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Abstract
Cannabinoid hyperemesis syndrome (CHS) is an episodic syndrome of cyclic vomiting in the context of the prolonged use of cannabis. The Royal College of Emergency Medicine Toxicology Special Interest Group has produced guidance to support emergency medicine clinicians with the recognition and treatment of people experiencing CHS.
Considerations regarding recognition, investigation and communication are discussed, and recommendations regarding treatment options (which include haloperidol and capsaicin) are made. There is a focus on making recommendations on the best available evidence.
- toxicology
- gastro-intestinal
- poisoning
- drug abuse
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Preface
The Royal College of Emergency Medicine best practice guideline (BPG) was produced by members of the Toxicology Special Interest Group. BPGs use a multimodal search strategy to produce guidance for areas of clinical controversy where little robust evidence exists or areas of particular concern or anxiety to Fellows and Members.1 This BPG was originally published online in June 2023. There have been several limited changes made to reflect updates in the literature since the original publication.
Key recommendations
A diagnosis of cannabinoid hyperemesis syndrome (CHS) should be considered in presentations of nausea and vomiting with a cyclic pattern and where there is associated cannabis use. (Recommendation level C).
Patients should be encouraged to disclose their cannabis use and be reassured that this disclosure will not affect them adversely and will remain confidential. Care should be taken to ensure that patients do not feel stigmatised for their use of cannabis. (Recommendation level C).
Failure of standard antiemetic therapy to improve symptoms should lead to consideration of the use of haloperidol or capsaicin. (Recommendation level B).
Patients may struggle to accept a diagnosis of CHS for a variety of reasons. They should be supported with written information when a diagnosis of suspected CHS is made. This information should also identify sources of support and advice for helping those cannabis users wishing to achieve abstinence. (Recommendation level C).
A key to the Strength of Recommendations Taxonomy is given in table 1.
The Strength of Recommendations Taxonomy26
Scope
CHS is an episodic syndrome of cyclic vomiting in the context of the prolonged use of cannabis. It can be a challenging diagnosis to make, as vomiting episodes are not necessarily temporally related to increased cannabis use, and patients may find that cannabis use during an episode actually improves their symptoms. Identifying a relationship is made more difficult as patients may have weeks or months between episodes, and may develop the syndrome after many years of cannabis use. Identifying cannabis as the cause of symptoms may also be difficult due to patients’ reluctance to disclose cannabis use.
It is important to recognise that CHS is unlikely to be definitively diagnosed in the ED due to the current diagnostic criteria. However, there are many clinical features which can lead clinicians to suspect a diagnosis of CHS and there are several non-conventional treatments that may be efficacious in treating the symptoms of CHS and may help to confirm it. The essential prerequisite for a CHS diagnosis is the long-term use of cannabinoids. There are no laboratory or radiographic investigations that can be used to diagnose CHS.
The process of creating this guideline has included contemporaneous literature reviews for high-level evidence in the medical literature on recognition and management of CHS, as well as searches for consensus agreement publications where they exist (PubMed search for ‘cannabinoid hyperemesis’ with all article types reviewed by title and abstract for relevance). The guideline group have formed consensus on areas lacking clear answers.
Reason for development
There are current gaps in accurately defining the optimal classification, pathophysiology and treatment of CHS. This BPG has been written to bridge the current gap between evidence and the need for emergency clinicians to provide quality care and advice to patients suffering from this syndrome.
Patients presenting with CHS often experience a delay to diagnosis. They will typically have repeated visits to EDs, several hospital admissions and often describe poor symptom control with standard therapies, such as antiemetic medications.
This guideline has been written to increase emergency medicine clinician awareness of CHS, support the care of patients presenting to the ED with symptoms of CHS and help clinicians communicate the concept and management of CHS to patients.
Limitations of the evidence
Since first being identified in 2004, CHS recognition has grown rapidly. However, leading systematic reviews remain at high risk of being impacted by publication bias, and clinical management is still in its infancy, with only small randomised controlled trials (RCTs) on which to base treatment advice.
Background
7.8% of UK adults aged 16–59 years use cannabis, of whom 25.6% use cannabis at least weekly.2
While several mechanisms have been proposed, the exact pathophysiology of CHS is still unclear.3 While cannabis can act as an antiemetic at low doses, repeated high dose use can result in vomiting. A clinical syndrome of hyperemesis in the context of cannabis use has been recognised as early as 2004. While overall recognition remains poor, recognition is improving.4–6
CHS is thought to be the cause of a significant proportion of presentations for recurrent vomiting and abdominal pain in EDs.7 The diagnosis is frequently not considered, and the journey from onset to diagnosis can take an average of 4.1 years.8 Patients may be reluctant to volunteer information about cannabis use in the ED unless reassured that they will not face legal consequences.
Patients are typically regular cannabis users, presenting with cyclic episodes of vomiting or abdominal pain. They often report relief of symptoms with hot showers or baths.
At its most severe, CHS can be fatal, but many other patients experience significant pain and distress, electrolyte abnormalities, hypoglycaemia or renal failure.9 There is significant value in an early diagnosis for both treatment of the current episode, and prevention of future harm. Additionally, CHS often fails to resolve with standard antiemetic treatments. Some alternative therapies (which may not be routinely considered) have the potential to improve symptoms and avoid hospital admission.
Recognition
The features in box 1 should prompt suspicion of a diagnosis of CHS.
Frequency of features identified in diagnosis of cannabinoid hyperemesis syndrome16
Severe nausea and vomiting that recurs in a cyclic pattern over months (100%).
Age <50 years at time of evaluation (100%).
At least weekly cannabis use (97.4%).
Resolution of symptoms after cannabis cessation (96.8%).
Compulsive hot showers or baths with symptom relief (92.3%).
Abdominal pain (85.1%).
History of regular cannabis use for >1 year (74.8%).
The Rome IV diagnostic criteria for functional gastrointestinal disorders were defined in 2016.10 One of the three criteria for definitive diagnosis of CHS is ‘relief of vomiting episodes by sustained cessation of cannabis use’, and therefore a confirmed diagnosis of CHS is unlikely to be made in an ED. Unfortunately, this criterion has limited the ability of researchers to definitively identify research populations in patients attending the ED.11
Consideration should also be given to re-evaluating previous diagnoses for recurrent vomiting disorders. One study identified that large numbers of patients with a diagnosis of cyclic vomiting syndrome were current cannabis users, although it is difficult to know if this represents management of cyclic vomiting syndrome symptoms with cannabis use, or a cohort of patients with undiagnosed CHS.12
Given the lack of specificity of many features of CHS, exclusion of a major medical or surgical aetiology as the cause for the patient’s symptoms is essential. Potential other causes may include (but are not limited to):
vomiting due to a central nervous system pathology;
intra-abdominal pathology;
infection, especially gastrointestinal;
chronic nausea and vomiting syndrome;
cyclical vomiting syndrome;
diabetic gastroparesis.
Investigation
Complications of CHS are predominantly driven by poor food and fluid intake, and gastric losses due to intractable vomiting.
As well as following local policy for the investigation of abdominal pain and vomiting, specific consideration should be given to assessment for:
hypoglycaemia;
acute kidney injury;
electrolyte abnormalities (sodium, potassium, calcium, chloride, magnesium);
metabolic acidosis/alkalosis.
The presence of certain red flag signs or symptoms should alert clinicians to the possibility of an alternative diagnosis, such as:
unintentional weight loss, especially aged >50 years;
abdominal mass and/or change in bowel habit;
anaemia or Liver Function Test abnormality.
Communication
Clinicians should have sympathetic and non-judgemental discussions with the patient about their cannabis use, and recognise that patients may be nervous or reluctant to disclose their cannabis use. A variety of societal or health factors may lead to the use of cannabis, and harm from its use has been suggested to be lower than that of alcohol or tobacco.13 Although there is limited data from RCTs, many patient advocacy groups have reported cannabis to be a helpful substance when standard therapies have failed.14 Examples include Parkinson’s disease, multiple sclerosis or chronic pain.
The role of cannabis in medicine is increasing, and some cannabis-based products are available on prescription in the UK.15 Despite the number of current NHS prescriptions remaining low, it is recognised that thousands of private prescriptions have been issued.
Patients may struggle to accept the diagnosis of CHS for a variety of reasons:
Vomiting episodes are not temporally related to an increase in cannabis use.
Acute cannabis use often improves nausea.
Patients may have weeks to months between episodes.
Patients can develop the syndrome after using cannabis for <1 year or >11 years.16
Additionally, although it is easy to inform a patient they should stop using cannabis, cessation may be prove to be challenging.17 Sign-posting advice, or referral to local services for help with drug use, may improve the likelihood of successful cessation.
It is recommended that written information on CHS be provided to patients. An example of such a leaflet is included with this guideline (online supplemental file 1).
Supplemental material
Symptom management
Acute episode
CHS is recognised as often being resistant to routine antiemetic treatments such as cyclizine, dexamethasone, domperidone, metoclopramide, ondansetron, prochlorperazine and promethazine.18 19 Additionally, pain relief with opiates is frequently unsuccessful.
Normal departmental processes for the management of nausea and vomiting should be followed in the first instance. A potential exception to this is a patient presenting with a known diagnosis of CHS and continued cannabis use.
Patients with an established diagnosis of CHS who have continued to use cannabis may present in the prodromal stage of an episode, with nausea, abdominal discomfort and fear of vomiting. Initiating treatment prior to vomiting may be helpful in this group.
Refractory symptoms
For refractory nausea or vomiting in CHS, consider the use of haloperidol or capsaicin, which are both supported by small RCTs and systematic reviews.20–23 Suggested dosing is given in table 2.
Treatment for refractory nausea and vomiting in cannabinoid hyperemesis syndrome
Prior to administering haloperidol, obtain an ECG to check for QTc prolongation and correct any electrolyte abnormalities if conduction defects are present. Do not give haloperidol if the QTc is prolonged, or if a patient has Parkinson’s disease or Lewy body dementia. Patients should be monitored for acute dystonia after administration. Do not discharge patients from the ED with a prescription for haloperidol unless this forms part of a specialty management plan.
If treatment fails to relieve symptoms and a patient requires admission, access to a hot shower or bath should be offered for symptom relief.
Other treatments, supported by extremely limited evidence (insufficient data to make dosing recommendations) include:
benzodiazepines;
droperidol;
tricyclic antidepressants;
olanzapine;
levetiracetam;
proton-pump inhibitors;
beta-blockers.
Long-term management
The only definitive treatment that has been identified to prevent CHS is abstinence from cannabis.
Special populations
Pregnancy—CHS may be mistaken for hyperemesis gravidarum, highlighting the need for a careful history-taking in such cases.24
Paediatrics—CHS has been described in adolescent patients. Paediatric patients may be exposed to cannabinoids through passive smoking or breast milk, although we were not able to find case reports linking these exposures to CHS.25
Review
Further review usually within 3 years or sooner if important information becomes available.
Disclaimers
The college recognises that patients, their situations, EDs and staff all vary. This guideline cannot cover all possible scenarios. The ultimate responsibility for the interpretation and application of this guideline, the use of current information and a patient’s overall care and well-being resides with the treating clinician.
Research recommendations
Research is required to establish the prevalence of CHS in a UK setting, and optimal treatment strategies.
Audit standards
None.
Ethics statements
Patient consent for publication
Ethics approval
Not applicable.
Acknowledgments
The authors would like to thank RCEM Quality in Emergency Care Committee and Professor Gene Ong for editorial review of the guidelines prior to Emergency Medicine Journal publication
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Handling editor Gene Yong-Kwang Ong
X @cp_humphries
Contributors CH, MG: substantial contributions to the conception and design of the work. CH, MG: drafting the work and reviewing it critically. CH, MG: final approval of the version to be published. CH, MG: agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests CH: unpaid member of Department of Health and Social Care Drug Harms Assessment and Response Team Reimbursed for travel expenses to speak at conferences for Royal College of Emergency Medicine (RCEM), unpaid member of RCEM Toxicology advisory group. MG: unpaid member of RCEM Toxicology advisory group.
Provenance and peer review Not commissioned; internally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.