Case Report Synthetic Cannabis and Acute Ischemic Stroke Miya E. Bernson-Leung, MD,*† Lester Y. Leung, MD,* and Sandeep Kumar, MD* An association between marijuana use and stroke has been previously reported. However, the health risks of newer synthetic cannabinoid compounds are less well known. We describe 2 cases that introduce a previously unreported association between synthetic cannabis use and ischemic stroke in young adults. A 22-year-old woman presented with dysarthria, left hemiplegia, and left hemianesthesia within hours of first use of synthetic cannabis. She was healthy and without identified stroke risk factors other than oral contraceptive use and a patent foramen ovale without venous thromboses. A 26-year-old woman presented with nonfluent aphasia, left facial droop, and left hemianesthesia approximately 12 hours after first use of synthetic cannabis. Her other stroke risk factors included migraine with aura, oral contraceptive use, smoking, and a family history of superficial thrombophlebitis. Both women were found to have acute, large-territory infarctions of the right middle cerebral artery. Our 2 cases had risk factors for ischemic stroke but were otherwise young and healthy and the onset of their deficits occurred within hours after firsttime exposure to synthetic cannabis. Synthetic cannabis use is an important consideration in the investigation of stroke in young adults. Key Words: Ischemic stroke— stroke in young adults—cannabis—drugs of abuse—acute stroke. Ó 2013 by National Stroke Association Introduction Heavy cannabis use is associated with acute ischemic stroke (AIS).1-3 We describe 2 cases of AIS after first-time From the *Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and †Department of Neurology, Boston Children’s Hospital, Boston, Massachusetts. Received June 13, 2013; accepted July 22, 2013. Drs. Bernson-Leung and Leung are joint first authors. Author contributions: Miya E. Bernson-Leung, Lester Y. Leung, and Sandeep Kumar contributed to analysis, interpretation of data, and drafting the manuscript. All authors have seen and approved the final version of the manuscript. Disclosures: The authors have no potential conflicts of interest to disclose and no financial interests relevant to the subject of this manuscript. There were no sources of grant support. Address correspondence to Miya E. Bernson-Leung, MD, Department of Neurology, Boston Children’s Hospital, 300 Longwood Ave, Fegan 11, Boston, MA 02115. E-mail: miya.bernson-leung@childrens. harvard.edu. 1052-3057/$ - see front matter Ó 2013 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.07.030 use of synthetic cannabis. These agonists of cannabinoid receptor type 1 have emerged as recreational drugs used by adolescents and young adults and often evade detection by toxicology screens.4,5 Case Report Our first patient was a 22-year-old right-handed woman taking atomoxetine and an estrogen-containing oral contraceptive. She developed palpitations, dyspnea, and angor animi while smoking ‘‘K2.’’ A few hours later, she developed dysarthria and difficulty standing. Physical examination revealed drowsiness, inattention, dysarthria, left face and hemibody weakness, and hemianesthesia. Urine toxicology was positive for tetra-hydrocannabinol, benzodiazepines, and salicylates. Initial head computed tomography (CT) was negative, but magnetic resonance imaging revealed a right middle cerebral artery AIS. She did not receive thrombolysis because of late arrival. CT angiogram revealed a proximal right M1 occlusion with distal reconstitution (Fig 1). She had a patent foramen ovale Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2013: pp 1-3 1 2 M.E. BERNSON-LEUNG ET AL. Figure 1. Case 1: Magnetic resonance imaging FLAIR sequence (A) showing near-complete infarction of right MCA territory, with corresponding occlusion on CT angiography (B and C). Case 2: MRI FLAIR sequence (D) showing infarction of predominantly inferior division right MCA territory, with corresponding occlusion on CT angiography (E and F). Abbreviations: FLAIR, fluid-attenuated inversion recovery; MCA, middle cerebral artery; MRI, magnetic resonance imaging. but no deep vein thrombosis. Testing of serum vascular risk factors and hypercoagulability was negative. She started aspirin. In follow-up, she has limited ambulation and no use of her spastic left arm. Our second patient was a 26-year-old left-handed woman with tobacco smoking, migraine with aura, perinatal intraventricular hemorrhage without residual deficits, and family history of superficial thrombophlebitis who was taking an estrogen-containing oral contraceptive. She smoked ‘‘Peak Extreme’’ during a typical migraine. The next morning, she developed left facial weakness, left-sided numbness, and dysfluency. Initial head CT was unremarkable and symptoms resolved. The next day, she developed left-sided weakness and speech difficulty for which she sought care after 24 hours. She did not receive thrombolysis because of SYNTHETIC CANNABIS AND ACUTE ISCHEMIC STROKE late arrival. On our examination, she demonstrated impaired fluency and comprehension, left visual neglect, left facial weakness, difficulty initiating movements, left pronator drift, and hemianesthesia. Urine toxicology was negative for tetra-hydrocannabinol. CT angiogram revealed near occlusion of the right M1 segment, and magnetic resonance imaging revealed extensive middle cerebral artery territory infarction (Fig 1). She was treated with warfarin. Testing of serum vascular risk factors and hypercoagulability was negative. In follow-up, her speech and comprehension have improved. These cases illustrate a potential association between synthetic cannabis use and AIS. The increased potency of synthetic cannabinoids, cross-reactivity with other receptors, and multiple active metabolites may strongly promote a prothrombotic state in the setting of other minor risk factors for ischemic stroke.4,6 We hope that this report will improve awareness of this association and aid in stroke prevention in young individuals. 3 References 1. Singh N, Pan Y, Muengtaweeponsa S, et al. Cannabis-related stroke: case series and review of the literature. J Stroke Cerebrovasc Dis 2012;21:555-560. 2. Mateo I, Pinedo A, Gomez-Beldarrain M, et al. Recurrent stroke associated with cannabis use. J Neurol Neurosurg Psychiatry 2005;76:435-437. 3. Wolff V, Lauer V, Rouyer O, et al. Cannabis use, ischemic stroke, and multifocal intracranial vasoconstriction: a prospective study in 48 young patients. Stroke 2011;42:1778-1780. 4. Seely KA, Lapoint J, Moran JH, et al. Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuropsychopharmacol Biol Psychiatry 2012;39:234-243. 5. Food and Drug Administration. Schedules of controlled substances: placement of five synthetic cannabinoids into schedule I. Available at: http://www.deadiversion.usdoj. gov/fed_regs/rules/2012/fr0301_3.htm. Accessed December 5, 2012. 6. Brents LK, Reichard EE, Zimmerman SM, et al. Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity. PLoS One 2011;6:e21917.