Clinical Effects of Synthetic Cannabinoid Receptor Agonists Compared with Marijuana in Emergency Department Patients with Acute Drug Overdose

J Med Toxicol. 2016 Dec;12(4):335-340. doi: 10.1007/s13181-016-0558-4. Epub 2016 Jun 2.


Introduction: Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds originally intended as probes of the endogenous cannabinoid system or as potential therapeutic agents. We assessed the clinical toxicity associated with recent SCRA use in a large cohort of drug overdose patients.

Methods: This subgroup analysis of a large (n = 3739) drug overdose cohort study involved consecutive ED patients at two urban teaching hospitals collected between 2009 and 2013. Clinical characteristics of patients with the exposure to SCRAs (SRCA subgroup) were compared with those from patients who smoked traditional cannabinoids (marijuana subgroup). Data included demographics, exposure details, vital signs, mental status, and basic chemistries gathered as part of routine clinical care. Study outcomes included altered mental status and cardiotoxicity.

Results: Eighty-seven patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 cases, 70 controls, mean age 38.9 years, 77 % males, 31 % Hispanic). There were no significant differences between SRCA and marijuana with respect to demographics (age, gender, and race/ethnicity), exposure history (suicidality, misuse, and intent), vital signs, or serum chemistries. Mental status varied between SRCA and marijuana, with agitation significantly more likely in SCRA subgroup (OR = 3.8, CI = 1.2-11.9). Cardiotoxicity was more pronounced in the SCRA subgroup with dysrhythmia significantly more likely (OR = 9.2, CI = 1.0-108).

Conclusions: In the first clinical study comparing the adverse effects of SCRA overdose vs. marijuana controls in an ED population, we found that SCRA overdoses had significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana.

Keywords: Cannabinoids; Cardiotoxicity; Overdose.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Arrhythmias, Cardiac / chemically induced
  • Biomarkers / blood
  • Cannabinoid Receptor Agonists / adverse effects*
  • Cannabinoid Receptor Agonists / blood
  • Cannabinoid Receptor Agonists / urine
  • Cannabinoids / adverse effects*
  • Cannabis / adverse effects*
  • Cardiotoxicity / etiology
  • Cohort Studies
  • Demography
  • Drug Overdose / physiopathology*
  • Female
  • Hospitals, Urban
  • Humans
  • Intelligence Tests
  • Male
  • Marijuana Abuse / physiopathology*
  • Neurologic Examination


  • Biomarkers
  • Cannabinoid Receptor Agonists
  • Cannabinoids