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The Munchies, Marijuana and Happiness

The munchies may be the key to understanding depression.

Why does smoking marijuana produce the munchies? What does this peculiar response tell us about our brain? It turns out, quite a lot; particularly with regard to our ability to experience happiness and joy and to avoid obesity and depression. The craving for food while smoking is likely due to the stimulation of marijuana receptors in the feeding centers of our brain. The munchies drew the attention of neuroscientists who then conducted a series of clinical trials using a novel drug, called rimonabant, that potently block the brain's marijuana receptors. Their hope was that blocking the action of the brain's marijuana neurotransmitter system in the feeding center would produce an "anti-munchies" effect, thereby reducing food consumption and providing help to overweight patients. Right from the beginning, the drug worked very well. People reported significantly fewer cravings for food. In addition, many subjects reported that they were also less interested in drinking alcohol, smoking cigarettes or using cocaine. Not surprising, excitement in the medical community grew quickly about the potential benefits that this drug might provide, particularly because obesity is such a major health risk.

I was recently honored by an invitation to give a TED talk on this topic area. The video is available here.

Unfortunately, some major side effects were reported after long term treatment with the drug. The patients taking rimonabant reported feeling severely depressed and having serious thoughts about committing suicide. It was as though the patients had lost their ability to experience pleasure. It is now thought that rimonabant might have worked too well at blocking one particular type of marijuana receptor in the brain. What this discovery tells neuroscientists is that our endogenous marijuana system is normally involved, either directly or indirectly, in controlling our mood and allowing us to experience pleasure; antagonizing the actions of this chemical in the brain leads to depression with possibly dangerous consequences.

Recent studies have drawn some interesting links between the normal function of our brain's marijuana system and the action of anti-depressant drugs; it's all thanks to our attempts to understand the munchies.

When we are depressed our brains undergo many different biochemical changes; no one is quite certain which of these actually cause the typical feelings of sadness or hopelessness. One important depression-related change is a dramatic decline in the birth of immature neurons, known as neurogenesis, in a brain region called the hippocampus. Drugs that treat depression, such as Prozac and Zoloft, all induce a recovery in the rate of neurogenesis in the hippocampus. So what's the connection with marijuana and the munchies? The drug, rimonabant, that was so successful in reducing food cravings as it induced depression and thoughts of suicide, has been recently shown (by Beyer and colleagues at Pfizer) to significantly reduce neurogenesis. Let's flip this idea on its side and ask, "What would happen to neurogenesis if we exposed the brain to marijuana?" My lab investigated this idea and discovered that a small dose of marijuana, about only one puff, taken every day can reverse the age-related decline in neurogenesis that might underlie depression. Whether this approach might also work in young people remains to be determined.

What these studies teach us is that our brain's own marijuana neurotransmitter system is necessary for us to feel hungry, to experience happiness and to maintain the brain normal processes, such as neurogenesis, that prevent age-associated depression and cognitive decline. We've learned from our experience with rimonabant that it is dangerous to constantly antagonize this neurotransmitter system. What we do not know is whether it is dangerous to constantly stimulate it.

Marijuana and Coffee are Good for the Brain.

© Gary L.Wenk, Ph.D. author of Your Brain on Food (Oxford, 2010);

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