What causes vomiting in cannabis hyperemesis syndrome (CHS)?

From the Guidelines

Cannabis hyperemesis syndrome (CHS) causes vomiting primarily due to the paradoxical effects of long-term cannabis use on the body's endocannabinoid system, leading to dysregulation of the body's natural cannabinoid receptors, particularly CB1 receptors, as noted in the 2024 study by 1. While cannabis typically has anti-nausea properties in occasional users, chronic use disrupts normal endocannabinoid function in the digestive tract and brain. The main culprit is tetrahydrocannabinol (THC), which accumulates in fat cells with prolonged use, eventually causing dysregulation of the body's natural cannabinoid receptors. This dysregulation affects the hypothalamus, which regulates body temperature and vomiting, and disrupts normal gut motility. Additionally, THC alters the function of the area postrema (the brain's vomiting center) and affects transient receptor potential vanilloid subtype 1 (TRPV1) receptors, which explain why hot showers temporarily relieve symptoms, as discussed in the study by 1. Some key points to consider in the pathophysiology of CHS include:

• The role of CB1 receptors in the central nervous system, particularly in areas such as the dorsal vagal complex, which is critically important in the neurocircuits controlling emesis, as highlighted in the study by 1.
• The effects of THC on the vagus nerve and gut functions, including gastric motility and emptying, and inhibition of gastric acid secretion, as noted in the study by 1.
• The potential benefits of topical capsaicin in improving symptoms by activating TRPV1 receptors, as suggested in the study by 1. The only definitive treatment for CHS is complete cessation of cannabis use, as symptoms typically resolve within 1-2 weeks of abstinence, though they may recur if cannabis use resumes, as stated in the study by 1. It is essential to approach the management of CHS with a focus on counseling to achieve marijuana cessation, as well as considering the use of tricyclic antidepressants, such as amitriptyline, for long-term management, as recommended in the study by 1.

From the Research

Causes of Vomiting in Cannabinoid Hyperemesis Syndrome (CHS)

• The exact cause of vomiting in CHS is not fully understood, but it is believed to be related to the prolonged and high-dose use of cannabis, which disrupts the normal functioning of the endocannabinoid system 2.
• The endocannabinoid system changes caused by excessive cannabinoid administration can dysregulate stress and anxiety responses, thermoregulation, the transient receptor potential vanilloid system, and several neurotransmitter systems, which may contribute to the development of CHS 2.
• Cannabinoids produce a biphasic effect on nausea and vomiting, with low doses having an antiemetic effect and high doses producing emesis, which may also play a role in the development of CHS 2.
• The relief of symptoms with hot showers is a characteristic feature of CHS, and it is thought that the heat may help to regulate the body's thermoregulation and transient receptor potential vanilloid system, which are disrupted in CHS 3, 4.
• The role of cannabis in the regulation of nausea and vomiting is complex, and more research is needed to fully understand the mechanisms underlying CHS 3.

Potential Mechanisms

• The cannabinoid 1 (CB1) receptor is thought to play a key role in the development of CHS, as it is the primary target of the main psychotropic compound in cannabis, Δ9-tetrahydrocannabinol (THC) 2.
• The dysregulation of stress and anxiety responses, which are mediated by the endocannabinoid system, may also contribute to the development of CHS 2.
• The transient receptor potential vanilloid system, which is involved in the regulation of pain, temperature, and inflammation, may also be disrupted in CHS, leading to the characteristic symptoms of nausea, vomiting, and abdominal pain 2.

Treatment and Management

• The only known way to permanently end CHS is abstinence from cannabinoids 2, 4.
• Treatment with typical antiemetic drugs is often ineffective for CHS, but anxiolytic and sedative drugs, along with hot showers, may provide relief from symptoms 2, 5, 6.
• Droperidol, haloperidol, and lorazepam have been shown to be effective in reducing symptoms of CHS in some cases 5, 6.