Notes from the Field: Severe Illness Associated with Reported Use of Synthetic Cannabinoids — Mississippi, April 2015

Amelia M. Kasper, MD1,2; Alison D. Ridpath, MD2; Justin K. Arnold, DO3; Kevin Chatham-Stephens, MD1,2; Melissa Morrison, MPH4; Olaniyi Olayinka, MD1,2; Christina Parker5; Robert Galli, MD6; Robert Cox, MD, PhD5; Nykiconia Preacely, DrPH4,7; Jannifer Anderson7; Patrick B. Kyle, PhD6; Roy Gerona, PhD8; Colleen Martin, MSPH2; Josh Schier, MD2; Amy Wolkin, DrPH2; Thomas Dobbs, MD7

On April 2, 2015, four patients were evaluated at the University of Mississippi Medical Center (UMMC) in Jackson, Mississippi, for agitated delirium after using synthetic cannabinoids. Over the next 3 days, 24 additional persons went to UMMC with illnesses suspected to be related to synthetic cannabinoid use; one patient died. UMMC notified the Mississippi State Department of Health, which issued a statewide alert via the Health Alert Network on April 5, requesting that health care providers report suspected cases of synthetic cannabinoid intoxication to the Mississippi Poison Control Center (MPCC). A suspected case was defined as the occurrence of at least two of the following symptoms: sweating, severe agitation, or psychosis in a person with known or suspected synthetic cannabinoid use. A second statewide alert was issued on April 13, instructing all Mississippi emergency departments to submit line lists of suspected patients to MPCC each day. By April 21, 16 days after the first alert was issued, MPCC had received reports of approximately 400 cases, including eight deaths possibly linked to synthetic cannabinoid use; in contrast, during April 2012–March 2015, the median number of telephone calls to MPCC regarding synthetic cannabinoid use was one per month (range = 0–11). The Mississippi State Department of Health, with the assistance of CDC, initiated an investigation to better characterize the outbreak, identify risk factors associated with severe illness, and prevent additional illnesses and deaths.

During April 2–May 3, 2015, MPCC received reports of 721 suspected cases, including nine deaths associated with synthetic cannabinoid use. The weekly number of reports peaked at 214 reports during April 16–23. A majority of counties in the state (48 of 82 [59%]) reported at least one case. The investigative team chose the UMMC patient population as a convenience sample to better understand the characteristics of the illness. Using MPCC data, the Mississippi State Department of Health and CDC identified suspected cases among patients who received care at UMMC. The team then reviewed emergency medical service reports, electronic medical records, and MPCC records to collect information about reported synthetic cannabinoid use, initial symptoms, vital signs, physical examination findings, clinical laboratory data, illness course, treatments given, and disposition. Clinical specimens were sent to the Clinical Toxicology and Environmental Biomonitoring Laboratory at the University of California, San Francisco, for liquid chromatography-quadrupole time-of-flight mass spectrometry, which tests for 109 different synthetic cannabinoids and metabolites.

Among the 721 suspected cases, 119 (17%) patients received care at UMMC; all 119 medical records were abstracted. Patients ranged in age from 14 to 62 years (median = 31 years), and 101 (85%) were male. Eighty-three patients (70%) were treated and released by the UMMC emergency department. Thirteen (11%) patients were admitted to general inpatient services, and 12 (10%) were admitted to intensive care services. Three patients (3%) died at UMMC. Vital signs information was available for 115 patients, of whom 48 (42%) had tachycardia (heart rate >100 beats per minute), and 35 (30%) had elevated (>140 mmHg) systolic blood pressure. Among all 119 patients, 38 (32%) exhibited aggressive or violent behavior, and 30 (25%) showed confusion. Sixteen (13%) patients were reported to have both agitation/aggression and depressed mental status (e.g., somnolence or unresponsiveness). Univariable analysis showed significant associations between a previous medical history of mental illness (odds ratio = 4.4; 95% confidence interval = 1.4–14.2) or substance abuse (odds ratio = 5.0; 95% confidence interval = 1.5–16.0), and more severe outcomes (intensive care admission or death).

Among 89 patients who had urine drug screen results at UMMC, 60 (67%) were positive for tetrahydrocannabinol (THC), the main psychoactive component in cannabis. Nineteen (21%) were positive for cocaine. Synthetic cannabinoids cannot be detected on routine, clinical urine drug screens. Among the 16 serum specimens tested at the University of California, San Francisco, to date, 10 (63%) have tested positive for a recently described synthetic cannabinoid or one of its predicted metabolites.* Four (25%) specimens were positive for other substances, including benzodiazepines (three), opioids (two), phencyclidine (one), and mitragynine (one), a plant-based opioid agonist that is currently legal in Mississippi. Results are pending from specimens from an additional 75 patients from UMMC and 143 patients from other Mississippi hospitals.

The current outbreak of illnesses associated with synthetic cannabinoid use in Mississippi is part of a larger, multistate outbreak (1). To date, this is the largest outbreak of synthetic cannabinoid–associated adverse events ever recorded (2–4). Synthetic cannabinoids represent a wide variety of compounds that bind with variable affinities to the cannabinoid receptor; in general, they are stronger cannabinoid receptor agonists compared with THC. The effects of synthetic cannabinoids vary by type. As novel synthetic cannabinoids continue to be developed and trafficked, health care providers, public health officials, laboratory scientists, and law enforcement officials should continue to work together to identify strategies to curb synthetic cannabinoid use, strengthen surveillance in order to detect and monitor outbreaks, and optimize patient care.

Acknowledgments

Paul Byers, MD, Theresa Kittle, MPH, Joy Sennett, MHS, Nora Truhett, Sheryl Hand, Mississippi State Department of Health; Mark LeVaughn, MD, Mississippi State Medical Examiner's Office; University of Mississippi Medical Center's Office of Integrity and Compliance; Royal Law, MPH, Division of Environmental Hazards and Health Effects, National Center for Environmental Health, CDC.

1Epidemic Intelligence Service, CDC; 2Division of Environmental Hazards and Health Effects, National Center for Environmental Health, CDC; 3Georgia Poison Center; 4Career Epidemiology Field Officer, CDC ; 5Mississippi Poison Center; 6University of Mississippi Medical Center; 7Mississippi State Department of Health; 8Department of Laboratory Medicine, University of California San Francisco.

Corresponding author: Amelia Kasper, akasper@cdc.gov, 770-488-3433.

References

1. Law R, Schier J, Martin C, et al. Notes from the field: increase in reported adverse health effects related to synthetic cannabinoids—United States, January–May 2015. MMWR Morb Mortal Wkly Rep 2015;62:618–9.
2. CDC. Notes from the field: severe illness associated with reported use of synthetic marijuana—Colorado, August–September 2013. MMWR Morb Mortal Wkly Rep 2013;62:1016–7.
3. CDC. Acute kidney injury associated with synthetic cannabinoid use—multiple states, 2012. MMWR Morb Mortal Wkly Rep 2013;62:93–8.
4. CDC. Notes from the field: severe illness associated with synthetic cannabinoid use—Brunswick, Georgia, 2013. MMWR Morb Mortal Wkly Rep 2013;62:939.