Can Genetic Tests Help Diagnose Cannabinoid Hyperemesis Syndrome?

This article was originally published on WeedMaps and appears here with permission.

As awareness of cannabinoid hyperemesis syndrome (CHS) expands, both among medical doctors and patients, we are collectively becoming more and more able to identify a condition that has been historically hard to diagnose. After all, it seems counterintuitive that cannabis can cause many of the symptoms it's used to treat. 

Researchers are taking the current understanding of this severe and often debilitating condition one step further by attempting to pinpoint genetic markers that could be used to more readily diagnose CHS. This could potentially prevent those who are vulnerable from developing it in the first place.

Below, find out how CHS relates to genetics and what is being done in the medical world to combat the onset of the cannabis-based condition. 

What is cannabinoid hyperemesis syndrome?

Still not widely known or completely understood, cannabinoid hyperemesis syndrome is a condition that is characterized by a strong, and often enduring, sensitivity to THC — and possibly other cannabinoids. CHS causes ongoing abdominal pain, cramping, nausea, and vomiting when cannabis is consumed.

What causes CHS?

While our understanding of the condition is still developing, CHS seems to occur most often in folks who consume high-potency cannabis and cannabis products regularly for long periods of time. What is happening in the body is a long-term and intense stimulation of the endocannabinoid system (ECS), along with other receptors and systems outside the ECS.

While medical science is still working to uncover the more complex and nuanced factors contributing to CHS, according to Dr. Ethan Russo, a renowned pioneer in cannabis research, it might be fair to say that CHS isn't a functional gastrointestinal disorder so much as a “manifestation of gene and environmental interaction in a rare genetic disease, unmasked by excessive THC exposure.”

What doesn't cause CHS? Pesticides. 

Dr. Russo thinks it's important to dispel the myth that CHS is caused by the pesticides or neem oil used in plant cultivation. “That just doesn't hold water as an explanation,” Dr. Russo said. “There are more pesticides in use now than when CHS was first discovered, and pesticide reactions are quite different to what we see with CHS. Additionally, it's been shown that synthetic cannabinoids, which are quite potent, can induce CHS — and while they are not pure, they don't have pesticides in them.”

The difficulty and high cost of diagnosing CHS

The primary symptoms of CHS — cyclic abdominal cramping, nausea, and vomiting — are not unique to this condition, making CHS hard to diagnose. Because of this, CHS is considered among doctors to be a “diagnosis of exclusion,” or a diagnosis that is made when all other probable causes are ruled out. 

According to an estimate made in a 2019 study, it took the average ER a whopping $76,920.92 in related testing expenses to diagnose CHS, while a 2018 paper estimated the average patient cost of a CHS-related emergency room visit to be over $4,600.

One thing that makes CHS easier to pinpoint is the habitual or ritualistic behavior of taking hot showers or baths, which patients learn tends to relieve their symptoms temporarily. Another is relief from the topical application of capsaicin cream, which in effect acts much in the same way, physiologically speaking, as taking a hot shower or bath.

While hot baths and showers, the topical application of capsaicin creams, and sometimes even antipsychotic drugs might be used to relieve symptoms, at present the only known cure for CHS is complete abstinence from cannabis.

How prevalent is CHS?

Historically, there has been inconsistent reporting around CHS diagnoses. People with CHS often end up in emergency rooms when cyclic vomiting becomes severe and their health becomes jeopardized. Due to the fact that CHS is not widely known or understood in the medical community, coupled with the reality that most doctors receive little to no education or training around the endocannabinoid system, CHS is often misdiagnosed or labeled as being caused by cannabis use disorder.

Not only is this troubling because it unfairly ties CHS to substance abuse in the medical community, but it also means that we don't have a solid grasp on exactly how prevalent CHS is among cannabis consumers and patients. According to Dr. Russo, CHS is likely a lot more common than we realize.

One epidemiological study, conducted at Bellevue Hospital in New York City, surveyed over 2,000 patients admitted to the ER who presented with cyclical vomiting. They found that over 30% of these patients, who identified as consuming cannabis for more than 20 days per month and found relief with hot showers, likely suffered from CHS. When extrapolated to the US population, they estimated that 2.75 million Americans might suffer from CHS. 

What does genetics have to do with CHS?

The more we learn about cannabis, cannabinoids, and human physiology, the more refined our understanding becomes as to how the plants interact with and impact our bodies.

While there isn't a substantial amount of research looking specifically at CHS, thanks to the forward-thinking work of geneticists and cannabis researchers, we are starting to put together a preliminary picture as to how genetics might impact the development of CHS.

In partnership with the cannabis genetics testing company, Endocanna Health, Dr. Russo looked at the genetics of 28 patients suffering from cannabis hyperemesis syndrome. What they found were five gene mutations, called single nucleotide polymorphisms (or SNPs) with plausible causative roles in CHS. 

These five genes impact everything from dopamine activity to pain responses, mood regulation, and gut disturbances:

COMT gene 

The COMT (catechol-O-methyltransferase) gene provides instructions for making an enzyme that helps break down stimulatory neurotransmitters like dopamine in the brain. When there is a malfunction in these genes, there might be an excess of dopamine, which can lead to more risk-taking behaviors and less inhibition around things like gambling or substance abuse, for example. 

According to Dr. Russo, COMT is also associated with depression, rumination of thought, OCD, ADHD, and psychosis. Fifty-six percent of the CHS patients in the study had mutations in this gene.

TRPV1 gene

This gene is involved in the development of TRPV1 receptors, which are activated by a wide variety of physical and chemical stimuli — most notably those involved in heat perception. 

Activation of the TRPV1 receptors often leads to painful and burning sensations, and it's through interaction with TRPV1 that cannabinoids are able to offer pain relief. In Russo's study, 71% of patients had mutations of this gene, which helps shed some light on the abdominal pain, gut disturbances, and the relief from capsaicin creams and hot showers that are common among folks suffering from CHS.

CYP2C9 gene

This gene provides instructions for making the CYP2C9 enzyme, which is involved in breaking down steroid hormones and fatty acids. It is also involved in metabolizing prescription drugs and THC. Forty-six percent of the patients in Russo's study had mutations on this gene, and he hypothesizes that this mutation could inhibit the breakdown of THC, which would then lead to higher than normal concentrations in the body. 

At high concentrations, THC can create a biphasic response, which means it can create the exact opposite effects it does at lower concentrations or doses. This would make sense of the nausea and vomiting that we don't typically associate with a cannabis experience.

DRD2 gene

The DRD2 gene is responsible for the creation of the dopamine receptor D2. This receptor is the target of many antipsychotic drugs and had mutations in 60% of CHS patients in Russo's study. Drugs that target D2 receptors are pro-emetic, meaning they can induce nausea and vomiting, and they often affect gut motility, so it makes sense that a malfunction in the gene encoding this receptor would occur with CHS. 

These receptors are also associated with depression, anxiety, nicotine use, Tourette Syndrome, and chronic pain, which could point to other susceptibilities CHS patients might have.

ABCA1 gene

The ABCA1 gene is part of a family of genes responsible for creating proteins that act as carriers for other molecules to cross cell membranes, making them important to basic cell function along with our general metabolism and the creation of high-density lipoprotein (HDL) cholesterol. 

This gene mutation was present in 68% of the CHS patients in Russo's study, and while more research would be needed, he believes it could signal that CHS patients might be more susceptible to coronary artery disease (CAD), heart attacks, type II diabetes, and Alzheimer's.

The future of diagnosing CHS

Russo's study is the first of its kind, and the largest study to date looking specifically at cannabinoid hyperemesis syndrome. 

While there is certainly more to uncover in and around the genetic underpinnings of CHS, this study provides us with several clues and a good battery of tests that can be used to more effectively and cost-efficiently screen folks for CHS, and to help heavy cannabis consumers understand if they might be susceptible to CHS. This could save both doctors and patients a lot of time and expense in the ER.

Companies like Endocanna Health are banking on the future of genetics testing in the cannabis space, for both patients and consumers. While Dr. Russo was a skeptic at first, he's come around to the potential this field has in really helping people. He now serves as an unpaid scientific advisor at Endocanna, and sees promise in genetic testing.

“This is a relatively new technology but I have looked at a lot of reports, and the correlations seem to be very good. I am a believer that this is helpful to a lot of people. I started out as a skeptic, but I do think this is helpful technology at this point and it stands to improve the more it is utilized.”