We thank Drs. Yoo, Liu, and Villamagna for reading our recently published article and appreciate their insights regarding the difficult nature of diagnosing cannabinoid hyperemesis syndrome (CHS) in patients using synthetic cannabinoids and the potentially large health burden of this illness.

Our systematic review identified the three referenced case reports of CHS [1–3] secondary to synthetic cannabinoid use and we included them in our synthesis. Although the clinical toxidromes associated with synthetic cannabinoids can differ from those of natural cannabinoids, synthetic cannabinoids interact with the CB1 receptor [4] and since these cases meet our criteria for CHS diagnosis [5], we believe that these cases should be labeled as CHS and treated as such.

Certainly, questioning about synthetic cannabinoids is warranted when CHS is suspected. Given that many patients do not consider synthetic cannabinoids a “drug,” it may be prudent to query the use of all “herbal products” in a thorough evaluation of cyclic vomiting in an otherwise well individual in whom other etiologies of cyclic vomiting have been ruled out.

It is unclear how many cases of CHS are attributable to synthetic versus naturally occurring cannabinoids. Clearly, synthetic cannabinoids are the fastest growing and most abused class of new psychoactive substances [6]. The failure to capture this drug class by traditional drug screens paired with the rising popularity should prompt clinicians to consider synthetic cannabinoids as a cause of CHS.