Designer drugs have been problematic over the years. Products such as K2 and Spice, which contain synthetic cannabinoids, are marketed as incense and are widely available on the Internet and at various specialty shops. The effects are reported as cannabis-like after smoking them. In addition, use of these synthetic cannabinoids will not appear on a routine urine toxicology screen. Recently, K2 became a popular alternative to marijuana among youths. Health implications of these designer drugs are not completely understood. Little has been reported about the harmful effects of K2. We report here the first (to our knowledge) cases of myocardial infarction (MI) after smoking K2. Three patients presented separately to the emergency department complaining of chest pain within days after the use of K2. Acute MI was diagnosed in each case on the basis of electrocardiogram changes and elevated troponin levels. Coronary angiography was performed, and the results were normal for the first 2 patients. The incidence of ST-elevation MI is low among teenagers, and association with drug use should be suspected. Public education and awareness need to be heightened about the possible health implications of K2.
K2 (Dallas, Texas, manufacturer unknown) is a collection of herbs and spices that have been treated with synthetic cannabinoids that, when smoked, provides a marijuana-like effect. Although marketed as an incense blend, K2 has recently become a popular alternative to marijuana, likely because of its widespread availability and undetectable nature on routine urine drug screens (UDSs).1 A variety of synthetic cannabinoids included in this herbal blend, the most common of which is JWH-018, have been described. John W. Huffman (JWH) originally developed JWH-018 and other synthetic cannabinoids at Clemson University in 1995 as part of his research into the effects of cannabinoids on the brain and peripheral receptors and possible medical uses for tetrahydrocannabinol (THC) analogues.2
Increased use of K2 was first noticed in Europe in 2008.3,4 The physiologic effects of K2, Spice (Dallas, Texas, manufacturer unknown), and similar products are reportedly stronger than natural cannabis.3,4 There is a lack of information about the complete chemical composition and toxicology of the chemicals contained in these products. Chemical analysis of these herbal mixtures has revealed various synthetic cannabinoids including JWH-018, JWH-073, JWH-398, JWH-250, HU-210, and CP-47 497, among others.3,–,5 Although myocardial infarction (MI) has been reported after marijuana use,6 the health effects and toxicity of synthetic cannabinoids contained in K2 and Spice products have not been clearly defined.
We report here 3 cases of ST-elevation MI associated with recent exposure to the synthetic cannabis product K2.
A previously healthy 16-year-old male high school athlete presented with a 3-day history of midsternal chest pain. The initial electrocardiogram (ECG) revealed ST-segment elevation in the inferolateral leads (Fig 1), and his initial troponin level was 3 ng/mL (normal: <0.4 ng/mL). He admitted to smoking K2 1 day before presentation and marijuana in the previous 3 weeks. An echocardiogram revealed normal function, no segmental wall-motion abnormalities, and normal coronary artery origins. On hospital day 2 he complained of worsening chest pain. An ECG revealed more pronounced ST-segment elevations, and his troponin level increased to 25 ng/mL. Emergent coronary angiography revealed normal coronary arteries. His UDS was positive for δ-9-THC on admission.
A 16-year-old boy presented with a 1-week history of chest pain. He described the chest pain as episodes of “soreness,” each of which lasted for ∼30 minutes. An episode of severe chest pain prompted his visit to the emergency department. An ECG revealed ST-segment elevation in the inferolateral leads (Fig 2), and his initial troponin level was 11.6 ng/mL. An echocardiogram revealed normal function, no segmental wall-motion abnormalities, and normal coronary artery origins. He admitted to smoking marijuana 2 weeks before presentation, but he had smoked K2 3 days before presenting with chest pain. His UDS was negative for cannabis and cocaine. Coronary angiography revealed normal coronary arteries.
A 16-year-old boy presented with a 3-day history of chest pain. The pain was retrosternal and episodic, lasting for 1 to 2 hours at a time. The initial ECG revealed ST-segment elevation (Fig 3), and he was found to have an elevated troponin level of 7 ng/mL. Although he smoked marijuana occasionally, his most recent use was 3 weeks before presentation. He admitted to more recent K2 use (1 week before the onset of chest pain). Echocardiography results were normal, and his troponin level peaked at 12 ng/mL during his hospital admission. His UDS was positive for THC. Urine testing for 2 synthetic cannabinoid metabolites (JWH-018 and JWH-O73) was performed, and the results were negative.
Chest pain is a common complaint among adolescents presenting to emergency departments.7 Ischemic chest pain in the pediatric population is uncommon, and MI is exceedingly rare.7 Among drugs of abuse, marijuana and cocaine have led to MI in adolescents.6,–,8
It is well known that marijuana has pathophysiological effects on the cardiovascular system. The physiologic effects of THC are mediated by stimulation of the sympathetic nervous system through release of norepinephrine9 and also by parasympathetic blockade. THC has been shown to increase cardiac output by as much as 30%.10 Marijuana use can increase the heart rate from 20% to 100% in a dose-dependent manner, which leads to increased oxygen demands on the myocardium. Heart-rate increases start in the first 10 minutes after smoking and last up to 3 hours.11,–,16 Smoking marijuana also leads to an increase in carboxyhemoglobin levels, which results in a decrease in oxygen-carrying capacity.10,15 Interference with the integrity of peripheral vascular response has been postulated to be one of the pathophysiological mechanisms for cardiac events during cannabis smoking.10
First described by Bachs and Mørland16 in 1979, several cases of MI associated with marijuana use have been reported in the literature, and most patients had normal coronary arteries.6,16 In an autopsy study from Norway, THC was the only drug found in postmortem samples from 6 patients who had sustained unexplained sudden death,16 which suggests an association between THC exposure and sudden death. Myocardial ischemia, ventricular tachycardia, and fibrillation have all been linked to marijuana use.11,12 A cross-over study by Mittleman et al11 found that marijuana use increases the risk of MI 4.8 times in the first hour after use. The vasoconstrictor effect of marijuana has been also been postulated to be responsible for both transient ischemic events and strokes.17,18 Few data are available about the pharmacodynamics and pharmacokinetics of synthetic cannabinoids. They have been studied in vitro, but human data regarding adverse clinical effects and duration of effects remain largely unknown. The herbs in the incense blend of K2 are also largely unknown, and their contribution to clinical effects is unclear.
All of our patients were healthy adolescents with no significant past medical history or family history of premature cardiac disease. All 3 patients presented within a 3-month time period, and patients 1 and 2 presented within 2 weeks of each other. It is unknown if these 3 cases involved the same “batch” of synthetic K2. It is interesting to note that, with the exception of the THC found in patients 1 and 3, results of the UDS in all 3 cases were negative (including for cocaine and amphetamines). All 3 patients had normal physical examinations and vital signs that remained within normal limits throughout their hospital stays. Although all 3 patients reported smoking marijuana occasionally, they also gave history of smoking K2 in the days before the onset of chest pain, which suggests an association between K2 and acute MI. The dose of synthetic cannabinoid inhaled by our patients is not known, and it is not known if other vasoactive substances were present in the K2. Synthetic cannabinoids have a higher binding affinity for cannabinoid receptors, which causes higher potency and clinical effects.3,4 Marijuana use is quite common among teenagers. According to the National Survey on Drug Use and Health in 2009, 16.7 million Americans aged 12 or older used marijuana at least once per month. Few cases of MI in proximity to smoking marijuana among healthy teenagers have been reported, which suggests that either K2 or K2 in combination with marijuana was a possible inciting factor for MI in these healthy teenagers.
Specialized testing for synthetic cannabinoids was only attempted in case 3. Although results of the UDS for synthetic cannabinoid metabolites were negative in that case (urine was tested for JWH-018 and JWH-073 by a commercial laboratory), the limited number of analytes tested for raises the possibility that other analytes could have been present. Of the compounds tested for, few synthetic cannabinoids can be detected of the hundreds that have been developed over the years. Makers of synthetic drugs have the advantage of knowing which analytes are detectable by current methods, which allows them to stay “ahead of the curve” by altering the drug's chemical composition. It is entirely possible that analytes not tested for could be responsible for the physiologic effects seen in our patients. Unlike marijuana, we do not have sufficient data regarding the excretion of K2 metabolites and the length of time that UDS results will remain positive after K2 use.
These cases bring attention to the possible adverse health effects of synthetic cannabinoids. According to the American Association of Poison Control Centers' National Poison Data System, poison centers received 2869 calls in 2010 that involved use of different synthetic marijuana products.19 One hundred eighty-six calls about exposure to synthetic cannabis were made to the Texas Poison Center Network in the year 2011. The most common complaints included increased heart rate, elevated blood pressure, chest pain, and nausea. Lack of information regarding the origin of these compounds as well as other chemicals possibly contained in these products makes their use dangerous and unpredictable. The US Drug Enforcement Administration (DEA) recently used its emergency scheduling authority to temporarily control 5 chemicals (JWH-018, JWH-073, JWH-200, CP-47497, and cannabicyclohexanol).20 This ruling will make the sale and possession of these products illegal for at least for 1 year. As of May 4, 2011, 28 states have taken action, either administratively or through enacted legislation, to ban chemical substances related to synthetic cannabinoids. Currently, 35 states have legislation pending, including states that currently have administrative bans in place.21 Despite these steps, K2 is still readily available in many parts of the United States and on the Internet. Commercial laboratories are developing additional testing for synthetic cannabinoid metabolites because of the rapidly evolving nature of this issue. Until there is permanent legislation in place to ban these substances and effective screening tests for their use, these products will continue to be popular among teenagers and young adults.
Although chest pain is a common presenting complaint of teenagers seen in emergency departments, chest pain from cardiac causes remains exceedingly rare. Use of illicit drugs causing chest pain and myocardial ischemia, however, must remain part of the differential diagnosis. Because synthetic cannabinoids do not currently show on routine toxicology screening tests, careful questioning is necessary to elicit a history of exposure to K2 or similar products. Pediatricians and other health care providers in primary care, specialty care, and urgent/emergency care settings should be on alert for drug-induced toxicities despite negative drug-screen results. These cases should be reported not only to local health authorities but also to national-level authorities including poison control centers and the Drug Enforcement Administration. Further research is needed to evaluate the toxic effects of these synthetic cannabinoids. Education for parents, health care workers, and adolescents about the potential health risks from using these products is essential. K2 is not safe, undetectable fake marijuana but, rather, a potent and potentially harmful drug of abuse.
- Accepted June 28, 2011.
- Address correspondence to Arshid Mir, MD, Division of Pediatrics, Department of Cardiology, UT Southwestern Medical Center, 1935 Medical District Dr, Dallas, TX 75235. E-mail:
Drs Mir and Obafemi wrote the initial draft of the article, and Drs Young and Kane helped with the initial draft and revised the final draft.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
- UDS —
- urine drug screen
- JWH —
- John W. Huffman
- THC —
- MI —
- myocardial infarction
- ECG —
US Department of Justice, Drug Enforcement Administration. Schedules of controlled substances: temporary placement of five synthetic cannabinoids into schedule I. Available at: www.deadiversion.usdoj.gov/fed_regs/rules/2011/fr0301.htm. Accessed August 1, 2011
Clemson University. John W. Huffman. Available at: www.clemson.edu/chemistry/people/huffman.html. Accessed August 1, 2011
- Sobolevsky T,
- Prasolov I,
- Rodchenkov G
- Selbst SM,
- Ruddy R,
- Clark BJ
- Mittleman MA,
- Lewis RA,
- Maclure M,
- Sherwood JB,
- Muller JE
- Renualt PF,
- Schuster CR,
- Heinrich R,
- Freeman DX
- Lawson TM,
- Rees A
American Association of Poison Control Centers. Fake marijuana spurs more than 4,500 calls to U.S. poison centers [press release]. Available at: www.aapcc.org/dnn/Portals/0/prrel/revisedk2releaseapril20.pdf. Accessed August 1, 2011
US Department of Justice, Drug Enforcement Administration. DEA moves to emergency control synthetic marijuana [press release]. Available at: www.justice.gov/dea/pubs/pressrel/pr112410.html. Accessed February 10, 2011
National Conference of State Legislatures. Synthetic cannabinoids legislation. Available at: www.ncsl.org/?Tabid=22431. Accessed August 1, 2011
- Copyright © 2011 by the American Academy of Pediatrics