Scientist drum up support for blocking cannabinoid receptors

[budman]

The LAST thing I want to do is BLOCK my CB 'receptors'. I need all the help I can get...every last one of them.

Brain's Receptors Sensitive To Pot May 'open Door' In Treating Drug Dependence, Brain Disorders

Article Date: 07 Jun 2006 - 0:00am (PDT)
Medical News Today

A team of Johns Hopkins researchers developed a new radiotracer--a radioactive substance that can be traced in the body--to visualize and quantify the brain's cannabinoid receptors by positron emission tomography (PET), opening a door to the development of new medications to treat drug dependence, obesity, depression, schizophrenia, Parkinson's disease and Tourette syndrome.

Discovery of the [11C]JHU75528 radioligand, a radioactive biochemical substance that is used to study the receptor systems of the brain, "opens an avenue for noninvasive study of central cannabinoid (CB1) receptors in the human and animal brain," explained Andrew Horti, assistant professor of radiology at Johns Hopkins Medicine, Baltimore, Md. He explained that there is evidence that CB1 receptors play an essential role in many disorders including schizophrenia, depression and motor function disorders. "Quantitative imaging of the central CB1 using PET could provide a great opportunity for the development of cannabinergic medications and for studying the role of CB1 in these disorders," added the co-author of "PET Imaging of Cerebral Cannabinoid CB1 Receptors with [11C]JHU75528."

Cannabinoid receptors are proteins on the surface of brain cells; they are most dense in brain regions involved with thinking and memory, attention and control of movement. The effects of tetrahydrocannabinol (THC), the primary psychoactive compound in marijuana, are due to its binding to specific cannabinoid receptors located on the surface of brain cells. "Blocking CB1 receptors presents the possibility of developing new, emerging medications for treatment of obesity and drug dependence including alcoholism, tobacco and marijuana smoking," said Horti.

The usefulness of in vivo (in the body) radioligands for studying cerebral receptors by PET depends on the image quality, and a good PET radiotracer must display a high level of specific receptor binding and low non-specific binding (binding with other proteins, cell membranes, etc.), said Horti. "If the non-specific binding is too high and specific binding is too low, the PET images become too 'noisy' for quantitative measurements," he noted. "We developed a PET radiotracer with a unique combination of good CB1 binding affinity and relatively low non-specific binding in mice and baboon brains," he added. "Previously developed PET radioligands for imaging of CB1 receptors were not suitable for quantitative imaging due to the high level of image 'noise,'" he added.

"Even though PET methodology was developed 30 years ago, its application for studying cerebral receptors is limited due to the lack of suitable radioligands," said Horti. "Development of [11C]JHU75528 will allow noninvasive research of CB1 receptor," he added, indicating that Johns Hopkins researchers need to complete various safety studies and obtain Food and Drug Administration approval before [11C]JHU75528 can be used for PET imaging in people.

"This discovery would not have been possible without involvement of many highly qualified researchers, including the teams of Robert Dannals and Dean Wong and support of Richard Wahl, director of the nuclear medicine department," said Horti.

Maryann Verrillo
mverrillo@snm.org
Society of Nuclear Medicine
http://www.snm.org/

Imagine if they did discover something that would permanently block the receptors, and dumped it in the water supply...and that's EXACTLY the kind of thing our government would do.

[palmspringsbum]

Big Pharma's Strange Holy Grail
Cannabis Without Euphoria?

CounterPunch
By FRED GARDNER
July 8/9, 2006

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

[Midnight toker]

Investing in the obesity drug market

Rob Fannon
Published : Wed 26 Jul, 2006
The Daily Reckoning



Over half UK adults are overweight. One in five is classified as obese.

And the numbers have been rising...

The problem triggers an increase in associated health problems such as diabetes, cancer and heart disease. Such was the stark warning to MPs recently from the Medical Research Council’s centre for nutrition.

In the US the problem is even more acute. But where there’s a health problem, the big pharmaceutical companies see an opportunity...

One-third of Americans are obese. Two-thirds are overweight. The World Health Organization estimates that there are 1 billion obese people throughout the world – one person out of every six.

Obesity leads to a host of medical maladies – high blood pressure, coronary heart disease, stroke, diabetes, and osteoarthritis. This short list of conditions represents the main artery of current blockbuster drug markets (those drugs logging more than $1 billion in annual sales).

Imagine getting a crack at a main source of all these problems – simple estimates peg the potential obesity-related drug market to be well over $10 billion per year! For investors in the pharmaceutical and biotech industry, there’s at least one reason to smile at the continued obesification of America. There’s a lot of opportunity in high BMIs (obesity is defined as a body mass index greater than 35).

With generic competition plaguing top-selling cholesterol and heart-disease drugs like Lipitor® ($11 billion annually for Pfizer), Zocor® ($5 billion annually for Merck), and Plavix® ($5 billion annually for both Sanofi-Aventis and Bristol-Myers Squibb) – Big Pharma is in a desperate search for the next blockbuster drug.

There are a few obesity drugs currently on the market but, thus far, none has emerged as the huge seller the industry seeks.

Xenical® by Roche Pharmaceuticals (ROG.VX) blocks fat absorption in the gut, but causes pretty severe gastrointestinal side effects. GlaxoSmithKline (NYSE: GSK) tried unsuccessfully to get regulatory approval to sell the drug over-the-counter in the United States.

Abbott Laboratories (NYSE: ABT) launched Meridia® with less than stellar sales because the drug could not be given to any patients with hypertension or heart problems – conditions afflicting practically every obese person.

The latest front-runner is Acomplia® by Sanofi-Aventis (NYSE: SNY). The drug blocks the cannabinoid receptor that reportedly gives marijuana smokers the "munchies," thereby decreasing food cravings and over-eating. Acomplia was once hailed as the next wonder drug, with possible uses in smoking cessation, diabetes, cholesterol, alcoholism, and obesity.

<span class=postbold>Acomplia received regulatory approval in Europe for obesity treatment, and is now in the midst of its first commercial launch. FDA approval was delayed, but is likely to come sometime this year. It is estimated that worldwide sales could be $5 billion, while others question the side-effect profile for the drug, citing nausea, depression, and high dropout numbers from the clinical trials.</span> We’ll all be closely watching for early sales numbers from Acomplia’s launch to gauge prescribing habits for doctors treating obesity and related disorders.

One thing is for certain, competition in the obesity drug market will be fierce; it’s highly likely there will be more than one winner.

Presently, there are approximately 10 drugs in clinical trials with at least another 100 candidates in the discovery stage.

There’s plenty to play for here in a market that is big in every way.


Good investing,

Rob Fannon
for The Daily Reckoning

<span class=postbold>See Also</span>: Pregnancy

[Midnight toker]

August 05, 2006

The Times
Body&Soul


Junk medicine: anti-obesity drugs
by Nigel Hawkes

Fat chance of a cure


The medicalisation of obesity goes ahead at full tilt. Increasingly, fat people are not seen as self-indulgent or slothful but as victims of an “obesogenic environment”, incapable of taking their fate in their own hands and prime candidates for medication.

Indeed, even to suggest that this is a matter for individual decision, and not for national hand-wringing, is to step over an invisible line. Overweight people are victims and to imply that they have brought their problems on themselves is to deny their victimhood.

So turning obesity into a medical problem suits everybody: the Government because it has decided that obesity is a problem but has no idea how to deal with it; obese people because they can console themselves that they have a disease; and the drug companies, which see a pot of gold in developing anti-obesity drugs and vaccines.

Acomplia, a drug that reduces weight by acting on the appetite pathway, got a rapturous reception in June when it won a licence from the European drug regulatory agency. This week a team from California reported success with an obesity vaccine. Scientists from the Scripps Research Institute, in La Jolla, reported that when they gave rats a vaccine against a hunger hormone called ghrelin, the animals were able to eat what they wanted without putting on fat.

If this vaccine ever becomes a reality for human beings, it will be aimed at “yo-yo” dieters whose weight oscillates wildly. What gives the vaccine its unique selling proposition, however, is that it appears to affect the rats’ metabolism, not just their appetite. Fat people often claim — possibly with some justification — that their metabolism is different from leaner folk. A vaccine that could put that right would have the punters clamouring.

But changing people’s metabolism, or messing with their hormones, is not a trivial matter. Drugs that are to be used by healthy people, such as the Pill and HRT, have to meet far more stringent safety requirements than those intended for the ill.

So the medicalisation of obesity matters because if the overweight are defined as ill, it lowers the threshold of safety that a drug has to meet. And there are dangers in that, as another of this week’s stories pointed out.

Acomplia is a close relation of the cannabinoids, the active ingredients in marijuana. But while hash can give users the “munchies” — a powerful desire for food — Acomplia is designed to do the opposite. Both work by affecting a chemical called anandamide, which has effects both in the brain and in other organs as well.

A study of the effects of marijuana, this time among mice, showed that it can disturb the anandamide balance and cause a lot of complications in pregnancy, including ectopic pregnancies, when the foetus is implanted in the wrong place.

The research did not show that the same was true for Acomplia but it suggested it might be. No drug that has yet been invented has effects but no side-effects, so we must be especially careful that the anti-obesity drugs really do more good than harm.

But surely the benefits of cutting weight will outweigh any small side-effects? Maybe, but actually the health benefits of being thin are not quite as clear-cut as everybody believes. Being fit is more important than not being fat, as an abundance of evidence has shown.

Among the middle-aged, those who live longest are those who are a little overweight but not obese.


So we should beware of the obesity panic driving us into medical solutions until we are really sure that the cure is safe.

Ten years ago, the hugely popular slimming drug Fen-phen was removed from the US market after it was found to have caused heart problems. It would be careless to make the same mistake again.

<hr class=postrule>
Nigel Hawkes is Health Editor of The Times. Mark Henderson is away

[budman]

I think it's no accident routine 'drug' screening was announced the same day. They're going to 'prescribe' pharmaceuticals that block the cannabinoid receptors and 'treat' anyone that doesn't like it.

More Selective Treatment Options For Metabolic,<br>Central Nervous System Disorders?

14 Sep 2006
Medical News Today

The study which shows that enzyme builds neurotransmitters via newly discovered pathway, directed by Scripps Research Professor Benjamin Cravatt, Ph.D., is published in the September 8 issue of The Journal of Biological Chemistry.

The new study describes a pathway-different than the one previously suggested-for the biosynthesis of neurotransmitter lipids, N-acyl ethanolamines (NAEs), which include the endogenous cannabinoid ("endocannabinoid") anandamide. The high activity of the enzyme a/b hydrolase4 (Abh4) in areas such as the central nervous system suggests that the pathway makes a "potentially major contribution" to endocannabinoid signaling.

Endocannabinoids are naturally produced substances similar to the active ingredient D9-tetrahydrocannabinol (THC) in marijuana. Cannabinoid receptors were first discovered in 1988; the first endocannabinoid, anandamide, which shares some of the pharmacologic properties of THC, was identified in 1992.

Other research has shown that the endogenous cannabinoid system helps control food intake, among other critical processes, by acting on cannabinoid receptors in the central nervous system. The system drives consumption of fat and calorie-rich foods and the amount of fat stored or expended and plays a significant role in energy homeostasis.

"At least one cannabinoid receptor antagonist is on the verge of approval for the treatment of obesity-metabolic disorders," said Cravatt. "Enzymes involved in endocannabinoid biosynthesis, such as the one highlighted in our study, can be viewed as complementary drug targets. One potential advantage of this approach is that it may prove more selective than a receptor antagonist. By inhibiting enzymes such as Abh4, we may be able to disrupt the activity of a single class of endocannabinoids, rather than all of them."

In the new study, the researchers provide biochemical evidence of an alternative pathway for NAE biosynthesis in vivo and demonstrate that these new routes are especially important for the creation of a number of NAEs, including anandamide. The researchers also isolated and identified the enzyme Abh4 by combining traditional protein purification and functional proteomic technologies, concluding that Abh4 "displayed multiple properties" that would be expected of an enzyme involved in NAE biosynthesis.

However, the authors of the study noted, the unique contribution that this Abh4-mediated route makes to the production of NAEs in vivo is yet to be determined and will require "the generation of genetic or pharmacological tools that selectively [interrupt] this pathway."

"The continued pursuit of additional enzymes involved in NAE biosynthesis should further enrich our understanding of the complex metabolic network that supports the endocannabinoid/NAE system in vivo," Cravatt said. "From a therapeutic perspective, any of these enzymes could represent an attractive drug target for a range of human disorders in which disruption of endocannabinoid signaling by cannabinoid receptor antagonists has proven beneficial."

<hr class=postrule>
Gabriel Simon of Scripps Research was the other author of the study, titled "Endocannabinoid biosynthesis proceeding through Glycerophospho-N-Acyl ethanolamine and a role for a/b hydrolase 4 in this pathway."

The research was supported by the National Institutes of Health, the Skaggs Institute for Chemical Biology, and the Helen L. Dorris Institute for the Study of Neurological and Psychiatric Disorders of Children and Adolescents.

<hr class=postrule>
<small>About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel.

Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Currently operating from temporary facilities in Jupiter, Scripps Florida will move to its permanent campus in 2009.

Contact: Keith McKeown
Scripps Research Institute
Article URL: http://www.medicalnewstoday.com/medical ... wsid=51667</small>

[palmspringsbum]

Public release date: 17-Oct-2006

Contact: Lisa Esposito
press@cfah.org
Center for the Advancement of Health

Latest weight-loss pill offers modest results, blocks 'munchies'


A new drug billed as a magic bullet for obesity -- rimonabant (Acomplia) -- does help people lose weight, although not that much weight, and also helps lower cardiac risk factors, according to a review of studies.

Rimonabant went on sale in Europe in July, and U.S. approval is pending before the Food and Drug Administration. The drug works in a new way, suppressing the appetite by targeting the brain cells involved in the "munchies" familiar to marijuana users.

"The use of rimonabant after one year produces modest weight loss of approximately 5 percent" of body weight, found reviewers led by Cintia Curioni, at the State University of Rio de Janeiro, in Brazil. "Compared with placebo, a 20-milligram pill produced a 4.9 kilogram greater reduction in body weight in trials with one-year results."

This translates to weight loss of a little under 11 pounds.

The review looked at four randomized controlled trials comparing rimonabant at two dosages and with placebo, after one or two years of treatment.

Participants, all overweight or obese, followed a "mild" low-calorie diet, adjusted for individual body weight.

<span class=postbold>Only the higher dose -- 20 milligrams -- had significant impact on weight, waist circumference, cholesterol levels and blood pressure.

However, the higher dose brought on more, and more serious, side effects than both the lower dose and placebo.</span>

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care.

Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.

The rimonabant studies took place in 350 trial centers in the United States, Canada and Europe.

The 6,625 participants were at least 18 years old and overweight or obese. One study focused solely on people being treated for type 2 diabetes; another comprised people with high cholesterol or high blood pressure -- important factors in heart disease risk .

The authors described the weight loss pattern: "After the 36th week, the level of weight loss decreased and the body weight was maintained practically until the end of the studies." One study evaluated data after two years: "Patients who stayed on 20 mg rimonabant seemed to maintain their weight loss, while those who were re-randomized to placebo gained significant weight."

People on the larger dose lost an average 1.5 inches on their waistlines. They also showed a slight dip in blood pressure. The higher drug dose significantly lowered blood lipids (fats) and increased high-density lipoprotein ("good" cholesterol) by 3.5 mg/dl compared to placebo.

<span class=postbold>But on the flip side, side effects included nausea, dizziness, headache, joint pain and diarrhea. <b>More serious side effects included psychiatric and nervous system disorders.</b></span>

Obesity drugs, which often come on the market with great fanfare, can end up being withdrawn in a flurry of lawsuits -- like Fen/Phen -- or simply produce underwhelming results for people expecting a magic bullet.

"Every time a new drug comes along, it gets a lot of attention. The natural course is that people who want it will try it, and people with have some lackluster results," said Kelly Brownell, Ph.D., director of the Rudd Center for Food Policy and Obesity at Yale University.

"Few people lose enough weight to make themselves happy, more lose enough weight to get some medical benefit but overall results for most treatments for obesity are disappointing," Brownell said.

Rimonabant has been billed for several years as a potential panacea for the most troublesome of habits – obesity, smoking and possibly alcohol addiction. Studies on its use in smoking-cessation studies are currently under way.

Curioni's team compared its results to a previous review of orlistat and silbutramine, the only drugs approved in the United States for long-term obesity treatment:

"The weight loss associated with rimonabant was slightly greater compared to that related to silbutramine use, with more positive impact on cardiometabolic risk. The effects compared with orlistat appear to be greater weight loss and less frequent adverse effects."

No head-to-head comparisons had been done at the time of the review.

The biggest difference may be in how rimonabant works, by blocking the cannabinoid receptors in the brain. Brownell called rimonabant's ability to suppress munchies "an interesting finding. The issue of food and addiction hasn't been explored very much; it should be."

The review authors noted that the four reviewed studies were sponsored by Sanofi companies. <span class=postbold>With the studies all being sponsored by the drug-maker, results "probably represent a best-case scenario,"</span> Brownell said.

None of the studies analyzed drug costs. <span clas=postbold>"The fundamental problem is that even if one of these drugs caused significant weight loss, the cost would be so prohibitive that it wouldn't be worthwhile on a public health basis," Brownell said. "And only a few people would be able to afford them." </span>


<center>###</center>

FOR MORE INFORMATION: Health Behavior News Service: Lisa Esposito, Editor, at (202) 387-2829 or www.hbns.org.

Curioni C, André C. Rimonabant for overweight or obesity (Review). The Cochrane Database of Systematic Reviews 2006, Issue 4.

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.


By Lisa Esposito, Editor
Health Behavior News Service

So, even if the drug worked, it would be far too expensive to be profitable. So why are they doing it? And why isn't the 'discovery' that blocking the cannabinoid receptors can cause psychiatric and nervous system disorders considered significant?

Not to mention that blocking them can cause, "nausea, dizziness, headache, joint pain and diarrhea."

[palmspringsbum]

Obesity drug may help Type 2 diabetes

Last Updated: Friday, October 27, 2006 | 2:02 PM ET
CBC News

An experimental obesity drug also appears to help reduce the health risks from Type 2 diabetes, researchers say.

The Sanofi-Aventis drug rimonabant, also called Acomplia, reduced risk factors for heart disease in people with Type 2 diabetes compared with those taking a placebo, European researchers report in Friday's online issue of the medical journal The Lancet.

Diabetes is a leading cause of heart disease, kidney failure, blindness and amputation. It kills more than 40,000 people a year in Canada.

In Type 2 diabetes, weight gain, poor nutrition and lack of exercise reduce the ability of insulin manufactured by the body to control levels of glucose (blood sugar) properly, producing a condition called insulin resistance.

Prof. Andre Scheen of the University of Liege in Belgium and his team studied 1,047 overweight and obese people with diabetes who did not respond to standard treatments.

The participants, who lived in 11 countries in Europe and North and South America, were randomly assigned to take either 5 g or 20 mg of the drug daily or a placebo for one year.

All participants were told to follow a diet that provided slightly fewer calories than they needed and were advised to exercise.

After a year, the weight loss results were:<ul class=postlist><li>Those in the 5 mg group lost 2.3 kilograms. </li>

<li>The 20 mg group lost 5.3 kilograms. </li>

<li>Placebo group participants lost 1.4 kilograms. </li></ul>Those who took the higher dose of the drug showed better blood glucose control, higher HDL or "good" cholesterol and improved triglyceride or blood fat levels, and reduced waist circumference — a sign of less abdominal fat.

"The improved blood sugar control plus weight loss achieved with rimonabant is very encouraging," Scheen said in a release. "Today, most medications for Type 2 diabetes are associated with weight gain and it is difficult for people with diabetes to lose weight and keep it off."

Side-effect questions

But it's premature to conclude that the drug helped diabetes risk beyond its weight-loss effects, two Scottish diabetes experts said in a commentary accompanying the study.

"The suggestion that [Acomplia] increases depression and anxiety is concerning," Stephen Cleland and Naveed Sattar wrote.

In each group, about one-third of the participants dropped out, which is common in weight-loss studies. Most did not drop out because of side-effects, but 11 people or three per cent of those in the high-dose group said depression led them to drop out, compared with three volunteers or 0.9 per cent in the placebo group and none in the lower-dose arm of the study.

Some people taking the drug also developed nausea, vomiting and anxiety.

Rimonabant is the first drug that works by blocking the cannabinoid-1 receptor, the same one marijuana targets in the brain. When the receptor is blocked in laboratory animals, they eat less and lose weight.

Regulators in Europe licensed the drug as a weight-loss pill in June, in combination with diet and exercise, for people who are obese and at risk for diabetes. In the U.S., the Food and Drug Administration has asked the company for more information about the drug. Rimonabant is not included in Health Canada's database of approved drugs.

Critics caution it's not known what other effects rimonabant may have on the metabolism, noting blockbuster drugs tested on thousands of people have shown unexpected side-effects when sold to millions of patients for years.

The research was sponsored by the drug's manufacturer.

[palmspringsbum]

Colorado Professor Says Long-Term Use of Drugs Like Acomplia May Be 'Disasterous'

The Acomplia Report
December 14, 2006


An organization that favors repeal of U.S. laws prohibiting use of marijuana has published a story questioning whether diet drug Acomplia (rimonabant), which blocks the same CB-1 receptors that are stimulated by cannabis, may turn out to have "disasteous" medical consequences.

The article that appeared on Dec. 14th on the website of NORML, an organization that claims to represent the interests of "the tens of millions of Americans who smoke marijuana responsibly," noted that Acomplia works by blocking the natural binding of cannabinoids to neuronal CB1 receptors, causing users to lose their appetites.

It said that because the endocannabinoid receptor system is believed involved in regulation of a broad range of primary biological functions -- including mood regulation, blood pressure, bone density, reproduction and motor coordination as well as appetite -- some experts worry that long-term use of Acomplia may eventually contribute to a host of significant adverse health effects.

"CB1 receptors commonly play protective roles in minimizing the consequences of free-radical induced, age-related illnesses, ... as well as the aging process itself," University of Colorado at Colorado Springs biology professor Dr. Robert Melamede is reported as saying.

"The long-term use of CB1 antagonist drugs such as Acomplia may turn out to be disastrous [because] they may promote the illnesses that CB1 activity normally protects against," Melamede concludes.

The article also reports that In preclinical trials, newborn mice injected with Rimonabant refuse feeding and often die days after birth. It said mice genetically bred to lack the CB1 receptor also suffer from numerous health defects such as cognitive decline, hypoalgesia, decreased locomotor activity, and increased mortality compared to healthy controls.

[palmspringsbum]

<i>But society who produces discontent can hardly be treated with drugs.</i>

<a href=http://www.rivistaonline.com/Rivista/ArticoliPrimoPiano.aspx?id=3211 target=_blank>Rivistaonline.com</a>


Rimonabant, the drug treatment pill will be soon available on the market

di Valerio Di Paola
14/01/2007

A pill to stop smoking marijuana. As happens in science fictions, you have just to swallow it and your bad habit, boredom, conscious choices or, sometimes, real pains will be suddenly removed. It is the stake of Nida, the US Institute of Drug Abuse, which have decided to implement an experimental health record with Rimonabant, the first stop smoking marijuana pill. Now Federsed, the Italian Federation Services for Drugs <table class=posttable align=right width=180><tr><td class=postcell><img class=postimg src=bin/pills.jpg></td></tr></table>and other Addictions, decided to grasp the challenge too. This federation, which includes some of the existing national services for addictions treatment, has recently come back from a trip to US to know the Nida Experts and to "formalise an agreed protocol concerning potential collaboration on clinical research focused on addictions prevention". Until now, says Alfio Lucchini, head of Federsed, nothing has been taken for granted: Rimonabant is still waiting the permission to be used in such different way in US, permission to be granted by the Food and Drug Administration, the agency in charge of medical drugs circulation in US. The reason lays in the fact that this pill is, besides a drug treatment, a "fat" remedy.

The Rimonabant is an obesity treatment drug and to this purpose it will be sold in Italy next summer, saving rejection by the Ministry of Health who is now verifying the viability of the drug in accordance with the National law. Already in May 2006, the Italian magazine Panorama reported that it was sufficient to "digit on Google research engine the word Rimonabant to get more than 6oo,ooo results". An extended list ranging from health news to financial analysis and chats on overweigh. Despite the exited expectancy, after the first two years of medical treatment, the clinical studies showed, while constant, a small weigh reduction. On the other hand, the magazine's newsletter Xenia reported the drug is likely to worsen neurological injuries in case of stroke and it may facilitate the rise of multiple sclerosis (MS). The risk for Rimonabant is to become a prescription drug and to be sold on online pharmacies and taken without medical prescription, as one does with mints, as it is the case with different sexual stimulants. By the way, the attention on Nida is focused on other reasons: the pill is supposed to stop the brain receptive of endocannabinoids, natural substances activating hunger and existing in irregular amount in obese people. Focusing on a master of fact, that is smoking stimulates appetite, scientists have found out that the active principle of cannabis runs through the same receptive as endocannabinoids. One pill is enough to neutralize it.

Proven that testing is working, the pill won't treat marijuana lighter users. Mr Lucchini points out the Federsed is intended to make use of it in order to treat "troublesome addictions". The drug is not aimed just to marijuana but also to hard cocaine and heroine addicts. Furthermore, the Sanofi Aventis, the Rimonabant International Company producer, shall be also available to allow a change in the drug public image, passing from a fat treatment to a drugs treatment pill. A multibillionaire contract offered by the state is always attracting; the Sanofi, however, may decide not to get involved with drugs and be satisfied with the 5 billion dollars it is certain to gain through the obesity treatment pill selling within 2010. Nevertheless, a question remains unanswered: is it reasonable to treat drugs addicts with a pill? On one side, there are the supporters of medical treatment considered as the only way-out for drug users, in constant search for a pharmacologic solution to pains and troubles of social order. On the other, the drugs-as-choice and result-of-discontent supporters. But society who produces discontent can hardly be treated with drugs. Federsed promised to explain his reasons on a press conference due to be arranged in near future: the conference will be coupled with a left-leaning manoeuvre by the ruling government aimed to a progressive reassessment of the national drugs law. We wait for what is next .

Traslation from Italian by Ilaria Maccaroni

[palmspringsbum]

It seems to me we have a series of studies here that prove that cannabis prevents depression, anxiety, nausea, and even death (from suicide).

Merck Pill Derived From Pot Research Curbs `Munchies' (Update2)

By Elizabeth Lopatto

Jan. 8 (Bloomberg) -- Merck & Co.'s experimental diet pill, developed using research on marijuana, may curb the munchies and lead to weight loss, a study says.

Patients taking the pill, taranabant, lost an average of 6 to 12 pounds, depending on dose. Those given a placebo lost about 3 pounds during the 12-week study, published today by the journal Cell Metabolism. The research is in the second of three phases of testing needed for U.S. marketing approval.

About 31 percent of Americans over the age of 20 have abnormally high body fat, according to the National Institute of Diabetes and Digestive and Kidney Diseases. The drug targets a receptor found in the brain and gastrointestinal tract discovered through study on marijuana, the researchers wrote.

``It's known that when you smoke marijuana, which is a natural chemical that stimulates the receptor, the marijuana has beneficial effects on nausea,'' said Steven Heymsfield of Merck, the study's head researcher. The effect on the receptor, called CB1, explains why, he said.

Unlike marijuana, taranabant blocks the CB1 receptor, suppressing appetite. Side effects include anxiety, nausea, vomiting and frequent bowel movements, according to the study. All were more pronounced in the higher doses.

Larger studies will be done to determine the specific profile of the side effects, Heymsfield said. A bigger trial, the third phase of marketing tests, will end this year, he said.

``The major hurdle is psychiatric,'' Heymsfield said. ``We know with what we've seen that there are some effects of anxiety and depression related to the mechanism of the drug.''

<span class=postbigbold>Shares Rise </span>

Merck, based in Whitehouse Station, New Jersey, rose $1.74, or 3 percent, to $59.66 at 4:05 p.m. in New York Stock Exchange composite trading, the biggest increase since October. The stock has increased 35 percent in the past 12 months.

Merck said last month that it expects to file for marketing approval of taranabant by the end of 2008. Spokesman Ian McConnell declined to give a peak-sales forecast for the drug.

A similar drug, Sanofi-Aventis SA's Zimulti, was withdrawn by the company from consideration for marketing approval after an advisory panel found that the company's safety data were insufficient and that the weight lost in clinical trials didn't justify the danger of psychiatric or neurological side effects. Paris-based Sanofi has said it will resubmit the pill to the U.S. Food and Drug Administration.

<span class=postbigbold>FDA Delay </span>

The FDA had delayed a decision on the drug, marketed as Acomplia outside the U.S., three times because of concerns it was unsafe. U.S. regulators reviewing the company's application found that people who took the drug were twice as likely to have thoughts of suicide as those on a placebo.

Three patients taking the drug killed themselves during clinical trials, Sanofi officials said in June 2007.

Obese patients taking Acomplia, whose chemical name is rimonabant, were three times as likely as those taking a placebo to develop anxiety, according to a study published in November in the U.K. medical journal The Lancet.

``The balance, of course, is the efficacy and the safety, and that's where rimonabant had questions about whether the benefits were balanced by adverse affects,'' said Christopher P. Cannon, a doctor at Brigham and Women's Hospital in Boston, in a telephone interview last week.

The effects demonstrated in this study are similar, though not identical, said Cannon, who has consulted for Sanofi. He said other doctors have told him that Acomplia has helped their patients lose weight and that the neurological side-effects have been manageable.

<span class=postbigbold>New Family </span>

Both pills belong to a new family of drugs that block receptors in the brain and organs linked to hunger signals. The so-called CB1 receptors, when working properly, help regulate food intake and how the body uses and stores fats and sugars.

CB1 receptors were discovered by scientists attempting to understand the psychoactive components of marijuana. They found that the body produces similar chemicals of its own, called endocannabinoids. These chemicals may stimulate food intake. Acomplia and taranabant work by partially blocking the receptor so that fewer endocannabinoids can be sensed.

To contact the reporter on this story: Elizabeth Lopatto in New York at elopatto@bloomberg.net .

Last Updated: January 8, 2008 16:11 EST

[palmspringsbum]

'Munchies' drug offers hope to the obese

The Telegraph
By Nic Fleming, Medical Correspondent
Last Updated: 2:09am GMT 09/01/2008


A weight-loss drug that suppresses "the munchies" could bring new hope to obese people.

Early trials found that those with weight problems given the pill consumed up to 22 per cent fewer calories than those taking placebos.

They also burned more fat and expended more energy when they were inactive.

advertisementEven people who took very small doses of taranabant experienced significant weight loss. Taranabant is the second anti-obesity drug developed as a result of scientists investigating why people who smoke cannabis often experience sharp increases in appetite.

It was discovered that the endocannabinoid system - which regulates the response of nerve cells to stimuli such as hunger, pain and anxiety - can become over-activated in response to cannabis.

This can lead to an increased desire to eat, known as "the munchies".

Researchers discovered the opposite effect could be achieved by blocking cannabinoid receptors on the surface of brain cells.

A group of 533 obese patients was given placebos or daily doses of 0.5mg, 2mg, 4mg or 6mg of the drug, far less than the 20mg dose in a similar weight-loss pill.

After 12 weeks the average weight lost in each group was 2.6lb (1.2kg), 6.4lb (2.9kg), 8.6lb (3.9kg), 9lb (4.1kg) and 11.6lb (5.3kg) respectively.

The team behind the new study, published yesterday in the journal Cell Metabolism, then conducted a separate 24-hour food intake and energy expenditure study involving 36 overweight and moderately obese people.

Those given single 4mg doses reduced their calorie intake by one per cent, while those given 12mg doses cut theirs by 22 per cent.

The study's author Steven Heymsfield, of Merck Research Laboratories, said the surprise finding that such low doses were effective meant some of the side-effects associated with another similar medication could be avoided.

He said: "We didn't expect weight loss at all doses. The effects of marijuana on appetite have been known for millennia from its medicinal and recreational use.

"The ingredient responsible stimulates cannabinoid receptors. When you block the cannabinoid system with an antagonist like taranabant, you suppress appetite.

"But all we have here is 12 weeks. We don't yet know what will happen at six months or a year."

Those given taranabant also experienced side-effects including nausea and vomiting, as well as greater irritability, than those given placebos. A larger clinical trial is under way.

A recent report warned that 60 per cent of men and 50 per cent of women in Britain could be clinically obese by 2050 unless dramatic action is taken, with the cost likely to reach £45 billion a year in treatment and lost earnings.

The first drug derived from research into cannabis users' appetite, called rimonabant but sold as Acomplia by the company Sanofi-Aventis, was launched in June 2006. Early trials suggested it could help almost a quarter of overweight people to lose 10 per cent of their body weight. It was also shown to help people give up smoking.

The drug was given a UK licence to be taken alongside changes in diet and exercise for overweight people at risk of developing type 2 diabetes.

However the US Food and Drug Administration last year refused to licence the drug, pointing to research suggesting a link with increased risk of suicidal thoughts, even among patients with no history of depression.

<hr class=postrule>
<center><small>Information appearing on telegraph.co.uk is the copyright of Telegraph Media Group Limited and must not be reproduced in any medium without licence. For the full copyright statement see Copyright </small></center>

[palmspringsbum]

Results Of Clinical Trial Of Experimental Weight-Loss Drug

Medical News Today
09 Jan 2008

The first clinical studies of an experimental drug have revealed that obese people who take it for 12 weeks lose weight, even at very low doses. Short-term studies also suggest that the drug, called taranabant - the second drug designed to fight obesity by blocking cannabinoid receptors in the brain - causes people to consume fewer calories and burn more, researchers report in the January issue of Cell Metabolism, a publication of Cell Press. Cannabinoid receptors are responsible for the psychological effects of marijuana (Cannabis sativa), and natural "endocannabinoids" are important regulators of energy balance.

"The effects of marijuana on appetite have been known for millennia from its medicinal and recreational use," said study author Steven Heymsfield of Merck Research Laboratories. "The ingredient responsible stimulates cannabinoid receptors. When you block the cannabinoid system with an antagonist like taranabant, you suppress appetite." However, the drug, developed by Merck, also comes with an increased risk of adverse side effects at higher doses, the study shows, including mild to moderate gastrointestinal and psychiatric effects.

The first proof of concept that so-called cannabinoid 1 receptor (CB1R) inverse agonists might offer an obesity therapy came from studies of another drug, developed by Sanofi-Aventis, called rimonabant. That drug is now in use for weight loss in several European countries as an adjunct to diet and exercise but has not received FDA approval for use in the United States.

Taranabant is a structurally novel, highly selective, potent CB1R inverse agonist, Heymsfield's team said. Preclinical studies in animals showed that it can cause weight loss at doses that block just 30 percent of cannabinoid receptors. To extend those findings to humans in the new studies, the researchers first used positron emission tomography (PET) imaging to identify a dose that would bind about 30 percent of cannabinoid receptors in the human brain. They found that 4 to 6 milligrams of taranabant was enough to achieve that goal.

A multicenter, double-blind, placebo-controlled clinical trial including 533 obese patients showed that the drug induces significant weight loss at doses ranging from 0.5 to 6 milligrams. "That was surprising," Heymsfield said. "We didn't expect weight loss at all doses."

The researchers then conducted separate food intake and energy expenditure studies in overweight and moderately obese people who took a single 4- or 12-milligram dose of taranabant. Those studies showed that people taking 12 milligrams of the drug consumed 27 percent fewer calories than those taking a placebo. People taking the drug also expended more energy while at rest and appeared to burn more fat.

The studies also found that higher doses of the drug caused two types of adverse events, Heymsfield said. These negative side effects included gastrointestinal upset, including nausea and vomiting, as well as increased irritability. Marijuana is often used to combat the nausea associated with chemotherapy drugs, Heymsfield noted, and it also tends to make people mellower. "Here, again, [these drugs] have the opposite effect."

A larger, phase III clinical trial of taranabant is now underway to further explore its effects, Heymsfield said. "All we have here is 12 weeks; we don't yet know what will happen at six months or a year."

<hr class=postrule>
Article adapted by Medical News Today from original press release.

<small>The researchers include Carol Addy, Merck Research Laboratories, Boston, MA; Hamish Wright, Merck Research Laboratories, Rahway, NJ; Koen Van Laere, Division of Nuclear Medicine, University Hospital and Katholieke Universiteit Leuven, Leuven, Belgium; Ira Gantz, Merck Research Laboratories, Rahway, NJ; Ngozi Erondu, Merck Research Laboratories, Rahway, NJ; Bret J. Musser, Merck Research Laboratories, Rahway, NJ; Kaifeng Lu, Merck Research Laboratories, Rahway, NJ; Jinyu Yuan, Merck Research Laboratories, Rahway, NJ; Sandra M. Sanabria-Bohorquez, Imaging Research, Merck Research Laboratories, West Point, PA; Aubrey Stoch, Merck Research Laboratories, Rahway, NJ; Cathy Stevens, Merck Research Laboratories, Rahway, NJ; Tung M. Fong, Merck Research Laboratories, Rahway, NJ; Inge De Lepeleire, MSD Europe, Inc., Brussels, Belgium; Caroline Cilissen, MSD Europe, Inc., Brussels, Belgium; Josee Cote, Merck Research Laboratories, Rahway, NJ; Kim Rosko, Merck Research Laboratories, Rahway, NJ; Isaias N. Gendrano III, Merck Research Laboratories, Rahway, NJ; Allison Martin Nguyen, Epidemiology, Merck Research Laboratories, Upper Gwynedd, PA; Barry Gumbiner, Merck Research Laboratories, Rahway, NJ; Paul Rothenberg, Merck Research Laboratories, Rahway, NJ; Jan de Hoon, Center for Clinical Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium; Guy Bormans, Division of Nuclear Medicine, University Hospital and Katholieke Universiteit Leuven, Leuven, Belgium; Marleen Depre, Center for Clinical Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium; Wai-si Eng, Imaging Research, Merck Research Laboratories, West Point, PA; Eric Ravussin, Division of Health and Performance Enhancement, Pennington Biomedical Research Center, Baton Rouge, LA; Samuel Klein, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO; John Blundell, Institute of Psychological Sciences, University of Leeds, Leeds, UK; Gary A. Herman, Merck Research Laboratories, Rahway, NJ; H. Donald Burns, Imaging Research, Merck Research Laboratories, West Point, PA; Richard J. Hargreaves, Imaging Research, Merck Research Laboratories, West Point, PA; John Wagner, Merck Research Laboratories, Rahway, NJ; Keith Gottesdiener, Merck Research Laboratories, Rahway, NJ; John M. Amatruda, Merck Research Laboratories, Rahway, NJ; and Steven B. Heymsfield, Merck Research Laboratories, Rahway, NJ.

Source: Cathleen Genova
Cell Press</small>

[palmspringsbum]

January 14 2008: 10:20 AM EST

Merck's risky research bets

<span class=postbigbold>The drug giant is looking at weight loss and cholesterol treatments that could be blockbusters -- and may pose worrisome side effects.</span>

By John Simons, writer

(Fortune) -- Merck has pulled off a remarkable comeback in the last two years. Now the pharma giant is conjuring medicines with a new scientific swagger, making two particularly risky bets.

Each of these controversial development projects - an experimental weight-loss pill and a cholesterol-lowering treatment - resemble a drug that Merck's peers, Sanofi-Aventis (SNY) and Pfizer (PFE, Fortune 500), spent nearly $1 billion to develop and yet failed to bring to the U.S. market.

Merck's progress is being closely watched. It wasn't long ago that Merck Research Labs was in the doldrums. In 2003, the company was forced to discontinue development of four potential blockbuster drugs - including a potentially lucrative antidepressant and a diabetes treatment - because its research didn't pan out.

Then came 2004's Vioxx recall and the ensuing lawsuits. The central question in the Vioxx legal cases was whether Merck's scientists knew that their arthritis pain medicine increased patients' risk of heart attack and stroke, but pushed the blockbuster to market nonetheless. Last November, Merck (MRK, Fortune 500) agreed to pay $4.85 billion to settle thousands of Vioxx product liability cases.

<span class=postbigbold>Turning a corner</span>

While the Vioxx cases were wending their way through the courts, the company's research operation was turning a corner. Since 2006, Merck has introduced eight new medicines, including Gardasil, a vaccine to prevent cervical cancer, Januvia, a diabetes medication, and Isentress, a treatment for HIV. All the while, the company has continued to orchestrate important licensing deals to help replenish its pipeline. Investors have rewarded the company's resurgence, as Merck's shares have risen 75% since the beginning of 2006.

With a renewed sense of confidence, Merck is delving into high-risk research on the weight-loss and cholesterol fronts because they offer the highest rewards. For instance the World Health Organization now recognizes obesity, for instance, as a global epidemic. Two-thirds of Americans are currently overweight and worldwide, the number of obese adults and children is expected to grow by 75% to 700 million over the next seven years. Although many drugs exist to battle weight gain, none are terribly effective and most carry uncomfortable side effects. A safe, effective weight-loss drug could easily garner $2 billion in annual sales, according to industry analysts.

The same goes for Merck's potential cholesterol-lowering medicine. Cholesterol drugs are a top-selling treatment category, lead by Pfizer's Lipitor which garnered $12.9 billion in sales in 2006. "Assuming the safety issues can be dealt with, these are huge potential markets," says Herman Saftlas, an analyst with Standard & Poors. "In the current environment, you have to take your shot," Saftlas continues, noting the research productivity drought that is plaguing Big Pharma.

The riskiest of Merck's current projects is taranabant, a treatment that until recently was hailed as an elegant solution for attacking excess weight. Rather than working in the gut, taranabant manipulates the brain to suppress appetite. More specifically, the drug acts on the same receptors in the brain that cause marijuana-smokers to experience hunger. Taranabant, in essence, causes a patient to experience the reverse-munchies.

<span class=postbigbold>Side effects</span>

This month, however, a review of data on taranabant in the January issue of the scientific journal Cell Metabolism finds that although the treatment helps obese patients shed pounds, at higher doses it causes "psychiatric side effects." Those ill effects could draw closer scrutiny from the FDA when Merck files taranabant for approval later this year.

In the published review, researchers note that patients in a mid-stage study of the Merck drug lost 8 to 14 pounds over a 12 week period. The 553 patients were taking doses of taranabant ranging from 0.5 milligrams to 6 milligrams. Researchers noted that some patients experienced depression, anxiety, and irritability.

Merck has publicly disclosed its taranabant results to scientific peers and investors - once at a medical meeting in New Orleans last October, and again last month in its annual business briefing with investors and financial analysts. And the review is consistent with work Sanofi-Aventis did on a similar drug sold in Europe as Zumulti. Sanofi's drug failed to gain U.S. approval last summer due to its side effect profile, which experts say included suicidal thoughts and depression in some patients.

Merck officials say their drug differs from Sanofi's enough to warrant further research.

"We think taranabant could be a valuable tool for physicians and patients," says Merck spokesperson Amy Rose. "But its midway through phase III studies right now. Once those studies are done, we'll be able to make a better decision on whether to file [for FDA approval] or not."

As if its research on taranabant weren't risky enough, Merck's scientists are conducting phase II studies on the cholesterol medicine, anacetripib. This drug is similar to a Pfizer compound known as torcetripib, which increased blood pressure and cardiovascular risk in some patients in a late-stage 2006 trial. Pfizer abandoned research on torcetripib in December of 2006, after spending roughly $800 million on its discovery and development.

The Merck treatment regulates the body's "cholesteryl ester transfer protein" or CETP, raising "good" cholesterol while lowering "bad" cholesterol. In its studies of anacetripib thus far, Merck scientists say they have not seen increases in patient blood pressure or cardiovascular risk that Pfizer observed with its cholesterol drug.

Could Merck derail its comeback if its taranabant and anacetripib projects fail? Deutsche Bank analyst Barbara Ryan doesn't believe so. "If these drugs were to fail, I don't think it would be a negative. Merck's valuation is based on the new products, which are doing well. And these experimental treatments are at least five or six years from being on the market."

Mike Krensavage, an analyst with Raymond James & Associates agrees. "Both taranabant and anacetripib are risky bets. But they're risks worth taking," says Krensavage.

The question is whether Merck can succeed where the world's two largest drug companies failed.

[palmspringsbum]

Wednesday, Jan. 16, 2008

The Diet-Pill Dilemma


Time

As the obesity crisis worsens and more pharmaceutical companies are hoping to improve their bottom line by shrinking their customers' bottoms. After all, we are a short-cut society (who wouldn't rather pop a pill than engage in the hard work of exercise and calorie restriction?) with a short memory (remember the fen-phen diet-drug combo that led to a gazillion lawsuits?). The good news is that according to a recent report in the British Medical Journal, three relatively new antiobesity drugs helped patients lose a moderate amount of weight while doing such things as lowering cholesterol and reducing the incidence of diabetes. The bad news is that the list of possible side effects doesn't end there.

The study found that both of the diet pills the U.S. Food and Drug Administration (FDA) has approved for long-term use may lead to a modest weight loss of about 5% to 10% of a person's total body mass within the course of a year. But sibutramine, which was approved as a prescription drug in 1997 and is sold under the trade name Meridia, has been associated with increased blood pressure, insomnia and constipation. Meanwhile, orlistat, which since February has been heavily marketed as the over-the-counter aid Alli, can cause oily bowel movements so frequently that the package insert suggests women wear a panty liner when starting the regimen.

Such unappetizing details make one wonder what a diet drug has to do to get rejected by an FDA panel—Which is what happened this summer to the much hyped rimonabant. Approved by the European Drug Agency in June 2006 and sold under the name Acomplia, rimonabant takes a different weight-loss route than Meridia, which revs up metabolism and creates a feeling of fullness, and Alli, which reduces fat absorption from food. Rimonabant is the first of a new class of drugs designed to keep the user from getting the munchies. That's right: knowing that marijuana and other forms of cannabis stimulate the appetite, scientists wondered what might happen if they blocked the brain's cannabinoid receptors. Early studies suggested the anticannabinoid crew was on to something. Not only did the desire for food seem to diminish with rimonabant but other cravings, like nicotine, were easier to control.

But it turns out there's a downside to blocking parts of the brain that are responsible for pleasure, relaxation and pain tolerance. A study published last month in the Lancet looked at more than 4,000 patients who had been given either 20 mg of rimonabant or a placebo (sugar pill) in double-blinded trials—meaning the participants didn't know which of the two pills they were getting and neither did their doctors. The results were downright depressing. Literally. Patients receiving rimonabant were 2.5 times as likely as placebo recipients to discontinue treatment because of depressive disorders. They were also three times as likely to stop taking the drug because of anxiety. The FDA panel nixed rimonabant's application for approval due to concerns that the drug increases the risk of suicidal thoughts.

I know. This is probably the last thing you want to read this time of year amid all the marathon meals and the candy dishes on virtually every tabletop. But instead of searching for a magic weight-loss pill, you might heed a few simple tips to help get through the calorie-laden holidays. Try eating water-dense foods like salad and fruit at the beginning of a big meal. Push your plate away before you feel full; this will give your stomach time to send signals to your brain that you've had enough and really don't have room for seconds. And more important, don't be one of those people who plan to start a diet on Jan. 1. New Year's resolutions hardly ever work and mainly serve as an excuse to binge during the months beforehand. Sources: British Medical Journal and Mayo Clinic