Cannabis Hyperemesis Syndrome: What Do We Know?
College of Pharmacy, University of Florida, Gainesville, FL, USA
Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, FL, USA
Article notes
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Received 2024 Apr 22; Accepted 2024 Apr 28; Collection date 2024 Jan-Dec.
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Keywords: Cannabis hyperemesis syndrome, Cannabis safety, Cannabis adverse events, Cyclical vomiting
Defining Cannabis Hyperemesis Syndrome
A form of hyperemesis known as cannabis hyperemesis syndrome (CHS) has gained attention as a potential cannabis safety concern. CHS was first described as cyclical vomiting that occurred in individuals with prolonged cannabis use [1], but there is no official definition or criteria to diagnose patients with CHS at the time of this writing. CHS is considered a diagnosis of exclusion, and the American College of Gastroenterology describes common characteristics, which include the following [1–3]:
- Age <50 at the onset of symptoms
- Prolonged, regular cannabis use (>1 year for at least weekly)
- Abdominal pain
- Resolution of symptoms upon discontinuation of cannabis
- Compulsive hot showers/baths or symptom resolution with hot showers/baths
- Severe nausea and vomiting with episodes reoccurring over months
- Failure of symptom relief from traditional antiemetics
- Weight loss
The US surgeon general released a statement in 2021 warning of potential risk of CHS in chronic cannabis users that further advised caution when ingesting edibles, which have delayed effects that can result in overconsumption and thereby result in increased delta-9-tetrahydrocannabinol (THC) exposures [4]. Despite increasing awareness of CHS by clinicians, the mechanism explaining CHS development remains elusive. One proposed mechanism hypothesizes that THC potentially causes emesis by binding to cannabinoid type 1 receptors on the neurons that are in the vomiting center of the brain [5]. It is not clear how this would prompt cyclical vomiting, but THC (which is highly lipophilic) can cross the blood-brain barrier, resulting in potential accumulation of THC in the brain and overstimulation of receptors [5]. Another proposed mechanism suggests that genetic mutations interfering with cannabinoid metabolism lead to over-accumulation and adverse events like CHS [5].
In this piece, we identify studies and case reports that examine characteristics of patients with CHS and describe the trialed pharmacological and behavioral interventions, along with their successes and failures. We synthesize the developing CHS literature for clinicians to promote prompt CHS recognition and inform patients on risk. See the online supplemental material (for all online suppl. material, see https://doi.org/10.1159/000539182) for in-depth literature search and identification procedures, along with the full results of data extraction from reviewed studies.
Characterization of CHS Cases
From 29 case reports and case series identified on CHS presentation as of 2024, representing 36 unique individuals, the ages of people represented in cases ranged from a low of 15 years old to a high of 47 years old [6–34]. Most reports (21 | 29) described frequency of cannabis use as daily or multiple times per day in cases. Most unique participants represented in case reports (24 | 36) used cannabis for 1 year or longer (see Table 1). Analytical observational studies and their characterizations of CHS cases are described in online supplementary materials [35–42].
| Participants, n (%) | |
|---|---|
| Frequency of cannabis use | |
| Daily | 21 (58) |
| Weekly | 5 (14) |
| Not stated | 8 (22) |
| Regular use (unspecified) | 2 (5.6) |
| Duration of cannabis use | |
| One year | 2 (5.6) |
| Greater than one year but less than ten | 9 (25) |
| Greater than or equal to ten years | 13 (36) |
| Not stated/unspecified | 12 (33) |
Pharmacological Treatments Trialed for CHS
Most case reports included information on trialed pharmacological CHS treatments, and pharmacological treatments were not described for 15 individuals. The most frequently trialed pharmacological treatment was antiemetics, which also represented the pharmacological treatment failed most often, which is in line with CHS characterization (see Table 2 for specific agents within each medication class). Antipsychotics, anti-reflex medications, and hydration were reportedly trialed frequently in cases, but with no reported successful symptom resolution. No pharmacological treatment trialed, as documented in case reports and case series, resulted in complete symptom relief.
| Drug class | Specific medications/agents | Cases receiving treatment, n (%)* | Failed treatment in cases (%)* |
|---|---|---|---|
| Antiemetic | Droperidol, aprepitant, metoclopramide, promethazine, nabilone, prochlorperazine diphenhydramine, and unspecified antiemetics | 10 (18) | 48 (49) |
| Anti-reflux medications | Ranitidine, calcium carbonate, pantoprazole, unspecified proton pump inhibitor, and unspecified antacid | 6 (11) | 10 (10) |
| Anticholinergics | Dicyclomine and hyoscyamine | Not reported | 3 (3.1) |
| Antidepressants | Amitriptyline, paroxetine, and sertraline | Not reported | 3 (3.1) |
| Antispasmodics | Butyl hyoscine bromide | 1 (1.8) | Not reported |
| Antipsychotic | Haloperidol | 9 (16) | 3 (3.1) |
| Antiepileptic | Lorazepam | 3 (5.3) | 2 (2) |
| Analgesic | Topical capsaicin, acetaminophen, tramadol, hydromorphone | 5 (9) | 9 (9.2) |
| Antibiotics | Ceftriaxone | 1 (1.8) | 1 (1) |
| Alpha 2 adrenergic agonist | Clonidine | Not reported | 1 (1) |
| Anti-inflammatory | Corticoids | Not reported | 1 (1) |
| Prokinetic (5-HT4 receptor agonist) | Tegaserod and prucalopride | Not reported | 2 (2) |
| Alpha 1 blocker | Tamsulosin | 1 (1.8) | Not reported |
| Vitamin D analog | Calcitriol | 1 (1.8) | Not reported |
| Antidiuretic | Furosemide | 1 (1.8) | Not reported |
| Hydration | Normal saline | 4 (7) | 9 (9.2) |
| Not stated | Not applicable | 15 (26) | 6 (6.1) |
Behavioral Treatments Trialed for CHS
The majority of non-pharmacological or behavioral treatments trialed for CHS as documented among case reports and case series consisted of hot showers or baths, or similar applications of heat (see Table 3). Symptom relief was achieved in all cases where trial of hot showers is documented (26 | 26) and for the majority of cases (17 | 25) where behavior modification, consisting of cannabis smoking reduction, cessation, or switching cannabis formulations, was trialed. One case documented in reports described a patient that was referred in to a rehabilitation facility, and symptom resolution was not achieved in that case (0 | 1), nor in cognitive behavioral therapy (0 | 1). The specific amount of reduction in cannabis smoking that resulted in symptom resolution was not documented in cases with successful symptom relief, though all reports of trialed abstinence resulted in symptom relief.
| Non-pharmacological therapies attempted | Cases trialing therapy (%)a | Cases with symptom relief (%)b |
|---|---|---|
| Hot showers or other forms of heat application | 26 (72) | 26 (100) |
| Behavior modificationc | 25 (69) | 17 (68) |
| Cognitive behavioral therapy | 1 (2.7) | 0 (0) |
| Drug rehabilitation facilities | 1 (2.7) | 0 (0) |
| Motivational enhancement therapy | 1 (2.7) | 0 (0) |
| Not stated | 7 (19) | Not applicable |
Addressing CHS in Clinical Practice
Understanding of CHS and characterization of CHS epidemiology is still developing. All patients identified in case reports or case series were <50 years of age, when age was reported, and most were using cannabis daily at the time of symptom onset; however, it is unclear whether younger age is a risk factor for CHS development or whether younger adults with CHS-related symptoms were more likely to be considered as suitable for case report documentation. The most trialed non-pharmacological therapies were heat application via hot showers, baths, or heating pads, and behavior modification, where most of these trialed therapies resulted in symptom relief. Numerous medications were trialed in case reports and case series, with varying responses, and there was no consistent pharmacological treatment option resulting in definitive symptom resolution in most cases, though it should be noted that failed treatment with antiemetics appears to be a reliable indicator of CHS.
Clinicians can apply the commonalities from case presentation and management from these CHS cases to identify patients at risk for CHS and then can provide guidance on non-pharmacological, or pharmacological, treatment options when CHS is diagnosed or suspected. As increasing numbers of patients consume cannabis for medical and non-medical purposes, further guidance on risk communication for CHS will need to be developed, but first, diagnostic criteria will need to be formalized. Clinicians can consider using validated cannabis risk screening tools when determining whether education or intervention recommendations are appropriate in patients that report prolonged and frequent cannabis use.
Acknowledgment
Evidence in Context is part of the outreach effort of the Consortium for Medical Marijuana Clinical Outcomes Research to examine and discuss implications of research into cannabis and cannabinoids for clinical practice, thus providing a translational approach to these studies to make clear, concise, and actionable evidence available for clinicians and patients.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
A.G. is supported by State of Florida appropriations to the Consortium for Medical Marijuana Clinical Outcomes Research (mmjoutcomes.org). D.S. reports no financial disclosures.
Funding Statement
A.G. is supported by State of Florida appropriations to the Consortium for Medical Marijuana Clinical Outcomes Research (mmjoutcomes.org). D.S. reports no financial disclosures.
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References
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