On Thursday, we challenged Well readers to figure out why a 25-year-old man who had recently given up heroin, cocaine and marijuana had a sudden attack of nausea and vomiting so severe that he had to go to the hospital. Two big clues were provided. His nausea and vomiting eased when he took a hot shower, and he regularly used an herbal product that he bought in a neighborhood store called Spice, said to be synthetic marijuana.
We got more than 300 responses. Several of you correctly identified the syndrome as cannabinoid hyperemesis. But given that this young man had a urine toxicology screen that showed he had no cannabinoids in his system, I was also looking for you to link that syndrome to his use of Spice.
Several of you did just that, but the first was Dr. Martine Lamy, an intern in child psychiatry at Cincinnati Children's Hospital Medical Center. Dr. Lamy told me that she had cared for a patient who had the exact same presentation. The young man she had seen, an athlete on a college team, had first developed cannabinoid hyperemesis when he smoked marijuana. Once the college started drug-testing all athletes, she tells me, the whole team switched to Spice, which does not show up on urine screens.
The correct diagnosis is…
Cannabinoid hyperemesis caused by smoking synthetic marijuana.
The Diagnosis:
Cannabinoid hyperemesis, first described in 2004, is a syndrome of nausea and vomiting, compulsive bathing and chronic marijuana use. Dr. James H. Allen, an internist in Adelaide Hills, Australia, became intrigued with a patient who had been repeatedly admitted to the hospital with what was then called psychogenic cyclic vomiting – vomiting because of psychological rather than physiological causes. Oddly, the patient was also constantly showering.
Dr. Allen noticed that the symptoms improved during hospitalization with no intervention and recurred once the patient was sent home. He also noted that at home the patient was a chronic heavy marijuana user and hypothesized that the vomiting might be caused by the drug, while easing of symptoms was linked to abstinence.
Over the next several years, Dr. Allen noted similar patterns in other patients admitted with vomiting disorders. In 2004, he published a report on 10 patients found to have with what he called cannabinoid hyperemesis.
Each patient in his case series smoked marijuana daily; each had developed intermittent nausea and vomiting. All had used marijuana for years before they developed these episodic bouts of nausea and vomiting. And remarkably, nine of the 10 patients reported that hot showers eased their symptoms when everything else failed. All symptoms resolved when these patients gave up marijuana – and then reappeared when they resumed their cannabis use.
A Marijuana Syndrome, Without the Marijuana:
Dr. Allen's case series prompted recognition of similar patients around the world. The mechanism by which marijuana – a drug otherwise recognized for its antiemetic properties – induces vomiting in some chronic heavy users is not well understood. There are several hundred organic compounds in marijuana, and many have been noted to have complex effects on both the brain and the gut.
However, this patient had no marijuana in his system. He said he hadn't smoked it in several months. He did, however, acknowledge using so-called synthetic marijuana. This product, sold under such names such as Spice and K2, has been sold in smoke shops and small stores throughout the United States and Europe since the mid-2000s.
The product looks like dried herbs and, though the labeling often carries the warning "not for human consumption," it is frequently smoked or brewed into tea. The list of ingredients often includes herbal components that have long had the reputation of having marijuana-like psychoactive properties. However, when analyzed, these compounds are often not found, and the effect is provided by chemicals that resemble marijuana's cannabinoids sprayed onto the dried plants.
Many of the most popular of these synthetic cannabinoids were developed in the 1980s by a researcher from Clemson University who created several molecules that bind to the cannabinoid receptors in the brain, stimulating it in a way that is similar to that of the original. Pharmaceutical companies were investigating these molecules to treat pain but abandoned the effort because of the difficulty of isolating the desired qualities of the drug from the unwanted psychoactive effects. Chemical analyses of the products sold as synthetic marijuana has been shown to contain one or more of these chemicals.
In the United States, the Drug Enforcement Agency has tried, with limited success, to ban these products. Several states have also passed laws prohibiting their sale. Nevertheless they are still easy to find around the country.
How the Diagnosis Was Made:
The patient had been admitted to the hospital with a diagnosis of pancreatitis, an inflammation of the pancreas. However, after Dr. Virginia Brady, the resident who talked with and examined the patient that day at Waterbury Hospital, she wasn't sure that was what he had.
Nausea and vomiting are common symptoms of pancreatitis, and he did have very high levels of the enzymes made by the pancreas in his blood. But pancreatitis is an excruciating injury to a very delicate organ, and this patient had no abdominal pain. That made no sense to the young doctor.
Moreover, his story had a familiar ring. The nausea he described – starting in the early hours of the morning, causing terrible and unremitting vomiting that ebbed with a hot shower – sounded like a syndrome she'd seen many times before in patients who smoked pot regularly. Despite marijuana's potent anti-nausea properties, some regular users get episodes of nausea and vomiting that is, strangely, made better when they take a hot shower. Somehow the water – as hot as they can stand it – makes the nausea disappear. It was the defining quality of the syndrome when it was first described by Dr. Allen in 2004.
But this guy said he hadn't smoked marijuana in months. The people Dr. Brady had seen with cannabinoid hyperemesis usually smoked every day. Maybe the patient had relapsed after all.
Dr. Brady ordered a urine toxicology screen; that would show if he had used marijuana recently. However, she knew that methadone clinics like the one this young man visited since he had stopped using heroin tested their patients regularly, so she suspected that he was telling the truth. He probably hadn't smoked pot.
But he did smoke Spice. Could that have caused the young man's illness? Dr. Brady hurried to a computer and looked for a link between Spice and pancreatitis. Nothing. There were a few reports suggesting a link between marijuana and pancreatitis, but nothing about this synthetic marijuana. Moreover, the people in those case reports had the typical symptoms of pancreatitis – nausea, vomiting and abdominal pain. This patient had no pain.
What about the vomiting? Could this so-called synthetic marijuana cause cannabinoid hyperemesis – even if it wasn't the real thing? It seemed unlikely, and yet his symptoms were so typical. She turned to Google to search for the terms cannabinoid hyperemesis and Spice.
Sure enough, there it was – two recent case reports describing several regular synthetic marijuana users who developed a syndrome that was indistinguishable from cannabinoid hyperemesis caused by the real stuff.
Smoking a Lot of Spice:
Dr. Brady went back to the patient. How much synthetic marijuana did he smoke? A lot, he told her. Sometimes 3 to 4 grams a day. With real marijuana, a couple of tokes in the morning would keep him relaxed for most of the day. With the synthetic stuff, the feeling of being relaxed never lasted, and he was constantly chasing it by smoking more and more.
She asked him if he'd heard about cannabinoid hyperemesis. He had. But he hadn't smoked pot since November, he told her. She explained that she was concerned that the stuff he was smoking – the synthetic version – might be a good enough fake to give him the same symptoms.
When the team visited the patient the next morning, he was already dressed and ready to go. No abdominal pain, no nausea. He hadn't vomited in over 12 hours. He was worried that he wouldn't get out of the hospital in time to get his methadone.
What about Spice? the doctor asked. If he went back to smoking it, he'd end up back in the hospital. Never again, he promised. He never wanted to feel that way again. He was out the door within the hour.
How the Patient Is Doing:
I spoke with the patient recently. After several days, he did go back to smoking Spice. And he's been back in the hospital twice in the month since Dr. Brady first saw him.
It's strange, but perhaps not unexpected. In the original case reports of cannabinoid hyperemesis, few of the pot smokers diagnosed with this syndrome were willing to give up their drug, even when they knew it made them so sick. It's perhaps just one more way that the synthetic stuff is like the real thing.
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