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BLOWING AWAY THE SMOKESCREEN

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Blowing away the smokescreen

RAPHAEL MECHOULAM

Raphael Mechoulam is in the Faculty of Medicine, The Hebrew
University, Ein Kerem Campus, Jerusalem 91120, Israel.


The Science of Marijuana
by Leslie L. Iversen
Oxford University Press: 2000. 283 pp. stlg18.99, $29.95

The use of Cannabis sativa stretches back to the distant
past. The Assyrians, ancient Egyptians, Indians and Chinese
used it in medicine, and perhaps at times for recreation and
in religious rites. Its use continued for millennia and parallels that
of opium. Yet modern research on cannabis has always lagged behind
that on Papaver somniferum, the opium poppy. Whereas morphine was
isolated from opium early in the nineteenth century,
delta-9-tetrahydrocannabinol, the active constituent of cannabis, was
not fully identified until 1964. The first opiate receptors and
endogenous opiates were described in the 1970s, but those of the
cannabinoids were not discovered for another 20 years.

Today, however, cannabinoid research is a central topic of
investigations in many fields, particularly in neuroscience. Two
receptors have been identified: CB1, found mostly in the central
nervous system, and CB2, present mostly in the immune organs. Two
endocannabinoids _ anandamide and 2-arachidonyl glycerol _ have been
isolated; antagonists and knockout mice for CB1 and CB2 receptors are
available.

The endocannabinoids are involved in neuromodulation, in the immune
system and even in reproduction. Cannabinoid receptors interact with
the opiate, GABA, dopamine and glutamate systems. We have learnt much
about the effects of endocannabinoids on short-term memory, pain
regulation, neuroprotection, appetite and blood-pressure regulation.
Clinical work has shown that the endocannabinoid system may be
involved, either as a (neuro)protector or as the villain, in diverse
medical conditions such as Parkinson's disease, schizophrenia,
Tourette's syndrome and even miscarriage. Anandamide, the more
thoroughly investigated endocannabinoid, has been billed as heading
"for the big [neurotransmitter] league".

These advances are admirably described and critically discussed by
Leslie Iversen, an eminent pharmacologist with wide experience both in
academia and in industry. Having also served on numerous official
bodies dealing with drugs, he is in a position to deal objectively
with the political and social as well as the scientific aspects of the
cannabis issue. He presents the history, biology and medical aspects
of cannabis and cannabinoids with a critical eye, and his style is
superb.

Over the past two decades a strong grass-roots movement to
legalize cannabis as a therapeutic drug has led to political
pressure in several countries; the measure has been approved in
several US state referenda. Campaigners point out that it
reduces vomiting after cancer chemotherapy, enhances the
appetite of people with AIDS and is active against pain,
glaucoma, multiple sclerosis and many other conditions.
Numerous prestigious groups _ among them a House of Lords
committee _ have looked at the scientific data. Iversen's own

analysis of the evidence for its clinical effectiveness indicates that
it is woefully inadequate by modern standards: well-controlled
clinical trials are urgently needed, he says.

His analysis of the "medical marijuana' issues and of the trend
towards legalization (or decriminalization) is even-handed. He
supports the view of the editor of the New England Journal of
Medicine that "a policy that prohibits physicians from alleviating
suffering by prescribing marijuana for seriously ill patients is
misguided, heavy-handed and inhumane", although he expresses his view
in milder terms _ he would allow compassionate use in some
well-established conditions. In the United Kingdom, for example, he is
in favour of changing its legal status to that of a Schedule II drug,
permitting doctors to use it on a named-patient basis. And he believes
that if well-controlled trials yielded positive data "it would be hard
for any government to resist an application for the approval of
cannabis or a cannabinoid as a medicine". Is he somewhat naive about
politicians?

On the use of cannabis as a recreational drug Iversen is much more
cautious. Its short-term adverse effects are mild _ mostly changes in
time and distance estimation. However, as was the case with tobacco
years ago, we may not have yet seen the results of long-term use.
Cannabis smoke, like that of tobacco, is of course carcinogenic. Does
it represent a medical or social danger? The jury is still out, but
the data are not encouraging. Recent work indicates that
delta-9-tetrahydrocannabinol promotes tumour growth by inhibiting
certain antitumour immunity. Yet pot-smokers do not seem to have
excessive cancer rates. As Iversen points out, epidemiological surveys
are clearly needed to follow future developments.

Iversen has written an excellent, well- balanced, non-specialist book
covering both the biological and social aspects of cannabis. I
strongly recommend it.

Forwarded by:

Arthur Livermore, Director
Falcon Cove Biology Laboratory
44500 Tide Avenue
Arch Cape, OR 97102
503-436-1882