A look at the drug and a rare condition of its heavy use

Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith.

It's rare, but some daily longtime users of marijuana develop a condition that leads to repeated and severe bouts of vomiting.

Here to tell us more about this condition is Dr. Christine Stork. She's a doctor of pharmacy and a clinical professor of emergency medicine at Upstate, and she's part of the upstate New York Poison Center. Welcome back to "The Informed Patient," Dr. Stork.

Christine Stork, PharmD: Thank you so much. Happy to be here.

Host Amber Smith: What can you tell us about cannabinoid hyperemesis syndrome?

Christine Stork, PharmD: The cyclic vomiting that we see in patients presenting to emergency care after having this syndrome report a history of daily high-level use of cannabis for months and years prior to having this syndrome.

And it's really very interesting in that it could be many other things. People present to emergency care for cyclic vomiting, and there's a variety of medical causes that could be and need to be evaluated in these syndromes, but the difference is that many of these patients describe relief with heat, and most of that heat is surrounding the use of hot showers. So they'll say they'll get in a hot shower, they'll feel better, and then they'll remove themselves from the shower, and the symptoms will come back.

Host Amber Smith: Does this affect old and young, male and female?

Christine Stork, PharmD: Yeah, there's no real free disposition to having this. It can occur in all people. Again, the use pattern is fairly high use of cannabis, again, over a period of time, so we don't see it in too many younger folk, who are just starting to use cannabis, but once people become kind of older, teenage years, certainly in the college population and moving beyond, then we do have patients who have this and present with it.

Host Amber Smith: Do you see it in people who smoke cannabis, or what about ingesting edibles? Is that a risk also?

Christine Stork, PharmD: It's pretty interesting that it's not seen as much with edible marijuana products, and it's really unclear as to why that is. But some hypotheses have to do with dose. So when smoking a cannabis product, the blood levels, so the amount of cannabis that's in your body, is high almost immediately.

And then if you're continually using the product throughout the day, again, you're maintaining this high level of cannabis. When you ingest an edible cannabis product, the level kind of creeps up over a period of time, and then it goes down over a period of time. And we don't have a lot of people who are continually using edible marijuana type products throughout the day.

Host Amber Smith: Well, how soon after becoming a daily user might this develop? You said months to years. Could it be as soon as a couple months?

Christine Stork, PharmD: Not usually, but again, if someone escalates their use and has a very high level of use daily, it could be within months. It's usually within years, and it's usually somebody who's built up their use over time.

And pharmacologically, it's not exactly known how this results in vomiting because we all know that cannabis products are used as anti-emetics, or anti-vomiting agents. So the current thought process is that when you use cannabis, it interacts with cannabinoid receptors. They have their own receptors, and those receptors modulate other activities throughout the body, so the normal things, like, in your brain, your chemo receptor trigger zone is central causes of vomiting and, when interacted, are causing enhanced activity or decreased activity there, you'll have anti-vomiting effect. But I wonder if it really has to do with a little bit of drug withdrawal, because you're using this high-level product over long periods of time, that intermittent flux, or the change that this high-level use has on your other neuro systems then results in a perceived lack of some neurotransmitters that would result in this cyclic vomiting.

So it really requires that high-level use over a prolonged period of time.

Host Amber Smith: So is the cyclic vomiting the first symptom? Do you wake up one day and this begins? Or are there other symptoms that would clue someone in that this is about to start?

Christine Stork, PharmD: I think most of the time people have gastrointestinal effects that start first.

So they may have some nausea, or they may have some other kind of gastritis-type effects, like feeling not well in their upper gastrointestinal system over time. And then that will then evolve with continued use into having vomiting and then vomiting that's difficult to manage over time.

So it doesn't all kind of flip a switch, and you're starting to vomit.

Host Amber Smith: So you mentioned that a hot shower often makes these people feel better. So that would stop the vomiting at least temporarily, or does that have a lasting power?

Christine Stork, PharmD: It's mostly a temporary effect, so you feel better while that heat is interacting with what we think is a substance they call substance P within our neurosensory system. Again, it's fairly complicated, but there's another receptor. There's TRCP, that we think is influenced by that cannabinoid effect or long-term cannabinoid effect. And that's also the reason why topical substances that modulate substance P, which is also influenced with pain, not just vomiting, they sometimes are effective for this cyclic vomiting. So the known drug that's out there that people will use occasionally is capsaicin, which is usually for, more pain phenomenon, but there are cases, and case series, where it has been effective for cyclic vomiting.

Host Amber Smith: Have you ever seen this in weekend users of marijuana? So, maybe they don't use for five days, but then they use heavily on the weekends, or does it have to be daily?

Christine Stork, PharmD: It really has to be daily, chronic, high-level use to result in this. Unfortunately, they're the same people that have some degree of at least psychological dependence on these medications.

So it's very difficult for them to go without using these cannabis products. So again, it's not usually a weekend user, so they're usually recreationally using the product, not dependent in any fashion. It's just part of their social activity, so it usually does not occur in those patients.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith.

I'm talking with Dr. Christine Stork. She's a doctor of pharmacy and clinical professor of emergency medicine at Upstate, and she's part of the Upstate New York Poison Center. We're talking about cannabinoid hyperemesis syndrome, which is rare, but can be severe.

Now, Dr. Stork, how is this diagnosed if someone comes to the emergency room with vomiting that they can't control?

Are there tests that will be done?

Christine Stork, PharmD: Diagnosis includes all the other potential medical causes that are, disposition-wise, more important, could require things like surgery or more aggressive medications, but are not cannabinoid hyperemesis. They're something else.

So, that whole evaluation will likely occur, and then questioning the patient as to their use of cannabis products and any relief measures really does clue the caregivers into the diagnosis of cannabinoid hyperemesis. Once that has been established or is on the kind of higher level of the differential as to what is causing the symptoms, then the clinician can use things that, as I talked about, like capsaicin. But more often, we'll use things that inhibit dopamine receptor activities. So we know that it's also affiliated with dopamine 2 and dopamine 3 receptors. So giving drugs like we, what we classically would call antiemetics or antipsychotics, that have that activity, is very useful in helping these patients and turning off that cyclic vomiting episode.

So, it's a mix. There's no blood test for it, and there's no diagnostic screen for it, unfortunately. But getting those clues in the (patient's) history, ruling out more severe diagnostic findings, and then using those treatment modalities and seeing the effect, is really how these patients are treated.

Host Amber Smith: So it can be treated. Now, can they take the treatment and still continue using marijuana? Will that work?

Christine Stork, PharmD: Unfortunately, the only real treatment that will stop the cyclic vomiting for sure is, abstinence from cannabis smoking products. And that is seen throughout the (medical) literature as a cyclical event, where people will start using their cannabis product, they'll go on to have gastric distress and then have the cyclic vomiting and to recognize that, "Geez, I can't do this; this is awful," stop using the cannabis product, symptoms will go away, and then weeks, months later, the whole thing starts up again.

Host Amber Smith: Is there research that would show why some heavy users develop the syndrome and others don't?

Christine Stork, PharmD: There really is not much out there to help define that patient population. But I really think it has to do with the individual, their receptors and how their receptors respond to having that high level of cannabinoid receptor activity occurring after use. So there is likely a genetic predisposition to some of this, but none of that's known.

It's all conjecture at this point.

Host Amber Smith: So, I know this is somewhat rare, but it can be severe. Do people end up hospitalized with this, and what are the risks of this if it's not treated?

Christine Stork, PharmD: Usually, no. Usually, patients do not need to be hospitalized because the clinicians at this point are pretty clued in, in terms of figuring out the person has the cannabinoid hyperemesis, and then, treatment.

However, if it's not identified, not treated, and the patient continues to have cyclic vomiting, consequences include not being able to achieve nutrition and also dehydration. And both of those things can require hospitalization in those patients. I don't know if there's a 100% response rate to the therapies that we have. So in non-responders, those patients may need some hospitalization until the effects of their cannabinoid use wears off. So supportive measures are really the mainstay of therapy, but dehydration really can cause a lot of altered or even significant findings in some of these patients.

Host Amber Smith: Well, let me ask you a little more about how marijuana affects the body in general. What does it do to the digestive tract?

Christine Stork, PharmD: It has more of a secondary messenger effect throughout the body.

So cannabinoid receptor, we call it agonism, but when a drug is, or in this case, cannabis, is interacting with those receptor sites, it then goes on to secondary messenger type things. So for regular cannabis use, for example, if someone is using it while they're having chemotherapy, and they're not eating well, it actually is an appetite stimulant.

So it almost has anti-nausea, appetite-stimulation effects, which, again, speaks to the ying and the yang of, sporadic low-level use. And the doses that are used for that are very low doses,somewhere between 1 and 5 milligrams, very low doses, whereas a very high-level use over prolonged period of time would lead to the exact opposite.

Host Amber Smith: Does it have effects, lasting effects, on the brain and the heart?

Christine Stork, PharmD: I think some of that is still being researched. The problem with most cannabis products is that they were scheduled (classified) so early in their development by the Food and Drug Administration such that they were considered a Schedule 1, meaning that they have no human use.

And during that time, if someone designates that the chemical has no therapeutic use, you can't do research on that chemical. And that has been a struggle throughout many years. So knowing the long-term effects is really hard to know at this point because it's been such a short period of time, still federally regulated, so federal research trials are not ongoing. So this is more local research trials, but maybe sometime In the future, we'll know whether there's lasting effects of of use and then, what level use, kind of weekend use, as you had mentioned, or chronic high-level use as well.

Host Amber Smith: With marijuana being legal to purchase and use in New York now, I'm curious if the poison center is receiving more calls tied to marijuana usage.

Christine Stork, PharmD: We are, but not in the population that's, going out there and buying these products, so they seem to be relatively safe for adults who are using these products in an occasional manner.

It does have acute clinical effects, as we all know, appetite stimulation, but also neurologic effects, and that it causes some alteration in the central nervous system. And that is many times the desirable effect. The kind of unintended consequence that we're seeing at the poison center is when small children, toddlers, are getting into their caregivers' cannabis-containing product.

And even in the past we weren't so concerned about the (marijuana) cigarettes because, as you know, marijuana leaf cannot be absorbed from the gastrointestinal tract because it needs a fatty substrate to be absorbed. So that wasn't a huge deal. It's a much bigger deal, say, to ingest cigarettes themselves,from a toddler perspective, versus the actual cigarette. However, edible marijuana products cause severe toxicity in toddlers and after very small doses. And then, what toddler eats one gummy? As these thingsare being promoted and many times look like edible, candy-type products, their chances of getting higher doses is also higher, and we see a lot of significant effects in this age population.

Mental status, depression, like coma, is commonly found in this patient population. It takes time for this to develop because the peak sometimes is two, three, four hours after the ingestion. Some of these patients also develop the need to have a breathing tube, which is really consequential, requires the intensive care unit, and some of these patients have developed seizures.

So toddlers we do see every year, at least for the past several years, even prior to it being legalized, every year we're seeing about a doubling of our case volume.

Host Amber Smith: And now that it's legal and out there for purchase and use, are there people who shouldn't try marijuana at all for medical reasons?

Christine Stork, PharmD: I think the biggest population who may be at risk from using these products are people who have underlying psychiatric illnesses or are predisposed to psychiatric illnesses. Many people will use and say they use cannabis products for anxiety or depression, but the research thus far is showing that it actually does not help and may make things worse for anxiety and depression and people at risk for having psychosis.

We know that cannabis use, even the first-time use, can cause acute psychosis. Most of the time that resolves. It doesn't mean all the time it resolves. So that would be the highest group of problematic, or people who may want to stay away from using cannabis products.

Host Amber Smith: Well, getting back to the hyperemesis syndrome, at what point should a user seek medical help for vomiting, or would they necessarily need medical help?

Christine Stork, PharmD: I think, many times, once someone's having hyperemesis, meaning they're continually vomiting, they really do need to seek help. I think if their stomach's bothering them, they should stop their cannabis use, and then hopefully they will not progress to having that cyclic vomiting.

But I would encourage people who, they're vomiting and it's not stopping, they should seek medical help because we have things that can help them stop vomiting and move on. And they also need to stop their cannabis use.

Host Amber Smith: Well, Dr. Stork, thank you so much for making time for this interview.

Christine Stork, PharmD: OK, thank you. Thanks so much.

Host Amber Smith: My guest has been Dr. Christine Stork from the Upstate New York Poison Center. She's a clinical professor of emergency medicine and a doctor of pharmacy at Upstate. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe.

Find our archive of previous episodes at upstate.edu/informed.

This is your host, Amber Smith, thanking you for listening.