VIII Preface
At cannabinoid meetings in the past, very few representatives of the pharmaceu-
tical companies were present. Now the picture has changed. At least two synthetic
cannabinoids are in advanced phase III clinical trials. SR-141716, a CB 1 antagonist,
developed by Sanofi, represents a new type of appetite modulator, and HU-211,
developed by Pharmos, is a neuroprotectant in head trauma. If the clinical trials are
successful, both drugs may represent pharmaceutical breakthroughs in important
therapeutic areas. Numerous companies are following in their footsteps. Other
clinical conditions apparently are also being looked into. Sleep disorders, inflam-
matory conditions, neurodegenerative diseases, liver cirrhosis and even cancer
represent possible targets.
What can we expect in the future? Compared to the classical neurotransmit-
ters dopamine, serotonin, norepinephrine, and acetylcholine, we still know very
little about anandamide and 2-AG. There are strong indications that additional
anandamide/cannabinoid receptors exist, but their identification and cloning is
still elusive. As both anandamide and 2-AG are arachidonic acid derivatives,
their leukotriene-type and prostaglandin-type metabolites may be of biological
importance—but, are they? It has been shown that the cannabinoids are rather
unique retrograde messengers at the synapse. But the actual messengers have not
been identified. Are they anandamide and 2-AG? There are initial indications that
the endocannabinoid system is involved in numerous, additional, unrelated bio-
logicalconditionssuchasstress,boneformation,aggression, addictive behaviours.
We know very little of any possible endocannabinoid involvement. And the list is
long.
People smoke cannabis in order to change their mood. The tricyclic cannabi-
noids (and possibly the endocannabinoids) certainly alter mood, social behaviour
and emotions. But we know next to nothing of the chemistry of emotions. Until
quite recently the field of emotions was left to the poets and some psychologists
and psychiatrists. From the point of view of a chemist or a pharmacologist, un-
fortunately, we have very few tools to approach problems of emotions. Could the
endocannabinoids represent such tools?
The present book is an outstanding summary of many aspects of cannabinoid
research. It represents a stepping-stone to many unsolved problems in biochem-
istry, pharmacology, physiology and the clinic. Perhaps it will help generate novel
ideas, such as how to approach the scientific study of emotions.
Spring, 2005
Professor Raphael Mechoulam
Department of Medicinal Chemistry
and Natural Products, Medical Faculty,
Hebrew University,
Jerusalem 91120, Israel
(e-mail: [email protected])