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.

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

Beyond THC: The New Generation of Cannabinoid Designer Drugs

Method validation of a survey of thevetia cardiac glycosides in serum samples.

The present case report deals with a lethal intoxication with arsenic mixed into butter. It describes the course of events over about two days on the basis of the statements by the persons involved, the clinical findings after the belated hospitalisation of the victim, the results of the first pathological autopsy, the forensic autopsy performed after exhumation and the results of the chemical-toxicological investigations. The results are discussed in relation to the later confession of the female perpetrator and her statements regarding a previous unsuccessful murder attempt by poisoning. It also presents the judgement pronounced by the court and the reasons given for it.

Lethal intoxication with arsenic using prepared butter

In this publication, benzodiazepines, opioids, and further drugs were analyzed in exhumed brain and liver tissue samples in 116 cases (total) after 9.5-16.5 years of burial. Solid phase extraction followed by liquid chromatography-tandem mass spectrometry was applied. Data from literature is listed summarizing the detectability of the presented analytes after a certain time of burial. In our study, 60% of the analyzed benzodiazepines, 100% of the opioids, and 82% of further drugs were detectable. Only the benzodiazepines lorazepam, nitrazepam, flunitrazepam, and its metabolite norflunitrazepam, and the drugs butylscopolamine, metronidazole, and omeprazole were not detectable at all. Percentage of positive findings (total, and separately for brain and liver tissue) and postmortem period are listed for each analyte. Correlation of detectability depending on postmortem period and condition of tissue are presented exemplarily for midazolam. No substantial correlation was observed. Despite a long time of burial, most benzodiazepines, opioids, and further drugs were detectable in the examined tissue samples. Our results may be a good support for future exhumations in which toxicological analyses are relevant.

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/pdf/10.1002/dta.3029

Determination of drugs in exhumed liver and brain tissue after over 9 years of burial by liquid chromatography–tandem mass spectrometry—Part 2: Benzodiazepines, opioids, and further drugs

Sir, Caffeine is an alkaloid which can be found in coffee, tea leafs, or kola nuts. It is responsible for a relative mild stimulation of the central nervous system and is the most frequently consumed substance with centrally stimulating effects (1). Therefore, nowadays it is not possible to imagine the life without caffeine. The newest trend among caffeine consumers who want to provide a higher stimulating effect is beverages sold as energy drinks and loaded with this substance together with other additives such as sugar and herbal components (2). Symptoms of caffeine consumption are dose-dependant, and in higher doses, even intoxications can be expected. Regular caffeine use can also lead to addiction with a withdrawal syndrome after discontinuation of consumption (3). Although numerous toxic effects have been described, lethal caffeine intoxications are rare and therefore not reported in the literature frequently (4–6). This substance is also a popular ingredient of different legal highs which main components responsible for the desired effect are analyzed with complex analytical methods (7). Caffeine is detected in the majority of biological samples due to dietary exposure to this substance. However, this drug gained also attention in the bodybuilding scene and is widely used as supplement. The bodybuilders can find a lot of information in the internet, which suggests using caffeine powder/ pills instead of coffee (8). It is stated that in this form, a better dosage control can be achieved. However, a big problem is the caffeine tolerance, which occurs after multiple caffeine use and diminishes its value for exercise performance. This fact is a reason why higher caffeine doses would be needed to achieve the expected stimulating effect. Bodybuilders are also advised to consume caffeine pills/powder early in the morning, about 1 h before the workout (to achieve the highest stimulating effect). This strategy enables also the elimination of caffeine during the day, so no interference with the sleep should occur. The problem of caffeine abuse in the bodybuilding scene was described by FitzSimmons et al. In this documented case, a caffeine intoxication with a caffeine serum concentration of 12.3 mg/L was reported (9). However, after three days on the ward, the patient remained seizure-free and had normal renal function. Caffeine toxic levels are considered to be 15 mg/L and higher, and lethal concentrations are expected to be above 100 mg/L (4). In this context, we wanted to mention the following case. A 25-year-old was found dead on the floor of his office. The last time he was seen alive by his friends was the day before death. Vomit was found on the body and in the surrounding area. No preexisting illness was known. However, a year before, he passed a psychiatric examination in consequence of his aggressive behavior. The only auxiliary information provided by the police was the fact that the decedent was an active bodybuilder and consumer of different drugs which he used to enhance his performance. The fact that he was mentally fragile was also known. The autopsy did not show any signs of violence or pathological change of the organs. On the basis of this information and investigations performed by the police, toxicological analyses were strongly recommended by the forensic pathologists. After the postmortem materials were screened for different drugs on the basis of cloned enzyme donor immunoassay (CEDIA—urine), gas chromatography–mass spectrometry (GC-MS —urine), and high-performance liquid chromatography with diode array detection (HPLC-DAD—heart blood), very high signals for caffeine were obtained. Other relevant substances could not be detected. The appropriate quantification was applied with HPLC-DAD (calibration range: 10–300 mg/L; limit of detection/ quantification: 0.12/0.43 mg/L). The HPLC-DAD analyses performed revealed a caffeine concentration of 255 mg/L in femoral blood and of 214 mg/L in heart blood. A documented series of 14 fatalities after caffeine overdosage revealed a blood concentration range of 79–344 mg/ L (10). As caffeine concentrations in human blood greater than 100 mg/L are considered to be lethal (4), the quantified caffeine values could explain the cause of death. The achieved results are consistent with the case history, because the deceased was an active bodybuilder and caffeine powder consumer. Therefore, the death was caused by accidental caffeine intoxication on the basis of bodybuilding performance enhancement. A competing cause of death could not be found. The popularity of caffeine consumed in form of coffee, pills/ powder, or other beverages is responsible for the fact that this drug is present in most forensic samples, when a general unknown analysis is performed. However, caffeine as a drug with toxic effect (in higher doses) on human health is often underestimated. It has to be considered that caffeine concentrations above 15 mg/L can cause toxic symptoms (5,6). As caffeine taken in excess can cause tremor, tachycardia, vomiting, convulsions, cardiac arrhythmias, coma, and death, it should be always considered in the forensic expertise. In fatalities in the bodybuilding scene this drug is very important, because overconsumption of different substances is quite common to enhance the bodybuilding performance (like demonstrated in this letter). This overconsumption may cause different toxic effects or even be lethal, when higher concentrations are reached.

Letter to the Editor—The Problem of Caffeine Consumption in the Bodybuilding Scene

This chapter describes the importance and the use of gas chromatography (GC) in forensic toxicology. GC is for instance commonly applied in the determination of volatile compounds. Ethanol determination, congener analysis and the determination of further volatile substances by means of headspace techniques are described as exemplary uses. Moreover, GC-MS plays an important role in the confirmation analysis of drugs of abuse. Other fields of application of GC-MS are hair testing and systematic toxicological analyses. In each section, application examples are given and relevant particularities are discussed in the context of forensic analysis.

Jörg Teske

Papers

Method validation of a survey of thevetia cardiac glycosides in serum samples.

Lethal intoxication with arsenic using prepared butter

Determination of drugs in exhumed liver and brain tissue after over 9 years of burial by liquid chromatography–tandem mass spectrometry—Part 2: Benzodiazepines, opioids, and further drugs

Letter to the Editor—The Problem of Caffeine Consumption in the Bodybuilding Scene

GC in Forensic Toxicology