BIG PHARMA'S STRANGE HOLY GRAIL

Cannabis Without Euphoria?

The International Cannabinoid Research Society held its 16th annual
meeting June 24-28 at a hotel on the shores of Lake Balaton, about 80
miles southwest of Budapest. Most of the 350 registrants were
scientists -chemists, pharmacologists-employed by universities and/or
drug companies.

The sponsor given top billing was Sanofi-Aventis, manufacturer of a
synthetic drug, known variously as "SR-141716A," "Rimonabant," and
"Acomplia," that blocks cannabinoid receptors in the brain.

Additional support came from Allergan, AstraZeneca, Bristol-Meyers
Squibb, Cayman Chemical, Eli Lilly, Elsohly Laboratories, Merck,
Pfizer, two Hungarian companies -Gedeon Richter Pharmaceutical and
Sigma-Aldrich- and G.W. Pharmaceuticals. Researchers affiliated with
other drug companies presented papers and posters and audited the
proceedings. For most the holy grail is a product that will exert the
beneficial effects of cannabis without that bad side-effect known as
"euphoria."

It so happened that on the next-to-last day of the ICRS meeting,
Sanofi got approval to start selling its cannabinoid-receptor blocker
in England as an anti-obesity pill. R. Stephen Ellis, MD -one of two
California doctors in attendance-informally asked Sanofi researchers
what happens when a Rimonabant/Acomplia user ingests external THC
- -i.e., smokes a joint?

Apparently, the company hasn't studied the interaction. "If this drug
becomes the blockbuster they anticipate," says Ellis, "We are going
to be seeing many, many patients who use cannabis for, say, chronic
pain and take Rimonabant to lose weight. Will the beneficial effects
be negated?

Will they require different dosages? Probably -because there will be
two molecules, THC and Rimonabant, competing for the same receptor
sites." According to the pharmacologists, Rimonabant will outcompete
THC, but not shut it out completely.

Sanofi reps said they expect U.S. approval for Rimonabant/Acomplia by
next spring, maybe sooner, and Bloomberg News quotes stock analysts
who foresee $5.5 billion in annual sales. (Sanofi may use the name
"Zimulti" in the U.S.) Although company spokespersons are careful to
say the cannabinoid-antagonist drug is for obese patients with
diabetes and/or high cholesterol, it will be prescribed to countless
millions of people who want to lose a few pounds.

Some 13,000 people have taken Rimonbant in clinical trials.

In the largest trial, subjects lost 14 pounds the first year and 2.4
pounds the second year. But they gained the weight back when they
stopped taking the drug, implying that you have to take it as long as
you live to maintain the effect.

As the involvement of so many corporate labs in the ICRS suggests,
many more drugs that exert effects via the body's endocannabinoid
system will be introduced in the years ahead.

T.M. Fong of Merck enthusiastically described his team's discovery of
a new "inverse agonist" that led to "food intake reduction and weight
loss" in mice and rats. Competition for Rimonabant/Acomplia/Zimulti
is already in the pipeline.

The attitude of ICRS scientists towards Rimonabant is surprisingly
fearless. Esther Fride of the College of Jedea and Samaria presented
a paper that flatly asserted "cannabinoid CB1 receptor antagonists
induce weight loss without undesirable side effects." The paper was
entitled "Undesirable Weight Gain Caused by Prolonged Use of
Anti-Depressant Medication May be Prevented With Rimonabant Without
Loss of Antidepressant Effectiveness." Fride and co-author Nikolai
Gobshtis worked with mice and rats, using a measure of depression
known as the "forced-swim test" in which swimming and struggling are
supposedly good signs, floating a sign of giving up (depression). The
bottom line to the consumer: if you're gaining weight on Prozac
("After short term weight loss," Fride noted, "antidepressant
medication, when administered for prolonged periods, often induces
weight gain"), you can take Rimonabant.

We'll provide more news from the ICRS meeting in future dispatches
- -including encouraging findings by Donald Abrams, MD, re vaporization
and results from a Canadian study in which 13 of 14 patients who used
G.W.'s Sativex for severe pain and spasticity reported relief (mild
to very good). It was my sad honor to stand by and answer questions
about a poster by Tod Mikuriya, MD, who canceled his planned trip to
Hungary for health reasons. Meanwhile back in California the DEA has
sent an extraordinary letter of complaint to the Medical Board of
California, alleging that four doctors in the San Diego area have
been approving cannabis use for conditions that they - the DEA
agents- don't consider sufficiently grave.

The Board has initiated investigations based on the complaint.

The reality is, doctors who know something about how the cannabinoid
system works are going to be far better suited than their uneducated
counterparts to monitor and treat a population in which millions are
taking Rimonabant/Acomplia and its inevitable imitators.