Endocannabinoids cause post sleep-dep binge

It sounds counter-intuitive, but an extra hour or two asleep in bed can help to reduce the risk of becoming obese. Less sleep, on the other hand, seems to be a potent stimulus to over-eat, and especially to binge on high-calorie, fatty and sugary treats. But why is this? As she explains to Chris Smith, Surabhi Bhutani, from San Diego State University, has discovered that sleep deprivation leads to a surge in the body’s own cannabis-like endocannabinoid chemicals. These, she’s found, cause a region of the brain called the insula to slacken it’s inhibitory grip on the brain’s olfactory areas, making delicious treats smell too tempting to resist…

Surabhi Bhutani - There is a huge body of research that suggests that chronic lack of sleep is associated with overall poor health and there is a bunch of data showing that when you do not get enough sleep you increase your food intake, and people become more reactive to unhealthy foods and foods in particular that are high in sugar and fat that we call junk food. What we really wanted to understand was why people crave these high fat foods after a sleepless night.

Chris Smith - Back in the past, when people first began to flush out this association between not getting enough sleep and then rebound overeating, one speculation was that the hunger hormone “ghrelin” - which is produced by the stomach and is suppressed by sleep - that goes up. So there's just a rebound overeating to compensate. So is it as simple as that?

Surabhi Bhutani - It's more complicated than just hunger hormones increasing, because there are a lot of studies showing that people may not really physically feel hungry, but they still go for all those foods that are high in calories. So there has to be a different mechanism where, basically, it connects your sleep loss with consumption of very high calorie foods; so your brain, or your body, saying that I really want a doughnut, or I really want potato chips!

Chris Smith - So you're saying that there's a switch in terms of food choices but it's not necessarily just driven by overall increase in hunger?

Surabhi Bhutani - Exactly.

Chris Smith - And what do you think underpins that then?

Surabhi Bhutani - We definitely think that there are some brain signals that may be playing a role in overeating of not-so-healthy foods, and past research primarily has shown that sleep deprivation increases certain endocannabinoids. So these endocannabinoids are basically these naturally produced neurotransmitters that bind to some of the receptors in the brain and affect feeding behaviour. So they're very similar to cannabis-like compounds that can cause cannabis-related munchies. On the other hand, we also kind of know that sense of smell is also really tightly related to how we choose food items and, in particular, animal studies have shown that these endocannabinoids enhance food intake by increasing the activity of brain areas that process odours. So what we thought was that, maybe we can put all of this together and ask if what people choose to eat when they are sleep deprived is related to how the brain responds to food smells.

Chris Smith - Where in the pathway would you see this effect manifest then? Would it be at the receptor level - how sensitive the receptors are to the molecules that make foods smell and taste the way it does? Would it be in the olfactory bulb where the first processing occurs? Or would it be a cortical level, where the olfactory tracts go into the brain and start depositing signals relative to what they think they're smelling?

Surabhi Bhutani - That's a very interesting question, because it's very difficult to tell exactly where the processes are happening. So, you mentioned olfactory bulb: you really can’t image olfactory bulb in humans. But what we found in our study was that, when people were sleep deprived so they only slept for four hours, the following day when we scanned their brains inside an MRI scanner and made them smell these delicious food odours and also some of the non-food odours, the piriform cortex - the region of the brain where smells are processed - in that particular region the patterns of food versus non-food odours were significantly different in the sleep deprived state. So what this means in simple terms is the smell processing region in the brain goes into this “hyperdrive” - it sharpens the food odours for the brain so it can better differentiate between food and non-food odours.

Chris Smith - And how do you tie that to changes in the end0cannabinoid system, these natural brain chemicals that mimic cannabis?

Surabhi Bhutani - The piriform cortex also sends signals or information out to other brain regions, in particular insula cortex. So insula receives signals that are important for food intake, and when a person is sleep-deprived, signaling between the piriform cortex - the smell processing region - and the insula, that connection was not as strong. So the signaling actually reduced. And we also found that, because of this reduction in communication, people ended up eating more energy-dense food. Now, how is it connected to the endocannabinoids, or the neurotransmitters? When we did the blood analysis, we saw that people had certain components of this endocannabinoid system very high in the blood. And those people also consumed very high energy-density food. So, putting all this together, our results suggest that the sleep deprivation really influences this endocannabinoid system, which in turn alters this connection between piriform cortex and insula cortex and, ultimately, leads to a shift towards foods which are high in calories.

Chris Smith - What would happen if you did this experiment then in an anosmic individual, or people with, say, Kalman syndrome who can’t smell things, or people who've had head injuries and the nose doesn't work properly; are they immune to the appetite-boosting effects of sleep deprivation?

Surabhi Bhutani - That is a very interesting question. So, interestingly, there aren't really any studies done in this area with anosmic individuals, so there is no research out there showing that sleep deprivation can really affect those people who can't really smell. So it'll be interesting to do those kinds of research in future and kind of see whether they are more protected towards these effects of overeating or sleep related overeating or not.