Herbal Blends Research Articles

Antioxidant properties and phenolic composition of "Composed Yerba Mate".

The online version contains supplementary material available at (10.1007/s13197-020-04961-x).

Influences of dietary herbal blend and feed restriction on growth, carcass characteristics and gut microbiota of growing rabbits

The objective of the present study was to determine the effect of feed restriction systems, herbal mixture and their interactions on growth performance, carcass traits, and microbial aspects of growing New Zealand White (NZW) rabbit kept from 5 to 13 weeks of age. A 3 × 4 factorial arrangement was performed, including three feed restriction systems (ad-libitum, 90%, and 80% of ad-libitum) and four dietary supplementation levels of herbal mix (0, 0.30%, 0.50% and 0.70%). A total number of 120 rabbits (male and female ratio 1:1) at five weeks of age were randomly allotted into twelve experimental groups (n = 10 each). Results showed a significant decrease in body weight, body weight gain and feed intake in restricted-fed rabbits compared to the control group (ad-libitum). HERBS levels significantly influenced the growth performance and carcass traits of rabbits. The herbal blend had a positive effect on reducing the population of pathogenic microorganisms and increasing the population of lactic acid bacteria. Conclusively, it could be concluded that the feed restriction system has beneficial effects in the improvement of feed conversion ratio (FCR), weight gain, and carcass traits. In addition, HERBS supplementation to the growing rabbits resulted in significant improvements in growth performance, carcass characteristics, and microbial aspects of rabbits kept from 5 to 13 weeks of age. Highlights: This work investigated the effect of feed restriction systems (FRS), herbal mix (HERBS), and their interactions with rabbits. Restricted feed decreased live body weight during all ages studied. Feed conversion ratio, weight gain and carcass traits were improved due to FRS. The HERBS improved the growth, carcass traits, and microbial aspects of rabbits.

Synthetic Cannabinomimetics: A Brief History and the Challenges They Pose for the Forensic Chemist

Since the first detection of synthetic cannabinomimetics in herbal smoking blends in 2008 the clandestine production of these compounds, based on seizure data, increased in number every year until ~2012. In recent years there has been a decline in synthetic cannabinomimetic production both in number and diversity. The synthetic details of the first generation cannabinoids were documented in the scientific and medical literature making production comparatively simple. Subsequent generations of synthetic cannabinoids involved more complex but still very practicable synthetic chemistry. This resulted in a period of rapid growth in synthetic cannabinoids creating a health crisis and problems for forensic chemists faced with many substances for which no certified reference materials existed. Routine forensic chemistry laboratories were well practiced at identifying known drugs using chromatographic–mass spectrometric techniques and comparison to reference materials. However as synthetic cannabinomimetics, often referred to in the literature as synthetic cannabinoids, appeared in large numbers, few laboratories were equipped with the nuclear magnetic resonance (NMR) spectrometers and high resolution mass spectrometers (HRMS) required for identification of unknown substances. These developments also challenged public prosecutors for opinions from forensic experts as to the legality or otherwise of these novel drugs.

Assessment of safety and efficacy of Karallief® Easy ClimbTM, an herbal extract blend for supporting joint health: a double-blind, placebo-controlled, randomized clinical trial

Background: Osteoarthritis is common among the aging population worldwide. The current techniques to manage osteoarthritis focus on relieving pain and slowing the progression of the disease. Herbal or natural supplements have shown promise in achieving both these treatment goals. Two new proprietary herbal extract blends, Karallief® Easy ClimbTM (KEC) and herbal extracts with glucosamine (HEG), are combinations of several natural products shown to be effective in the treatment of knee osteoarthritis. The current study tested the efficacy and safety of KEC and HEG versus a placebo control.Methods: This is a randomized, double-blind and placebo-controlled study. A total of 120 patients were divided into 3 groups and were given KEC, HEG and Placebo in the ratio 1:1:1. Treatment results were assessed using the 30 second chair stand test, WOMAC test, knee flexion test and joint space measurement using X-rays of the knee joint.Results: The study found that the herbal supplements HEG and KEC significantly reduced osteoarthritis-related knee pain and increased joint mobility and were safe to use during 120 days of treatment. Both supplements resulted in an improvement in the 30 second chair stand test results, WOMAC pain scores, knee flexion, and joint space width as measured by X-ray, as compared to the placebo.Conclusions: Natural supplements such as HEG and KEC improve knee osteoarthritis symptoms and can be a safe and effective treatment option for patients with osteoarthritis.

The effect of henna and linseed herbal ointment blend on wound healing in rats with second-degree burns

The treatment of skin burns is one of the most important challenge in medical science. The aim of this study is evaluation of the efficacy of Artaderm herbal ointment containing the Henna (Lawsonia inermis) extract, Linseed (Linum usitatissimum) oil, and Honey Wax on wound healing in the rat with second-degree burn wounds. The Artaderm ointment had an effective role in controlling burn wound infections due to its antimicrobial and anti-inflammatory properties. In this study, 64 male Wistar rats were randomly divided into 8 groups (n = 8). Four groups received Artaderm, 1% Silver Sulfadiazine (SSD 1%), Cod Liver Oil and Fundermol (Alpha) ointments which used in common practices for burn injuries. Another three groups received Henna, Linseed, and Honey Wax alone and a control group that just underwent a second-degree burn injury without any treatments. A second-degree burn was formed on the back of each rat and dressed daily with one of the agents. Burn wounds were macroscopically and microscopically evaluated on the 7th, 14th, and 21st day after burn induction. Rats treated with the Artaderm ointment had significantly faster wound contraction as well as shorter healing time than the rest groups. No scar was observed in rats treated with the Artaderm ointment on the 21st day, while this level of improvement was not observed in other groups at the same time. More than 90% of wounds were healed after on the 14th day in rats treated with Artaderm (94.10 ± 0.18) and Alpha (92.05 ± 0.23) ointments. According to these findings, it can be concluded that Artaderm herbal ointment can be used as a proper alternative for healing of wounds in second-degree burns.

In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells.

JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as "spice," "herbal incense," or "herbal blend," as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug's toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150μM JWH-018 over 24h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P<0.05. JWH-018 produced oxidative stress in SH-SY5Y cells that could be an underlying mechanism of JWH-018 neurotoxicity. Additional in vivo animal and human-based studies are needed to confirm our findings.

Simultaneous determination of 4F-MDMB BINACA, a new synthetic cannabinoid, and its metabolites in human blood samples by LC-MS/MS

Methyl 2-(1-(4-fluorobutyl)-1H-indazole-3-carboxamide)-3,3-dimethylbutanoate) also referred to as 4F-MDMB BINACA(M0), is a recently introduced synthetic cannabinoid (SC) that was identified in herbal blends submitted to the Istanbul Narcotics Laboratory of Council of Forensic Medicine (CFM), in March 2019. A sensitive analytical method was developed to be able to detect and quantitate 4F-MDMB BINACA(M0) and its two metabolites, 4F-MDMB BINACA {3,3-dimethylbutanoic acid ((S)-2-(1-(4-fluorobutyl)-1H-indazole-3-carboxamido)-3, 3-dimethylbutanoic acid)} (M1), and 4F-MDMB BINACA-N-4-hyroxybutyl (methyl (S)-2-(1-(4-hydroxybutyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate) (M2) in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The samples were prepared using a solid-phase extraction method. The method validation was performed in terms of linearities, limits of detection (LODs), limits of quantification (LOQs), recoveries, matrix effects, process efficiencies, accuracies, and precisions, was also applied to six blood samples from cases of autopsy in the CFM, Istanbul.

Acute, Subacute, and Genotoxicity Assessments of a Proprietary Blend of Garcinia mangostana Fruit Rind and Cinnamomum tamala Leaf Extracts (CinDura®).

The present communication describes a battery of toxicity studies that include an acute oral toxicity, a subacute twenty-eight-day repeated oral dose toxicity, and genotoxicity studies on a herbal formulation CinDura® (GMCT). This proprietary herbal composition contains the extracts of the Garcinia mangostana fruit rind (GM) and the Cinnamomum tamala leaf (CT). The toxicological evaluations were performed following the Organization for Economic Cooperation and Development (OECD) guidelines. The acute oral toxicity study in Wistar rats suggests that the median lethal dose of CinDura® is at least 2000 mg/kg body weight. Acute dermal and eye irritation tests in New Zealand white rabbits indicate that the test item is nonirritant to the skin and eyes. A twenty-eight-day repeated dose oral toxicity study was conducted in male and female Wistar rats using daily doses of 250, 500, and 1000 mg/kg body weight, followed by a fourteen-day reversal period for two satellite groups. The CinDura®-supplemented animals did not show any sign of toxicity on their body weights, organ weights, and on the hematobiochemical parameters. The gross pathology and histopathological examinations indicated no treatment-related changes in the experimental animals. Overall, the no-observed-adverse-effect level (NOAEL) of the herbal blend is 1000 mg/kg body weight, the highest tested dose. Also, the results of the bacterial reverse mutation test and the erythrocyte micronucleus assay in mouse bone marrow suggest that CinDura® (GMCT) is neither mutagenic nor clastogenic.

Combined Extract of Vitis vinifera L. and Centella asiatica Synergistically Attenuates Oxidative Damage Induced by Hydrogen Peroxide in Human Umbilical Vein Endothelial Cells.

Endothelial cell injury caused by oxidative stress is a critical factor in the initial stage of vascular diseases. Thus, identification of more effective antioxidants is a promising strategy to protect against endothelial cell injury. Recently, synergistic effects between phytochemicals have received renewed attention for their role in the treatment of various diseases. Vitis vinifera L. and Centella asiatica are well-known medicinal plants with various biological effects. However, the combination of the two has not previously been studied. Here, we investigated the effects of V. vinifera L. leaf and C. asiatica extract combination (VCEC), a standardized herbal blend comprising V. vinifera L. leaf extract (VE) and C. asiatica extract (CE), for its antioxidant activity and for the protection of endothelial cells against hydrogen peroxide (H2O2)-mediated oxidative damage in human umbilical vein endothelial cells (HUVECs). VCEC showed higher antioxidant activity than VE or CE in oxygen radical antioxidant capacity assays. In HUVECs, VCEC significantly suppressed increases in the production of intracellular reactive oxygen species, decreased levels of nitric oxide and vascular endothelial-cadherin, and increased endothelial hyperpermeability triggered by H2O2. Treatment with VE or CE alone ameliorated HUVEC injury in a pattern similar to VCEC, although their effects were significantly weaker than VCEC. Overall, VCEC exhibited a substantial synergistic effect on protecting endothelial cells against oxidative damage through its antioxidant activity. Therefore, VCEC could be developed as a potential agent for reducing the risk of vascular diseases related to oxidative stress.

Bioactive compounds in water extracts prepared from rosehip‐containing herbal blends

In this study, rosehip tea and two rosehip-containing blends, along with their infusions and decoctions, were investigated. The first blend contained hibiscus and rosehip, while the second one was a mixture of rosehip, apple, pear, and St. John's wort. It was established that the carbohydrates were a major constituent in all samples. However, the highest protein, ash, and uronic acids content were detected in a hibiscus-containing blend. The rosehip material exhibited the highest lipid content, while higher levels of natural pigments were determined in St. John's wort-containing blend. The uronic acids and fructose were the major components in the rosehip extracts, while sucrose and organic acids (malic, quinic, neochlorogenic, chlorogenic acid) predominated in the hibiscus-containing extracts. Infusions exhibited higher phenolic acid content and antioxidant activity than the decoctions. However, the decoction could be preferred as method of extraction regarding polysaccharide accumulation. Both extracts had a very low caloric value. Practical applications The results of the current study would provoke tea companies and producers to take interest in the design of a new herbal blend with modified composition and improved health benefits through a small amount of easily extractable polysaccharide-rich herbal material. They may also recommend another appropriate method for consumers to improve the extraction of significant bioactive substances. In addition, the different forms of the water extracts, obtained from rosehip-based tea blends, could be used directly or after proper processing as ingredients in food supplements.

The Novel Psychoactive Substance Cumyl-CH-MEGACLONE: Human Phase-I Metabolism, Basic Pharmacological Characterization and Comparison to Other Synthetic Cannabinoid Receptor Agonists with a γ-Carboline-1-One Core.

Synthetic cannabinoids (SC) remain one of the largest groups of new psychoactive substances on the European drug market. In December 2018, Cumyl-CH-MEGACLONE, a novel SC based on a γ-carboline-1-one core structure, was firstly identified in Hungary and later also other European countries. This work aims to reveal the pharmacological characteristics and phase-I metabolism of Cumyl-CH-MEGACLONE and compare the data to its analogs Cumyl-PEGACLONE and 5F-Cumyl-PEGACLONE. The purified substance was characterized by means of gas chromatography-mass spectrometry (GC-MS), liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QToF-MS), attenuated total reflection infrared spectroscopy (ATR-FTIR) and nuclear magnetic resonance spectroscopy. Phase-I metabolites were identified by LC-QToF-MS analysis combined with a scheduled precursor ion list of authentic urine samples and confirmed by comparison with metabolites built in vitro by pooled human liver microsome assays. Pharmacological data were obtained in a competitive ligand binding assay and a receptor activation assay at the human cannabinoid receptor 1 (hCB1). The structure of 5-cyclohexylmethyl-2-(2-phenylpropan-2-yl)-2,5-dihydro-1H-pyrido[4,3-b]indol-1-one (semisystematic name: Cumyl-CH-MEGACLONE) was identified in a herbal blend as the main active ingredient. Investigation of phase-I biotransformation of Cumyl-CH-MEGACLONE led to three monohydroxylated metabolites (M08, M10 and M13) as reliable urinary markers for proof of consumption. At the hCB1, Cumyl-CH-MEGACLONE shows high binding affinity with Ki=1.01nM (2.5-fold higher than JWH-018), an EC50 of 1.22nM and high efficacy with EMAX=143.4% above constitutive activity of the receptor (1.13-fold higher than JWH-018). Comparison to the analogs 5F-Cumyl-PEGACLONE and Cumyl-PEGACLONE (both are hCB1 full agonists carrying a 5-fluoropentyl or pentyl chain instead of the cyclohexylmethyl moiety) suggests that Cumyl-CH-MEGACLONE is more likely to resemble the pharmacologic profile of the latter one.

Zyflamend, a Unique Herbal Blend, Inhibits Adipogenesis Through the Coordinated Regulation of PKA and JNK

Abstract Objectives The prevalence of obesity and its comorbidities has sparked a worldwide concern to address rates of adipose tissue accrual. Recent studies have demonstrated a novel role of Zyflamend, a natural herbal extract, in regulating lipid metabolism in several cancer cell lines through the activation of the AMPK signaling pathway. Yet, the role of Zyflamend in adipogenic differentiation and lipid metabolism remains largely unexplored. The objective of this study is to investigate the effects of Zyflamend on white 3T3-MBX pre-adipocyte differentiation and elucidate the molecular mechanisms. Methods 3T3-MBX pre-adipocytes were treated with Zyflamend, and the expression of various key adipogenic and lipolytic regulators was examined. We also investigated the effects of Zyflamend on pre-adipocyte survival, proliferation, and cell cycle. Results Zyflamend treatment altered cell cycle progression, attenuated proliferation, and increased cell death of 3T3-MBX pre-adipocytes. In addition, treatment with Zyflamend inhibited lipid accumulation during the differentiation of 3T3-MBX cells, consistent with decreased expression of lipogenic genes and increased lipolysis. Mechanistically, Zyflamend-induced alterations in adipogenesis were mediated, at least in part, through the activation of AMPK, PKA, and JNK. Inhibition of AMPK partially reversed Zyflamend-induced inhibition of differentiation, whereas the inhibition of either JNK or PKA fully restored adipocyte differentiation and decreased lipolysis. Conclusions Taken together, the present study demonstrates that Zyflamend, as a novel anti-adipogenic bioactive mix, inhibits adipocyte differentiation through the activation of PKA and JNK pathways.Our findings suggest that Zyflamend supplementation might help in developing novel anti-obesity therapeutic strategies. Funding Sources This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R00DK100736) to A.B.

Direct and Fast Screening of New Psychoactive Substances Using Medical Swabs and Atmospheric Solids Analysis Probe Triple Quadrupole with Data-Dependent Acquisition.

New psychoactive substances (NPS) have become a serious public health problem, as they are continuously changing their structures and modifying their potency and effects on humans, and therefore, novel compounds are unceasingly appearing. One of the major challenges in forensic analysis, particularly related to the problem of NPS, is the development of fast screening methodologies that allow the detection of a wide variety of compounds in a single analysis. In this study, a novel application of the atmospheric solids analysis probe (ASAP) using medical swabs has been developed. The swab-ASAP was coupled to a triple quadrupole mass analyzer working under a data-dependent acquisition mode in order to perform a suspect screening of NPS in different types of samples as well as on surfaces. The compounds were automatically identified based on the observed fragmentation spectra using an in-house built MS/MS spectra library. The developed methodology was applied for the identification of psychoactive substances in research chemicals and herbal blends. The sensitivity of the method, as well as its applicability for surface analysis, was also assessed by identifying down to 1 μg of compound impregnated onto a laboratory table. Another remarkable application was the identification of cathinones and synthetic cannabinoids on the fingers of potential consumers. Interestingly, our data showed that NPS could be identified on the fingers after being in contact with the product and even after cleaning their hands by shaking off with a cloth. The methodology proposed in this paper can be applied for routine analyses of NPS in different matrix samples without the need to establish a list of target compounds prior to analysis.

Infusions of Herbal Blends as Promising Sources of Phenolic Compounds and Bioactive Properties.

Several plants have been used for medicinal applications and have been traditionally consumed as decoctions and infusions. Although some herbs are used alone as a beverage, they are often blended in mixtures to maximize their effects. Herein, the nutritional characterization of six infusions from herbal blends was evaluated using the official methods of analysis (AOAC international). A further characterization of the individual phenolic profile was also performed by HPLC-DAD/ESI-MSn, and finally bioactive potential was determined by evaluating the antioxidant, cytotoxic, anti-inflammatory, and antimicrobial activities of each blend. The wide variety of plants in each sample led to variability in the results for all analyzed parameters. However, blends containing 15% Laurus nobilis L. and 15% Juglan regia L. in their composition showed higher sugar content and energy contribution; higher concentration of phenolic compounds (phenolic acids and flavonoids); greater antioxidant, cytotoxic, and anti-inflammatory capacity; and also better antimicrobial effects against all the tested bacterial and fungal strains. Further studies will be necessary to evaluate the real synergistic effects that these two species show in the presence of other plants, and to evaluate their potential for application in various food, pharmaceutical, and nutraceutical products as infusion preparations.

Investigation on the consumption of synthetic cannabinoids among teenagers by the analysis of herbal blends and urine samples

The use of synthetic cannabinoids (SCs), which escape conventional detection systems, may be a good alternative to elude routine drug analysis for cannabis. The detection of these drugs in urine is unusual due to their complete and fast metabolism, therefore requiring alternative strategies. In this work, an investigation has been made on SCs consumption by minors (less than 18 years old) in juvenile offenders’ centres. 667 urine samples (from 127 minors) were collected after their permits with stay at home. We also studied the SCs from 7 herbal blends available at the smartshop frequented by the minors. Both, urine and herbal blends, were analysed by liquid chromatography coupled to high resolution mass spectrometry. The analysis of urine confirmed the absence of more than 200 SCs investigated. Thus, the focus was made on metabolites reported for those SCs identified in the herbal blends collected from the smart-shop. The major metabolites of XLR-11 and UR-144 (N-pentanoic acid and N-(5-hydroxypentyl)) were found in several urine samples. Apart from the main metabolites included in the initial searching, a thorough investigation of more metabolites for these SCs was additionally performed, including MS/MS experiments for the tentative identification of compounds detected in the urine samples. The 16 samples positive to the XLR-11 metabolites were assigned to 6 minors, only 2 of which had recognized consumption. On the basis of the results obtained, preventive and therapeutic interventions must be implemented to reduce the consumption of psychoactive substances and to improve the risk-perception of these substances by minors.

Bio-Synthesis and Characterization of CS–Ag Nano Hydrogel for Antibacterial Application

An environmental technique of herbal mediated blend of Ag nanoparticles is a substantial stage in the ground of nanotechnology. Chitosan (CS) is a polymer which is biocompatible and antibacterial. In this work, we have synthesized CS–Ag Nano hydrogel which is form with chitosan-based hydrogel merged in the herbal synthesized Ag nanoparticles. These green synthesized Ag-nanoparticles made from Polygonum bistorta plant leaves and described with the assistance of UV-vis spectrophotometer, and Dynamic Light Scattering (DLS). In this work our main focus to synthesized CS–Ag Nano hydrogel. These hydrogel was described by Fourier transform infrared (FTIR) spectroscopic method, X-ray diffraction (XRD) method, and contact angle. Nanoparticle size distribution was within 1 to 100 nm by DLS and the optimum wavelength was noted in 400 to 450 nm by UV-vis spectroscopic readings. A good antibacterial behavior has been displayed by these synthesized CS–Ag Nano hydrogel films against both E. coli (gram –ve) and S. aureus (gram +ve) with the maximum 7 mm inhibition zone.

Application of Gas Chromatography-Mass Spectrometry for the Identification and Quantitation of Three Common Synthetic Cannabinoids in Seized Materials from the Jordanian Market.

Synthetic cannabinoids (SCs) were developed to mimic the effects of Δ9-tetrahydrocannabinol on humans. SCs were distributed in the form of herbal blends, with smoking being the main method of consumption. These synthetic compounds have a wide range of physical, behavioral, and harmful effects on the body. However, this study aimed to identify and quantify three common SCs including AB-FUBINACA, AB-CHMINACA, and XLR-11 in the seized materials from the Jordanian market by gas chromatography coupled with mass spectrometry (GC–MS). A liquid–liquid extraction sample preparation technique was applied to 100 different seized samples obtained from the Anti-Narcotics Department of Public Security in a period between 2017 and 2018. Profiling of the seized samples revealed different distributions of the targeted SCs in the obtained samples. Upon quantitation, concentrations of these SCs varied greatly within and among the samples. The use of GC–MS analysis provided a powerful technique in the detection and identification of SCs. This study revealed the current and trends of SC use in the Jordanian illicit substance market, which was previously unclear. Future studies are required to explore new SCs and their influence in different biological samples.

Adding more "spice" to the pot: A review of the chemistry and pharmacology of newly emerging heterocyclic synthetic cannabinoid receptor agonists.

Synthetic cannabinoid receptor agonists (SCRAs) first appeared on the international recreational drug market in the early 2000s in the form of SCRA-containing herbal blends. Due to the cannabimimetic effects associated with the consumption of SCRAs, they have acquired an ill-informed reputation for being cheap, safe, and legal alternatives to illicit cannabis. Possessing high potency and affinity for the human cannabinoid receptor subtype-1 (CB1 ) and -2 (CB2 ), it is now understood that the recreational use of SCRAs can have severe adverse health consequences. The major public health problem arising from SCRA use has pressed legislators around the world to employ various control strategies to curb their recreational use. To circumvent legislative control measures, SCRA manufacturers have created a wide range of SCRA analogs that contain, more recently, previously unencountered azaindole, γ-carbolinone, or carbazole heterocyclic scaffolds. At present, little information is available regarding the chemical syntheses of these newly emerging classes of SCRA, from a clandestine perspective. When compared with previous generations of indole- and indazole-type SCRAs, current research suggests that many of these heterocyclic SCRA analogs maintain high affinity and efficacy at both CB1 and CB2 but largely evade legislative control. This review highlights the importance of continued research in the field of SCRA chemistry and pharmacology, as recreational SCRA use remains a global public health issue and represents a serious control challenge for law enforcement agencies.

Combination of stable isotope ratio data and chromatographic impurity signatures as a comprehensive concept for the profiling of highly prevalent synthetic cannabinoids and their precursors

In this study, we utilized elemental analyser (EA) and gas-chromatography (GC) isotope ratio mass spectrometry (IRMS) and ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) in a comprehensive profiling approach assessing the chromatographic impurity signatures and δ13C and δ15N isotope ratios of synthetic cannabinoids from police seizures and internet test purchases. Main target of this study was the highly prevalent synthetic cannabinoid MDMB-CHMICA (methyl (2S)-2-([1-(cyclohexylmethyl)-1H-indol-3-yl]formamido)-3,3-dimethylbutaoate). Overall, 61 powder and 118 herbal blend (also called “Spice-Products”) samples were analysed using both analytical techniques and evaluated in a joint model to link samples from a common source. As a key finding, three agglomerates of Spice-product samples with similar dates of purchase were identified in the IRMS data, possibly representing larger shipments of MDMB-CHMICA, each produced with the same precursor material, successively delivered to the European market. The three agglomerates were refined into multiple sub-clusters based on the impurity profiling data, each representing an individual synthesis batch. One of the agglomerates identified in the IRMS data was found to consist two groups of four sub-clusters, respectively, with majorly different impurity profiles, demonstrating the necessity for both analytical techniques to extract the maximum amount of information from a limited sample pool. Additionally, 31 samples containing the recently surfaced synthetic cannabinoid Cumyl-PeGaClone (5-pentyl-2-(2-phenylpropan-2-yl)-2,5-dihydro-1H-pyrido[4,3-b]indol-1-one) were analysed for their and δ13C and δ15N isotope ratios to put the isotopic data recorded for MDMB-CHMNICA in a more global perspective. Three building blocks of precursor chemicals (indole, tert-leucine, cumylamine) potentially used for the synthesis of the two named synthetic cannabinoids were acquired from different global vendors and measured for their δ13C and δ15N isotope ratios to better understand variations in the isotopic composition of the synthetic cannabinoids and to trace their origin.

A Clinical Study Assessing Efficacy of an Herbal Blend on Menopausal Symptoms and Quality of Life

A Clinical Study Assessing Efficacy of an Herbal Blend on Menopausal Symptoms and Quality of Life