Toxicological Characterization of GHB as a Performance-Enhancing Drug

Performance-enhancing drugs (PEDs) are represented by several compounds used to ameliorate the image, the appearance, or an athletic or non-athletic performance. Gamma-hydroxybutyrate (GHB) is an endogenous molecule first used as anesthetic and then marketed as a nutritional supplement with a wide diffusion in the bodybuilding community. The aim of the present work is to provide a toxicological characterization of the use of GHB as a PED, including the scientific basis for its use, the patterns of use/abuse, and the health risks arising from its consumption in this peculiar recreative setting. A literature search was performed on multiple databases including experimental studies on humans and animals as well as epidemiological reports and forensic case reports/series. Experimental studies demonstrated that the use of GHB as a PED is motivated by the release of growth hormone and the induction of sleep. However, the panel of desired performance-related effects was much wider in real cases and epidemiological studies. Even though the use of GHB among bodybuilders has decreased, its use to enhance some kind of performance, particularly sexual ones or social-communicative ones, as well as means to increase mood and perceived energy, is still common

Hair testing of GHB: an everlasting issue in forensic toxicology

In this paper, the authors present a critical review of different studies regarding hair testing of endogenous γ-hydroxybutyrate (GHB), concentrations in chronic users, and values measured after a single GHB exposure in drug facilitated sexual assault (DFSA) cases together with the role of a recently identified GHB metabolite, GHB-glucuronide. Content: The following databases (up to March 2017) PubMed, Scopus and Web of Science were used, searching the following key words: γ-hydroxybutyrate, GHB, GHB glucuronide, hair. The main key words “GHB” and “γ-hydroxybutyrate” were searched singularly and then associated individually to each of the other keywords. Summary: Of the 2304 sources found, only 20 were considered appropriate for the purpose of this paper. Summing up all the studies investigating endogenous GHB concentration in hair, a very broad concentration range from 0 to 12 ng/mg was found. In order to detect a single GHB dose in hair it is necessary to commonly wait 1 month for collecting hair and a segmental analysis of 3 or 5 mm fragments and the calculation of a ratio between the targeted segment and the others represent a reliable method to detect a single GHB intake considering that the ratios presently proposed vary from 3 and 10. The only two studies so far performed, investigating GHB-Glucuronide in hair, show that the latter does not seem to provide any diagnostic information regarding GHB exposure

Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists

BackgroundSynthetic cannabinoid receptor agonists (SCRAs) have become the largest group of new psychoactive substances monitored by the European Union Early Warning System. Despite the wide diffusion on the market, data regarding effects, toxicities, and mechanisms as well as toxic/lethal doses are still scarce.MethodsA comprehensive literature search for articles published up to January 2019 was performed in multiple electronic databases. Only cases of death in which toxicological analyses revealed the presence of SCRAs in blood or urine and at least an external examination was performed, including those occurred in emergency departments, were included.ResultsOf 380 studies identified, 354 were excluded, while 8 additional manuscripts were included through the screening of relevant references cited in the selected articles. A total number of 34 manuscripts (8 case series and 26 case reports) were included.ConclusionsTypical toxic ranges for SCRAs have not been so far identified, and the results of toxicological analyses should be interpreted with caution. In death cases involving SCRAs, a thorough post-mortem examination is a prerequisite to assess the role of the substance use in the deceased and to identify a probable mechanism of death. Even after a comprehensive analysis of clinical, circumstantial, toxicological, and autoptic data, the cause and manner of death remain unclear in some cases

Correlation between blood and oral fluid psychoactive drug concentrations and cognitive impairment in driving under the influence of drugs

The effects of drugs on driving performance should be checked with drug concentration in the brain and at the same time with the evaluation of both the behavioural and neurophysiological effects. The best accessible indicator of this information is the concentration of the drug and/or metabolites in blood and, to a certain extent, oral fluid. We sought to review international studies on correlation between blood and oral fluid drug concentrations, neurological correlates and cognitive impairment in driving under the influence of drugs. Methods : Relevant scientific articles were identified from PubMed, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE up to April 2017. Results : Up to 2010, no epidemiological studies were available on this matter and International scientists suggested that even minimal amounts of parent drugs in blood and oral fluid could affect driving impairment. More recently, epidemiological data, systematic reviews and meta-analysis on drugged drivers allowed the suggestion of impairment concentration limits for the most common illicit drugs. These values were obtained comparing driving disability induced by psychotropic drugs with that of established blood alcohol limits. Differently from ethyl alcohol where both detection methods and concentration limits have been well established even with inhomogeneity of ranges within different countries, in case of drugs of abuse no official cut-offs have yet been established, nor any standardized analytical protocols. Conclusion : Multiple aspects of driving performance can be differently affected by illicit drugs, and even if for few of them some dose/concentration dependent impairment has been reported, a wider knowledge on concentration/impairment relationship is still missin

Fulminant ischemic colitis with a fatal outcome after cocaine snorting: Case report and literature review

Abstract Snorting represents the most common route of administration for recreational powdered cocaine, and it is considered less dangerous than other routes of intake (i.e., intravenous; crack inhalation; etc.). A case of fulminant ischemic colitis with a fatal outcome, which occurred in a 19-year-old man after cocaine snorting, is presented in this report. Although several cases are reported in the literature, no one has involved people aged less than 20 years. The young man showed unspecific symptoms, which began about 2 h after the cocaine intake and the physicians were unable to make the diagnosis. This report may assist doctors treating young men who have consumed cocaine to consider this possible complication in all young adults (teenagers) in the presence of unspecific symptoms

Psychomotor performances relevant for driving under the combined effect of ethanol and synthetic cannabinoids: A systematic review

ObjectiveTo determine whether the acute co-consumption of ethanol and synthetic cannabinoids (SCs) increases the risk of a motor vehicle collision and affects the psychomotor performances relevant for driving.DesignSystematic review of the literature.Data sourcesElectronic searches were performed in two databases, unrestricted by year, with previously set method and criteria. Search, inclusion and data extraction were performed by two blind authors.ResultsTwenty articles were included, amounting to 31 cases of SCs-ethanol co-consumption. The impairment of psychomotor functions varied widely between studies, ranging from no reported disabilities to severe unconsciousness. Overall, a dose-effect relationship could not be observed.ConclusionDespite the biases and limitations of the literature studies, it seems likely that the co-consumption poses an increased risk for driving. The drugs might exert a synergistic effect on the central nervous system depression, as well as on aggressiveness and mood alterations. However, more research is needed on the topic

Editorial: The Challenge Posed by New Synthetic Opioids: Pharmacology and Toxicology

Diverted prescription opioid analgesics (e.g., oxycodone, hydrocodone, hydromorphone), failed opioid drug candidates (e.g., benzamide derivatives), and various legal and illegal fentanyl analogs (e.g., acetyl fentanyl, furanylfentanyl, carfentanil) constitute the class of New Synthetic Opioids (NSOs), which is currently posing a global public health threat (Pichini et al., 2018). Due to the low cost of materials and equipment required for clandestine laboratory production and enormous profit potential, NSOs are establishing a strong position on the illegal drug market as stand-alone products, adulterants in heroin, or constituents of counterfeit prescription medications. Recently, NSOs have been involved in a significant spike of acute intoxications (classic opioid toxidrome) and overdose deaths in North America, challenging healthcare professionals, law enforcement agencies fighting against their diffusion, and policymakers trying to restrain their use (Marchei et al., 2018; Busardò et al., 2019). Since there is little information available regarding the pharmacology and the toxicology of NSOs in abuse settings, the main purpose of this Research Topic was to fill the current knowledge gap. The topic covers basic scientific, epidemiological, and clinical aspects of NSOs and includes 3 reviews, 3 mini-reviews, 1 original article, 2 case reports, and 1 opinion

Molecular Insights and Clinical Outcomes of Drugs of Abuse Adulteration: New Trends and New Psychoactive Substances

Adulteration is a well-known practice of drug manufacturers at different stages of drug production. The intentional addition of active ingredients to adulterate the primary drug may enhance or mask pharmacological effects or may produce more potent drugs to increase the number of available doses and the dealer\u27s profit. Adulterants found in different drugs change over time in response to different factors. A systematic literature search in PubMed and Scopus databases and official international organizations\u27 websites according to PRISMA guidelines was performed. A total of 724 studies were initially screened, with 145 articles from PubMed and 462 from Scopus excluded according to the criteria described in the Method Section. The remaining 117 records were further assessed for eligibility to exclude articles without sufficient data. Finally, 79 studies were classified as non-biological (n = 35) or biological (n = 35 case reports; n = 9 case series) according to the samples investigated. Although the seized samples analyses revealed the presence of well-established adulterants such as levamisole for cocaine or paracetamol/acetaminophen for heroin, the reported data disclosed new adulteration practices, such as the use of NPS as cutting agents for classic drugs of abuse and other NPS. For example, heroin adulterated with synthetic cannabinoids or cocaine adulterated with fentanyl/fentalogues raised particular concern. Notably, adulterants play a role in some adverse effects commonly associated with the primary drug, such as levamisole-adulterated cocaine that may induce vasculitis via an autoimmune process. It is essential to constantly monitor adulterants due to their changing availability that may threaten drug consumers\u27 health

Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry Assay for Quantifying Fentanyl and 22 Analogs and Metabolites in Whole Blood, Urine, and Hair

Recently, synthetic opioid-related overdose fatalities, led by illicitly manufactured fentanyl and analogs, increased at an alarming rate, posing a global public health threat. New synthetic fentanyl analogs have been constantly emerging onto the drug marked for the last few years, to circumvent the laws and avoid analytical detection. Analytical methods need to be regularly updated to keep up with the new trends. In this study, we aimed to develop a new method for detecting the newest fentanyl analogs with a high sensitivity, in whole blood, urine, and hair. The method is intended to provide to clinical and forensic toxicologists a tool for documenting consumption. We developed a comprehensive ultra-high-performance liquid chromatography-tandem mass spectrometry method for quantifying fentanyl and 22 analogs and metabolites. Urine samples were simply diluted before injection; a liquid-liquid extraction was performed for blood testing; and a solid phase extraction was performed in hair. The chromatographic separation was short (8 min). The method was validated with a high sensitivity; limits of quantifications ranged from 2 to 6 ng/L in blood and urine, and from 11 to 21 pg/g in hair. The suitability of the method was tested with 42 postmortem blood, urine, or hair specimens from 27 fatalities in which fentanyl analogs were involved. Average blood concentrations (±SD) were 7.84 ± 7.21 and 30.0 ± 18.0 μg/L for cyclopropylfentanyl and cyclopropyl norfentanyl, respectively (n = 8), 4.08 ± 2.30 μg/L for methoxyacetylfentanyl, (n = 4), 40.2 ± 38.6 and 44.5 ± 21.1 μg/L for acetylfentanyl and acetyl norfentanyl, respectively (n = 3), 33.7 and 7.17 μg/L for fentanyl and norfentanyl, respectively (n = 1), 3.60 and 0.90 μg/L for furanylfentanyl and furanyl norfentanyl, respectively (n = 1), 0.67 μg/L for sufentanil (n = 1), and 3.13 ± 2.37 μg/L for 4-ANPP (n = 9). Average urine concentrations were 47.7 ± 39.3 and 417 ± 296 μg/L for cyclopropylfentanyl and cyclopropyl norfentanyl, respectively (n = 11), 995 ± 908 μg/L for methoxyacetylfentanyl, (n = 3), 1,874 ± 1,710 and 6,582 ± 3,252 μg/L for acetylfentanyl and acetyl norfentanyl, respectively (n = 5), 146 ± 318 and 300 ± 710 μg/L for fentanyl (n = 5) and norfentanyl (n = 6), respectively, 84.0 and 23.0 μg/L for furanylfentanyl and furanyl norfentanyl, respectively (n = 1), and 50.5 ± 50.9 μg/L for 4-ANPP (n = 10). Average hair concentrations were 2,670 ± 184 and 82.1 ± 94.7 ng/g for fentanyl and norfentanyl, respectively (n = 2), and 10.8 ± 0.57 ng/g for 4-ANPP (n = 2)