Cannabinoid Hyperemesis Syndrome: A Review of Potential Mechanisms
Department of Psychology and Collabortive Neuroscience Program, University of Guelph, Guelph, Canada.
*Address correspondence to: Linda A. Parker, PhD, Department of Psychology and Collabortive Neuroscience Program, University of Guelph, Guelph, Canada N1G 2W1,
Department of Psychology and Collabortive Neuroscience Program, University of Guelph, Guelph, Canada.
Introduction: Cannabinoids have long been known for their ability to treat nausea and vomiting. Recent reports, however, have highlighted the paradoxical proemetic effects of cannabinoids. Cannabinoid hyperemesis syndrome (CHS) is characterized by cyclical episodes of nausea and vomiting, accompanied by abdominal pain following prolonged, high-dose cannabis use, which is alleviated by hot baths and showers. Little is known about the cause of this syndrome.
Discussion: Cannabinoids produce a biphasic effect on nausea and vomiting, with low doses having an antiemetic effect and high doses producing emesis. Presentation and treatment of CHS are similar to cyclical vomiting syndrome as well as chemotherapy-related anticipatory nausea and vomiting, suggesting that these phenomena may share mechanisms. The prevalence of CHS is not known because of the symptomatic overlap with other disorders and the lack of knowledge of the syndrome by the public and physicians. Treatment with typical antiemetic drugs is ineffective for CHS, but anxiolytic and sedative drugs, along with hot showers, seem to be consistently effective at reducing symptoms. The only known way to permanently end CHS, however, is abstinence from cannabinoids. Case studies and limited pre-clinical data on CHS indicate that prolonged high doses of the main psychotropic compound in cannabis, Δ 9 -tetrahydrocannabinol (THC), result in changes to the endocannabinoid system by acting on the cannabinoid 1 (CB1) receptor. These endocannabinoid system changes can dysregulate stress and anxiety responses, thermoregulation, the transient receptor potential vanilloid system, and several neurotransmitters systems, and are thus potential candidates for mediating the pathophysiology of CHS.
Conclusions: Excessive cannabinoid administration disrupts the normal functioning of the endocannabinoid system, which may cause CHS. More clinical and pre-clinical research is needed to fully understand the underlying pathophysiology of this disorder and the negative consequences of prolonged high-dose cannabis use.
Cannabinoid Hyperemesis Syndrome: A Review of Potential Mechanisms Department of Psychology and Collabortive Neuroscience Program, University of Guelph, Guelph, Canada. *Address correspondence
He loved weed. Then the vomiting began. Months later, he died
Her son died from effects of a rare condition called cannabinoid hyperemesis syndrome (CHS) which developed from smoking marijuana. Indianapolis Star
The doctors told Regina Denney and her son Brian Smith Jr. what was causing his severe vomiting and abdominal pain.
Neither the teenager nor his mother believed what they said: smoking weed.
Smoking marijuana, the two knew, was recommended to cancer patients to spur the appetite. How could it lead to Brian’s condition?
As the months went by and the pounds slipped off Brian’s once healthy frame, it was clear that whatever was causing his stomach troubles had just the opposite effect.
Brian kept smoking. The symptoms continued on and off.
Last October, after another severe bout of vomiting, the teenager died. He was 17 years old.
Five months later, as Denney pored over a coroner’s report for answers, she finally accepted that marijuana played a pivotal role in her son’s death. The autopsy report, which Denney received in March, attributed her son’s death to dehydration due to cannabinoid hyperemesis syndrome.
A week before he died, Brian Smith Jr., right, enjoyed time with his nephew Zayden. Brian died in 2018 from dehydration after excessive vomiting. The vomiting was a result of a rare condition called cannabinoid hyperemesis syndrome. (Photo: Kelly Wilkinson/IndyStar)
“We had never heard about this, had never heard about marijuana causing any vomiting. He and I were like, ‘Yeah, I think it’s something else,’ ” Denney said. “Brian did not believe that was what it was because of everything we had ever been told about marijuana. … It didn’t make any sense.”
Cannabinoid hyperemesis syndrome, also known as CHS, can arise in response to long-term cannabis use. The syndrome consists of vomiting, nausea and abdominal pain, which can often be alleviated by taking hot showers.
Doctors say CHS is on the rise, but they are not certain why. Marijuana is more available than in years past, and it is more potent.
Rarely does CHS result in death.
‘Basically, they smoked weed’
Denney didn’t like the fact that her teen son started smoking at 13, but she figured the situation could be worse. Brian and she had a strong relationship, and he always had been honest with her about his use of marijuana.
For the most part, Brian was a good kid who had a tightknit group of friends who called themselves the GBS, Gimber Block Savages, after the south side street where many of them lived. Although they called themselves a gang, Denney said, they never caused any trouble.
“Basically, they smoked weed,” she said.
About two years after Brian started smoking, he began using a lot more, perhaps to help deal with depression, Denney said. He dropped out of school after ninth grade and started working full-time with an uncle who had a tree-trimming business. Brian helped clear brush.
The job provided enough money to support his marijuana habit, another reason Denney felt there was no reason for her to intervene. After all, many of Brian’s peers were using heroin or methamphetamine.
Regina Denney talks about her late son, Brian Smith Jr., Monday, Sept. 9, 2019. He died in 2018 from dehydration after excessive vomiting. The vomiting was a result of a rare condition called Cannabinoid Hyperemesis Syndrome (CHS) developed from smoking marijuana. Denney now wants to get the word out about this rare condition. (Photo: Kelly Wilkinson/IndyStar)
“I thought, ‘OK, if that’s all he’s doing, smoking marijuana, pick and choose your battles,’ ” she said. “If this is the worst thing he’s doing, I’m OK. He’s not in any trouble legally. He’s not playing with guns, robbing people and stealing things. He’s supporting his own habit. I thought, ‘OK, this is what it is.’ ”
Denney had no reason to be concerned about cannabinoid hyperemesis syndrome. She, like many others, had never heard of it.
‘A totally underdiagnosed entity’
A few years ago, many doctors had no idea this condition existed. First described 15 years ago, CHS symptoms follow heavy cannabis use and include intense stomach pain, bouts of vomiting and debilitating nausea.
A study published last year in the journal Basic & Clinical Pharmacology & Toxicology surveyed urban emergency room patients who smoked marijuana 20 or more days a month. Of the 155 who said yes, almost a third experienced CHS symptoms.
“A lot of papers prior to mine would say it’s very rare,” said Joseph Habboushe, one of the study’s authors and a clinical associate professor of emergency medicine at NYU Langone Health in New York City, who saw his first case five or six years ago. “Emergency room doctors on the front-line lines, we know that it’s a totally underdiagnosed entity.”
On the other side of the country, Dr. Jeff Lapoint and his colleagues saw an influx of patients with CHS symptoms about six years ago. Lapoint is the director of the division of medical toxicology at Kaiser Permanente Southern California and practices in San Diego, which he said is home to both craft beer and craft marijuana.
Many of Lapoint’s patients returned time after time when the next bout hit, seeking relief from their stomach woes.
“We would see lots of it. We would see an alarming amount of it,” Lapoint said. “People were coming in all the time, and physicians didn’t know what to do with them.”
Lapoint said he and his colleagues have seen fewer such cases lately.
Habboushe concluded in his study that as many as 2.75 million regular cannabis users may suffer from symptoms of CHS, though many of them may be mild. Mild symptoms can serve as a warning to discontinue cannabis use to avoid more severe distress down the line, Habboushe said.
A study this year in the Journal of Forensic Science described two people in Canada who died from CHS and a third for whom the condition contributed to death.
‘It makes no sense’
Brian was Denney’s baby, her boy after two girls. From the time he was a child, he suffered from acid reflux and often took medicine to ease the symptoms.
Brian, who loved sports and the movie “Twilight,” was close to his family and called himself his mother’s “snuggle bunny.” He was beloved uncle BubBub to his toddler nephew, Zayden. He was a loyal friend, once giving up his bed so a buddy who was homeless had a place to sleep. As a teen, he split time between Denney’s home and that of his father.
In April 2018, Brian felt ill. At first everyone, including his pediatrician, thought his acid reflux was acting up. He lost 40 pounds and frequently complained of nausea that led him to avoid food.
A few days into the illness, he called his mother and told her he couldn’t stop vomiting. Denney drove to his father’s house to take him to the hospital. On the way to Franciscan St. Francis Health, Denney had to stop multiple times for Brian to vomit.
Brian complained of tingling in his face. When they got to the hospital, half his face was numb, the muscles in his hands and legs constricted and froze, and he projectile vomited.
Denney assumed he was having a stroke.
Within a few minutes, he was hooked up to oxygen and a heart monitor. Medical staff placed IVs in each arm. Tests revealed his kidneys were failing, and many of his other lab values were abnormal. No one could tell what was behind the attack, though they knew the frequent vomiting left him dehydrated.
Another emergency room doctor poked her head in the door and asked two questions: Do you smoke marijuana often? Do you take frequent hot showers?
Yes, Brian said. Yes.
You have CHS, the doctor said.
The following day, Brian was discharged with an appointment to follow up with a gastroenterologist in July.
Although neither Denney nor Brian accepted the diagnosis completely, she urged him to consider not smoking as a process of elimination. He agreed, but he struggled with nausea and was too sick to work.
The GI doctor took a tube of blood, did no further testing and confirmed the earlier diagnosis: CHS.
Denney remained unconvinced, thinking the specialist was too quick to accept the emergency room doctor’s diagnosis without doing any confirmatory testing.
“Going to the GI doctor, I thought we’re going to finally get an answer. We’re going to finally know what we need to do to make him better,” she said. “Then when they didn’t run any other tests, it was like, ‘OK, so why are we not doing them?’ It makes no sense.”
After that visit, Brian returned to his dad – and started smoking again.
He told Denney he had symptoms the whole time he wasn’t smoking, so what was the point of quitting?
‘The dose makes the poison’
Experts aren’t 100% sure what’s behind the relatively sudden advent of this condition. They suspect that more potent cannabis may be to blame, along with several states’ decision to legalize the drug for medicinal purposes or altogether.
In the 1970s, THC concentration in most marijuana would be about 7%, Lapoint said. The mean concentration has risen to 15% to 30%, and it’s possible to make extracts with 99% THC.
“Marijuana was the joke of the toxicology world when it was 7%,” Lapoint said. “People never got sick. … But now if you make the concentration 99%, it’s just like if a 17-year-old kid goes to a frat party and has a beer. That’s a lot different than drinking shots of Everclear 151. Just like anything, the dose makes the poison.”
The best treatment for CHS is to stop using cannabis entirely, Habboushe said.
Once a person develops the condition, he or she has probably done something permanent. Further exposure to cannabis highly increases risk of recurrence. Persuading patients to accept this can be difficult, Habboushe said.
“There’s a lot of denial,” he said. “A lot of patients are really heavy marijuana smokers, and they really don’t want to believe that it’s related to cannabis and hard for them to believe because they have been using cannabis forever.”
‘Don’t give up’
In July Brian moved back in with Denney. She knew he was not going to give up smoking, but she thought being around his nephew would encourage him to smoke less.
A few months passed. Brian did not put back the weight, but he seemed to be a bit better.
Then came Oct. 7. Brian started feeling ill again. Denney and her daughters had concert tickets, so she went to buy him Gatorade and popsicles to stem the nausea and asked his father to come and stay with him.
When they returned from the concert, he started vomiting nonstop. They rushed to the St. Francis emergency room, where doctors transferred him to Riley Hospital for Children. Once more, Brian was rehydrated.
Denney said her son cut back on smoking, but a few weeks later, he went to visit his cousins. “I know they smoked,” Denney said. “That’s just what he did.”
When she picked him up Oct. 21, he felt a little nauseated but had not been vomiting.
Three days later, Denney woke up around 5 a.m. to find her son sitting in the living room and clutching his stomach.
Regina Denney keeps a cabinet full of Brian’s keepsakes and his urn in her bedroom. (Photo: Kelly Wilkinson/IndyStar)
He told her it was his acid reflux but he was fine. Then he started vomiting again.
“He was throwing up so much,” Denney said. “I was taking the bucket in there and holding it for him because he didn’t have the energy to hold it.”
For the first time, Brian told her he was going to quit smoking.
He grabbed his lower back, saying it hurt bad.
Remembering his kidneys had suffered in his previous attacks, Denney called 911.
Before the paramedics arrived, she found her son lying on his side.
She rolled him over. He was not breathing.
Denney screamed. She started doing chest compressions. Her daughter’s boyfriend ran across the street to get their neighbor, a Navy veteran.
“I kept telling him, ‘Fight, B, fight. I need you. Don’t give up.’ I begged God to take me instead,” Denney said.
The paramedics arrived and worked on Brian for about 45 minutes to no avail. On Oct. 24, Brian died.
Because he died at home, detectives had to investigate, and the coroner prepared a report. It took five months for Denney to receive a copy. It arrived on her birthday in early March.
Soon after Brian’s death, Denney found edibles in his backpack.
She asked herself again and again what she should have done. Should she have forced him to go to rehab?
Denney devoted herself to helping raise awareness about CHS. She started a Facebook group in Brian’s name. She talks about Brian and CHS every chance she gets. She keeps Brian close to her, wherever she is.
Photos of her son hang on the walls in her bedroom. On her dresser sits a dark urn emblazoned with a gold marijuana leaf that contain’s Brian’s ashes. His sister chose it. She knew her brother would have liked it.
Follow Shari Rudavsky on Twitter: @srudavsky
Cannabinoid hyperemesis syndrome, known as CHS, can arise in response to long-term cannabis use. It's what led to the death of Brian Smith Jr., 17.