Endocannabinoids and the regulation of their levels in health and disease.

Abstract

“PURPOSE OF REVIEW:

Endocannabinoids are defined as endogenous agonists of cannabinoid receptors, that is, of the two G-protein-coupled receptors for the Cannabis psychoactive principle Delta-tetra-hydrocannabinol. Two such endogenous mediators have been most thoroughly studied so far: anandamide and 2-arachidonoylglycerol. Here we review the mechanisms for the regulation of their levels under physiological and pathological conditions, and recent findings on their role in disease.

RECENT FINDINGS:

It is becoming increasingly clear that, although both anandamide and 2-arachidonoyl-glycerol are produced and degraded ‘on demand’, the levels of these two compounds appear to be regulated in different, and sometimes even opposing, ways, often using redundant molecular mechanisms. Alterations of endocannabinoid levels have been found in both animal models of pain, neurological and neurodegenerative states, gastrointestinal disorders and inflammatory conditions, and in blood, cerebrospinal fluid and bioptic samples from patients with various diseases.

SUMMARY:

Endocannabinoid levels appear to be transiently elevated as an adaptive reaction to re-establish normal homeostasis when this is acutely and pathologically perturbed. In some chronic conditions, however, this system also contributes to the progress or symptoms of the disorder. As a consequence, new therapeutic drugs are being designed from both stimulants and blockers of endocannabinoid action.”

http://www.ncbi.nlm.nih.gov/pubmed/17353660

The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance

Abstract

“During the last few years, the endocannabinoid system has emerged as a highly relevant topic in the scientific community. Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors, named CB1 receptor and CB2 receptor, first discovered as the molecular targets of the psychotropic component of the plant Cannabis sativa, participate in the physiological modulation of many central and peripheral functions. CB2 receptor is mainly expressed in immune cells, whereas CB1 receptor is the most abundant G protein-coupled receptor expressed in the brain. CB1 receptor is expressed in the hypothalamus and the pituitary gland, and its activation is known to modulate all the endocrine hypothalamic-peripheral endocrine axes. An increasing amount of data highlights the role of the system in the stress response by influencing the hypothalamic-pituitary-adrenal axis and in the control of reproduction by modifying gonadotropin release, fertility, and sexual behavior. The ability of the endocannabinoid system to control appetite, food intake, and energy balance has recently received great attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptor and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control metabolic functions by acting on peripheral tissues, such as adipocytes, hepatocytes, the gastrointestinal tract, and, possibly, skeletal muscle. The relevance of the system is further strenghtened by the notion that drugs interfering with the activity of the endocannabinoid system are considered as promising candidates for the treatment of various diseases, including obesity.”

I. Introduction

“THE FIRST STEPS in the discovery of the endocannabinoid system date back almost 4000 yr, when the therapeutic and psychotropic actions of the plant Cannabis sativa were first documented in India (1). Over the last 40 yr, after Gaoni and Mechoulam (2) purified the psychoactive component from hemp, a stunning amount of research has revealed the endocannabinoid system as a central modulatory system in animal physiology.

Elements of the endocannabinoid system comprise the cannabinoid receptors, the endogenous lipid ligands (endocannabinoids), and the machinery for their biosynthesis and metabolism (3, 4). Despite public concern related to the abuse of marijuana and its derivatives, the research on the endocannabinoid system has recently aroused enormous interest not only for the physiological functions, but also for the promising therapeutic potentials of drugs interfering with the activity of cannabinoid receptors. This review aims to provide an overview on the pivotal role of the endocannabinoid system in the modulation of the neuroendocrine and peripheral endocrine systems. Moreover, in the context of the recently proposed therapeutic applications of cannabinoid receptor antagonists in the treatment of obesity, the key role of the endocannabinoid system in the control of eating behavior, food intake, and energy metabolism will be discussed in the light of the recent data obtained from human and animal studies.”

http://edrv.endojournals.org/content/27/1/73.long

How many sites of action for endocannabinoids to control energy metabolism?

Abstract

“The promising results obtained by clinical trials using Rimonabant to tackle visceral obesity and related disorders recently promoted a remarkable impulse to carry out detailed investigations into the mechanisms of action of endocannabinoids in regulating food intake and energy metabolism. The endocannabinoid system has been known for many years to play an important role in the modulation of the neuronal pathways mediating the rewarding properties of food. However, in the last few years, with the advanced understanding of the crucial role of the hypothalamic neuronal network in the regulation of appetite, several studies have also directed attention to the orexigenic role of the endocannabinoid system, substantiating the well known appetite stimulating properties of derivatives of Cannabis sativa. Furthermore, the last 2 years have seen a number of relevant publications emphasizing the role of endocannabinoids as significant players in various peripheral metabolic processes. To date, the roles of the endocannabinoid system in influencing energy metabolism have proved to be more complex than was formerly believed. However, the diverse ability to modulate both central and peripheral processes highlights the pivotal involvement of the endocannabinoid system in the control of metabolic processes. This review describes the roles of endocannabinoids and the cannabinoid type 1 receptor (CB1) in the control of energy balance.”

http://www.ncbi.nlm.nih.gov/pubmed/16570104

Marijuana smokers are thinner, less likely to be obese than non-smokers, according to new study

“Stoners may spend a lot of time on the couch and craving White Castle, but they apparently don’t let their bodies go to pot.

People who smoke marijuana regularly are less likely to be obese than non-pot smokers, according to a new study by French researches.

“We found that cannabis users are less likely to be obese than non-users,” Dr. Yann Le Strat, French psychiatrist and co-author of a new study in the American Journal of Epidemiology told MSNBC. “We were so surprised, we thought we had [made] a mistake.”

Using data from two epidemiologic studies of U.S. adults, researchers found that between 22% to 25% of participants who didn’t smoke pot were obese.

But only between 14% and 17% of those people who admitted to taking a toke at least three times a week were overweight.

Le Strat said other factors, such as the stoners’ level of physical activity or diets, could have contributed to the results, but his team tried to rule out those factors.

The researches were also quick to point out that sucking on a bong isn’t the key to a tight tummy.

“The take-home message is certainly not ‘smoke cannabis, it will help you lose weight,'” Le Strat said. “The possibility that cannabis is associated with a lower risk of obesity remains an interesting hypothesis, but certainly does not counterbalance its negative effects on health and mental health.””

http://articles.nydailynews.com/2011-09-04/entertainment/30136983_1_cannabis-marijuana-smokers-smoke-pot

The Marijuana Diet: Study Says Pot Smokers Tend to be Skinnier (Really)

“You know the stereotype: Marijuana user = Jonah Hill-looking dude who lives on his friend’s couch.

But if you look at the daily smokers around you, and we know you have daily smokers around you, this being the pot shop capital of the nation and all, what are you looking at?

You see skinny people.

For the first time, a study seems to back up the observation that stoners are actually lithe
Research published last week in the American Journal of Epidemiology (via our friends at SF Weekly) finds that weed smokers on average are more likely to have normal weight.

Parsing data, researchers found that 22 percent of nonsmokers were overweight while only 14 percent of bud aficionados were. Those ID’d as potheads had to smoke at least three times a week under the study.

What munchies? This might explain why pot-smoking women are often, well, smoking hot.

Interesting, because one of the arguments for legalizing medical marijuana is that it can be used to boost the appetites of AIDS sufferers and cancer patients who have trouble keeping weight on.

Still a valid use? Whatever works.

But we do know that the Marijuana Diet sounds way cooler than any eating plan South Beach Miami has ever produced.”

[@dennisjromero/djromero@laweekly.com]

http://blogs.laweekly.com/informer/2011/09/marijuana_skinny_fat_study.php

Study links pot smoking and weight loss – ABC News

“Researchers have found a surprising link between smoking marijuana and a lower risk of obesity.”

 

“Although a common side effect of cannabis is the “munchies,” the results of a French study showed about a 10 percent lower rate of obesity in people who frequently smoke marijuana compared with those who never have.

Researchers believe some components of marijuana may help people lose weight, however they emphasized that people should not smoke marijuana to lose weight.”

http://abclocal.go.com/wabc/story?section=news/health&id=8345422

Anti-Obesity diet drug from cannabis works!

“For those whose New Year’s resolution was to yet again try to lose those extra kilos help may be at hand in the form of a new wonder drug derived from cannabis.

At first glance cannabis appears an unlikely candidate in the search for a weight-loss miracle drug, but the very same compound which switches off the same brain circuits that make people hungry when they smoke cannabis, could may well be the first blockbuster anti-obesity drug ever.”

http://www.news-medical.net/news/2006/01/17/15421.aspx

Cannabis could be used to treat obesity

“Cannabis could be used in drugs to help people overcome obesity, according to new UK research.

Researchers at GW Pharmaceuticals have discovered two compounds in cannabis leaves that help our bodies burn more energy, the UK’s Daily Telegraph reported.

The company is developing a drug to treat “metabolic syndrome”, which occurs when people suffer obesity, diabetes and high blood pressure, which increases their risk of heart disease and stroke.

Tests in mice showed the cannabis compounds improved their metabolism, which resulted in lower cholesterol in the bloodstream, plus less fat in key organs, such as the liver.

Now a trial is underway with 200 people and researchers hope the drug can treat metabolic syndrome.

Dr Stephen Wright, director of research and development at GW Pharmaceuticals, said they expect results in late 2012.

“The results in animal models have been very encouraging. We are interested in how these drugs effect the fat distribution and utilisation in the body as a treatment for metabolic diseases,” Dr Wright said.

“Humans have been using these plants for thousands of years so we have quite a lot of experience of the chemicals in the plants.”

Cannabis is illegal in the UK but GW Pharmaceuticals has been granted permission to grow it in secret greenhouses in the country’s south.

They are growing a type of cannabis with different quantities of compounds called cannabinoids.

While cannabis is known for inciting the “munchies”, these compounds, called THCV and cannabidiol, appear to suppress the appetite, while helping control sugar levels in the blood and fat levels throughout the body.

It appears THCV also helps cells that produce insulin work more effectively.

Now researchers are hoping the drugs will help people suffering type 2 diabetes and other obesity-related diseases.”

http://health.msn.co.nz/healthnews/8496828/cannabis-could-be-used-to-treat-obesity

Does pot prevent obesity? What new marijuana study says

“(CBS) Move over, fad diets. Scientists have identified something else that might keep off excess weight.

Smoking pot.

That’s right, marijuana users are less likely to be obese than their non-toking counterparts, according to a new study.

Doesn’t pot-smoking cause the munchies?

Actually, the researchers behind the study had been expecting to find that marijuana smokers would weigh more than non-users.

“Cannabis is supposed to increase appetite,” study author Dr. Yann Le Strat, a psychiatrist at Louis-Mourier Hospital in Colombes, France, told MSNBC. “We found that cannabis users are less likely to be obese than non-users. We were so surprised, we thought we had [made] a mistake.”

For the study – published online in the August 24 issue of the American Journal of Epidemiology – researchers analyzed data from two large population surveys of U.S. adults. The researchers found obesity rates in people who “just say no” were 22 percent and 25.3 percent in each survey, respectively. But study participants who puffed pot at least three times a week had obesity rates of 14.3 percent and 17.2. The study didn’t actually prove smoking pot causes weight-loss.

“There could be many other reasons why pot smokers have less obesity,” Andrea Giancoli, a registered dietitian and spokesperson for the American Dietetic Association, told MSNBC. “Maybe they’re inclined to exercise more, be outdoors more, eat more fruits and vegetables. There could be all kinds of confounding factors that could make the results null and void.”

Potheads might be more physically active? Seriously?

“I would be surprised that cannabis use is associated with a higher rate of physical activity, but this cannot be ruled out,” Le Strat told Fox News. Another possibility, he said, is that certain compounds in cannabis might help people lose weight, and could serve as an area of future research.

Should folks trying to lose weight consider picking up a bong instead of a barbell?”

http://www.cbsnews.com/8301-504763_162-20102773-10391704.html

Marijuana Slims? Why Pot Smokers Are Less Obese

“If cannabis causes the munchies, how is it possible that pot smokers are thinner than nonsmokers?

A new study published in the American Journal of Epidemiology finds an intriguing connection between marijuana use and body weight, showing that rates of obesity are lower by roughly a third in people who smoke pot at least three times a week, compared with those who don’t use marijuana at all.

Researchers analyzed data from two large national surveys of the American population, which together included some 52,000 participants. In the first survey, they found that 22% of those who did not smoke marijuana were obese, compared with just 14% of the regular marijuana smokers. The second survey found that 25% of nonsmokers were obese, compared with 17% of regular cannabis users.”

Read more: http://healthland.time.com/2011/09/08/marijuana-slims-pot-smoking-linked-to-lower-body-weight/#ixzz29gb31XKW