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.

FRED GARDNER is the editor of O’Shaughnessy’s Journal of the California Cannabis Research Medical Group. He can be reached at: fred@plebesite.com





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Fred Gardner is the managing editor of O’Shaughnessy’s. He can be reached at fred@plebesite.com

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