Deep Dive: Cannabinoid Hyperemesis Syndrome

Updated: Oct 22

This 2,300-word homework assignment is made available at no cost until November 15 as a preview of the new Higher Learning LV course Cannabis Foundation.


Welcome to the homework assignment for Cannabis Foundation: Module 6—Endocannabinoid System, Lesson 4—Cannabinoid Hyperemesis Syndrome. Here, the controversial topic of Cannabinoid Hyperemesis Syndrome (CHS) is explored.


A range of research—from 2004 in Australia to the most recent 2021 study in the U.S.—has demonstrated that the controversial condition Cannabinoid Hyperemesis Syndrome (CHS) is more than imagined by its sufferers. Although only a few hundred cases of CHS are known to exist, which is a very small portion of the community of daily cannabis consumers, leading researchers and medical professionals have acknowledged that it is real.

The symptoms of CHS include nausea and vomiting from which, sufferers report anecdotally, they gain benefits from taking long, hot showers. Many who have been diagnosed with CHS report that they found relief when they ceased consuming cannabis. The first reported case of CHS dates back more than a quarter century to 1996.


A variety of theories have attempted to explain this mysterious syndrome. Pesticides and other contaminants have been one theory. A psychosomatic origin, involving scenarios in which doctors tell CHS patients "it's all in your head" has been another. The most recent peer-reviewed research, however, points toward a different source of this strange condition.


Genetic Source?

More precisely, the latest research suggests that Cannabinoid Hyperemesis Syndrome may result from a genetic abnormality, or mutation, that is triggered and put into action only in those who consume relatively large quantities of cannabis (more specifically, delta-9 THC) over a lengthy period of time.


Of millions of daily cannabis consumers throughout North America, only a small fraction of these display symptoms of CHS. This is because most marijuana consumers lack this genetic mutation and resulting disease, theorizes the latest research.

While adult-use legalization has produced literally millions of daily cannabis consumers throughout North America, only a small fraction of these have displayed the symptoms of CHS. This is because most marijuana consumers lack this genetic mutation and resulting disease, theorizes this recent research on the topic.


2004 Study

In 2004, a team of researchers in South Australia published a research study that purported to discover this condition. The study, entitled "Cannabinoid Hyperemesis: Cyclical Hyperemesis in Association with Chronic Cannabis [Use]," was published in the journal Gut.


Although the study was conducted in 2004, the first case of Cannabinoid Hyperemesis Syndrome investigated by the researchers dated back to 1996.


The research found that a group of long-term daily cannabis consumers were suffering an almost identical set of symptoms: Nausea, vomiting, abdominal pain and—during the acute phase of the syndrome—abnormal bathing behavior.

Noted the scientists, "In all cases...chronic cannabis [use] predated the onset of the cyclical vomiting illness. Cessation of cannabis abuse led to cessation of the cyclical vomiting illness in seven [of 10] cases."


The study's researchers identified 19 patients who were daily cannabis consumers and exhibited a cyclical vomiting illness. Of this group, 10 patients refused to give consent or were otherwise disqualified, reducing the sample size to nine.


Concluded the researchers, "In all cases...[daily] cannabis [consumption] predated the onset of the cyclical vomiting illness. Cessation of cannabis [use] led to cessation of the cyclical vomiting illness in seven [of 10] cases."


"Cessation of cannabis [use] led to cessation of the cyclical vomiting illness in seven [of 10] cases." — 2004 Australian research study

2011 Study

A similar study entitled "Cannabinoid Hyperemesis Syndrome" was conducted in December 2011 at Temple University and published in the journal Current Drug Abuse Reviews. It concluded that this controversial disorder typically strikes young adults who have been regular consumers of cannabis for multiple years.

If allowed to go unchecked and to enter the acute (hyperemetic) stage, the study's researchers reported that Cannabinoid Hyperemesis Syndrome can result in weight loss and dehydration, with retching so severe that it can occur up to five times per hour.


Concluded the researchers: "Cannabinoid Hyperemesis Syndrome is a new and under-recognized clinical entity. Although its prevalence is unknown, numerous publications have preliminarily established its unique clinical characteristics. CVS [Cyclic Vomiting Syndrome] should be considered as a plausible diagnosis in the setting of patients with recurrent intractable vomiting and [a] strong history of [heavy] cannabis [consumption]."


2018 Study

A 2018 study entitled "Emergency Department Treatment of Cannabinoid Hyperemesis Syndrome: A Review" that was published in the American Journal of Therapeutics investigated the topic of CHS from the perspective of hospital emergency room visit reports (an arguably skewed, although relevant, study design).


Wrote the researchers, "cannabinoid hyperemesis syndrome (CHS) is a syndrome of cyclic vomiting associated with chronic cannabis use. As cannabis consumption steadily increases each year, CHS is becoming a commonplace and costly occurrence in hospitals nationwide. Currently, there are no best treatment strategies agreed upon universally."


Most of what is known about CHS has been derived from case reports. "Consequently, the pathophysiology of the syndrome is unclear, and its occurrence in some cannabis users, but not others, is not understood."

The study's authors reported that most of what is known about CHS has been derived from case reports. "Consequently, the pathophysiology of the syndrome is unclear, and its occurrence in some cannabis users, but not others, is not understood."


This study design was that of a literature review in which the scientists analyzed all studies about CHS conducted until 2017. It concluded that a CHS diagnosis should be consider for any cannabis consumer "presenting with persistent nausea and vomiting." The study recommended a diagnosis of CHS "if the patient demonstrates regular and chronic cannabis use, intractable nausea and vomiting, cyclical vomiting, relief of symptoms with hot baths, and resolution of symptoms after cannabis cessation."


The study concluded that CHS is increasingly prevalent and that it is a "complicated problem for health care providers and patients" and that more research, particularly clinical trials involving human participants, are necessary to better understand this strange condition that is suffered by a very small percentage of cannabis consumers.


Pushback + Misdiagnosis

However, not all experts have agreed that Cannabinoid Hyperemesis Syndrome is legitimate. The authors of a 2006 review study published in Gut entitled "Cannabis Hyperemesis Causation Questioned" criticized the original 2004 research cited above, labeling it a "poor study design."

Wrote the study's authors: "Cannabis has been consumed for many centuries and is currently used by millions of people in many countries. It is hard to believe that a distinctive syndrome caused by cannabis has never been noted before by users or clinicians."


According to physician Dr. Frank D'Ambrosio, a Los Angeles doctor who recommends cannabis medicine to some of his patients, "Since CHS is so rare, I’d also be careful of misdiagnosis. Other gastrointestinal problems may be at play, and cannabis could be either helpful or hindering in such cases."


"Other gastrointestinal problems may be at play, and cannabis could be either helpful or hindering in such cases." — Dr. Frank D'Ambrosio, Los Angeles

Although more research is necessary, is it possible that some humans may be predisposed to exhibiting negative side effects—such as nausea, vomiting, and intestinal pain—after years of chronic cannabis consumption? Could ceasing the intake of marijuana help those who might be suffering this condition?


Latest Scientific Research

In July 2021, a group of researchers released a research study entitled "Cannabinoid Hyperemesis Syndrome Survey and Genomic Investigation" that was published in the journal Cannabis and Cannabinoid Research.

The objective of the study was to "investigate genetic mutations underlying CHS. Patients with CHS diagnosis and ongoing symptoms were compared with current cannabis users lacking symptoms."


"We have discovered the genetic basis for an unusual syndrome. This is one of the true, unusual side effects of cannabis usage," said one of the study's authors during a 2021 podcast interview. "You may hear from people that cannabis doesn't have side effects. That's nonsense. It's a medicine. Everything has side effects," said the scientist.


The researcher described the controversial syndrome as a "relatively rare condition that is increasingly identified. The reason is the availability of higher THC potency material in most areas, so this is something that people need to know about, both in the medical community as well as consumers."


Of those who had previously attempted to cease cannabis consumption with the goal of reducing or eliminating their negative symptoms, 75 percent reported withdrawal symptoms that included "anxiety, depression, insomnia, and irritability."

The study involved 205 subjects who seemed to suffer from CHS and 54 control subjects, but only 28 of the subjects and 12 controls completed genomic (genetic) testing and the overall study. This was due to a variety of factors cited by the researchers, including a refusal on the part of some participants to accept that their condition might result from THC or another chemical component of the plant.


This relatively small sample size has been criticized as being too small to produce scientifically relevant data. Said Vincenzo Di Marzo, a biochemist who studies cannabinoids and molecular genetics at the Université Laval in Quebec, during an interview for an article published in the MIT Technology Review, "You have to validate it with much larger cohorts. I would have used a thousand patients, not just 28."


"Somewhere along the way, [participants] got cold feet," reported one of the study's authors. "To be honest, we had a lot of pushback from the cannabinoid hyperemesis community. There were people who questioned our motives and actually dissuaded other people from [participating]." Despite these challenges, the researchers identified five statistically significant genes that may cause CHS in some heavy cannabis consumers.


This single study is in no way conclusive; it is not wise to assume that CHS is genetic in origin. This research obviously suffers from a painfully small cohort of participants. In its defense, this study was organized by celebrated cannabis researcher Dr. Ethan Russo. In the end, this study merely indicates that there may be a genetic link to this strange condition—not that there actually is.


Patients Paranoid from Pot?

"It's hard to explain this without sounding judgmental, but people with CHS are highly suspicious of the medical community," reported the researchers. "It's been documented in other studies. Compliance is not very good," they wrote.

The study's authors explained that general practitioner doctors commonly suggest to CHS patients that they cease consumption of cannabis, but that "almost nobody can who has this." They explained that a high degree of suspicion and even paranoia is "part of the diagnosis, we're afraid."


They explained that the core source of this strange disease seems to be delta-9 THC rather than a different cannabinoid or perhaps a terpene produced by the herbal plant species. Although the most common consumption avenue among CHS patients is smoking, it can also result from other forms of use, including vaporization ("vaping") and ingestion (edibles).


Of those study participants who had previously attempted to cease cannabis consumption with the goal of reducing or eliminating their negative symptoms, 75 percent reported withdrawal symptoms that included "anxiety, depression, insomnia, and irritability."

All test subjects featured a history of nausea and vomiting "often lasting days to years" and the following characteristics:

  • 86% were daily or greater-than-daily cannabis users.

  • 97% smoked cannabis.

  • 54% vaporized cannabis.

  • 91% utilized loose-leaf cannabis flower (primarily by smoking).

  • 59% employed cannabis concentrates (typically via vaporization).

"Overall, there are only several hundred reported cases [of CHS] in the literature. Although, from talking to emergency departments and gastroneurologists, they're seeing this more often," reported the pioneering study.

The scientists explained how CHS is "an unusual constellation of symptoms" that affects people solely in the context of "heavy [daily] use of THC-rich cannabis material."


Onset Pathway

The typical pathway of onset for CHS involves a heavy and long-term cannabis consumer slowly developing nausea, vomiting, and abdominal pain. However, the full syndrome involves nausea, vomiting, and abdominal pain coupled with "a characteristic method of treatment that people have discovered" in which they spend hours each day in a hot shower or bath.


Sufferers claim that this bathing activity temporarily alleviates their symptoms. However, the study's authors explained that this bizarre hot shower remedy, over time, "leads to all kinds of problems."

The THC molecule



Difficult to Diagnose

The scientists described how CHS is difficult to diagnose and even more challenging to treat. "Typically, people who have this end up either hospitalized or in emergency rooms with increasing frequency." They explained that conventional antiemetics (drugs that treat nausea and vomiting) are typically not effective for CHS patients.


The research study concluded that CHS is indeed real and not the result of psychosomatic phenomenon and imagination, as some critics have claimed—much to the relief of patients attempting to be taken seriously while seeking answers to and relief from their condition.


The study's authors concluded that "CHS can contemporaneously be conceived of, not as a 'functional' GI [gastrointestinal] disorder, but rather as a manifestation of gene–environment interaction in a rare genetic disease unmasked by a...reaction to...THC exposure."


Conclusions

Peer-reviewed research investigations conducted since 2004 have validated the controversial disorder called Cannabinoid Hyperemesis Syndrome. Although theories of pesticide poisoning have pervaded social media, 2021 research by Ethan Russo indicates that the cause of CHS may be genetic.


Only a few hundred cases of CHS have been documented in the research literature. Thus, it appears that this disorder affects a very small percentage of regular daily consumers of cannabis.

Only a few hundred cases of CHS have been documented in the research literature. Thus, it appears that this disorder affects a very small percentage of regular daily consumers of cannabis.


Regardless of the root cause, CHS manifests in daily, heavy cannabis consumers who suffer from cyclic nausea, vomiting, and abdominal pain. CHS patients indulge in hot baths and showers to seek relief from their symptoms. The best current treatment for this bizarre condition is cessation from cannabis.


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