The current study investigated trends in rates of CHS ED visits from 2013 to 2021 in Nevada. We found a steady increase in rates of CHS ED visits during this period with an apparent increase after commercialization for recreational use. In addition, patients aged 21–29 years were the most common in those with CHS ED visits and females more frequently visited ED than males.

Our study correlated with previously reported trends of an increase of CHS rate among patients visiting hospitals in North America [10–13]. Recent studies have found that rates of CHS ED visits are increased after commercialization of the cannabis market [11–13]. After medical cannabinoid legalization, rates of cannabis dependency and persistent vomiting have shown an increasing trend [15]. In line with these increasing rates, ED staff in regions where legal commercialized cannabis markets exist needs greater awareness of CHS symptoms. In Nevada, ED visits due to complaints of CHS have significantly increased after the commercialization of cannabis for recreational use. CHS ED visits increased rapidly during the COVID-19 pandemic after March 2020. However, COVID-19 was not a factor causing such a rapid increase. A cross-sectional study conducted in Ontario, Canada has also found large increases in CHS ED visits during the period of the COVID-19 pandemic [13]. Because the period of COVID-19 in the current study was relatively short, it might not fully reflect the effect of COVID-19.

We evaluated factors associated with the CHS group compared with the non-CHS group. The prevalence of cannabis use disorder among those aged 12–25 appeared to increase with time since the initiation of the survey conducted by the Substance Abuse and Mental Health Services Administration [16]. In our study, 41.6% of patients with cannabis-related ED visits were in the age group of 12–29 years. This age group showed the highest prevalence of CHS. In addition, we found that CHS ED visits occurred more commonly in women than in men. Other studies about CHS have shown similar results regarding age and sex [10, 13]. Our study showed that patients using cannabis with other substances including opioid, alcohol, smoking, and sedatives were fewer in the CHS group than in the non-CHS group. Because there were few studies comparing CHS and non-CHS groups, we could not determine the exact cause for the differences between the two groups. One of explanations was that antipsychotics for treating mood disorders could control symptoms during the hyperemetic phase. For prevention and long-term management of CHS, tricyclic antidepressants or benzodiazepines were the mainstay of therapy to achieve symptom control [17]. Because CHS had various diagnostic characteristics, it might be under-diagnosed at ED. Several practical criteria such as at least weekly cannabis use for over 1-year, severe nausea and vomiting that recurs in a cyclic pattern, accompaniment of abdominal pain, resolution of symptoms after stopping cannabis, and compulsive hot baths with symptom relief have been used for identifying patients with CHS [18]. The use of synthetic cannabis might lower the incidence of CHS. Chronic stimulation of cannabinoid 1 receptors by various cannabinoids found in the natural marijuana plant plays a role in the pathogenesis of CHS. Although a case of CHS caused by synthetic cannabinoid has been reported [19], CHS might be lower in synthetic users than in natural users.

Access to recreational cannabis dispensaries plays a role in CHS and ED visits due to CHS. It has been reported that the availability of recreational cannabis dispensaries, the presence of storefront signage indicating the availability of cannabis, and signs promoting health benefits of cannabis are associated with increased cannabis use in both youths and adults [20]. Compared with adults, youths might have more probabilities of transitioning from cannabis non-users to users when they reside in recreational cannabis commercialization states [21]. As for the stigmatization concern of cannabis illegality for those who have been sent to the criminal justice system, civil liberties advocates support recreational marijuana decriminalization across states. According to a recent study, youth marijuana possession arrest rates are unchanged in marijuana decriminalization states [22]. From this evidence, we speculate that there is an urgent need of evaluating health and criminal justice outcomes in youths since the State of Nevada has a new legal establishment of cannabis consumption lounges.

The legalization of marijuana has led to an increase in cannabis use as indicated by increasing rates of positive cannabinoid immunoassay and increasing use of cannabis-related diagnosing codes at ED [3]. Cases related to synthetic cannabinoid use have been increasingly reported [23]. However, the diagnosis of synthetic cannabis is challenging because it is not currently detectable in standard urine or serum immunoassay drug screenings. Synthetic cannabinoid is much more potent than natural cannabis because it is a full agonist with a binding affinity five times higher [23]. Such stronger binding has led to numerous adverse reactions including hypertension, tachycardia, agitation, confusion, hallucination, chest pain, seizure, and syncope. High school students using synthetic cannabinoids tend to engage in risky violent, mental, and sexual behaviors [24]. Synthetic cannabinoid use and related effects are expected to increase further. Thus, healthcare providers should be aware of CHS and other potential toxicities [25]. Our study might have underestimated the prevalence of CHS ED visits because it could not consider synthetic cannabinoid use. Healthcare providers working in ED should be aware of the stakeout role of synthetic cannabis that is not usually detected by a spot urine drug screening test in ED [25].

Resource utilization in the ED and health system is expected to be affected by the study results [2, 3]. High ED use for CHS triggers congestion in the ED waiting room, public health care cost, episodic care rather than preventive and continuity of care. Hospital admission rates may also have arisen because of cannabis-related ED visits [15].

The present study has several limitations. First, we defined CHS as a combination of diagnostic codes of cannabis-related disorder and vomiting because currently there is no diagnostic code of CHS. Our study might have underestimated the burden of CHS. Second, changes of CHS incidence could be caused by a greater awareness of CHS by ED physicians and the willingness of patients to disclose cannabis use. Third, the study period in the current study was relatively short. Effects of cannabis-related ED visits were not fully evaluated especially during the COVID-19 pandemic.

In conclusion, there was a substantial increase in CHS ED visits in Nevada and a clear-cut increase after commercialization of recreational cannabis. These CHS ED visits were common in young adults and women. Further research including a large population based on administrative health databases is needed to explore trends of CHS and related factors.