Acute Poisonings From Synthetic Cannabinoids — 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010–2015

Anne M. Riederer, ScD; Sharan L. Campleman, PhD; Robert G. Carlson, PhD; Edward W. Boyer, MD, PhD; Alex F. Manini, MD; Paul M. Wax, MD; Jeffrey A. Brent, MD, Ph


Morbidity and Mortality Weekly Report. 2016;65(27):692-695. 

In This Article


Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States.[1,2] Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008.[3] Fifteen synthetic cannabinoids are Schedule I controlled substances,[3] but enforcement is hampered by the continual introduction of new chemical compounds.[1,3] Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Δ9-tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity.[4,5] Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects;[4,6,7] chronic use might lead to psychosis.[6,8] During 2010–2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases[1,2] and underscoring the need for prevention.

In 2010, the American College of Medical Toxicology established the ToxIC Case Registry as a toxicology surveillance and research tool. Participating sites agree to record basic data on patients evaluated at local hospitals and clinics in cases where consultation by a medical toxicologist is requested; reported cases therefore represent severe or potentially severe toxicities. As of November 2015, there were active sites in 41 U.S. cities, with a few cities, such as Boston and New York City, having multiple sites. The registry is overseen by the Western Institutional Review Board and site-specific institutional review boards.

Temporal trends in the ToxIC synthetic cannabinoid case entries were investigated. Mixed logistic regression was used to evaluate the association between year and annual percentage of synthetic cannabinoid cases (among total cases, any agent), by site. The lme4 package in R (R Foundation for Statistical Computing, Vienna, Austria) was used to fit the model, accounting for intrasite and intragroup (e.g., participants in ToxIC's designer drug subregistry) correlation. To evaluate model fit, a deviance test was conducted, comparing the full model to a reduced model without the year variable. Sensitivity analyses were also conducted by dropping one site at a time and refitting the model.

During January 1, 2010–November 30, 2015, a total of 42,138 cases of toxic exposure were logged by 101 participating hospitals and clinics (Figure 1). Among these, 456 cases (at 50 ToxIC sites) involved synthetic cannabinoids, either as the sole toxicologic agent (n = 277) or as a component of a multiagent exposure (n = 179). Although most sites reported <20 synthetic cannabinoid cases, large sites in Harrisburg, Pennsylvania, New York City, Phoenix, Arizona, and Rochester, New York each recorded ≥30 synthetic cannabinoid intoxication cases. In contrast, during the same period, only 13 cases were logged by ToxIC involving nonsynthetic cannabinoids (i.e., cannabis) as the sole toxicological agent; among these, the majority (n = 11) were children (aged 2–6 years) or teenagers (age 13–18 years).

Figure 1.

Toxicology Investigators Consortium (ToxIC)* registry cases caused by all agents and by synthetic cannabinoid, by U.S. registry site location§ — January 1, 2010–November 30, 2015
*ToxIC is a select, volunteer network and thus not geographically representative of the United States or the cities where participating sites are located; many sites joined ToxIC after its establishment in 2010 by the American College of Medical Toxicology.
As primary agent or part of multiagent exposure.
§As of November 2015, there were active ToxIC registry sites in 41 U.S. cities, with a few cities (e.g., Boston and New York City) having multiple sites.

Among all 456 synthetic cannabinoid intoxication cases, 322 (70.6%) occurred in persons aged 19–65 years and 125 (27.4%) occurred in persons aged 13–18 years; 379 (83.1%) patients were male. The most common street names of synthetic cannabinoids reported by patients or accompanying friends and family members were K2 and Spice. In 415 (91.0%) cases, the patient had clinical signs or symptoms of intoxication; specific toxicologic treatments were administered to 267 (58.6%) patients, whereas the rest received standard supportive care and monitoring before being discharged. No specific synthetic cannabinoid antidotes exist.

Among the 277 (61%) patients who reported synthetic cannabinoids as the sole toxicologic exposure, the system most commonly affected was the central nervous system ( Table ), manifested by agitation, central nervous system depression/coma, and delirium/toxic psychosis, with seizures and hallucinations reported less frequently. Information on death during hospitalization was available for 246 (54%) patients. Among these, three (1.2%) deaths were recorded. The first occurred in a male aged 17 years, who suffered a cardiac arrest after reportedly taking a single "hit" of K2/Spice; the second occurred in an adult male with respiratory depression, agitation, and delirium/toxic psychosis after allegedly taking a synthetic cannabinoid and oxycodone; and the third occurred in an adult male with similar signs, who developed acute kidney injury after reportedly taking a synthetic cannabinoid, a synthetic cathinone (commonly known as bath salts), and the psychedelic drug lysergic acid diethylamide (LSD).

During 2010–2015, the annual percentage of synthetic cannabinoid cases among sites increased in all four U.S. Census regions; during 2014–2015, the annual percentage increased in all regions except the South (Figure 2). The largest overall increases during these periods took place in the Northeast, primarily driven by increases at the New York City sites. Less distinct but discernable increases occurred at sites in several other cities nationwide, and a decrease occurred at the Rochester, New York, site; heterogeneous patterns occurred elsewhere (not shown). In the mixed regression analysis, the deviance test indicated that including year in the model provided a significantly (p<0.05) better fit, evidence of a statistically significant temporal trend. In the sensitivity analyses, including the year variable improved model fit in a statistically significant manner, in each iteration (i.e., when the model was refit after dropping one site at a time).

Figure 2.

Percentage of reported ToxIC* registry cases caused by synthetic cannabinoids, by U.S. Census region — 2010, 2014, and 2015
*ToxIC is a select, volunteer network and thus not geographically representative of the United States or the cities where participating sites are located; many sites joined ToxIC after its establishment in 2010 by the American College of Medical Toxicology.
Includes only cases from sites that reported any synthetic cannabinoid cases.