SCIENTIFICALLY AND MEDICALLY SPEAKING, THC IS ON THE WRONG GOVERNMENT LIST

The Drug War

The recent Supreme Court ruling that federal authorities may prosecute
individuals for the possession and use of medical marijuana, even in the 11
states that permit it, reopened longstanding questions.

What kind of scientific data exist to clarify just how useful -- or harmful
- -- marijuana actually is? And why does the Drug Enforcement Administration
assign it to the same class of controlled substances as heroin and LSD? As
director of a laboratory funded by the National Institutes of Health to
study how drugs act on the brain, I'm committed to answering that first
question, which could help with the second.

When my colleagues and I look dispassionately at the available data on
marijuana, we see a Janus-faced drug with many adverse, even dangerous
properties, even as it presents an exciting and largely untapped
therapeutic potential.

But science's ability to tap marijuana's potential is inhibited by the
DEA's inappropriate classification of it as a Schedule I controlled
substance. It's true that marijuana and its active ingredient -- a chemical
in the tetrahydrocannabinol (THC) family of compounds -- can produce
undesirable effects in experimental animals and human subjects alike.

A single marijuana cigarette has been shown to impair the judgment of a
professional pilot in a flight simulator, and one injection of THC
significantly reduces a rat's ability to navigate a maze. Long-term use of
these drugs may also have adverse consequences. Most importantly, perhaps,
and contrary to common misconceptions, a growing number of studies show
that prolonged exposure to marijuana or THC can cause addiction.

This is best seen in lab experiments with monkeys that learn to
selfadminister THC by pressing a lever that allows the drug to be delivered
directly into a vein. The animals will work hard to get that fix, though
not as hard as they would for cocaine or other more addictive drugs.

What's more, a marijuana withdrawal syndrome has been demonstrated in
frequent long-term users of this drug: It is characterized by mild but
distinctive symptoms, including loss of appetite, irritability and
depression. But marijuana and THC also appear to have significant medical
benefits. As drugs go, THC is a very safe compound: It would take about 70
pure grams of it -- about the weight of a chocolate bar -- to seriously
harm a 150-pound adult.

Indeed, it has been approved by the Food and Drug Administration for a
human medicine and is currently used, under the trade name Marinol, to
reduce nausea and stimulate appetite in patients suffering from HIV/AIDS or
undergoing chemotherapy. Recent tests suggest these drugs may have much
broader medical uses. Marinol has been shown to reduce the physical and
vocal tics caused by Tourette's syndrome, a neurological disorder with no
satisfactory drug treatment. A 2004 report suggests that oral sprays of a
marijuana extract marketed under the name Sativex might reduce muscle
spasms in patients with multiple sclerosis.

Various animal experiments have confirmed the therapeutic significance of
THC and its derivatives, revealing novel potential applications in such
areas as neuropathic pain, cancer, glaucoma and atherosclerosis.
Nevertheless, ever since the Controlled Substances Act (CSA) became law in
1970, both marijuana and THC have been listed on Schedule I, the list of
drugs "with a high potential for abuse" and with "no currently accepted
medical use." The data obviously contradict that assessment. The error was
highlighted by a DEA decision made in 1999 to move Marinol -- but not THC
- -- to Schedule III, which includes much less dangerous compounds, such as
the antihyperactivity drug Ritalin. As a result, the very same chemical,
THC, is now assigned to two different CSA schedules.

This is patently absurd. Marijuana, the smokable leaf, may well belong in
Schedule I -- I'm a neuroscientist and a pharmacologist, not a medical
doctor or sociologist, and I'm not going to address this issue.

But THC, the chemical compound, does not. A larger problem is raised by
lumping marijuana and THC together with far more hazardous drugs.

If we fail to identify the varying degrees of danger posed by different
substances, we undermine the credibility of our legislation and hinder its
effectiveness. Any young person who has smoked marijuana and seen a friend
ravaged by heroin can tell the difference between these drugs.

Why can't we? Actually we can -- at least at a scientific level.

During the past decade the properties of marijuana have been studied in
great detail and its actions are now well understood. When marijuana smoke
enters the lungs, its THC component dissolves into the blood and spreads
rapidly throughout the body. It then combines with protein molecules
present on the surface of many cells in the brain.

These molecules selectively recognize THC, much as a lock fits a key. They
are called cannabinoid receptors (after the Latin name for the marijuana
plant, Cannabis). Heroin binds to a different class of protein molecules,
called opiate receptors -- just as lock-and-key specific as the
cannabinoids, but with different effects.

The two receptors are not interchangeable. Take, for example, the question
of addiction.

Research indicates that when THC stimulates cannabinoid receptors in the
brain, it engages a complex circuit of neural cells and transmitters that
are normally involved in the response to rewarding stimuli, such as tasty
foods.

A brief burst of activity in this circuit produces only a pleasant
sensation, but if the stimulus persists for a long time (as it does with
frequent and heavy marijuana use) it can eventually cause changes in the
neural circuit that result in tolerance -- the need to take larger amounts
to produce the same effect -- and dependence -- the feelings of unease and
craving experienced when prolonged drug use is suddenly stopped. Heroin's
interaction with its opiate receptors triggers a much more intense
sensation of pleasure than does marijuana.

But heroin's withdrawal is far more severe emotionally than marijuana's,
and its myriad physical symptoms including shivering and pain. It's not a
higher degree of the same response; it's a different response to a
different chemical reaction. All potential benefits of marijuana, such as
its ability to increase appetite and ease nausea, are also caused by the
binding of THC to its brain receptors.

This is a main trouble with developing medicinal uses for marijuana: If a
single receptor is responsible for all the drug's actions, how can we tease
apart the good from the bad? One way might be to forgo smoked marijuana and
find better methods to deliver THC -- for example, metered aerosols such as
those used in asthma -- that would allow patients to take just enough to
control their symptoms and minimize unwanted side effects. Another way may
be to take advantage of the fact that cannabinoid receptors did not evolve
in the human brain to give us the opportunity to experience a high, but to
combine with a set of THClike chemicals produced by brain cells, whose
functions include the control of pain and anxiety. If we could design
chemicals that tweak the levels of these transmitter substances, we perhaps
could boost their normal effects.

Our lab and others are working in this direction to create new classes of
painkiller, antianxiety and antidepressant drugs. That research sometimes
faces extra bureaucratic hurdles because of THC's Schedule I status.

But that isn't the main reason the drug and its derivatives should be
reclassified; far more important is having realistic drug laws that
penalize drug abuse but also encourage medical progress. Advocates have
pressed for THC to be reclassified since the CSA's enactment, pleas that
have gone unheeded so far. Perhaps the Supreme Court decision will inspire
citizens and medical organizations to take a fresh look at the scientific
evidence without being blinded by prejudice. This evidence suggests that,
while marijuana is an addictive drug that requires careful monitoring, its
active constituents can be useful in medicine when appropriately employed.

But it's hard to get this message across: All too often, the voice of
science and reason is lost in a polarized shouting match.