Introduction: Emergency physicians increasingly encounter young patients with protracted, forceful hyperemesis associated with heavy cannabis use, previously termed “cyclic vomiting.” The national discourse on liberalization of cannabis has largely ignored this poorly understood condition. We wondered to what degree hyperemesis cannabis is an idiosyncratic reaction, like motion sickness or migraine, versus a more predictable dose-response effect of heavy, prolonged use. Methods: As part of a larger case-control study using structured interviews, we measured cannabinoid concentrations in scalp hair of both cases and controls. Cases were required to have an emergency visit for vomiting, 2+ episodes of severe vomiting in the previous year, history of near-daily use of cannabis for 6+ months, positive urine Δ9-tetrahydrocannabinol (THC) and age 16-55 years; exclusion criteria were chronic opioid use, synthetic cannabinoid use, or established alternative diagnosis. Age- and sex-matched chronic cannabis-using controls without vomiting were identified via social referral primarily from the cases themselves. Scalp hair was analyzed for THC, cannabinol (CBN), cannabidiol (CBD) and 11-nor-9-carboxy-THC (THC-COOH) by LC-MS/MS (limit of quantification ~15 pg/mg hair; accuracy <5%) in an independent laboratory blinded to subject classification. Results: We obtained satisfactory hair and urine samples from 18 cases (median [IQR] age 27 [20,31] years; 12 male) and 13 controls. THC and CBN concentrations were higher in cases than controls (THC 240 [120,820] vs 99 [73, 290] pg/mg; CBN 63 [33, 260] vs 15 [negative, 76] pg/mg; each P<0.05). CBD and THC-COOH were often unquantifiable to undetectable in both cases and controls. Conclusion: Hyperemesis cannabis patients have substantially higher hair cannabinoid concentrations than their peers without vomiting, although there is some overlap. The association cannot demonstrate a direct dose-response with THC--confounding (e.g. other cannabinoids, external smoke deposition), altered metabolism and reverse causation (e.g. seeking temporary symptom relief by using more cannabis) could also yield a positive association. Nevertheless, these findings support counselling patients with hyperemesis to reduce or discontinue using cannabis. They also support national regulatory initiatives including education, labelling, and progressive taxation based on potency intended to discourage excessive use.