Case report Synthetic cannabinoid induced acute respiratory depression: Case series and literature review Mark Henry Alon a, * , Margaret Olibrice Saint-Fleur b a Department of Internal Medicine, New York City HealthþHospitals Harlem, Columbia University College of Physicians and Surgeons, New York, NY, USA b Department of Internal Medicine, Division of Pulmonary Medicine and Critical Care Medicine, New York City HealthþHospitals Harlem, Columbia University College of Physicians and Surgeons, New York, NY, USA article info Article history: Received 11 December 2016 Received in revised form 23 July 2017 Accepted 24 July 2017 abstract Synthetic Cannabinoids are a street drug that is widely attainable and cheap compared to natural cannabis, and has variable potency and unpredictable effects with no commercially available diagnostic test to confirm its presence. Similar to natural cannabis, Synthetic Cannabinoid intoxication can present in several ways with the most common emergency room presentations to be of neurologic and psy- chiatric manifestation. The respiratory depressive effect of Synthetic Cannabinoids has not been well documented in medical literature. We report four patients admitted in the Intensive Care Unit with acute respiratory failure necessitating endotracheal intubation after use of Synthetic Cannabinoid. All patients had a reversal of respiratory failure in less than 24 h, three patients had a complicated course due to aspiration pneumonia. All four patients exhibited aggressive behavior, with two of them diagnosed with Bipolar Disorder and Cocaine Use Disorder. The effect of Synthetic Cannabinoids in peripheral receptors such as chemoreceptors and barorecep- tors can increase bronchial airway resistance. It is postulated that CB1 receptor stimulation could be one of the possible mechanisms of synthetic cannabinoid-induced respiratory depression. Chemical gases released after its inhalation may also cause damage to the bronchiolar epithelium and has the potential to disrupt the protective surfactant layer in the alveoli, which then could interfere with effective gas exchange leading to hypoxia and acidosis. The stimulation of CB1 receptors have a series of downstream signaling effects in the G protein-coupled pathway and mitogen-activated protein kinase (MAPK) pathway, causing suppression of both excitatory and inhibitory neuronal activity. The aforementioned molecular changes in the central nervous system after CB1 receptor stimulation could impact respiration. The use of Synthetic Cannabinoids can cause respiratory depression in individuals without an un- derlying pulmonary disease and adds to the growing number of literature about the presentation and debilitating adverse events from its consumption. Although there is no specific toxidrome associated with it, clinicians should have a high index of suspicion with its use especially in patients presenting with a history of drug overdose. © 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction Synthetic cannabinoid-related emergency department visits in the northeast region of the United States have been steadily increasing, with more than 1200 emergency room encounters occurring every month since July 2016 [1e3]. Males account for 90% of these visits with a median age of 37. Most of the patients are residents of shelters and individuals with psychiatric illnesses [1]. It is reasonable to project that this current epidemic will slowly affect every state as its use becomes more rampant. In the advent of marijuana legalization in some states such as Colorado, California, Maine, and Nevada, consumption of synthetic cannabinoids has been very appealing due to its availability and cheaper price compared to its natural counterpart. It is usually purchased as pulverized herbs to be ingested, used as incense or rolled with natural marijuana to be smoked. They are cleverly packaged as well to entice consumers who would not otherwise consume cannabis [4,5]. * Corresponding author. E-mail address: markhenry.alon@nychhc.org (M.H. Alon). Contents lists available at ScienceDirect Respiratory Medicine Case Reports journal homepage: www.elsevier.com/locate/rmcr http://dx.doi.org/10.1016/j.rmcr.2017.07.011 2213-0071/© 2017 The Authors. Published byElsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Respiratory Medicine Case Reports 22 (2017) 137e141