Review explores how the endocannabinoid system connects stress, nausea, vomiting, and cannabis hyperemesis | Research

The takeaway

A narrative review examines how the endocannabinoid system regulates stress, nausea, and vomiting, and how prolonged cannabis use may dysregulate these processes, contributing to cyclic vomiting syndrome and cannabinoid hyperemesis syndrome.

People experiencing cannabis-related nausea or vomiting, and healthcare providers managing CHS or CVS.

Cannabis can be both antiemetic and pro-emetic depending on dose, duration, and ECS dysregulation

What the researchers found

The endocannabinoid system normally regulates nausea, vomiting, and anxiety. Cannabis can have both antiemetic and pro-emetic effects depending on dose and duration. Chronic use may dysregulate the ECS, altering its homeostatic control and potentially contributing to the paradoxical nausea and vomiting seen in cyclic vomiting syndrome (CVS) and cannabinoid hyperemesis syndrome (CHS).

Why it matters

Cannabinoid hyperemesis syndrome and cyclic vomiting syndrome can be debilitating conditions that do not respond well to standard antiemetics. Understanding how the ECS becomes dysregulated through chronic cannabis use could lead to better treatments for these increasingly common conditions.

The numbers in context

The review notes that classical serotonin-targeting antiemetics may not be effective for CVS or CHS. Cannabis produces paradoxical dose-dependent effects: antiemetic at some doses but pro-emetic at higher doses or with chronic use.

How the study worked

Narrative review examining the endocannabinoid system's role in stress, nausea, and vomiting regulation, the effects of prolonged cannabis use on ECS function, and the evidence linking ECS dysregulation to CVS and CHS pathophysiology.

What this study cannot tell us

Narrative review without systematic methodology. The mechanisms linking ECS dysregulation to CVS and CHS are still largely hypothetical. The distinction between CVS and CHS remains debated in the medical community.

How to read the evidence

Narrative review synthesizing preclinical and clinical evidence on ECS regulation of nausea and vomiting, with focus on mechanistic pathways.

When this study was published

Published in 2025.

The bigger picture

The paradox of cannabis being both a treatment for and cause of nausea highlights the complexity of endocannabinoid signaling. As cannabis use becomes more prevalent and products become more potent, CHS is likely to increase, making understanding of these mechanisms clinically urgent.

Questions still open

At what threshold of cannabis use does the antiemetic effect flip to pro-emetic? Can ECS function be restored after cessation, and how long does recovery take? Would targeted ECS therapies (rather than cannabis itself) avoid the hyperemesis problem?

Common questions

How can cannabis both prevent and cause vomiting?

At moderate doses and acute use, cannabinoids activate the endocannabinoid system's natural anti-nausea pathways. But chronic heavy use may dysregulate these pathways, eventually producing the opposite effect.

What is cannabinoid hyperemesis syndrome?

CHS is a condition in chronic cannabis users characterized by severe cyclical nausea, vomiting, and abdominal pain that typically resolves only with cannabis cessation and is often temporarily relieved by hot showers.

Read the original research

Endocannabinoid signaling in stress, nausea, and vomiting.

Neurogastroenterology and motility, 37(3), e14911

View on PubMed ↗Publisher’s paper ↗

Citation

DeVuono, Marieka V; Venkatesan, Thangam; Hillard, Cecilia J. (2025). Endocannabinoid signaling in stress, nausea, and vomiting.. Neurogastroenterology and motility, 37(3), e14911. https://doi.org/10.1111/nmo.14911