Endocannabinoid system and cannabis hyperemesis syndrome: a narrative update

Abstract

Cannabis use has been increasing in the United States and throughout the world. It is derived from one of the earliest plants cultivated by humans -Cannabis sativa. Cannabis (also called marijuana) is the most commonly used psychoactive substance worldwide. The cannabis plant has more than 400 chemicals, of which more than 100 cannabinoids (such as cannabigerol, cannabidiol, and cannabinol) have been identified. The endocannabinoid system (ECS) plays an essential role in the effects of cannabis on end organs. Although cannabis use has been reported for many decades, some of its unique adverse effects of nausea, vomiting, and abdominal pain, termed as cannabis hyperemesis syndrome (CHS), were noted recently. The legal status of cannabis in the United States has been rapidly changing from state to state. The incidence of CHS is expected to rise with rising access to cannabis in the United States. Furthermore, CHS is frequently underdiagnosed due to a lack of uniform criteria, subjective nature of symptoms, and overlap with cyclical vomiting syndrome (CVS). Understanding the ECS and its role in biphasic response (proemetic and antiemetic) of CHS is critical to explain its pathophysiology. As the use of cannabis increases globally, awareness of CHS is warranted for early recognition and prompt treatment to avoid complications. We describe the putative mechanism of CHS with an overview of the clinical features in these patients. Furthermore, we highlight the differences between CHS and CVS with important differentials to consider. We provide a narrative update on the current evidence on CHS pathophysiology, diagnosis, treatment, and identifying research gaps.

Pathophysiology and Therapy of Associated Features of Migraine

“…Both nausea and cyclic vomiting syndrome patients have a decreased connectivity between the sensorimotor network and the insula, which manages viscero-sensory processing [ 22 ] and may be regulated by the endocannabinoid system [ 23 ]. Cannabis can act as a pro-emetic or antiemetic and can cause cannabis hyperemesis syndrome, which shares similar features to cyclic vomiting syndrome [ 24 ], and whose recommended treatment is cannabis cessation [ 25 ]. Remarkably, the management of cyclic vomiting syndrome consists predominantly of treatments also used for migraine [ 26 ].…”

Paediatric cannabinoid hyperemesis

“…Lipolysis induced by ACTH (adrenocorticotropic hormone) during periods of physiological stress or food deprivation may release this store of THC back into the bloodstream wherein it is available to bind ECS receptors, adding to the chronic user's acute consumption and leading to re-intoxication . These high levels of THC at receptors then induce or worsen emetic drive [15,21 ▪▪ ].…”

“…This then predisposes the patient to hyperemesis during activation in stress states when, in addition to re-intoxication, the HPA axis mediates increased vagal-nerve firing and subsequent emesis [13]. Furthermore, gastric emptying is slowed by CB1 receptor activation in the enteric nervous system [21 ▪▪ ].…”

“…The adult (known as Rome IV) criteria include a requirement for complete resolution of symptoms after prolonged abstinence, meaning that no patient meets the criteria at the time of acute presentation. This has led to criticism that the Rome IV criteria are useful for research and investigative use, but less helpful for clinical diagnosis and treatment [21 ▪▪ ]. In addition, data on the relationship of symptom resolution to cessation are incomplete, with no definition of a standard time period for ‘cessation’ [14].…”

Acute Treatment of Adolescent Cannabinoid Hyperemesis Syndrome With Haloperidol, Lorazepam, and/or Capsaicin: A Single Institution Case Series

“…The only known long-term effective treatment for CHS is continued abstinence from cannabis use. 2,3 The effect of delta-9-tetrahydrocannabinol (THC) on the body is largely driven by its action on the cannabinoid receptors CB-1 and CB-2, 4 but the specific pro-emetic mechanisms resulting in CHS remain unknown. Standard antiemetic therapy has failed to demonstrate a significant improvement in the acute symptoms of CHS for the majority of both adolescent and adult patients.…”