Synthetic cannabinoids: Epidemiology, pharmacodynamics, and clinical implications

“K2” and “Spice” drugs (collectively hereafter referred to as Spice) represent a relatively new class of designer drugs that have recently emerged as popular alternatives to marijuana, otherwise characterized as “legal highs”. These drugs are readily available on the Internet and sold in many head shops and convenience stores under the disguise of innocuous products like herbal blends, incense, or air fresheners. Although package labels indicate “not for human consumption”, the number of intoxicated people presenting to emergency departments is dramatically increasing. The lack of validated and standardized human testing procedures and an endless supply of potential drugs of abuse are primary reasons why researchers find it difficult to fully characterize clinical consequences associated with Spice. While the exact chemical composition and toxicology of Spice remains to be determined, there is mounting evidence identifying several synthetic cannabinoids as causative agents responsible for psychoactive and adverse physical effects. This review provides updates of the legal status of common synthetic cannabinoids detected in Spice and analytical procedures used to test Spice products and human specimens collected under a variety of clinical circumstances. The pharmacological and toxicological consequences of synthetic cannabinoid abuse are also reviewed to provide a future perspective on potential short- and long-term implications.

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Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids

Congratulations to Dr. Baselt for the publication of his 10th edition and the expansion of his classic toxicology text to cover over 1,500 medications and chemicals. This enduring work provides a c...

Disposition of Toxic Drugs and Chemicals in Man

https://escholarship.org/content/qt8xh0s7nf/qt8xh0s7nf.pdf?t=oyg19p

Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review

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.

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Beyond THC: The New Generation of Cannabinoid Designer Drugs

A sensitive method for identifying and quantifying brucine by means of liquid chromatography-tandem mass spectrometry is presented in this article. Based on a solid-phase extraction for human serum, the validation indicated limits of detection and quantification of 0.12 and 0.23 ng/mL, respectively. In one case of lethal suicidal brucine monointoxication, brucine concentrations of 1.51 μg/mL, 1.69 μg/mL, 9.94 μg/mL, 16.4 μg/g, 0.99 μg/g, 0.75 μg/g, and 1.95 mg/g were determined in femoral blood, urine, bile collected from the gallbladder, liver tissue, cerebellum, cerebrum, and stomach contents, respectively.

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Fatal Intoxication Due to Brucine

Mixed consumption of cannabis and "Spice".

Sir, The relative long cocaine distribution chain is responsible for cocaine dilution with different cheaper components used as adulterants such as hydroxyzine, lidocaine, procaine, benzocaine, caffeine, boric acid, phenacetin, and levamisole (1). This psychoactive substance modification leads to a weight increase and in consequence to higher profits. Among these adulterants, levamisole gained a lot of attention in recent years, as this drug was reported as especially dangerous to cocaine consumers due to its numerous side effects on human health (agranulocytosis, ANCA-associated vasculitis, retiform purpura, and others) (2,3). Levamisole as an imidazothiazole derivative used to be applied as a veterinary anthelminthic medication but also to treat pediatric nephritic syndrome and rheumatoid arthritis (2). The reason for combining cocaine with levamisole is still unknown. It is believed that levamisole is added directly during cocaine manufacture to potentiate its effects. The prevalence of levamisole-adultered cocaine was investigated recently in North America and was reported to be as high as 88% (4). In this letter, we wanted to report the results of our study concerning the investigation of the levamisole prevalence in cocaine-positive blood samples analyzed in our laboratory and collected during police traffic controls. For these purposes, the LC-MS/MS analytical method used in the routine for the analysis of cocaine and its metabolites was modified to make a qualitative levamisole analysis possible simultaneously. Samples, which contained at least 1 ng/mL benzoylecgonine (cocaine metabolite), were defined as cocaine-positive samples and used in the data evaluation for the purpose of the levamisole prevalence determination. The analysis of 133 cocaine-positive samples in the stretch of 3 months (July–September 2014) revealed that 111 were also positive for levamisole, which equals in a levamisole prevalence of 83%. The LC-MS/MS analytical method applied for the qualitative analysis of levamisole based on the detection of two mass transitions (multiple reaction monitoring mode: 204.9/178.1 for the target and 204.9/123.0 for the qualifier) and was characterized by a limit of detection of 0.14 ng/mL. The presented study revealed that levamisole is present in the majority of cocaine consumed in Lower Saxony. The obtained prevalence was comparable with the data presented by Lynch et al. for cocaine samples in North America. Therefore, this drug has to be considered not only by clinicians in cocaine users with unexpected symptoms such as otherwise unexplained agranulocytosis (5) but also by forensic pathologists in their expertise (2). As the prevalence of levamisole seems to be quite high, and furthermore, different adverse effects of this drug are well known and documented, the application of analytical methods which detect not only cocaine and its metabolites but additionally levamisole can be very useful. Additionally, it has to be considered that the knowledge about adulterants in all illicit drugs and their effect on human health is very important and has a big impact on the correct data interpretation in the forensic/ clinical expertise.

Letter to the Editor—Consumption of Levamisole in Cocaine Preparations

A liquid chromatography–tandem mass spectrometry (LC–MS/MS) quantification method based on a direct protein precipitation with the mobile phase was developed, validated and applied for the analysis of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in human serum for forensic purposes. Chromatographic separation was performed with a Luna 5 µm C18 (2) 100 A, 150 × 2 mm analytical column and the elution with a programmed flow of a mobile phase consisting of A (H2O/methanol, 95:5, v/v) and B (H2O/methanol, 3:97, v/v), both with 10 mM ammonium acetate and 0.1 % acetic acid. The results of the validation experiments demonstrated that the strategy presented can be applied successfully for a fast, simple and cost effective LC–MS/MS analysis of THC and its metabolites. A potential conversion of THC-COOH glucuronide to THC-COOH during sample preparation/analysis could be excluded.

Simple protein precipitation-based analysis of Δ9-tetrahydrocannabinol and its metabolites in human serum by liquid chromatography–tandem mass spectrometry

Sarah Kohls, Barbara M Scholz-Böttcher, Jörg Teske & Jürgen Rullkötter* Institute for Chemistry and Biology of the Marine Environment (ICBM), Carl von Ossietzky University of Oldenburg, Carl-von-Ossietzky-Str. 9-11, D-26129 Oldenburg, Germany Landeskriminalamt Niedersachsen, Kriminaltechnisches Institut, Schützenstraße 25, D-30161 Hannover, Germany Institute of Legal Medicine of the Hannover Medical School (MHH), Carl-Neuberg-Str. 1, D-30625 Hannover, Germany E-mail: j.rullkoetter@icbm.de

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Jörg Teske

Papers

Fatal Intoxication Due to Brucine

Mixed consumption of cannabis and "Spice".

Letter to the Editor—Consumption of Levamisole in Cocaine Preparations

Simple protein precipitation-based analysis of Δ9-tetrahydrocannabinol and its metabolites in human serum by liquid chromatography–tandem mass spectrometry

Isolation and quantification of six cardiac glycosides from the seeds of Thevetia peruviana provide a basis for toxological survey