I with heroin, mescaline, and LSD, making it unavailable for

medical use. Despite this classification, the federal government allowed

a few patients to receive the drug as part of a compassionate use program.

Ideally, this program would have permitted data collection to help investigate

therapeutic effects. New research on animals and humans eventually

revealed medical potential for smoked marijuana, as well as individual

cannabinoids.

By the early 1990s, the number of applications to the compassionate

use program increased exponentially as people with AIDS sought relief

from nausea and loss of appetite. The Department of Health and Human

Services officially terminated the program in March 1992. Nevertheless,

by the fall of 1996, California and Arizona had passed legislation perMedical

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mitting medicinal use of the drug. At least half of the remaining states

have put forth comparable initiatives (Rosenthal & Kleber, 1999). These

laws, however, conflict with federal legislation. Thus, possession of cannabis,

even for medical purposes, remains a federal offense. Despite the

risks, the rates of use for medical marijuana remain high. Research has

continued, but only in very special circumstances, often using animals

rather than human participants.

Research Considerations

Although research cannot resolve all the legal and ethical issues related

to medicinal use of marijuana, it can address the drug’s efficacy in treatment.

Ideally, data on the utility of cannabis may inform these ethical

and legal debates. Several key issues are important in evaluating research

on medical marijuana. These concern the advantages and disadvantages

of case studies and randomized clinical trials, as well as the relative costs

and benefits of alternative medications. Case studies and randomized

clinical trials each provide important information. Almost all medical

uses of marijuana started with successful treatments of individual cases.

One person found the drug helped alleviate a symptom and simply

spread the news. Physicians published some of these reports, which occasionally

inspired formal research projects. These case studies are superb

for generating ideas for further work. Nevertheless, opinions vary on

whether or not they provide enough information to encourage prescribing

marijuana or cannabinoids. Fans of case studies emphasize that medical

problems have unique features. Essentially, every use of every therapy

is its own case study. Individual responses to drugs vary. As a result,

physicians alter dosages and treatments based on ideographic reactions.

Proponents of case studies also mention that many medications gained

widespread use based on only a few positive results, including aspirin,

insulin, and penicillin. They emphasize that large studies require considerable

time and expense, potentially preventing people from using a helpful

drug. These arguments in support of case studies can be particularly

compelling when previous research has already established a medication’s

safety. For example, a few studies in the mid-1970s showed that a daily

aspirin might help prevent a second heart attack. Yet a large study of the

treatment did not appear until 1988. Without a large clinical trial, physicians

did not recommend a daily aspirin to prevent a second heart at170

Understanding Marijuana

tack. This bias against smaller studies cost thousands of lives. Many people

died during the lag between the initial evidence and the completion

of a large clinical trial (Grinspoon & Bakalar, 1997).

In contrast, single cases also have many drawbacks. People tend to

publish and remember the successful treatments but forget the failures.

Without a placebo control, we do not know if improvements arose simply

from expectation. Many symptoms ebb and flow with time. Perhaps

some individual cases would have spontaneously recovered without any

treatment. To minimize these potential problems, researchers perform

randomized clinical trials. They randomly assign large samples of participants

to receive cannabinoids or a placebo. If the treatment group improves

more, the healing effects clearly do not stem from some natural

ebb and flow in the symptoms or from a patient’s expectations that the

drug will work. These studies are expensive and time consuming, but

they can provide the best data possible. Clinical trials of many drugs

receive funding from drug companies. Yet given the limited potential for

smoked marijuana to generate a profit for these companies, funding randomized

control trials to establish its medical efficacy remains difficult.

Another issue important to the evaluation of medical marijuana concerns

relative costs and benefits. Many evaluators suggest that cannabis

must outperform all other available drugs in order to receive approval

for treatment (IOM, 1999). Most supporters of this idea prefer established

drugs based on the belief that they have lower potential for abuse.

Physicians and patients must consider this cost relative to the drug’s advantages.

Critics of this idea accuse drug companies of interfering with

marijuana research because of its low potential for increasing their profits

(Herer, 1999). These critics highlight that the approval of other medications

usually requires simple evidence of safety and efficacy, not superiority

to other drugs. For example, the Food and Drug Administration

(FDA) approved fluoxetine (Prozac) based on its ability to relieve depression

better than a placebo. The FDA did not require data comparing

it to other standard antidepressants. Thus, marijuana should only need

evidence of efficacy and safety to receive approval for medical use.

In addition to established efficacy, the price of the drug and its side

effects also contribute to its costs and benefits. Price and side effects play

an important role in comparisons between oral THC, smoked marijuana,

and other medications. Dronabinol (Marinol), the synthetic version of

THC, costs as much as $13 for a 10 mg pill (Rosenthal & Kleber, 1999).

(Typical treatments can require two of these pills per day.) The price of

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dronabinol can drop to approximately $8 for pills purchased in bulk. (A

special program provides the drug to low-income patients at a reduced

rate.) The same 10 mg of THC appears in half of a typical marijuana

cigarette. This amount of cannabis costs less than $5 if purchased in bulk

on the underground market. The price could fall markedly if the National

Institute on Drug Abuse (NIDA) provided the marijuana or if the government

lifted legal sanctions. Thus, smoked marijuana is cheaper, providing

a clear advantage over oral THC and many other drugs.

Smoked marijuana also may have fewer side effects than oral THC

and many other drugs. Patients can smoke a small amount, notice effects

in a few minutes, and alter their dosages to keep adverse reactions to a

minimum. Long-term health effects appear in chapter 7, but smoked

marijuana for brief interventions or as a treatment for the terminally ill

has no more negative side effects than many other popular drugs.

Controlled studies reveal that cannabinoids can decrease pressure inside

the eye for glaucoma patients, alleviate pain, reduce vomiting, enhance

appetite, promote weight gain, and minimize spasticity and involuntary

movement. Other work suggests additional therapeutic effects for

asthma, insomnia, and anxiety. Yet only a few studies have compared

cannabinoids to established treatments for these problems. Case studies

and animal research suggest that the drug may also help a host of other

medical and psychological conditions. These include seizures, tumors,

insomnia, menstrual cramps, premenstrual syndrome, Crohn’s disease,

tinnitus, schizophrenia, adult attention deficit disorder, uncontrollable

violent episodes, post-traumatic stress disorder, and, surprisingly, drug

addiction. The cases may provide enough evidence to stimulate researchers

to conduct randomized clinical trials examining the impact of cannabinoids

on these problems. The evidence of marijuana’s effectiveness

for treating each of these medical conditions appears below.

Elevated Intraocular Pressure

Glaucoma, the name depicting a group of problems characterized by

raised pressure within the eye, affects over 67 million people worldwide.

Approximately 300 people out of every 100,000 suffer from the disorder.

More than 2 million Americans have glaucoma, 80,000 of whom cannot

see. The heightened pressure within the eye eventually damages the optic

disk, hindering vision dramatically. It is the leading preventable cause of

visual impairments. Only cataracts, a currently unpreventable condition,

cause blindness in more people. The prevalence of glaucoma increases

with age and varies with ethnicity. The most common form of the disorder

appears in 1% of people over age 60 and 9% of people over age

80. Individuals of African or Caribbean descent have higher rates. For

example, over 3% of Jamaicans develop the disease. Eliminating this disorder

could clearly minimize extensive financial costs and personal anguish

(IOM, 1999; Quigley, 1996; West, 1997).

Treatments for glaucoma have focused on techniques for decreasing

intraocular pressure to minimize damage to the optic nerve. Smoked

marijuana undoubtedly lowers the pressure within the eye, as established

over 30 years ago (Hepler & Petrus, 1971). At that time, the only drugs

available for lowering intraocular pressure caused aversive side effects.

Many patients on these medications reported blurred vision, headache,

frequent urination, and racing heart. Moreover, the drugs were ineffective

at lowering intraocular pressure for some people. Multiple surgical

techniques developed as interventions, but not without associated risks.

Synthetic THC in pill form also lowers intraocular pressure but suffers

the usual drawbacks associated with oral administration. (The pills do

not act as quickly as smoked marijuana. Patients report that monitoring

their dosage is easier with smoked cannabis, too.) Researchers developed

an eye drop containing THC, but it failed to decrease intraocular pressure.

A few glaucoma patients braved extensive bureaucratic burden to get

legal medical cannabis. They turned to the government’s compassionate

use program before it closed in 1992. Three glaucoma patients currently

receive cannabis cigarettes from the NIDA. Case studies document that

marijuana has kept their intraocular pressures down and preserved their

vision for many years (Randall & O’Leary, 1998).

Although smoked cannabis lowers pressure in the eye, it is not the

perfect treatment for glaucoma. One potential drawback of marijuana

concerns its short duration of action. Intraocular pressure creeps upward

within 3 or 4 hours of smoking cannabis. This predicament forces users

to smoke many times per day in order to avoid damage to the optic nerve.

Some patients may not adhere to a strict regimen like this one, particularly

over years and years of treatment. An alternative treatment that

would only require a single dosage per day would have a meaningful

advantage. This issue has become particularly important given recent

crackdowns against smoking in public. Anti-smoking laws might force

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medical users to delay their dosages while working or traveling. The cognitive

and subjective changes associated with marijuana intoxication also

seem like an aversive side effect, but most patients develop tolerance to

these reactions at the dosages needed to lower intraocular pressure.

After a decade of basic research, investigators in the West Indies developed

lower intraocular pressure. Unlike the first THC eye drops, Canasol can

decrease intraocular pressures up to 50% within 15 minutes. The drops

are inexpensive, have no psychoactive impact, and appear to cause few

side effects. They may work better when combined with other topical

agents that reduce pressures (West, 1997). Despite the potential benefits

of this relatively new treatment, people with years of experience using

marijuana to control intraocular pressure remain reluctant to risk their

sight by switching to a different medication. They report that changing

drugs after years of positive experience seems unnecessary (Randall &

O’Leary, 1998). New research on glaucoma treatment focuses on preserving

the optic nerve and retina rather than lowering the pressures.

Given the advent of Canasol and this new direction for research, the

Institute of Medicine has suggested that studies of smoked marijuana will

not be a priority for glaucoma research (IOM, 1999). Some patients may

choose the drug if all alternatives fail, but current medications seem appropriate.

Pain

Patients seek medical assistance for pain more often than any other symptom

(Andreoli, Carpenter, Bennet, & Plum, 1997). People experience a

variety of pains that include diffuse, throbbing pressures or sharp, specific

aches. Entire journals devote volumes to research on pain treatment.

Some therapies are quite simple and cause few side effects. For example,

a mere placebo can minimize pain in 16% of surgery patients (McQuay,

Carroll, & Moore, 1995). Relatively simple behavioral interventions also

decrease pain. Symptoms often vary with tension and mood. Thus, relaxation,

stress reduction, and biofeedback can help significantly (Morley,

1997). Alternative treatments, like acupuncture, alleviate symptoms in

some studies but not others, perhaps depending on the intensity and

location of the pain (Kleinhenz et al., 1999; Van Tulder, Cherkin, Berman,

Lao, & Koes, 1999).

Despite the success of other treatments, pharmacological interventions

remain extremely popular remedies for pain. The simplest include aspirin,

acetaminophen, ibuprofen, naproxen sodium, and other over-thecounter

analgesics. Americans consume over 10,000 tons of these drugs

a year. They are relatively cheap, have few side effects at appropriate

dosages, and work well for mild pain. Nevertheless, they all can be toxic.

An aspirin overdose can damage stomach lining, liver, and kidneys. A

dozen acetaminophen tablets can kill a child.

Other pain killers that help severe symptoms include opiates like morphine

and codeine. These work quite well even for extreme distress,

inducing analgesia and an indifference to pain. People take them to recover

from acute stressors like surgery. Chronic pain patients may have

pumps installed in their spinal cords to release these drugs continuously.

The primary drawbacks of the opiates concern their potential lethality

and high liability for abuse and dependence. Opiate overdoses can be

fatal. People develop tolerance quickly and often increase their doses

with continued use. Withdrawal from these drugs includes extremely

aversive flu-like symptoms and spastic muscle twitches (Maisto et al.,

1995). Thus, alternative pain medications with fewer problems could

prove extremely helpful.

An ideal analgesic would have little potential for abuse but still provide

inexpensive, rapid, complete relief without side effects. No single

drug has all of these qualities for treating the many types of pain. Thus,

investigators have developed a multitude of analgesics. Cannabis may

make a promising addition to this list. Physicians have used marijuana to

alleviate pain since the beginning of the first century, when Pliny the

Elder, the Roman naturalist, recommended it. The Asian surgeon Hua

T’o used cannabis combined with alcohol as an anesthetic by 200 A.D.

(Abel, 1980). In modern times, clinical lore and case studies support

cannabis-induced analgesia. A case study reveals that oral THC can reduce

phantom limb pain—the odd, aversive sensations that seem to come

from amputated body parts. Another case shows that smoked marijuana

can alleviate the pain of arthritis. A third suggests a tincture of cannabis

can relieve tooth and gum distress (Grinspoon & Bakalar, 1997). This

evidence generates intriguing hypotheses but cannot prove that effects

stem from expectancy rather than genuine pharmacology. Given the dramatic

impact of placebos on pain, examinations of expectancy remain

extremely important. Different types of research have addressed the analgesic

powers of smoked marijuana or the cannabinoids. In addition to

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these case studies, formal projects with larger samples also focus on this

issue. These projects include tests of marijuana’s painkilling effects on

laboratory-induced discomfort, as well as pain from surgery, headache,

and chronic illnesses like cancer.

Laboratory Stressors

Some studies examine the reactions of volunteers to aversive stimuli.

Participants ingest THC and then receive electric shocks or place their

fingers under hot lights or into freezing water. Initial research was not

encouraging. In the 1970s, this work offered little support for cannabis

as an analgesic. One study found THC actually increased sensitivity to

pain. Smoked marijuana yielding approximately 12 mg of THC made

people less tolerant to electric shocks (Hill, Schwin, Goodwin, & Powell,

1974). A 25 mg dose of oral THC failed to increase the threshold of

pain from cold water (Karniol, ShiraKawa, Takahashi, Knobel, & Musty,

1975). The only supportive study at the time revealed that intravenous

THC significantly increased the level of shock or pressure that participants

first indicated as painful. Yet this last study found that the drug

had no impact on the maximum amount of pain that participants could

tolerate (Raft, Gregg, Ghia, & Harris, 1977).

One criticism of these laboratory studies concerns the reliability of

their measures of pain. A person’s threshold for pain produced by electric

current is not particularly stable from one day to the next. The poor

repeatability of this measure inspired the development of a new, more

reliable test of pain threshold. The new test focuses on people’s reactions

to heat. Each participant places a finger in a specified position near a hot

light bulb and withdraws it when the heat starts to hurt. A photocell

detects the exact amount of time people leave their fingers near the bulb.

Reactions to this test of pain tolerance vary less than reactions to shock

or cold water. In short, this heat test is more reliable than the measures

used before.

Participants show marijuana-induced analgesia on this heat test. In one

study, they took up to 18 puffs of marijuana (3.5% THC) or placebo.

The marijuana allowed them to leave their fingers beneath the lamp

longer before experiencing pain. Generally, the more puffs of marijuana

that the participants took, the longer they could hold their fingers under

the light. These data support marijuana’s analgesic effects, using a more

reliable pain measure. Notably, this study also used stronger marijuana

than the previous one that found no analgesia (Hill et al., 1974). This

experiment suggests marijuana may reduce pain to laboratory stimuli.

Nevertheless, the results may not generalize to situations more relevant

to medical use. Thus, other work has focused on pain from surgery or

illness, which may have many more practical applications.