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

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.

/pdf/beyond-thc-the-new-generation-of-cannabinoid-designer-drugs-1ak6oxs9fw.pdf

Beyond THC: The New Generation of Cannabinoid Designer Drugs

Spice drugs as a new trend: Mode of action, identification and legislation

Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in human serum by liquid chromatography-tandem mass spectrometry.

The case history and toxicological findings of a fatal fentanyl intoxication due to ingestion of a transdermal patch are presented A 1-year-old otherwise healthy girl was put to bed and 2 h later she was found dead The autopsy revealed a 25-μg/h (42 mg) transdermal fentanyl patch in the stomach Toxicological analysis by liquid chromatography–tandem mass spectrometry with positive electrospray ionization yielded fentanyl and norfentanyl concentrations in the peripheral blood of 56 and 59 ng/ml, heart blood 190 and 89 ng/ml, and liver 235 and 26 ng/g, respectively The cause of death was determined to be a fentanyl overdose The investigation established that the child has unintentionally swallowed the patch, which had been lying on the floor

Fatal outcome in a child after ingestion of a transdermal fentanyl patch.

Scheduled multiple reaction monitoring algorithm as a way to analyse new designer drugs combined with synthetic cannabinoids in human serum with liquid chromatography-tandem mass spectrometry.

To avoid the detection of small fragmentation products of γ-hydroxybutyrate (GHB), a liquid chromatography–tandem mass spectrometry GHB quantification method in human serum supported by adduct formation was developed and validated. The continuous infusion of GHB/GHB-D6 made the identification of two adducts possible and GHB/GHB-D6 sodium acetate adduct fragmentation was used as target mass transition. A Luna 5 μm C18 (2) 100 A, 150 mm × 2 mm analytical column and elution with a programmed flow of the mobile phase consisting of 10 % A (H2O/methanol = 95/5, v/v) and 90 % B (H2O/methanol = 3/97, v/v), both with 10 mM ammonium acetate and 0.1 % acetic acid (pH = 3.2), were used. Protein precipitation with 1 mL of the mobile phase B was used as the sample preparation. The calculated limit of detection/quantification was 1 μg/mL. The presented study shows that the fragmentation of GHB sodium acetate adducts is an effective way of quantification of this small molecule and is an interesting alternative to other methods based on the detection of ions smaller than 85 Da. This fact together with the short analysis time of 3 min and the fast sample preparation make this method very attractive for forensic/clinical application.

Adduct supported analysis of γ-hydroxybutyrate in human serum with LC-MS/MS

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.

/pdf/fatal-intoxication-due-to-brucine-12ce93bq30.pdf

Jens-Peter Weller

Papers

Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in human serum by liquid chromatography-tandem mass spectrometry.

Fatal outcome in a child after ingestion of a transdermal fentanyl patch.

Scheduled multiple reaction monitoring algorithm as a way to analyse new designer drugs combined with synthetic cannabinoids in human serum with liquid chromatography-tandem mass spectrometry.

Adduct supported analysis of γ-hydroxybutyrate in human serum with LC-MS/MS

Fatal Intoxication Due to Brucine