Journal Article•
Acute Kidney Injury Associated with Synthetic Cannabinoid Use — Multiple States, 2012
15 Feb 2012-Morbidity and Mortality Weekly Report (Department of Health and Human Services)-Vol. 62, Iss: 6, pp 93-98
TL;DR: The results of the investigation determined that no single SC brand or compound explained all 16 cases, and public health practitioners, poison center staff members, and clinicians should be aware of the potential for renal or other unusual toxicities in users of SC products and should ask about SC use in cases of unexplained AKI.
Abstract: In March 2012, the Wyoming Department of Health was notified by Natrona County public health officials regarding three patients hospitalized for unexplained acute kidney injury (AKI), all of whom reported recent use of synthetic cannabinoids (SCs), sometimes referred to as \"synthetic marijuana.\" SCs are designer drugs of abuse typically dissolved in a solvent, applied to dried plant material, and smoked as an alternative to marijuana. AKI has not been reported previously in users of SCs and might be associated with 1) a previously unrecognized toxicity, 2) a contaminant or a known nephrotoxin present in a single batch of drug, or 3) a new SC compound entering the market. After the Wyoming Department of Health launched an investigation and issued an alert, a total of 16 cases of AKI after SC use were reported in six states. Review of medical records, follow-up interviews with several patients, and laboratory analysis of product samples and clinical specimens were performed. The results of the investigation determined that no single SC brand or compound explained all 16 cases. Toxicologic analysis of product samples and clinical specimens (available from seven cases) identified a fluorinated SC previously unreported in synthetic marijuana products: (1-(5-fluoropentyl)-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl) methanone, also known as XLR-11, in four of five product samples and four of six patients' clinical specimens. Public health practitioners, poison center staff members, and clinicians should be aware of the potential for renal or other unusual toxicities in users of SC products and should ask about SC use in cases of unexplained AKI.
Citations
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TL;DR: A comprehensive review, based on a systematic electronic literature search, of SC epidemiology and pharmacology and their clinical implications is presented, showing in vitro and animal in vivo studies show SC pharmacological effects 2-100 times more potent than THC.
549 citations
TL;DR: Survivors of AKI, particularly those who remain on renal replacement therapy, often have reduced quality of life and consume substantially greater health-care resources than the general population as a result of longer hospitalizations, unplanned intensive care unit admissions and rehospitalizations.
Abstract: Acute kidney injury (AKI) is a widespread problem of epidemic status. Compelling evidence indicates that the incidence of AKI is rapidly increasing, particularly among hospitalized patients with acute illness and those undergoing major surgery. This increase might be partially attributable to greater recognition of AKI, improved ascertainment in administrative data and greater sensitivity of consensus diagnostic and classification schemes. Other causes could be an ageing population, increasing incidences of cardiovascular disease, diabetes mellitus and chronic kidney disease (CKD), and an expanding characterization of modifiable risk factors, such as sepsis, administration of contrast media and exposure to nephrotoxins. The sequelae of AKI are severe and characterized by increased risk of short-term and long-term mortality, incident CKD and accelerated progression to end-stage renal disease. AKI-associated mortality is decreasing, but remains unacceptably high. Moreover, the absolute number of patients dying as a result of AKI is increasing as the incidence of the disorder increases, and few proven effective preventative or therapeutic interventions exist. Survivors of AKI, particularly those who remain on renal replacement therapy, often have reduced quality of life and consume substantially greater health-care resources than the general population as a result of longer hospitalizations, unplanned intensive care unit admissions and rehospitalizations.
539 citations
TL;DR: Clinical trials with globally acting CB1 antagonists in obesity/metabolic syndrome, and other studies with peripherally‐restricted CB1/2 agonists and inhibitors of the endocannabinoid metabolizing enzyme in pain, have introduced unexpected complexities, suggesting that a better understanding of the pathophysiological role of the ENDOCannabinoid system is required to devise clinically successful treatment strategies.
Abstract: The discovery of the endocannabinoid system, comprising the G-protein coupled cannabinoid 1 and 2 receptors (CB1/2), their endogenous lipid ligands or endocannabinoids, and synthetic and metabolizing enzymes, has triggered an avalanche of experimental studies implicating the endocannabinoid system in a growing number of physiological/pathological functions. These studies have also suggested that modulating the activity of the endocannabinoid system holds therapeutic promise for a broad range of diseases, including neurodegenerative, cardiovascular and inflammatory disorders; obesity/metabolic syndrome; cachexia; chemotherapy-induced nausea and vomiting; and tissue injury and pain, amongst others. However, clinical trials with globally acting CB1 antagonists in obesity/metabolic syndrome, and other studies with peripherally-restricted CB1/2 agonists and inhibitors of the endocannabinoid metabolizing enzyme in pain, have introduced unexpected complexities, suggesting that a better understanding of the pathophysiological role of the endocannabinoid system is required to devise clinically successful treatment strategies.
329 citations
TL;DR: To identify systematically the scientific reports of adverse events associated with the consumption of SCs in the medical literature and poison centre data, this work searched online databases and manually searched reference lists up to December 2014 to identify eligible studies.
Abstract: Context: Synthetic cannabinoids (SCs) such as “Spice”, “K2”, etc. are widely available via the internet despite increasing legal restrictions. Currently, the prevalence of use is typically low in the general community (<1%) although it is higher among students and some niche groups subject to drug testing. Early evidence suggests that adverse outcomes associated with the use of SCs may be more prevalent and severe than those arising from cannabis consumption. Objectives: To identify systematically the scientific reports of adverse events associated with the consumption of SCs in the medical literature and poison centre data. Method: We searched online databases (Medline, PsycInfo, Embase, Google Scholar and Pubmed) and manually searched reference lists up to December 2014. To be eligible for inclusion, data had to be from hospital, emergency department, drug rehabilitation services or poison centre records of adverse events involving SCs and included both self-reported and/or analytically confirme...
296 citations
TL;DR: With the legalization of marijuana for medicinal purposes and/or recreational use in many countries, physicians should be alert to the possibility that the use of marijuana or its potent synthetic analogues might be the underlying cause of severe cardiovascular events and pathologies.
Abstract: Dysregulation of the endogenous lipid mediators endocannabinoids and their G-protein-coupled cannabinoid receptors 1 and 2 (CB1R and CB2R) has been implicated in a variety of cardiovascular pathologies. Activation of CB1R facilitates the development of cardiometabolic disease, whereas activation of CB2R (expressed primarily in immune cells) exerts anti-inflammatory effects. The psychoactive constituent of marijuana, Δ9-tetrahydrocannabinol (THC), is an agonist of both CB1R and CB2R, and exerts its psychoactive and adverse cardiovascular effects through the activation of CB1R in the central nervous and cardiovascular systems. The past decade has seen a nearly tenfold increase in the THC content of marijuana as well as the increased availability of highly potent synthetic cannabinoids for recreational use. These changes have been accompanied by the emergence of serious adverse cardiovascular events, including myocardial infarction, cardiomyopathy, arrhythmias, stroke, and cardiac arrest. In this Review, we summarize the role of the endocannabinoid system in cardiovascular disease, and critically discuss the cardiovascular consequences of marijuana and synthetic cannabinoid use. With the legalization of marijuana for medicinal purposes and/or recreational use in many countries, physicians should be alert to the possibility that the use of marijuana or its potent synthetic analogues might be the underlying cause of severe cardiovascular events and pathologies.
273 citations
References
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TL;DR: An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology, and safety.
Abstract: Synthetic cannabinoids are functionally similar to delta9-tetrahydrocannabinol (THC), the psychoactive principle of cannabis, and bind to the same cannabinoid receptors in the brain and peripheral organs. From 2008, synthetic cannabinoids were detected in herbal smoking mixtures sold on websites and in “head shops” under the brand name of Spice Gold, Yucatan Fire, Aroma, and others. Although these products (also known as “Spice drugs” or “legal highs”) do not contain tobacco or cannabis, when smoked they produce effects similar to THC. Intoxication, withdrawal, psychosis and death have been recently reported after consumption, posing difficult social, political and health challenges. More than 140 different Spice products have been identified to date. The ability to induce strong cannabis-like psychoactive effects, along with the fact that they are readily available on the Internet, still legal in many countries, marketed as natural safe substances, and undetectable by conventional drug screening tests, has rendered these drugs very popular and particularly appealing to young and drug-naive individuals seeking new experiences. An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology and safety. Since legislation started to control the synthetic cannabinoids identified in these herbal mixtures, many new analogs have appeared on the market. New cannabimimetic compounds are likely to be synthesized in the near future to replace banned synthetic cannabinoids, leading to a “dog chasing its tail” situation. Spice smokers are exposed to drugs that are extremely variable in composition and potency, and are at risk of serious, if not lethal, outcomes. Social and health professionals should maintain a high degree of alertness for Spice use and its possible psychiatric effects in vulnerable people.
400 citations
"Acute Kidney Injury Associated with..." refers background in this paper
...The expectation of a more intense high than that induced by marijuana, easy access, affordability, and avoidance of detection by many commonly used urine drug tests all contribute to the growing abuse of SCs, especially among male adolescents (1,5)....
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...” Today, SC products are distributed worldwide under countless trade names and packaged in colorful wrappers designed to appeal to teens, young adults, and first-time drug users (1)....
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TL;DR: Ingestion of JWH-018 can produce seizures and tachyarrhythmias, and Clinicians, lawmakers, and the general public need to be aware of the potential for toxicity associated with synthetic cannabinoid use.
Abstract: Objective. To report a case of seizures and supraventricular tachycardia (SVT) following confirmed synthetic cannabinoid ingestion. Background. Despite widespread use of legal synthetic cannabinoids, reports of serious toxicity following confirmed use of synthetic cannabinoids are rare. We report severe toxicity including seizures following intentional ingestion of the synthetic cannabinoid JWH-018 and detail confirmation by laboratory analysis. Case Report. A healthy 48 year old man had a generalized seizure within thirty minutes of ingesting an ethanol mixture containing a white powder he purchased from the Internet in an attempt to get high. Seizures recurred and abated with lorazepam. Initial vital signs were: pulse, 106/min; BP, 140/88 mmHg; respirations, 22/min; temperature, 37.7 °C. A noncontrast computed tomography of the brain and EEG were negative, and serum chemistry values were normal. The blood ethanol concentration was 3.8 mg/dL and the CPK 2,649 U/L. Urine drug screening by EMIT was negativ...
195 citations
"Acute Kidney Injury Associated with..." refers background in this paper
...The increasing use of SCs by young persons, coupled with mounting evidence of adverse health effects, has led to state and federal legislation (3,6)....
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TL;DR: Most exposures to Δ-9-tetrahydrocannabinol homologs resulted in non-life-threatening effects not requiring treatment, although a minority of exposures resulted in more severe effects, including seizures.
178 citations
TL;DR: Compared to marijuana, synthetic cannabinoid exposures were more likely to been used through inhalation, to involve adults, to be used at a residence, and to result in serious outcomes.
Abstract: Synthetic cannabinoids have recently gained popularity as a recreational drug because they are believed to result in a marijuana-like high. This investigation compared synthetic cannabinoids and marijuana exposures reported to a large statewide poison center system. Synthetic cannabinoid and marijuana exposures reported to Texas poison centers during 2010 were identified. The distribution of exposures to the two agents with respect to various demographic and clinical factors were compared by calculating the rate ratio (RR) of the synthetic cannabinoid and marijuana percentages for each subgroup and 95% confidence interval (CI). The proportion of synthetic cannabinoid and marijuana exposures, respectively, were 87.3% and 46.5% via inhalation (RR 1.88, 95% CI 1.38-2.61), 74.9% and 65.7% in male (RR 1.14, 95% CI 0.87-1.51), 40.2% and 56.6% age ≤ 19 years (RR 0.71, 95% CI 0.52-0.98), 79.2% and 58.6% occurring at a residence (RR 1.35, 95% CI 1.02-1.82), 8.4% and 16.2% managed on-site (RR 0.52. 95% CI 0.28-1.00), and 59.3% and 41.4% with serious medical outcomes (RR 1.43, 95% CI 1.03-2.05). Compared to marijuana, synthetic cannabinoid exposures were more likely to be used through inhalation, to involve adults, to be used at a residence, and to result in serious outcomes.
112 citations
"Acute Kidney Injury Associated with..." refers background in this paper
..., tachycardia and hypertension), and approximately five times more likely to be associated with hallucinations (8)....
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TL;DR: A rapid ultra-performance liquid chromatography-tandem mass spectrometry method that has been applied to postmortem forensic casework received by the laboratory and has proven to be robust and reliable in determining trace concentrations of synthetic cannabinoids in human blood.
Abstract: Synthetic cannabinoids have been detected in various herbal blends sold legally in convenience stores, smoke shops, and on the Internet. Many of these compounds have extreme forensic significance. We developed and validated a rapid ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of trace concentrations of two of these compounds, JWH-018 and JWH-073, in human blood. Samples underwent liquid-liquid extraction at pH 10.2 into ethyl ether. Tandem mass spectrometry was performed in positive electrospray ionization mode with multiple reaction monitoring using two transitions and one calculated ion transition ratio for each analyte. Deuterated analogs were used as internal standards. Total run time was 2.6 min. The linear dynamic range was 0.05-50 ng/mL with a limit of detection of 0.01 ng/mL for each analyte. Intra-run imprecision (at two different concentration levels, 2 and 8 ng/mL) was 3.9-10.3% for JWH-018 and 3.5-6.2% for JWH-073. Inter-run imprecision was 6.5-7.2% for JWH-018 and 4.8-5.5% for JWH-073. Intra-run accuracy was 95.9-112.7% for JWH-018 and 92.6-104.7% for JWH-073. Inter-run accuracy was 99.1-107.0% for JWH-018 and 97.7-102.0% for JWH-073. Carryover, exogenous drug interferences, ion suppression and matrix selectivity were also assessed. The method has been applied to postmortem forensic casework received by the laboratory and has proven to be robust and reliable. Concentrations of authentic samples have ranged from 0.1-199 ng/mL for JWH-018 and 0.1-68.3 ng/mL for JWH-073.
105 citations