Could Anti-Marijuana Compound Hold Key To Weight?

Could Anti-Marijuana Compound Hold Key To Weight?
Posted by CN Staff on December 17, 2002 at 12:29:12 PT
Press Release
Source: EurekAlert
That people are getting fatter is not news. Around the globe, physically demanding occupations like farming and mining are now carried out by machines. Western values such as television and automobiles are now encroaching on the most isolated environments. Finally, a highly processed diet -- along with a sedentary lifestyle -- is the likely culprit in the high rates of obesity seen among indigenous peoples who were originally hunters and foragers. Now they eat a diet that is "entirely store bought and provided by truck." Scientists and anthropologists have observed that in some societies, a high rate of infectious disease seems to be keeping children's weight low or substandard while many of the adults are obese. In effect, very small children evolve very quickly into obese adults. 
The aesthetic qualities of obesity are the least of the problems associated with this spike in worldwide weight gain. The disorder is associated with an increased risk of life threatening conditions such as diabetes, hypertension and heart diseases, and weight loss has been reported to ameliorate these associated conditions. To prevent these chronic disorders, some try to reduce weight by caloric restriction; however the effort generally fails as most obese patients regain their lost weight thereafter. Therefore, medicinal treatment becomes a necessity. One facet currently being explored is the central regulators of food intake. This includes the cannabinoid system with its putative endogenous ligands anandamide and 2-arachidonoyl glycerol (2-AG). In addition to its many pharmacological activities, this system has been implicated in food intake regulation. Stimulation of appetite is one of the most commonly related effects of marijuana in humans and delta-9-tetrahydrocannabinol (?-9-THC), the main active component of this drug, has been reported to produce hyperphagia. The endogenous cannabinoids anandamide and 2-AG also stimulate feeding when administered to rats. SR141716, a potent and selective central cannabinoid (CB1) receptor antagonist, has been widely used to investigate the role of CB1 receptors in appetite regulation. SR141716 antagonizes the hyperphagia (excessive eating) induced by anandamide, 2-AG and (?-9-THC), primary ingredients in marijuana. These results provide strong evidence for the involvement of CB1 receptors in the regulation of feeding. In addition to modulating the effects of cannabinoids in animals, SR141716 has been shown to produce changes in ingestive behaviors when administered alone. Several studies have reported that SR141716 selectively attenuates the consumption of palatable food or drink. It decreases sucrose intake in rats, alcohol consumption in mice and sweet diet intake in marmosets while having little effect on bland food consumption. These results suggest that the blockade of the central cannabinoid system may alter the rewarding value of foods and so reduce eating. As the majority of human obesity is partly due to difficulty in regulating intake in the face of an increased availability of palatable foods, SR141716 may provide a new interesting way for the treatment of this disorder. Recently, a strong relationship between the endocannabinoid system and leptin, a helical protein secreted by adipose tissue and acting on a receptor site in the ventromedial nucleus of the hypothalamus to curb appetite and increase energy expenditure as body fat stores increase, was reported. Specifically, a deficiency of leptin has been found in obese animal subjects. SR141716 has been shown to induce a significant decrease in food intake and body weight gain and reduce the intake of a high fat diet in these obese rats. Now, a new research effort seeks to assess the effect of SR141716 in a diet-induced obesity (DIO) model. The Study  The authors of "Anti-Obesity Effect of SR141716, a CB1 Receptor Antagonist, in Diet-Induced Obese Mice," are Christine Ravinet-Trillou, Mich¨¨le Arnone, Claire Delgorge, Nadine Gonalons, Peter Keane, Jean-Pierre Maffrand, and Philippe Soubri¨¦, all from the Central Nervous System Research, Sanofi-Synth¨¦labo, Toulouse, Cedex, France. Their findings currently appear in the online edition of the American Journal of Physiology -- Regulatory, Integrative and Comparative Physiology. The publication is one of 14 journals produced monthly by the American Physiological Society (APS).  Methodology Rodents were fed a high fat diet to develop moderate obesity with an increase in energy intake and in insulin resistance. The objectives were to examine the effect of a chronic SR141716 treatment was investigated in C57BL/6 DIO mice, with emphasis on changes in food intake. The most effective dose tested in the Zucker rat study (10 mg/kg, orally) was used in this first experiment. In a subsequent experiment, which included plasma analyses, the effect of a lower dose (3 mg/kg) on adiposity was also assessed. Finally, to confirm whether the effects of SR141716 were mediated by CB1 receptor blockade, the compound was administered to CB1 receptor knockout mice fed a high fat diet.  Results This work describes the effect of blockade of CB1 receptors with SR141716 in a non-genetic model of obesity using high palatable diet fed mice. The ability of the compound to reduce food intake in this model was expected, as previous studies have already demonstrated such an effect in rodents and primates. In this study, SR141716 produced a marked acute lower rate of eating, and it appears that such an effect tends to diminished over chronic administration. In contrast, SR141716 induced a sustained effect on body weight, which remained low until the end of the 5-week experiment with 10 mg/kg/d SR141716, up to a 20 percent difference with DIO control mice). The weight loss was associated with a depletion of fat stores reaching about 50 percent after the dose of 10 mg/kg/d SR141716, as indicated both by the weight of abdominal fat pads and by the total body fat content. Furthermore, SR141716 corrected the insulin resistance and lowered plasma leptin, insulin and free fatty acid levels. Most of these effects were present but less pronounced at 3 mg/kg/d. In addition to its hypophagic action, SR141716 may influence metabolic processes as the body weight loss of SR141716-treated mice was significantly higher during 24 hour fasting when compared to vehicle-treated animals, and when a three-day treatment was compared to a pair feeding. SR141716 had no effect in CB1 receptor knockout mice, which confirmed the implication of CB1 receptors in the activity of the compound. Discussion and Conclusions Overall, there are many indications showing that endocannabinoids are key components of systems that regulate both feeding and body weight, and belong to the wide family of orexigenic substances. A further demonstration is the clear anti-obesity effect of the CB1 receptor antagonist SR141716 in a nongenetic model of obesity reported in this research. SR141716 sharply decreased body weight and adiposity of obese mice without sustained lower eating rates, and improved their insulin resistance. These effects were already seen at three mg/kg/d, and appeared more pronounced at 10 mg/kg/d. In contrast, no effect of SR141716 was observed in CB1 receptor knockout mice. Dietary-obese mice develop the characteristics of the abdominal obesity syndrome found in humans, including marked visceral obesity and diabetes. The high efficacy of SR141716 in this model suggests that CB1 receptor antagonists may constitute a new alternative for the treatment of appetite and body weight disorders in humans. Source: American Journal of Physiology -- Regulatory, Integrative and Comparative Physiology, currently published online. The journal is a publication of the American Physiological Society (APS). The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year. Editor's Note: A copy of the research article is available in pdf file to the press. To obtain a copy or to schedule an interview with a member of the research team, please contact Donna Krupa at 703-527-7357 (direct dial), 703-967-2751 (cell) or e-mail:  djkrupa1 aol.comComplete Title: Could an Anti-Marijuana Compound Hold The Key To Body Weight and Appetite Control?Source: EurekAlert (DC)Published: December 17, 2002Copyright: 2002 American Association for the Advancement of Science Website: Articles:Marijuana Munchies May Hold a Key to Obesity Dope on the Munchies Substance in Brain Trigger Appetite 
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Comment #10 posted by Trippin on January 17, 2003 at 15:31:35 PT
Ex-OverWieght Toker
Since I am cannabis user since childhood and was overwieght, I would like to add my comments.I was afflicted with peripheral neuropathy since age seven and at the same time had unexplainable wieght gain. I started smoking cannabis soon after that that I took from a friends older brother (shhh .. I know, it was the 60's, he didnt mind). It helps my nerve pain but didnt cause any weight gain since I had had weight gain before I ever took my first toke.I stayed overwieght until I was 22. I then lost weight by practically starving myself and doing double excersizes everyday and jogging miles a day which was very painfull in itself for a sick person as myself. I still was tokin. I stayed at ideal weight for 5 years. I was bed ridden for a few months and gained weight.I stayed overwieght until within the last 2 years when I had a bowel problem fixed. This caused me to finally lose weight again and have lost wieght to a point where I am only 20 lbs. over my ideal weight. And I'm still tokin.During my life I have experienced times where I would have uncontrollable munchies for long periods of time and then experience the exact opposite at times. I have known a few (no more then ten) other overwieght tokers and out of those only one or two have lost weight that I have seen.I dont like to toke before I eat, I like after meals better.
I havent really had much of a appetite for most of my life. I tend to eat small infrequent meals because if I try to eat a regular diet then I gain weight. I guess I'm really sensitive to the amount of food I eat.Besides the bowel problem I do have cancer and that probably has a lot to do with why I dont have a apettite. It is kind of embarrassing at times. I have turned down food when at public functions and private events and sometimes people get offended. But, I'd rather toke my cannabis and try and stay alive then to eat something and get sick in front of people.
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Comment #9 posted by fearfull on December 19, 2002 at 08:55:42 PT
Not sure about that
I am a daily smoker when I can afford it, yet I have always had serious problems with my weight. Also, I seem to gain weight when I do have pot available. But then again my wife always seems to force to eat when I'm not ready to, and almost alway just after I've "medicated" myself. Still, I would have to question the idea.
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Comment #8 posted by FoM on December 18, 2002 at 08:22:23 PT
TecHnoCult and Everyone
I haven't met anyone who is over weight who smokes Cannabis either. I've known people who drink alcohol that are heavy but not cannabis consumers.
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Comment #7 posted by TecHnoCult on December 18, 2002 at 08:11:06 PT
Good call! I really never noticed until you said something, but I usally try to smoke before my evening meal, because it makes it more enjoyable. During the day, when I don't smoke, I eat very litte. This article indicates that thc and endocannabinoids enhance the reward of eating food. It makes sense that if you become accustomed to that extra reward, that you would be less stimilated by food without it (cannabis.) It's funny, because years ago I starting taking notice of those poeples' weight that smoke cannabis, and despite the appetite increase, I don't know any obese daily smokers. THC
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Comment #6 posted by greek_philosophizer on December 17, 2002 at 20:27:30 PT:
hi elfman_420
I noticed the same effect. Loss of appetite when not 
high. 210 to 140 is really impressive. Congratulations.
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Comment #5 posted by elfman_420 on December 17, 2002 at 15:13:20 PT
Perhaps I can shed some light on this topic...
...since this is a big issue for me.I remember reading a similar article a while back that helped me understand how cannabis can help a person lose weight. The reason that this interests me is that I started smoking regularly a couple years or so ago, and since have lost 70 lbs, going from 210lbs to 140lbs. I believe a big part of my weight loss was due to cannabis.What happens is those same cannabinoids that affect a positive shift in appetite that help AIDS patients also stimulates a hormone to counteract the positive shift in appetite. This means that you can regulate your appetite simply by smoking before meals. When you aren't high, the hormone causes a negative shift in your appetite so you aren't hungry. I agree with Dr. Russo, however, that patients should just be given cannabis rather than isolating SR141716A which may not be as effective, or even have negative side effects when the other cannabinoids in cannabis aren't present.The other interesting part of this article is how they describe the cannabinoids effecting what the rats choose to intake in their systems. I have changed my diet dramatically since I started smoking regularly (I am now primarily vegetarian), and I always thought that was in big part due to my smoking, somehow. 
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Comment #4 posted by Sam Adams on December 17, 2002 at 14:49:24 PT
The phenomenon you're talking about is a side effect of American policy being driven by Big Pharm, the insurance corporations, and to a lesser extent, doctors. The answer to any problem must serve these constituencies, therefore, the answer is always surgery or drugs.Physical and mental health therapists, nurses, aides, athletic trainers, etc, have no stake. They've spent the last 10 years being beaten down by the private health insurance industry and being drowned out by a flood of political money from Big Pharm and Big Insurance.My question is, why should I give a flying f*** if people are fat? So they die of a heart attack at 60 instead of cancer or Alzheimer's at 85. But I guess we relegated control of how much one suffers, and when one dies, to the government a long time ago. 
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Comment #3 posted by greek_philosophizer on December 17, 2002 at 13:56:49 PT:
  We seem to have a cultural predisposition to be willing to totally screw around with the human body so as to ensure
some type of conformity. 
  It seems that the desire to categorize and label normal 
human behaviors had turned us into a pill for everything 
   Does your kid daydream or act exciteable? Thats not 
normal anymore - its Attention Deficit. Here is a pill for
your kid. Etc. Etc.  
               Kind Regards,
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Comment #2 posted by FoM on December 17, 2002 at 13:46:51 PT
Thanks Dr. Russo
I posted it but I don't understand it at all.
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Comment #1 posted by Ethan Russo MD on December 17, 2002 at 13:20:13 PT:
I am not sure why there is all this excitement about some study in lab animals, when this substance has already been tested in humans. Apparently it does cause weight loss, but figure this:Endocannabinoid activity regulates appetite, central pain, emotions, forgetting, seizure threshold, and a large variety of other basic functions.My prediction is that patients on SR141716A may well become prone to be depressed, anxious, nauseated, have epileptic seizures, migraines, diarrhea and chronic pain. If losing weight is worth that, be my guest.
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