Marijuana ‘munchies’: A key to losing weight?

5. March 2015
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Marijuana consumption is known to trigger increased appetite, known as having ‘the munchies’. Now, newly emerging knowledge on how marijuana regulates appetite could assist in the constant struggle against obesity.

Food is the fuel required by us humans in order to survive. But, how do we know when our energy levels are low and we need to refuel? This task is taken care of by certain circuits, specifically in the hypothalamus of the brain. These circuits let our body know when we need energy by making us feel hungry, or when we have enough energy by promoting the feeling of satiety.

Considering the fact that we all have such a fine-tuned mechanism for hunger regulated by our brain, why is obesity so prominent? That is because, like in every other system, things can always go wrong. Malfunctions can occur that prevent people’s brains from receiving critical signals telling them when to eat or not. Consider the hormones leptin and ghrelin. These hormones have been intensely discussed in the past few years, because of their significance in weight maintenance and obesity. Normally when we eat, leptin that is stored in our fat cells is released, signaling to the brain that we are full. Conversely, ghrelin is released when leptin levels are low, informing our brain that we need energy. In order for leptin to inform our brain that we have had enough to eat, it needs to get past the ‘blood-brain barrier’. In obese patients, it seems that the brain is somehow not receiving the satiety signal. Scientists speculate that this can be either because of leptin’s inability to cross the blood-brain barrier, or that the brain cannot interpret the signal correctly. Either way, the end result is the same. We eat more to gain fat and release more leptin, to try and push through the satiety signal to our brain.

Because of these malfunctions in our body–to–brain signals that can lead to obesity, researchers are always looking for targets they can use to develop hunger-regulating drugs. One of these targets is cannabinoid receptor 1 (CB1). Smoking marijuana is well known to cause sudden increased hunger, known as ‘the munchies’. With the help of the major active component of marijuana 9-tetrahydrocannabinol (9-THC), scientists discovered that CB1 seems to play a major role in the mechanism promoting ‘the munchies’. Therefore, by inhibiting CB1 it could be possible to assist weight loss, by decreasing appetite.

But, is it as simple as inhibiting CB1 to reduce weight?

Unfortunately, when developing drugs it is not usually as simple as finding a potential target. Pharmaceutical companies that tried to make use of the cannabinoid system to fight obesity, eventually had to stop research and withdraw their weight loss drugs from the market due to some major unwanted side-effects, such as depression.

The problem with CB1 is that it can be found both in brain cells, and in several peripheral tissues, mediating both psychotropic effects and modulating food intake. If we could understand more on how this receptor works for each specific function, this could help design drugs that are targeted specifically at suppressing appetite, without having all the unwanted side-effects.

Newly emerging insights on CB1 and appetite regulation

Now, with two recent studies published in Nature and Nature Neuroscience that provide more insight into how CB1 works to regulate appetite, there is hope in reviving research into weight loss drugs targeting cannabinoid receptors.

In the Nature study, Neuroscientist Tamas Horvath and his team at Yale University in New Haven, report that pro-opiomelanocortin (POMC) neurons may be key factors in regulating hunger in response to CB1 activation by cannabinoids. Normally, to promote the feelings of hunger or fullness, the brain is constantly communicating with peripheral organs of the body to assess energy levels. But, how does the brain deal with the signals it receives from our body to let us know if we should eat or not? This is accomplished through two different sets of neurons, the Agouti-related peptide (AgRP) and the POMC expressing neurons. AgRP neurons are known to be activated when energy levels are low, to increase hunger. So far, POMC neurons were thought to be activated under high-energy conditions to suppress hunger. Surprisingly, in this study the scientists show an opposite role for POMC neurons, promoting instead of suppressing hunger when induced by marijuana activated CB1.

So does this mean that POMC neurons have a dual role in appetite control? It would seem so! But how do POMC neurons switch between these two contradicting roles and how do they decide which way to go, hunger or satiety? Striving to answer this question, the researchers found that POMC neurons can secrete two different types of hormones, one promoting fullness known as α-melanocyte-stimulating hormone and another one urging us to eat known as β-endorphin. Which of these two hormones will be secreted seems to be regulated by the mitochondrial uncoupling protein 2 (UCP2). When UCP2 is induced by CB1 activation it seems to urge POMC neurons to secrete β-endorphin to promote hunger.

Taking another approach at examining the role of CB1 in cannabinoid induced hunger, Giovanni Marsicano, together with their colleagues showed an interesting effect of CB1 activation on sensory perception of food, published recently in Nature Neuroscience. More specifically, they observed that when giving fasted mice THC, CB1 expressed in the brain’s olfactory bulb promoted feeding by increasing the ability of the animals to smell food. In simple words, this means that the reason you want to eat more when smoking marijuana is because you smell food more intensely. Performing the same experiment in mice, genetically engineered to lack CB1 in their olfactory bulbs, reduced sensitivity to food in the presence of THC.

Can these new insights renew interest in CB1 inhibitors for weight loss?

Taken together, these recently emerging studies are providing scientists with new clues how the active components of marijuana act to regulate hunger in the human body. Is this knowledge enough to allow the renewal of interest in CB1 as a target to control appetite and aid in weight loss? Possibly yes, if pharmaceutical companies are able to use it to their advantage to design drugs that will specifically reduce appetite, without causing other serious side-effects. However, since the endocannabinoid system is very complex, controlling a large number of functions besides appetite, including emotions and mood, it will still take a great amount of knowledge to specifically target appetite control with CB1 directed inhibitors.

References:

Koch, K., et al. Nature (2015)

Soria-Gómez, E. et al. Nature Neuroscience (2014)
Yang, R. & Barouch, L. A. Circulation Research (2007)
Ahima, R. S & Antwi, D. A. Endocrinol Metab Clin North Am (2008)

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5 comments:

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Dear Guest #2,

We are always trying to publish high quality articles on DocCheck. Therefore, we are of course open to criticism. So, if you have any specific suggestions in order to further improve our articles, we would be happy to try and implement them.

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#5 |
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S. Frank
S. Frank

Nice, clear and comprehensive summary of the two studies and the scientific background. Mentioning all the important findings without over-estimating their impact or raising false hopes to fight obesity.

#4 |
  0
Dr.Kurian
Dr.Kurian

Really interesting! Thank you for breaking down the science to easily understandable form and putting it in the right perspective. Very well written and to the point.

#3 |
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Guest
Guest

Very badly written article…no copy editors on staff?

#2 |
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Michiel Vandenbosch
Michiel Vandenbosch

In Usa they are allready developping new strain..the Skinny weed ..thnxs fot the share

#1 |
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