Cannabis Research May Lead To Appetite Controlling Drugs

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Cannabis and weight loss


New research on mice seems to confirm that manipulation of the CB1 receptor outside the blood-brain barrier might hold promise for developing drugs that better control not only appetite but overall human metabolism.

It has long been a staple of conventional wisdom about cannabis that “marijuana causes the munchies”. In more scientific lingo in fact, what researchers are discovering as research on the impact of cannabinoids becomes more widespread, is that cannabis impacts the CB1 receptor that regulates appetite.

When the CB1 receptor is flooded with THC, it releases hunger-promoting hormones. That is why cannabis works so well to help people overcome nausea and begin eating again.

In contrast, suppressing those hormones is thought to aid in weight loss. That said, the mechanism by which the receptor kindles or kills appetite is not yet understood. However, because THC clearly impacts the CB1 receptor, understanding about how it impacts the hunger impulse is a becoming an important part of the research. Not only about the endocannabinoid system as a whole, but also about how cannabinoid-based drugs might be used to control not only the hormone-induced desire to eat food but also how to better control the entire metabolism process.

In fact, during the last decade, several drug companies tried to produce drugs targeting the manipulation of the CB1 receptor specifically to find an effective weight loss drug.

However, because the endocannabinoid system is so centrally linked to impacting just about every function of the human body, this is when and why the research hit some serious snags. Drug developers who were focussing on the full blockage (or agonist) of the CB1 receptor to control appetite ran into problems after these drugs were linked to depression and in some cases suicidal thoughts. Rimonabant, developed by Sanofi-Aventis in 2006 and Taranabant developed by Merck, never reached the market in the last decade because of such issues. As of 2008, research into this field with CB1 agonists was all but stopped as a result.

However, clues also began to emerge about that time that inhibitors might not need to cross the blood-brain barrier to be effective.

WHAT IS AM6545?

AM6545 is not an entirely new development. Research on its effects has been ongoing for at least the last six or seven years since the failure of other kinds of CB1 manipulating drugs and was initially started around the beginning of the century. Among other interesting findings – mice whose CB1 and CB2 receptors had been “knocked out” – i.e. were no longer functional due to surgery on the mice to disconnect the 10th cranial nerve - were not affected by AM6545. Mice who had working CB1 or CB2 receptors seemed to be positively impacted by the drug. In a nutshell? They ate less and lost weight.

And that is when an inquiry into AM6545 began in earnest. Researchers began to believe that selective inhibition of peripheral receptors could help treat metabolic conditions without inducing psychiatric effects. In other words, drugs that affected CB1 receptors without crossing into the brain, might hold a key to this puzzle.

Since then, research including at the Center for Drug Discovery at Northeastern University found that over 28 days of treatment, AM6545 created about a 12% weight loss (compared with 24% for Rimbonant). However, despite the fact that weight loss was about half, there did not seem to be any psychiatric side-effect. 

M6545 Mice CB1

Now a new study seems to provide another clue. AM6545 appears to block CB1 receptors in the central and peripheral nervous systems but does not cross the blood-brain barrier. This prevented gorging in mice who were fed a diet high in fat and sugar and became obese as a result. The mice lost weight after being treated with AM6545. Researchers at the University of California Riverside School of Medicine have published the results of their early research in the January 5 edition of Physiology and Behaviour.

According to the researchers, “Targeting peripheral CB1 receptors with antagonists (e.g. AM6545) that do not reach the brain may be an effective treatment strategy for metabolic syndrome and possibly eating disorders without deleterious psychiatric side effects inherent to brain-penetrant CB1-receptor inhibitors.”

Further, study authors also reported that obesity caused by a “western diet” that is high in fat and sugar is driven by enhanced endocannabinoid signalling at peripheral CB1 receptors.
This research is also seconded by a British study on the same in 2010. British researchers found that “peripheral rather than central CB1 receptors mediate the inhibition of food intake.”

THE ENDOCANNABINOID SYSTEM AS KEY HUMAN REGULATOR

Beyond the immediate impact of stimulation of the CB1 receptor – and further either at its “periphery” or in the brain itself – for this one aspect of research, what such findings also do is further open a door that has long remained shut because of prohibition.

Endocannabinoid system thc

In fact, the endocannabinoid system of the human body may hold many keys to better regulating the human body – from appetite control and stimulation to better processing of just about every part of the system. The impact on the liver, stomach, kidneys and gut itself are all critical components of this research. Further, how CB receptors – both 1 and 2 – can be manipulated is obviously becoming a wide-open field, with many promising impacts for overall human health – both preventive and curative.

FURTHER RESEARCH IS KEY

If anything, beyond the specifics of this latest finding of one specific drug, such research also proves that research of and about the endocannabinoid system if not the impact of externally applied cannabinoid-based substances holds vast promise. As the world begins, for the first time in the era of modern science, to shake off the continued stigma of cannabis, expect bigger and better things to come.

 

         
  Marguerite Arnold  

Written by: Marguerite Arnold
With years of writing experience under her belt, Marguerite dedicates her time to exploring the cannabis industry and the developments of the legalisation movement.

 
 
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