Pubdate: Sun, 12 Jun 2005
Source: Washington Post (DC)
Page: B03
Copyright: 2005 The Washington Post Company
Contact:  http://www.washingtonpost.com/
Details: http://www.mapinc.org/media/491
Author: Daniele Piomelli
Note: Daniele Piomelli is professor of pharmacology and director of the 
Center for Drug Discovery at the University of California, Irvine.
Bookmark: http://www.mapinc.org/mmj.htm (Cannabis - Medicinal)
Bookmark: http://www.mapinc.org/topics/tetrahydrocannabinol
Bookmark: http://www.mapinc.org/topics/Marinol
Bookmark: http://www.mapinc.org/topics/Sativex

SCIENTIFICALLY SPEAKING, THIS DRUG'S ON THE WRONG LIST

When the Supreme Court ruled last week that federal authorities have the 
power to prosecute individuals for the possession and use of medical 
marijuana, even in the 11 states that permit it, the news 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 am committed to answering that first 
question -- which could, in turn, help with the second.

When my colleagues and I look dispassionately at the available data on 
marijuana, we see a Janus-faced drug that has many adverse or 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 is true that marijuana and its active ingredient -- a chemical in the 
tetrahydrocannabinol (THC) family of compounds -- can produce a variety of 
undesirable effects in both experimental animals and human subjects.

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 the ability of a rat 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, who 
learn to self-administer 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.

Despite these negative points, 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 satisfied the strict requirements of the Food and Drug 
Administration for approval as a human medicine and is currently used in 
the United States, under the trade name of Marinol (manufactured by 
Unimed), to reduce nausea and stimulate appetite in patients suffering from 
HIV/AIDS, or undergoing chemotherapy for cancer. A manmade derivative of 
THC called Cesamet (manufactured by Eli Lilly) is prescribed in Europe for 
the same conditions.

Recent tests suggest that these drugs may have much broader medical uses. 
For example, clinical trials have shown that Marinol can reduce the 
physical and vocal tics caused by Tourette's syndrome -- a neurological 
disorder that still lacks a satisfactory drug treatment.

Another report published in 2004 suggests that oral sprays of a marijuana 
extract marketed under the name of Sativex might reduce muscle spasms in 
patients with multiple sclerosis, though additional work is needed to 
confirm the efficacy and safety of this approach. 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 
anti-hyperactivity drug Ritalin. As a result of this puzzling move, 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 am a 
neuroscientist and a pharmacologist, not a medical doctor or sociologist, 
and I am not going to address this issue.

But THC, the chemical compound, does not belong there.

A somewhat larger problem is raised by lumping marijuana and THC together 
with far more hazardous drugs: If we fail to identify the varying degree of 
danger posed by different substances, we undermine the credibility of our 
legislation and hinder its effectiveness at preventing drug abuse.

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 
of drug 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 -- so intense, indeed, that 
heroin addicts are at a loss to put it into words.

But heroin's withdrawal is far more severe emotionally than marijuana's, 
and unlike the latter, it causes a myriad of 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 one of the main sources of trouble with developing 
medicinal uses for marijuana: If a single receptor is responsible for all 
actions of the drug, how can we tease apart the good from the bad? One way 
to do this may be to forgo smoked marijuana and find better methods to 
deliver THC -- for example, metered aerosols such as those used in asthma 
- -- which would allow patients to take just enough drug to control their 
symptoms, minimizing unwanted side effects.

This strategy would also avoid inhaling the dangerous mixture of toxic and 
cancer-promoting chemicals present in marijuana smoke.

Another way to offset marijuana's risks 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. Rather, their original role is to 
combine with a set of THC-like 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 in the brain, we might be able to boost their normal effects.

Our lab and others throughout the world are now working in this direction 
with the goal of creating new classes of painkiller, anti-anxiety and 
antidepressant drugs.

Because of THC's Schedule I status, that research sometimes faces extra 
bureaucratic hurdles.

But preventing a few months of paperwork to a scientific project is not the 
main reason the drug and its derivatives should be reclassified to a 
schedule that is in accord with their medical utility. Far more important 
is the goal of having realistic drug laws in this country that penalize 
drug abuse but also encourage medical progress.

Ever since the enactment of the CSA, advocates have been pressing for THC 
to be reclassified. These pleas 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.
- ---
MAP posted-by: Richard Lake