ReviewCannabinoid hyperemesis syndrome: Review of the literature and of cases reported to the French addictovigilance network
Introduction
Cannabis has been known since antiquity and human usage is ancestral, particularly in traditional Chinese medicine (2727 BCE) (Brand and Zhao, 2017). It is the most widely used drug worldwide, with nearly 182.5 million users in 2014 according to the United Nations, i.e., 3.8% of the world population (United Nations Office on Drugs and Crime, 2016). According to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), the French are by far Europe's leading consumers, with a lifetime prevalence for the 15–64 year age group of 40.9% (European Monitoring Centre for Drugs and Drug Addiction, 2017). According to the Observatoire Français des Drogues et des Toxicomanies (OFDT – French observatory of drugs and drug addictions), cannabis ranks first of the most widely used illicit substances in France. In 2014, 17 million French citizens declared having taken cannabis during their lifetime; 4.6 million during that year, 1.4 million at least 10 times during that month and 700,000 daily (Beck et al., 2015). Current cannabis usage mainly concerns younger individuals (28% of 18–25 year-olds, 34% of men and 23% of women). It then decreases with age, dropping to only 2% of 55–64 year-olds. Among 18–25 year-old men and women, respectively 11% and 6% are regular cannabis users (Beck et al., 2015). Since the 1990s, there has been an increase in usage in France, in a context of clear increase in cannabis supply, and in particular of self-growing and local weed production (Beck et al., 2015).
The properties of cannabis are still being elucidated and some of these are used to treat certain medical ailments, in particular drug-induced nausea and vomiting, anorexia and loss of appetite in HIV seropositive patients, along with relief of chronic pain and spasticity in multiple sclerosis (Whiting et al., 2015). But cannabis is also responsible for many adverse effects. Some have been extensively described: decreased attention, psychiatric disorders, cannabis use disorder (defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as the continued use of cannabis despite clinically significant impairment, ranging from mild to severe), etc. While one other, paradoxically, has emerged very recently: cannabinoid hyperemesis syndrome (CHS) (Allen et al., 2004). This is a variant of cyclical vomiting syndrome associated with taking hot showers, in a chronic cannabis usage context. CHS was first described in 2004 by Allen et al. (2004) and legitimacy of this syndrome was recently approved by the recent ROME IV criteria released in May 2016 for Functional Gastrointestinal Disorders (category B3c) (Stanghellini et al., 2016). Allen et al. observed that the syndrome consists of several phases. They described a prodromic phase during which patients presented with morning nausea and vomiting for one or several days. These symptoms appear several months, or even several years before the episodes of abdominal pain. During this phase, patients retain their appetite. Then, they described a hyperemetic phase during which patients would vomit abundantly, while suffering from sweating, abdominal pain and polydipsia. No effective treatments have been recommended, despite the cases reported in the literature.
France is the only European country with a national system dedicated to observing and evaluating psychoactive products, medicines and drug abuse and potential addiction. The addictovigilance centres are in charge of collating cases of drug dependence, abuse and misuse related to the use of psychoactive substances, reported by healthcare professionals. There are thirteen of these French centres, organized in a network. The duties of the addictovigilance centres are laid out in the French Public Health Code (Code de la santé publique − Article R5132-112, n.d.). The three main duties of the CEIP-A (Centre d'Evaluation et d'Information sur la Pharmacodépendance – Addictovigilance – Centre for drug dependence evaluation and information) are: i) to collect data and evaluate the dependence potential of identified psychoactive medicines; French regulations require that all cases of severe abuse and severe drug dependence associated with the usage of substances or plants with psychoactive effects, along with all other medicines or products be reported (Code de la santé publique − Article R5132-113, n.d.; Code de la santé publique- Article R5132-114, n.d.), ii) to provide information concerning the risk of psychoactive substance abuse or dependence, and iii) to conduct scientific research.
The prevalence of cannabis usage in France is one of the highest worldwide (United Nations Office on Drugs and Crime, 2016) and France possesses a dedicated monitoring system. A study of this new clinical entity was thus considered necessary. The purpose of this work was to analyse French cases of CHS reported to the French addictovigilance network; our aim was to compare these French cases to those identified in the international literature in order to further our knowledge of the clinical criteria, pathophysiology and treatments for CHS.
Section snippets
Material and methods
We submitted a query to the addictovigilance network in June 2016. We analysed the notification files for cases of CHS reported to the French addictovigilance centres without time limitation.
For the retrospective analysis, we selected those patients presenting with cyclical symptoms of nausea, vomiting and abdominal pain, in a context of chronic cannabis or synthetic cannabinoid usage. We analysed the data derived from their “drug dependence case notification files”. In this context of
Study of cases reported to the addictovigilance network
In total, the addictovigilance network collected 29 notifications of CHS cases. The characteristics of these cases are given as a Supplementary Material.
The first notifications of CHS were reported only recently. Before 2013, this syndrome had never been reported to the addictovigilance centres; notifications increased markedly from 2015 onwards (Fig. 1).
All of these cases had a similar clinical presentation. Patients regularly presented with crisis episodes interspersed with calm periods.
Significant under-notification
The addictovigilance network upon which we based our work is unique in Europe; it benefits from significant expertise and strong connection, both of which were essential to us for effectively studying this syndrome. CHS remains poorly known to French healthcare professionals, probably accounting for the significant under-notification. Nevertheless, there were 29 French cases for 113 described cases reported in the literature, thus confirming the strength of the French addictovigilance network
Conclusions
We have only just begun to characterise CHS. It is defined by cyclical vomiting, accompanied by abdominal pain, ameliorated by taking hot baths or showers, in a context of chronic cannabis use. The pathophysiology remains unclear. Stopping cannabis usage remains the best treatments. Reported French cases display the same characteristics as the cases identified in the international literature. Considering the large number of notifications, we can assert that there is a CHS outbreak in France.
Conflict of interest
All authors declare that they have no conflicts of interest.
Role of funding source
Nothing declared.
Contributors
B.S., N.W. and C.V. contributed to conception and design of the study, wrote and edited the manuscript text. B.S., C.V., N.W., J.C., M.G., M.S., N.A., J.T., M.G., A.S., L.C. and S.P. contributed to acquisition, analysis and interpretation of data. C.V., P.C. and P.J. supervised the work, participated in revising the manuscript critically for important intellectual content. All authors reviewed the manuscript and give final approval of the version to be submitted and any revised version.
Acknowledgements
The authors thank Léonore Joseph from ADT-International, France for having translated the present manuscript from French to English.
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