TOXIC MARIJUANA SYNDROME YOU’VE NEVER HEARD OF: CANNABINOID HYPEREMESIS SYNDROME

Physician anesthesiologist at Stanford at Associated Anesthesiologists Medical Group
Richard Novak, MD is a Stanford physician board-certified in anesthesiology and internal medicine.Dr. Novak is an Adjunct Clinical Professor in the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University, the Medical Director at Waverley Surgery Center in Palo Alto, California, and a member of the Associated Anesthesiologists Medical Group in Palo Alto, California.
email rjnov@yahoo.com
phone 650-465-5997

Cannabinoid Hyperemesis Syndrome. Chances are you’ve never heard of it, but one of your patients, or someone you know, may develop this syndrome in the coming years. Cannabis use is common. According to The Washington Post, in 2017 more than half of American adults had tried marijuana at least once in their lives, and a total of 55 million Americans currently used the drug. This number approaches the total of 59 million cigarette smokers in America. Each year 2.6 million Americans become new cannabis users. The majority of marijuana users are male, earn under $50,000 a year, and lack a college degree. The 18–25 year old age group has the highest prevalence of marijuana use. 

Emesis is the medical word for vomiting. Hyperemesis means excessive vomiting. The number of people affected with Cannabinoid Hyperemesis Syndrome is estimated at about 2.7 million people in the United States per year. Cannabinoid Hyperemesis Syndrome (CHS) presents as a triad of chronic cannabis use, cyclic episodes of nausea and vomiting, and frequent hot bathing. If the patient withholds the history of chronic cannabis use, it’s difficult to impossible to make the correct diagnosis. Despite months of cyclical symptoms and thousands of dollars of Emergency Room visits and lab tests, the syndrome may not be correctly diagnosed or treated.

Let’s look at a case study of CHS to learn how it may present, and why it is uncommonly recognized:

A 25-year-old male presents for a diagnostic upper gastrointestinal endoscopy. He has a three-month history of persistent nausea, vomiting, and weight loss. His laboratory tests and CT scans of his abdomen and chest are normal. He carries a presumptive diagnosis of GERD (gastroesophageal reflux disease), and treatment with anti-acid drugs such as proton-pump inhibitors and H2-blockers have not improved the symptoms. The young man has been afraid to eat because of nausea and retching. He has been unable to work, and his sleep has been significantly impaired. He has lost weight from 150 pounds to his current weight of 135 pounds. On exam he appears well. His vital signs are normal, and his abdominal exam is negative for tenderness. He is scheduled for general anesthesia for the endoscopy procedure. He was referred for the upper GI endoscopy by his primary care doctor, and the gastroenterologist has yet to meet the patient.

Twenty minutes before his procedure, the anesthesiologist asks the patient if he takes any medicine or drugs. “Only the stomach pills my doctor prescribed,” he replies. “They aren’t working at all. I also use marijuana to decrease the nausea, but it’s not working either.”

“How frequently do you use marijuana?” the anesthesiologist asks. 

“Promise not to tell my parents?” he says. “I use a vape pen about 8 – 10 times a day.” 

“For how long have you been doing that?”

“About five years. I’ve increased my use over the past few months, because it’s supposed to be helpful for nausea, but it’s not working anymore.”

The anesthesiologist excuses himself, and sets off to find the gastroenterologist scheduled to do the procedure.  The anesthesiologist shares the cannabis history, and the gastroenterologist immediately says, “No one ever told me this patient was a chronic marijuana user. This changes everything. His history is classic for Cannabinoid Hyperemesis Syndrome.”

The gastroenterologist interviews the patient and confirms the correct clinical diagnosis. The treatment is immediate cessation of marijuana use, and the endoscopy is cancelled.

One week after stopping all cannabis use, the patient’s symptoms have completely resolved. He is eating well without nausea or vomiting, and has gained back 8 pounds.

Cannabinoid Hyperemesis Syndrome was first described in 2004 in a series of 9 patients from Australia.  In all of the cases, chronic cannabis abuse preceded the onset of a cyclical vomiting illness. Stopping cannabis led to cessation of the vomiting in seven cases. Three cases did not abstain and continued to have recurrent vomiting. Three other cases rechallenged themselves after a period of abstinence and relapsed to the same illness. Two of these cases abstained again, and remain well. The third case did not abstain, and remained ill. The majority of the patients displayed abnormal washing behavior during episodes of active nausea, in which they took repeated hot showers or baths, which temporarily relieved their symptoms.

Δ9-tetrahydrocannabinol (THC) is the principle psychoactive compound in cannabis. There are two distinct cannabinoid receptors, CB1 and CB2, in the human body, located predominately in the central nervous system and also in the gastrointestinal tract. THC stays in the body for a prolonged time, with an elimination plasma half-life of 20–30 hours. THC accumulates within body fat, and body fat serves as a long-term storage site. Typically THC can be used for its antiemetic (anti-nausea) property, and has been used to blunt nausea in cancer chemotherapy patients. With chronic use THC can induce a paradoxical nausea-inducing effect by unknown mechanisms on the central nervous system and the gastrointestinal system, causing the Cannabinoid Hyperemesis Syndrome. Patients with Cannabinoid Hyperemesis Syndrome are chronic users of cannabis who likely have large lipid reservoir stores of THC. 

CHS patients are typically young adults with a long history of marijuana use. There is usually a delay of several years following the onset of the chronic marijuana habit before the onset of symptoms. CHS patients often remain misdiagnosed. Erroneous diagnoses considered included a broad range of conditions affecting the gastrointestinal tract. In one study the average duration of cannabis use prior to onset of the recurrent vomiting was 19.0 ± 3.4 years, and had an average of 7.1 ± 4.3 emergency room visits, 5.0 ± 2.7 clinic visits, and 3.1 ± 1.9 admissions for the CHS syndrome. Daily marijuana use was typical, often exceeding 3 – 5 times per day. 

The three phases of CHS are prodromal, hyperemetic, and recovery. In the prodromal phase patients develop early morning nausea, a fear of vomiting, and abdominal pain. The hyperemetic phase includes episodes of intense and persistent nausea and vomiting. Patients vomit profusely, and can vomit or retch multiple times per hour. In the original 2004 Australian study, 70% of patients reported weight loss of at least 5 kg (11 pounds). Symptomatic patients typically undergo extensive diagnostic work ups, including laboratory and imaging studies, which are all normal or nondiagnostic. The recovery phase can last for days, weeks, or months. It occurs after the cessation of cannabis consumption, and is associated with return to normal eating patterns and original body weight.

The diagnosis of CHS must be made entirely by clinical history. The history of extensive previous cannabis use is universal, but may be unrealized if the patient withholds the information for personal reasons. A Mayo Clinic study in 2012 which included 98 patients, was the largest study to date. Characteristics of the Mayo CHS patients are shown in this table:

The Mayo series of 98 CHS patients helped establish these  diagnostic criteria. These criteria include: 

  • Essential for diagnosis: Long-term cannabis use. 
  • Major features: Severe cyclic nausea and vomiting, Resolution with cannabis cessation, relief of symptoms with hot showers or baths, abdominal pain epigastric or periumbilical, weekly use of marijuana. 
  • Supportive features: age less than 50 years, weight loss of > 11 pounds (5 kg), morning predominance of symptoms, normal bowel habits, negative laboratory, radiographic, and endoscopic tests.

Acute medical treatment for severe CHS episodes includes IV fluids for dehydration and supportive care. Traditional anti-emetic drugs such as Zofran have been largely ineffective. The only reliable long term treatment is the cessation of cannabis. The percentage of patients who relapse has not been quantified to date. The case series data in the medical literature currently document that many of the patients who return to cannabis use have recurrent CHS.

Voters have legalized the recreational use of cannabis in 11 states (California, Colorado, Washington, Oregon, Nevada, Maine, Alaska, Michigan, Illinois, Massachusetts, and Vermont). Because cannabis was legalized through popular vote and not via the usual Food and Drug Administration (FDA) channels, the drug did not undergo government scrutiny regarding toxicities and long term health effects. I discussed this topic in an earlier column.  

Cannabinoid Hyperemesis Syndrome should be considered as a plausible diagnosis in anyone with recurrent severe vomiting and a strong history of cannabis abuse. 

Because of recent legalization of recreational and medical cannabis use in many states, expect the incidence of Cannabinoid Hyperemesis Syndrome to increase. If your patient, or someone you know and love, develops recurrent severe vomiting in the setting of a strong history of cannabis abuse, the diagnosis may very well be Cannabinoid Hyperemesis Syndrome. 

The good news is that once the diagnosis is made, the syndrome is curable with cannabis abstinence.

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