What are the causes of cyclic vomiting syndrome?

Steve Wartenberg: Welcome back to our ongoing series on cyclic vomiting syndrome with Dr. V. I'm Steve Wharton-Bergen. This is Dr. Thongam Venkatesan, or Dr. V. We're going to talk about and have you fill us in on the causes of CVS. So I'm really interested and fascinated to learn what causes this really common disease.

Thangam Venkatasen, MD: So as I mentioned before, cyclic vomiting syndrome is a disorder of what we call gut-brain interaction. Now, unfortunately, CVS really hasn't been researched a lot due to different reasons, and we don't actually know the real cause of CVS, but we have some clues. There's been some research done over the past decade or so.

So what I can tell you is, like most disorders, it's multifactorial, so there's a combination of factors, so it could be genetic factors and also what we call host factors. Now, when I talk about genetic factors, there were certain mitochondrial DNA polymorphisms or what we call mutations, and there were some pediatric studies that showed that people with cyclic vomiting syndrome have these mitochondrial DNA sort of polymorphisms or mutations. But this didn't pan out as much in adults.

And aside from these genetic factors that are also environmental are host responses, and as I told you previously, stress is a huge trigger and stress is regulated by multiple systems in our body. There is something called the endocannabinoid system and the hypothalamic pituitary axis. And so these are also very important in the regulation of stress and nausea and vomiting. And so it looks like there could be some problems or abnormalities with that.

Some areas that we really need to delve into a little more is: are there any early life adversity or life experiences that somehow predispose a person to develop CVS versus others? So in short, we have a lot of clues, but we're not entirely certain yet.

Steve Wartenberg: Wow. So I just want to go back to one or two things you said. When you talked about the genetic possibility with a genetic mutation, is this one that is passed from a parent to a child?

Thangam Venkatesan, MD: So there's something called mitochondrial DNA, which you only get from your mother, and so there were certain polymorphisms or changes, if you will, in layman's terms, that were found in children with cyclic vomiting syndrome more so than in other normal children. Again, mitochondria very important for energy metabolism. This study was a negative study in adults, so there seems to definitely be some genetic predisposition to CVS, but we need to do a lot more research to know this.

Steve Wartenberg: So you mentioned cannabinoids and endocannabinoids, words I've not heard before. So if you could explain a little further what they are and their impact.

Thangam Venkatesan, MD: Yes. So I know that's a bit confusing. So basically cannabinoids are compounds of substances that have an affinity or act on what we call cannabinoid receptors. So cannabinoid receptors are actually present in the body and they're pretty much everywhere in your body, including your brain. And there's an area in your brain that is responsible for nausea and vomiting called the chemoreceptor trigger zone. And so it's densely distributed in those areas, as well. And as I mentioned before, it's very important for the regulation of nausea, vomiting, and stress.

Now, when you say cannabinoids, there are three types of cannabinoids. And yes, people kind of give me this bewildered look sometimes. So there's something called endocannabinoids, then we have phytocannabinoids, and then we have synthetic cannabinoids. So when we talk about phytocannabinoids, that's something that everybody knows about. So it's from the plant cannabis or marijuana.

Now we have something called endocannabinoids. Endocannabinoids actually compounds that we produce that's similar to almost say like marijuana, and they act on the same cannabinoid receptors. And they're very important really for regulating how we adapt to stress and also have a very important role in preventing us from throwing up and nausea and vomiting. And when you have exposure to chronic stress, it acts on the terminals, and then this actually produces endocannabinoids.

Now, the endocannabinoids then act on the presynaptic terminal or the neuron, and then it actually shuts down and brings the host or the patient or the person back to homeostasis and brings you back down to sort of a normal state, if you will. And so in short, the endocannabinoid system sort of keeps us cool, collected, calm, and it also prevents nausea and vomiting.

Steve Wartenberg: It's the opposite of adrenaline.

Thangam Venkatesan, MD: A little bit. Yeah, it puts the brakes on a little bit for us.

Steve: So you've mentioned cannabis, marijuana a couple of times and how it's from the plant and your body produces it. So how does cannabis use impact people with CVS?

Thangam Venkatesan, MD: I conducted a study amongst my patients and we looked at cannabis use patterns in cyclic vomiting syndrome. And really for the first time, we used what is called a validated questionnaire, which quantifies how much patients use cannabis. So we took all comers and then we found that about 22% of patients with cyclic vomiting syndrome, used cannabis more than four times a week. And so we would actually quantify that as daily or heavy use.

So I really want to emphasize here that somebody who uses cannabis or marijuana once a week or maybe twice a month, they really should not be called heavy users. That's really kind of described as occasional use.

To put it in a nutshell, we found that 22% were heavy users, and then most of them had actually abstained from cannabis for about a month or so, and we found that even though they abstained from cannabis for about a month, they didn't really report their symptoms to go away with cannabis. So I think it's kind of wrong to say that cannabis is causing it. And so certainly it can lead to hyperemesis or make or unmask CVS in certain ways.

The other thing we found in this study is we also found that patients who use cannabis actually said it improved their symptoms. Now again, this is by patient reports. So they said that it reduced symptoms of nausea, vomiting, abdominal pain. Many of them actually use it as an anxiolytic to relieve stress. Again, we really need to conduct more studies to understand the true effects of cannabis use in CVS because marijuana is an antiemetic.

Steve Wartenberg: An anti...

Thangam Venkatesan, MD: Antiemetic. It can stop nausea and vomiting, but that's only when you give it once or twice. But if you use it chronically, then it probably has actually different effects. So it's what we call a paradoxical effect, where low doses can have an antiemetic effect; while higher doses can actually lead to hyperemesis in perhaps patients who are already predisposed to CVS.

Steve Wartenberg: So what are some of the symptoms during an acute CVS flare?

Thangam Venkatesan, MD: This is a good segue to go to what we call the autonomic nervous system. So as I said, even though it says cyclic vomiting, patients in a flare don't just have vomiting: they have nausea, they have severe vomiting, they have abdominal pain, and then they have what is called autonomic symptoms. So they can have diarrhea, they can feel hot and cold, they can sweat excessively. Even though it's a vomiting disorder, you really have myriad symptoms, which is why a CVS flare can really be very debilitating.

Steve Wartenberg: Do some people have the range of symptoms from bad to horrible and it's similar all the time? Or can one person one time have it lower on the scale and higher on the scale? Or how does that work?

Thangam Venkatesan, MD: Typically? They tend to be "stereotypic." Stereotype means it just happens again and again. And typically they tend to have similar symptoms. Obviously, when we get them medications and we intervene, then you will alter the natural progression of the disease, and so then the symptoms would be a little different and hopefully better controlled.

Steve Wartenberg: So what is the research you've done into this, into studying these symptoms?

Thangam Venkatesan, MD: So the autonomic nervous system is really, you have something called the sympathetic nervous system and the parasympathetic nervous system. So if you think about it, the sympathetic nervous system helps you with different types of stress and it looks like there's some kind of imbalance. So we did actually do a prospective study, and so we looked at both the sympathetic and the parasympathetic nervous system.

And so we found in this study that I did that a significant portion, about 35% of patients, had postural orthostatic tachycardia syndrome. We also looked at something called pseudomotor function about sweating, and so we found that people really have a lot of abnormalities, almost 90% of patients had some form of abnormality of the autonomic nervous system. Following this, there were a few other studies that were done, as well, by other groups, and they also showed the same finding.

Now, obviously since 2010, we have slightly different tools. We have better tools to sort of measure this, and there's something called vagal efficiency. So one of my colleagues and collaborators, we did a study on this looking at vagal efficiency, actually this was mostly in children, and we found that they have what is called reduced vagal efficiency. And so the parasympathetic nervous system was not working as well, the one that kind of calms you down and put the brakes on.

And so hopefully there are certain therapies that can actually improve that, and so we are in the process of working on these therapies and looking at this in adults, which is one of my sort of ongoing projects at this time.

Steve Wartenberg: Wow, that's fascinating. So you're taking it as a system-wide approach of the whole body and how it reacts to stress and anxiety and life.

Thangam Venkatesan, MD: Absolutely.

Steve Wartenberg: Wow, that's interesting. So this was a great episode, and why don't you summarize a couple of the key points that people can take away?

Thangam Venkatesan, MD: Yeah, so I think at this point, we unfortunately don't know what causes cyclic vomiting syndrome. And really, if you want me to summarize it, I think it's a combination of genetic factors and environmental factors. It's an episodic disorder. And so I really think it's very important that we continue the research in this area to find the cause of CVS.

Steve Wartenberg: Thanks for watching, and stay tuned for more episodes on what you need to know about CVS with Dr. V.

The Ohio State University Wexner Medical Center logo

For more information, visit wexnermedical.osu.edu/CVS