Selected Topics: ToxicologySynthetic Cannabinoid Intoxication: A Case Series and Review
Introduction
Synthetic cannabinoid receptor agonists are becoming increasingly popular with adolescents as an abused substance (Table 1). Teens and young adults are presenting to Emergency Departments (EDs) with effects of smoking “Spice drugs.” These Spice drugs, used to attain an “herbal high,” are an herbal mixture marketed as legal marijuana, or a legal alternative to marijuana (Table 2). They are purported to have a similar psychoactive effect as cannabis. In December 2008, a European drug monitoring system found that these herbal mixtures contained synthetic indole derivatives that affect the Cannabinoids 1/Cannabinoids 2 receptors (CB1/CB2) (1). These drugs are widely marketed in Europe, the United States, and Japan, and easily accessible from the Internet. The packaging typically describes the content as herbal incense and “not for human consumption.” Many of these drugs are much more potent than delta-9-tetrahydrocannabinol (THC), therefore, the psychoactive dose may be < 1 mg 1, 2.
Synthetic cannabinoids that have been reported in “Spice” and “Spice-like” samples in Europe are JWH-018, JWH-073, JWH-398, JWH-250; HU-210; CP-47,497 and its homologues; and oleamide. The above agonists are lipid-soluble, non-polar, with typically 20–26 carbon atoms, which are fairly volatile (3). Chronic use of these drugs can lead to addiction syndrome and withdrawal symptoms similar to cannabis abuse (3). Several European countries and, more recently, the United States (US), have placed restrictions or banned the use and sale of Spice drugs due to the dangerous effects and abuse potential of the drugs 4, 5, 6, 7. The US Drug Enforcement Administration (DEA) has temporarily designated five of these chemicals (JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol) as Schedule I substances. This action makes selling and possession of these substances illegal for at least 1 year, giving the DEA and the US Department of Health and Human Services (DHHS) time to study whether these agents will be permanently controlled in the United States (7).
The potency and psychoactive effects of these agents make them potentially addictive and hazardous compounds. We report a series of cases presenting to our ED after the use of Spice drugs and provider request of a Toxicology consult. We will provide a review of the clinical, pharmacological, and legal aspects of synthetic cannabinoids.
Section snippets
Case 1
A 19-year-old woman was brought to the ED after reportedly having a seizure. She was smoking “Bayou Blaster®” with three friends when she began having jerking motions of the extremities. When paramedics arrived, the patient was awake but agitated and required physical restraints. She arrived with altered mental status, somnolent, and would not speak to ED personnel, but would repeat periodically, “Is this real?” On physical examination, the vital signs included a blood pressure of 153/84 mm Hg,
Pharmacokinetics/Pharmacology of Synthetic Cannabinoids
To date, two endogenous cannabinoid receptors, CB1 and CB2, are well characterized. CB1 and CB2 are G i/o protein-coupled receptors (GPCRs) that inhibit adenylyl cyclase activity and thereby inhibit the conversion of Adenosine Triphosphate (ATP) to cyclic Adenosine Monophosphate (AMP). They also inhibit N- and P/Q-type calcium channels. In addition, GPCRs activate A-type and inwardly rectifying potassium channels and mitogen-activated protein kinase. Under certain conditions, CB1 receptors can
Conclusion
In conclusion, complete pharmacological knowledge of synthetic cannabinoids is lacking, and further research is needed to gain a thorough understanding of the physical and psychological impact. Our cases presented over a 3-month period and illustrate increased use in our area. The clinical presentations are serious, and most cases required ambulance transfer to the ED, all adding to the drain of health care dollars. We recommend ED observation until the patient demonstrates clinical improvement
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