Cannabinoid hyperemesis syndrome (CHS) is associated with tetrahydrocannabinol, and rarely has been reported with cannabidiol. Can- nabidiol is used in treatment-refractory epilepsy. This is a case of a pediat- ric patient with Lennox-Gastaut syndrome on cannabidiol, who was started on the ketogenic diet with significant seizure reduction. However, within 6 months he developed monthly bouts of severe emesis unresponsive to con- ventional anti-emetic therapy. Based on the stereotypical nature of his vomit- ing episodes, CHS was suspected. Cannabidiol was discontinued and within 2 months his emesis resolved. He has had no increase in seizure frequency or hospitalizations for emesis since cannabidiol was discontinued nearly 1 year ago. This is the first case of CHS secondary to cannabidiol for refrac- tory epilepsy reported in the literature. We review the mechanism by which cannabidiol is believed to reduce seizures and be both anti- and pro-emetic, mainly through interactions with cannabinoid receptors and transient receptor channels.