One of the paradoxes of cannabis is that even though it’s known to alleviate nausea and vomiting in certain cases, particularly amongst cancer patients undergoing chemotherapy, it also causes nausea and vomiting in some users, a condition known as cannabis hyperemesis syndrome (CHS.) The symptoms of CHS can be so intense, it’s birthed a new term, “scromiting,” a portmanteau of screaming and vomiting, used to describe one side-effect of this condition. In the second phase of CHS, loud retching or screaming is a known symptom.
The main symptom of cannabis hyperemesis syndrome is severe or prolonged vomiting after consuming cannabis. CHS is not something that every cannabis user experiences, and research is still underway to identify why some users develop the condition, which typically only affects long-term heavy users. So, if you’re someone who uses on a casual basis, don’t worry, this is condition is unlikely to affect you. The exact cause is unknown though it’s believed to result from a desensitisation of cannabinoid receptors. To date, there’s only one cure and that necessitates stopping all use of cannabis.
What is Nausea and Emesis/Vomiting?
Vomiting is activated by a part of hypothalamus called the nucleus tractus solitarius, which is connected to the parts of the brain and nervous system that sense chemicals in the blood and the status of the gut. Bundles of neurons are relaying messages from different sources to the vomiting center using different neurotransmitters and neuromodulators to communicate these messages.
Both nausea and emesis are complex processes designed to protect against orally ingested toxic substances. However, they can also be a symptom of an underlying disease or a side effect of certain pharmaceuticals used for the treatment of pain such as opiates, chemotherapeutics and antiviral drugs. A number of drugs are available for the treatment of vomiting associated with chemotherapy but there’s specific interest in the use of cannabinoids for the treatment of nausea.
Cannabis hyperemesis syndrome is more difficult to diagnose. One study found that on average patients visit a doctor’s office or emergency room 3 to 5 times before receiving a correct diagnosis. They often go through a list of tests for pain, such as appendicitis or ectopic pregnancy. Today, it’s well known in US Emergency rooms but for years, it was a condition that the medical community did not take seriously. This article mentions a person who had their gallbladder removed before receiving a diagnosis of CHS.
People with CHS often experience weeks or months of stomach pain and/or nausea before the vomiting starts. In fact, CHS has three stages. The first stage includes symptoms such as nausea, abdominal pain, light heartburn and burping. The second stage is the hyperemetic phase, a period of constant vomiting after cannabis has been consumed. The third stage is the therapeutic stage, when all consumption of cannabis has stopped and the patient is in recovery.
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The Endocannabinoid System and Hyperemesis
The endocannabinoid system (ECS) made up of endocannabinoids located throughout the body, which are a type of lipid-based neurotransmitter that bind to cannabinoid receptors and cannabinoid receptor proteins in the central and peripheral nervous system. CB1 receptors are found in the nervous system, and CB2 receptors are found in immune cells and peripheral nervous system.
CB1 receptors are located along the gut wall but are found in the highest density in the myenteric and submucosal plexuses of the enteric nervous system, which is the nervous system in the gut. According to the work of biochemist Vincenzo Di Marzo at Quebec’s Laval University, most of the neurons in the vomiting center express the cannabinoid CB1R, which is the most abundant G protein-coupled receptor in the brain.
CB1R is also present in the peripheral nervous system and in the enteric nerves that connect the brain with the gut. When CB1R is activated it has the effect of inhibiting neuron synapsis. For this reason, the cannabinoid tetrahydrocannabinol (THC) can have the effect of inhibiting vomiting. Another study showed the presence of CB2 receptors in the vomiting center, and how stimulating them can also reduce vomiting.
Though the exact cause of CHS is unknown, hypotheses to explain the condition include 1. Accumulation of cannabis derivatives in the brain based on their lipid solubility and long-term half-life, 2. Degradation of some cannabis ingredients to some emetic metabolites 3. Delayed gastric emptying induced by cannabis and 4. Down-regulation or desensitization of the receptors due to chronic use.
Ethan Russo is a neurologist who is known for decades of research into cannabinoids and is also the founder of bio-tech venture Credo Science, who said that any CB1R agonist can cause cannabis hyperemesis syndrome. Di Marzo agrees that if a certain level of CB1 activity is required to keep the vomiting center calm, any desensitisation of those receptors could trigger sustained vomiting, as is the case with CHS.
Treatment for Cannabis Hyperemesis Syndrome
Desensitisation is a common biochemical response to restore homeostasis after chronic receptor activation. When a patient presents with constant vomiting, the first course of action is typically an anti-nausea drug. However, in the case of people with CHS, this is rarely effective. What appears to be more beneficial is a hot shower, which calms the feeling of nausea.
The beneficial effect of heat got doctors thinking about ways to help CHS patients warm up quickly in order to alleviate vomiting. One medical fellow in New York, LaPoint, was in emergency rooms there when the first cases of synthetic cannabinoid poisoning showed up. He started to think about TRPV1, one of the body’s heat-sensing receptors, and wondered if it might be involved in the therapeutic effect of hot baths on CHS patients.
TRPV1 is also present in the endocannabinoid system. It binds to the endocannabinoid anandamide and other phytocannabinoids, but not THC. TRPV1 is expressed in the vomiting center in the hypothalamus and in the Vagus, and its ligands tend to reduce vomiting in animal studies. Capsaicin has been used to reduce vomiting associated with chemotherapy.
In a review study on CHS in the journal Clinical Toxicology, researchers posited that TRPV1 works by diverting blood flow to the skin to cool the body down and reduce gut pain. It’s also possible that it blocks the release of neuropeptides from pain-receptive nerve fibers to the hypothalamus.
To test his hypothesis, LaPoint used an off-label application of a topical capsaicin cream to create a sensation of heat in the body. It also activated TRPV1, and was typically used to treat arthritic pain. How exactly the capsaicin cream works is not clear, but it’s possible that the pain caused by the cream overrides the pain of CHS.
Researchers are now keen to uncover what cannabinoid mechanisms are at work in this condition. Cannabinoids are hydrophobic, which means they are embedded in cell plasma membrane, where they easily reach and slip into receptor membranes. To identify which cannabinoids are at work in CHS, a research team at Brown University is now conducting a mixed-methods study that surveys patients arriving at the hospital with symptoms of CHS.
A small study by Ethan Russo’s team identified a group of gene variants specific to people with CHS. His company sells a genetic test based on the study’s findings but it has yet to be approved by the Food and Drug Administration.
Though it’s painful, for now, capsaicin cream remains a possible albeit unlikely treatment for cannabis hyperemesis syndrome. For a total cessation of symptoms, however, the most effective treatment is to stop using cannabis completely. Once cannabis use is stopped, it can take up to 3 months for all symptoms to clear up.
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