Cannabis hyperemesis syndrome: an update on the pathophysiology and management

Abstract

Cannabis hyperemesis syndrome (CHS) is a form of functional gut-brain axis disorder characterized by bouts of episodic nausea and vomiting worsened by cannabis intake. It is considered as a variant of cyclical vomiting syndrome seen in cannabis users especially characterized by compulsive hot bathing/showers to relieve the symptoms. CHS was reported for the first time in 2004, and since then, an increasing number of cases have been reported. With cannabis use increasing throughout the world as the threshold for legalization becomes lower, its user numbers are expected to rise over time. Despite this trend, a strict criterion for the diagnosis of CHS is lacking. Early recognition of CHS is essential to prevent complications related to severe volume depletion. The recent body of research recognizes that patients with CHS impose a burden on the healthcare systems. Understanding the pathophysiology of the endocannabinoid system (ECS) remains central in explaining the clinical features and potential drug targets for the treatment of CHS. The frequency and prevalence of CHS change in accordance with the doses of tetrahydrocannabinol and other cannabinoids in various formulations of cannabis. CHS is unique in presentation, because of the cannabis's biphasic effect as anti-emetic at low doses and pro-emetic at higher doses, and the association with pathological hot water bathing. In this narrative review, we elaborate on the role of the ECS, its management, and the identification of gaps in our current knowledge of CHS to further enhance its understanding in the future.

Keywords: Cannabis hyperemesis syndrome; cannabis; endocannabinoid system; marijuana.

Figure 1

Endocannabinoid system (ECS) with cannabinoid receptors (CB-1, CB-2) and enzymes involved in synthesis and degradation. Anandamide (AEA) & 2-AG (arachidonolyglycerol) both derived from arachidonic acid. 2-AG is significantly higher concentraion in the brain. It inhibits neurotransmitter release (by binding to CB-1 and by affecting Ca+ metabolism in neurons). CB-1 (brain predominately; also in smalll amounts in GI-enteric NS, NEC, enterocytes [affects permeability and motility], heart [myocytes], skeletal muscle, liver, reproductive system, and affarent pain nerve fibers). CB-2 predominately in macrophages in the spleen and small amounts in CNS peripheral tissues, Both are G-coupled receptors (GPCR)

Figure 2

Pathways involving cannabis on the central nervous system. After the ingestion of cannabis, the active componenet binds to CB1 receptors in the spinal cord and brain stem. It affects signaling at Nucleus Tractus Solitarius (NTS), which affects the vomiting center (VC, located in the medulla oblongata of the brain stem) and thalamus. Various brain stem nuclei depicted with interaction with the vomiting center. Dorsal vagal complex (composed of area postrema and NTS) is affected by cannabis. Right panel showing vomiting center with different affecters (and neurotransmitters) of the VC. CTZ (Chemoreceptor trigger zone); AP-Area Postrema; VC-Vomiting center