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Volker Auwarter - One of the best experts on this subject based on the ideXlab platform.
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O23: Hair analysis for synthetic cannabinoids: How does handling of herbal mixtures during forensic analysis affect the analyst's hair concentrations?
Toxicologie Analytique et Clinique, 2014Co-Authors: Volker Auwarter, Melanie Hutter, Merja A. Neukamm, Bjoern MoosmannAbstract:Introduction If narcotics police officers or other persons handling drug material at work are suspected of consuming drugs, hair analysis may be used to prove or refute such suspicion. However, it is known for many drugs that differentiation of actual drug use from external contamination can be challenging or sometimes impossible. The aim of this study was to evaluate the extent of external contamination caused by handling of synthetic cannabinoid containing drug material under realistic conditions in a forensic laboratory. Methods Hair of laboratory workers was systematically analyzed for synthetic cannabinoids with a validated LC-MS/MS method after a big seizure of legal high products had to be analyzed in our laboratory. Hair samples were taken two days after the last exposure and again one week later. In addition, hair samples of laboratory staff not directly in contact with the drug material and close relatives of exposed subjects were analyzed to check for cross contamination. Results All samples of persons who were in direct contact with drug material were tested positive for at least one of the synthetic cannabinoids (JWH-018, JWH-073, JWH-081, JWH-122, JWH-210, JWH-307, JWH-368, AM-2201, AM-2201 indazole derivative, AM- 2232, MAM-2201, RCS-4, XLR-11, 5F-PB-22, RCS-4 ortho isomer). Concentrations ranged from trace amounts up to a maximum of 170 pg/mg (JWH-210) and roughly reflected duration and intensity of exposition. There was no significant decline in concentrations from sample 1 to sample 2 (one week later). Unexpectedly, also subjects without direct contact to drug material showed measurable hair concentrations. In one case, a hair sample (21 cm) was taken 10 weeks after the last exposition with plant material. In this case, relevant concentrations of 5F-PB-22 were detected with an increase of concentrations from distal to proximal segments (7.9 – 20 pg/mg). Conclusion Depending on duration and intensity of exposition, relevant concentrations of synthetic cannabinoids may be found in hair samples of persons exposed to these drugs at work. Unexpectedly, even cross contamination from an exposed person to a close relative may occur and lead to (false) positive hair findings. Concentrations caused by contamination are in the typical range found in known users of these drugs and could lead to wrong conclusions. In contrast, detection of metabolites could strongly suggest an actual consumption. However, we did not detect such metabolites so far even in samples of known consumers of synthetic cannabinoids showing extremely high concentrations of the unchanged compounds. Therefore, body fluids have to be analyzed to unambiguously prove use of these drugs.
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Driving under the influence of synthetic cannabinoids (“Spice”): a case series
International Journal of Legal Medicine, 2014Co-Authors: Frank Musshoff, Melanie Hutter, Stefan Kneisel, Gerhard Kernbach-wighton, Wolfgang Bicker, Burkhard Madea, Volker AuwarterAbstract:Recreational use of synthetic cannabinoid receptor agonists—so-called “Spice” products—became very popular during the last few years. Several reports on clinical symptoms and poisonings were published. Unfortunately, most of these reports do not contain any analytical data on synthetic cannabinoids in body fluids, and no or only a limited number of cases were reported concerning driving under the influence (DUI) of this kind of drugs. In this article, several cases of DUI of synthetic cannabinoids (AM-2201, JWH-018, JWH-019, JWH-122, JWH-210, JWH-307, MAM-2201 (JWH-122 5-fluoropentyl derivative), and UR-144) are presented, focusing on analytical results and signs of impairment documented by the police or the physicians who had taken the blood sample from the suspects. Consumption of synthetic cannabinoids can lead to impairment similar to typical performance deficits caused by cannabis use which are not compatible with safe driving. These deficits include centrally sedating effects and impairment of fine motor skills necessary for keeping the vehicle on track. Police as well as forensic toxicologists and other groups should become familiar with the effects of synthetic cannabinoid use, and be aware of the fact that drug users may shift to these “legal” alternatives due to their nondetectability by commonly used drug screening tests based on antibodies. Sophisticated screening procedures covering the complete range of available compounds or their metabolites have to be developed for both blood/serum and urine testing.
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analysis of 30 synthetic cannabinoids in oral fluid using liquid chromatography electrospray ionization tandem mass spectrometry
Drug Testing and Analysis, 2013Co-Authors: Stefan Kneisel, Jürgen Kempf, Volker AuwarterAbstract:In recent years, the analysis of synthetic cannabinoids in human specimens has gained enormous importance in the broad field of drug testing. Nevertheless, the considerable structural diversity among synthetic cannabinoids already identified in 'herbal mixtures' hampers the development of comprehensive analytical methods. As the identification of the main metabolites of newly appearing substances is very laborious and time-consuming, the detection of the parent compounds in blood samples is the current approach of choice for drug abstinence testing. Whenever blood sampling is not possible however, the need for alternative matrices arises. In this article, we present a fully validated liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for the analysis of 30 synthetic cannabinoids in oral fluid samples collected with the Drager DCD 5000 collection device. The method proved to be suitable for the quantification of 28 substances. The limits of detection were in the range from 0.015 to 0.9 ng/ml, while the lower limits of quantification ranged from 0.15 to 3.0 ng/ml. The method was successfully applied to 264 authentic samples during routine analysis. A total of 31 samples (12%) was tested positive for at least one of the following synthetic cannabinoids: AM-694, AM-2201, JWH-018, JWH-019, JWH-081, JWH-122, JWH-203, JWH-210, JWH-250, JWH-307, MAM-2201, and RCS-4. Given that stabilization of the collection pads after sampling is warranted, the collection device provides satisfactory sensitivity. Hence, whenever blood sampling is not possible, the Drager DCD 5000 collection device offers a good tool for the analysis of synthetic cannabinoids in oral fluid in the broad field of drug testing. Language: en
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Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism.
Journal of Mass Spectrometry, 2013Co-Authors: Melanie Hutter, Stefan Kneisel, Volker AuwarterAbstract:Aminoalkylindoles, a subclass of synthetic cannabinoid receptor agonists, show an extensive and complex metabolism in vivo, and due to their structural similarity, they can be challenging in terms of unambiguous assignment of metabolic patterns in urine samples to consumed substances. The situation may even be more complicated as these drugs are usually smoked, and the high temperature exposure may lead to formation of artifacts. Typical metabolites of JWH-018 (Naphthalen-1-yl(1-pentyl-1H-indol-3-yl)methanone) were reportedly detected not only in urine samples collected after consumption of JWH-018 but also after AM-2201 (1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone) use. The aim of the presented study was to evaluate if typical JWH-018 metabolites can be formed metabolically in humans and if JWH-018 may be formed artifactually during smoking of AM-2201. Therefore, one of the authors ingested 5 mg of pure AM-2201, and serum as well as urine samples were analyzed subsequently. Additionally, the smoke condensate from a cigarette laced with pure AM-2201 was investigated. In addition, urine samples of patients after known consumption of AM-2201 or JWH-018 were evaluated. The results of the study prove that typical metabolites of JWH-018 and JWH-073 are built in humans after ingestion of AM-2201. However, the N-(4-hydroxypentyl) metabolite of JWH-018, which is the major metabolite after JWH-018 use, was not detected after the self-experiment. In the smoke condensate, small amounts of JWH-018 and JWH-022 (Naphthalen-1-yl[1-(pent-4-en-1-yl)-1H-indol-3-yl]methanone) were detected. Nevertheless, the results of our study suggest that the amounts absorbed by smoking do not significantly influence the metabolic pattern in urine samples. Therefore, the N-(4-hydroxypentyl) metabolite of JWH-018 can serve as a valuable marker to distinguish consume of products containing AM-2201 from JWH-018 use. Copyright © 2013 John Wiley & Sons, Ltd.
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acute toxicity due to the confirmed consumption of synthetic cannabinoids clinical and laboratory findings
Addiction, 2013Co-Authors: Maren Hermannsclausen, Stefan Kneisel, Bela Szabo, Volker AuwarterAbstract:Aims Recently, several synthetic cannabinoids were identified in herbal mixtures consumed as recreational drugs alternative to cannabis products. The aim was to characterize the acute toxicity of synthetic cannabinoids as experienced by emergency patients. Design This was a retrospective study targeting patients seeking emergency treatment after recreational use of synthetic cannabinoids. Setting and participants Patients were selected from the database of the Poisons Information Center Freiburg between September 2008 and February 2011. The inclusion criteria were: hospitalization, available clinical reports and analytical verification of synthetic cannabinoid uptake. In total, 29 patients were included (age 14–30 years, median 19; 25 males, four females). Measurements Clinical reports were evaluated and synthetic cannabinoids and other drugs were determined analytically. Findings CP-47,497-C8 (one), JWH-015 (one), JWH-018 (eight), JWH-073 (one), JWH-081 (seven), JWH-122 (11), JWH-210 (11), JWH-250 (four) and AM 694 (one) were quantified in blood samples. JWH-018 was most common in 2008–9, JWH-122 in 2010, and JWH-210 in 2011. Tachycardia, agitation, hallucination, hypertension, minor elevation of blood glucose, hypokalaemia and vomiting were reported most frequently. Chest pain, seizures, myoclonia and acute psychosis were also noted. Conclusions There appears to have been an increase in use of the extremely potent synthetic cannabinoids JWH-122 and JWH-210. Acute toxic symptoms associated with their use are also reported after intake of high doses of cannabis, but agitation, seizures, hypertension, emesis and hypokalaemia seem to be characteristic to the synthetic cannabinoids, which are high-affinity and high-efficacy agonists of the CB1 receptor. Thus, these effects are due probably to a strong CB1 receptor stimulation.
Stefan Kneisel - One of the best experts on this subject based on the ideXlab platform.
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Driving under the influence of synthetic cannabinoids (“Spice”): a case series
International Journal of Legal Medicine, 2014Co-Authors: Frank Musshoff, Melanie Hutter, Stefan Kneisel, Gerhard Kernbach-wighton, Wolfgang Bicker, Burkhard Madea, Volker AuwarterAbstract:Recreational use of synthetic cannabinoid receptor agonists—so-called “Spice” products—became very popular during the last few years. Several reports on clinical symptoms and poisonings were published. Unfortunately, most of these reports do not contain any analytical data on synthetic cannabinoids in body fluids, and no or only a limited number of cases were reported concerning driving under the influence (DUI) of this kind of drugs. In this article, several cases of DUI of synthetic cannabinoids (AM-2201, JWH-018, JWH-019, JWH-122, JWH-210, JWH-307, MAM-2201 (JWH-122 5-fluoropentyl derivative), and UR-144) are presented, focusing on analytical results and signs of impairment documented by the police or the physicians who had taken the blood sample from the suspects. Consumption of synthetic cannabinoids can lead to impairment similar to typical performance deficits caused by cannabis use which are not compatible with safe driving. These deficits include centrally sedating effects and impairment of fine motor skills necessary for keeping the vehicle on track. Police as well as forensic toxicologists and other groups should become familiar with the effects of synthetic cannabinoid use, and be aware of the fact that drug users may shift to these “legal” alternatives due to their nondetectability by commonly used drug screening tests based on antibodies. Sophisticated screening procedures covering the complete range of available compounds or their metabolites have to be developed for both blood/serum and urine testing.
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analysis of 30 synthetic cannabinoids in oral fluid using liquid chromatography electrospray ionization tandem mass spectrometry
Drug Testing and Analysis, 2013Co-Authors: Stefan Kneisel, Jürgen Kempf, Volker AuwarterAbstract:In recent years, the analysis of synthetic cannabinoids in human specimens has gained enormous importance in the broad field of drug testing. Nevertheless, the considerable structural diversity among synthetic cannabinoids already identified in 'herbal mixtures' hampers the development of comprehensive analytical methods. As the identification of the main metabolites of newly appearing substances is very laborious and time-consuming, the detection of the parent compounds in blood samples is the current approach of choice for drug abstinence testing. Whenever blood sampling is not possible however, the need for alternative matrices arises. In this article, we present a fully validated liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for the analysis of 30 synthetic cannabinoids in oral fluid samples collected with the Drager DCD 5000 collection device. The method proved to be suitable for the quantification of 28 substances. The limits of detection were in the range from 0.015 to 0.9 ng/ml, while the lower limits of quantification ranged from 0.15 to 3.0 ng/ml. The method was successfully applied to 264 authentic samples during routine analysis. A total of 31 samples (12%) was tested positive for at least one of the following synthetic cannabinoids: AM-694, AM-2201, JWH-018, JWH-019, JWH-081, JWH-122, JWH-203, JWH-210, JWH-250, JWH-307, MAM-2201, and RCS-4. Given that stabilization of the collection pads after sampling is warranted, the collection device provides satisfactory sensitivity. Hence, whenever blood sampling is not possible, the Drager DCD 5000 collection device offers a good tool for the analysis of synthetic cannabinoids in oral fluid in the broad field of drug testing. Language: en
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Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism.
Journal of Mass Spectrometry, 2013Co-Authors: Melanie Hutter, Stefan Kneisel, Volker AuwarterAbstract:Aminoalkylindoles, a subclass of synthetic cannabinoid receptor agonists, show an extensive and complex metabolism in vivo, and due to their structural similarity, they can be challenging in terms of unambiguous assignment of metabolic patterns in urine samples to consumed substances. The situation may even be more complicated as these drugs are usually smoked, and the high temperature exposure may lead to formation of artifacts. Typical metabolites of JWH-018 (Naphthalen-1-yl(1-pentyl-1H-indol-3-yl)methanone) were reportedly detected not only in urine samples collected after consumption of JWH-018 but also after AM-2201 (1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone) use. The aim of the presented study was to evaluate if typical JWH-018 metabolites can be formed metabolically in humans and if JWH-018 may be formed artifactually during smoking of AM-2201. Therefore, one of the authors ingested 5 mg of pure AM-2201, and serum as well as urine samples were analyzed subsequently. Additionally, the smoke condensate from a cigarette laced with pure AM-2201 was investigated. In addition, urine samples of patients after known consumption of AM-2201 or JWH-018 were evaluated. The results of the study prove that typical metabolites of JWH-018 and JWH-073 are built in humans after ingestion of AM-2201. However, the N-(4-hydroxypentyl) metabolite of JWH-018, which is the major metabolite after JWH-018 use, was not detected after the self-experiment. In the smoke condensate, small amounts of JWH-018 and JWH-022 (Naphthalen-1-yl[1-(pent-4-en-1-yl)-1H-indol-3-yl]methanone) were detected. Nevertheless, the results of our study suggest that the amounts absorbed by smoking do not significantly influence the metabolic pattern in urine samples. Therefore, the N-(4-hydroxypentyl) metabolite of JWH-018 can serve as a valuable marker to distinguish consume of products containing AM-2201 from JWH-018 use. Copyright © 2013 John Wiley & Sons, Ltd.
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acute toxicity due to the confirmed consumption of synthetic cannabinoids clinical and laboratory findings
Addiction, 2013Co-Authors: Maren Hermannsclausen, Stefan Kneisel, Bela Szabo, Volker AuwarterAbstract:Aims Recently, several synthetic cannabinoids were identified in herbal mixtures consumed as recreational drugs alternative to cannabis products. The aim was to characterize the acute toxicity of synthetic cannabinoids as experienced by emergency patients. Design This was a retrospective study targeting patients seeking emergency treatment after recreational use of synthetic cannabinoids. Setting and participants Patients were selected from the database of the Poisons Information Center Freiburg between September 2008 and February 2011. The inclusion criteria were: hospitalization, available clinical reports and analytical verification of synthetic cannabinoid uptake. In total, 29 patients were included (age 14–30 years, median 19; 25 males, four females). Measurements Clinical reports were evaluated and synthetic cannabinoids and other drugs were determined analytically. Findings CP-47,497-C8 (one), JWH-015 (one), JWH-018 (eight), JWH-073 (one), JWH-081 (seven), JWH-122 (11), JWH-210 (11), JWH-250 (four) and AM 694 (one) were quantified in blood samples. JWH-018 was most common in 2008–9, JWH-122 in 2010, and JWH-210 in 2011. Tachycardia, agitation, hallucination, hypertension, minor elevation of blood glucose, hypokalaemia and vomiting were reported most frequently. Chest pain, seizures, myoclonia and acute psychosis were also noted. Conclusions There appears to have been an increase in use of the extremely potent synthetic cannabinoids JWH-122 and JWH-210. Acute toxic symptoms associated with their use are also reported after intake of high doses of cannabis, but agitation, seizures, hypertension, emesis and hypokalaemia seem to be characteristic to the synthetic cannabinoids, which are high-affinity and high-efficacy agonists of the CB1 receptor. Thus, these effects are due probably to a strong CB1 receptor stimulation.
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analysis of 30 synthetic cannabinoids in serum by liquid chromatography electrospray ionization tandem mass spectrometry after liquid liquid extraction
Journal of Mass Spectrometry, 2012Co-Authors: Stefan Kneisel, Volker AuwarterAbstract:The analysis of synthetic cannabinoids in human matrices is of particular importance in the fields of forensic and clinical toxicology since cannabis users partly shift to the consumption of ‘herbal mixtures’ as a legal alternative to cannabis products in order to circumvent drug testing. However, comprehensive methods covering the majority of synthetic cannabinoids already identified on the drug market are still lacking. In this article, we present a fully validated method for the analysis of 30 synthetic cannabinoids in human serum utilizing liquid-liquid extraction and liquid chromatography-electrospray ionization tandem mass spectrometry. The method proved to be suitable for the quantification of 27 substances. The limits of detection ranged from 0.01 to 2.0 ng/mL, whereas the lower limits of quantification were in the range from 0.1 to 2.0 ng/mL. The presented method was successfully applied to 833 authentic serum samples during routine analysis between August 2011 and January 2012. A total of 227 (27%) samples was tested positive for at least one of the following synthetic cannabinoids: JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-203, JWH-210, JWH-307, AM-2201 and RCS-4. The most prevalent compounds in positive samples were JWH-210 (80%), JWH-122 (63%) as well as AM-2201 (29%). Median serum concentrations were all below 1.0 ng/mL. These findings demonstrate a significant shift of the market of synthetic cannabinoids towards substances featuring a higher CB1 binding affinity and clearly emphasize that the analysis of synthetic cannabinoids in serum or blood samples requires highly sensitive analytical methods covering a wide spectrum of substances. Copyright © 2012 John Wiley & Sons, Ltd.
Ramesh K Ganju - One of the best experts on this subject based on the ideXlab platform.
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abstract 2018 cannabinoid receptor 2 agonist jwh 015 inhibits growth and metastasis of triple negative breast cancers through regulation of autophagy mechanism
Cancer Research, 2019Co-Authors: Nabanita Chatterjee, Subhadip Das, Dinesh K Ahirwar, Sanjay Mishra, Ramesh K GanjuAbstract:Metastasis to distant organs is the major cause of mortality associated with breast cancer. Triple-negative breast cancer (TNBC) subtype has been shown to be associated with worst patient survival due to high metastasis rate and lack of targeted therapies. Therefore, there is an utmost need to develop novel therapeutic strategies against TNBC growth and metastasis. Cannabinoids are known to possess anti-cancer activity. However, the associated psychotropic activity limits the therapeutic use of Cannabinoids in breast cancer patients. Here, we used synthetic cannabinoid JWH-015 which activates cannabinoid receptor 2 (CB2) and is devoid of psychotropic activity. In vitro molecular analysis revealed that JWH-015 induces TNBC cell death by activating autophagy associated apoptosis. In addition, we have further shown using in vivo tumor models, that JWH-015 potentially inhibits TNBC growth and metastasis through activation of autophagy mechanisms. Further analysis showed that JWH-015 treated tumors recruited the reduced number of macrophages compared to vehicle control treated tumors. In addition, there were more anti-tumor M1-type macrophages present in JWH-015 treated tumors. Conversely, vehicle control treated tumors possessed a higher number of pro-tumor M2-type macrophages. These observations have established the anti-metastatic potential of JWH-015 in different TNBC pre-clinical mouse models. The mechanistic studies have elaborated the role of JWH-015-induced autophagy in promoting tumor cell death to inhibit TNBC growth and metastasis. Citation Format: Nabanita Chatterjee, Subhadip Das, Dinesh K. Ahirwar, Sanjay Mishra, Ramesh Ganju. Cannabinoid receptor 2 agonist JWH-015 inhibits growth and metastasis of triple negative breast cancers through regulation of autophagy mechanism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2018.
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cannabinoid receptor 2 agonist inhibits macrophage induced emt in non small cell lung cancer by downregulation of egfr pathway
Molecular Carcinogenesis, 2016Co-Authors: Janani Ravi, Mohd W Nasser, Mohamad Elbaz, Nissar Ahmad Wani, Ramesh K GanjuAbstract:JWH-015, a cannabinoid receptor 2 (CB2) agonist has tumor regressive property in various cancer types. However, the underlying mechanism by which it acts in lung cancer is still unknown. Tumor associated macrophage (TAM) intensity has positive correlation with tumor progression. Also, macrophages recruited at the tumor site promote tumor growth by enhancing epithelial to mesenchymal (EMT) progression. In this study, we analyzed the role of JWH-015 on EMT and macrophage infiltration by regulation of EGFR signaling. JWH-015 inhibited EMT in NSCLC cells A549 and also reversed the mesenchymal nature of CALU-1 cells by downregulation of EGFR signaling targets like ERK and STAT3. Also, in vitro co-culture experiments of A549 with M2 polarized macrophages provided evidence that JWH-015 decreased migratory and invasive abilities which was proved by reduced expression of FAK, VCAM1, and MMP2. Furthermore, it decreased macrophage induced EMT in A549 by attenuating the mesenchymal character by downregulating EGFR and its targets. These results were confirmed in an in vivo subcutaneous syngenic mouse model where JWH-015 blocks tumor growth and also inhibits macrophage recruitment and EMT at the tumor site which was regulated by EGFR pathway. Finally, JWH-015 reduced lung tumor lesions in an in vivo tumorigenicity mouse model. These data confer the impact of this cannabinoid on anti-proliferative and anti-tumorigenic effects, thus enhancing our understanding of its therapeutic efficacy in NSCLC. Our findings open new avenues for cannabinoid receptor CB2 agonist-JWH-015 as a novel and potential therapeutic target based on EGFR downregulation mechanisms in NSCLC. © 2016 Wiley Periodicals, Inc.
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cannabinoid receptors cb1 and cb2 as novel targets for inhibition of non small cell lung cancer growth and metastasis
Cancer Prevention Research, 2011Co-Authors: Anju Preet, Zahida Qamri, Mohd W Nasser, Anil Prasad, Konstantin Shilo, Xianghong Zou, Jerome E Groopman, Ramesh K GanjuAbstract:Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide; however, only limited therapeutic treatments are available. Hence, we investigated the role of cannabinoid receptors, CB1 and CB2, as novel therapeutic targets against NSCLC. We observed expression of CB1 (24%) and CB2 (55%) in NSCLC patients. Furthermore, we have shown that the treatment of NSCLC cell lines (A549 and SW-1573) with CB1/CB2 and CB2-specific agonists Win55,212-2 and JWH-015, respectively, significantly attenuated random as well as growth factor-directed in vitro chemotaxis and chemoinvasion in these cells. We also observed significant reduction in focal adhesion complex, which plays an important role in migration, upon treatment with both JWH-015 and Win55,212-2. In addition, pre-treatment with CB1/CB2 selective antagonists AM251 and AM630, prior to JWH-015 and Win55,212-2 treatments, attenuated the agonist-mediated inhibition of in vitro chemotaxis and chemoinvasion. Additionally, both CB1 and CB2 agonists Win55,212-2 and JWH-133, respectively, significantly inhibited in vivo tumor growth and lung metastasis (~50%). These effects were receptor-mediated as pre-treatment with CB1/CB2 antagonists abrogated CB1/CB2 agonist-mediated effects on tumor growth and metastasis. Reduced proliferation and vascularization along with increased apoptosis was observed in tumors obtained from animals treated with JWH-133 and Win55,212-2. Upon further elucidation into the molecular mechanism, we observed that both CB1 and CB2 agonists inhibited phosphorylation of AKT, a key signaling molecule controlling cell survival, migration and apoptosis, and reduced MMP-9 expression and activity. These results suggest that CB1 and CB2 could be used as novel therapeutic targets against NSCLC.
Jürgen Kempf - One of the best experts on this subject based on the ideXlab platform.
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analysis of 30 synthetic cannabinoids in oral fluid using liquid chromatography electrospray ionization tandem mass spectrometry
Drug Testing and Analysis, 2013Co-Authors: Stefan Kneisel, Jürgen Kempf, Volker AuwarterAbstract:In recent years, the analysis of synthetic cannabinoids in human specimens has gained enormous importance in the broad field of drug testing. Nevertheless, the considerable structural diversity among synthetic cannabinoids already identified in 'herbal mixtures' hampers the development of comprehensive analytical methods. As the identification of the main metabolites of newly appearing substances is very laborious and time-consuming, the detection of the parent compounds in blood samples is the current approach of choice for drug abstinence testing. Whenever blood sampling is not possible however, the need for alternative matrices arises. In this article, we present a fully validated liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for the analysis of 30 synthetic cannabinoids in oral fluid samples collected with the Drager DCD 5000 collection device. The method proved to be suitable for the quantification of 28 substances. The limits of detection were in the range from 0.015 to 0.9 ng/ml, while the lower limits of quantification ranged from 0.15 to 3.0 ng/ml. The method was successfully applied to 264 authentic samples during routine analysis. A total of 31 samples (12%) was tested positive for at least one of the following synthetic cannabinoids: AM-694, AM-2201, JWH-018, JWH-019, JWH-081, JWH-122, JWH-203, JWH-210, JWH-250, JWH-307, MAM-2201, and RCS-4. Given that stabilization of the collection pads after sampling is warranted, the collection device provides satisfactory sensitivity. Hence, whenever blood sampling is not possible, the Drager DCD 5000 collection device offers a good tool for the analysis of synthetic cannabinoids in oral fluid in the broad field of drug testing. Language: en
Barry K. Logan - One of the best experts on this subject based on the ideXlab platform.
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rapid and sensitive screening and confirmation of thirty four aminocarbonyl carboxamide naca and arylindole synthetic cannabinoid drugs in human whole blood
Drug Testing and Analysis, 2017Co-Authors: Marykathryn Tynon, Annette Ervin, Matthew Mcmullin, Sherri L. Kacinko, Joseph Homan, Barry K. LoganAbstract:We describe the development and validation of a method for the screening and confirmation of a range of chemically diverse synthetic cannabinoid drugs in human whole blood. The method targets the better known arylindole compounds as well as the emerging aminocarbonyl/ carboxamide (NACA) compounds. The approach consists of two separate extraction procedures designed to optimize recovery of each of these two classes, followed by analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The most significant novel compounds added were AB-FUBINACA, ADBICA, 5 F-ADBICA, ADB-PINACA, ADB-FUBINACA, ADB-FUBINACA, 5 F-ADB-PINACA, 5 F-ADB-PINACA, AB-PINACA, AB-CHMINACA, and ADB-CHMINACA. A third procedure is described for the quantitative confirmation of those compounds for which deuterated internal standards permitted quantitative analysis, including JWH-018, JWH-122, JWH-081, JWH-210, AM-2201, XLR-11, and UR-144. The methods were successfully validated according to Scientific Working Group in Forensic Toxicology (SWGTOX) protocol for 34 compounds in common use in the United States in the period of 2014 and 2015, although other substances, unknown at the time may have been introduced to the market over the same time period. The method was determined to be free from carry-over between samples, and no interference was found from other common therapeutic abused or novel psychoactive drugs. The methods were applied to the analysis of 1142 blood samples from forensic investigations, including post-mortem examinations and driving impairment cases. The drugs most frequently detected were AB-CHMINACA (18.6%), ADB-CHMINACA (15%), XLR-11 (5.5%), AB-FUBINACA (4.5%), AB-PINACA (3.9%), and ADB-FUBINACA (2.3%). Copyright © 2016 John Wiley & Sons, Ltd.
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Blood Synthetic Cannabinoid Concentrations in Cases of Suspected Impaired Driving
Journal of Analytical Toxicology, 2013Co-Authors: Jillian K. Yeakel, Barry K. LoganAbstract:Twelve cases of suspected impaired driving are discussed in which the drivers who subsequently tested positive for synthetic cannabinoid drugs underwent a psychophysical assessment. The attitude of the drivers was described as cooperative and relaxed, speech was slow and slurred and coordination was poor. Pulse and blood pressure were generally elevated. Horizontal gaze nystagmus was assessed in nine of the subjects, but was present in only two. The most consistent indicator was a marked lack of convergence. In all cases where a Drug Recognition Expert (DRE) officer evaluated and documented impairment (10 cases), it was attributed to the DRE cannabis category. Performance in field sobriety tests was variable, ranging from poor to minimal observable effect. Synthetic cannabinoid testing was performed by LC‐MS-MS. Positive results included: JWH-018 (n 5 4), 0.1‐1.1 ng/mL; JWH-081 (n 5 2) qualitative only; JWH-122 (n 5 3), 2.5 ng/mL; JWH-210 (n 5 4), 0.1 ng/mL; JWH250 (n 5 1), 0.38 ng/mL and AM-2201 (n 5 6), 0.43‐4.0 ng/mL. While there is good evidence of psychophysical impairment in these subjects, further structured data collection is needed to fully assess the relationship between synthetic cannabinoid use and psychomotor and cognitive impairment.
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Identification of Synthetic Cannabinoids in Herbal Incense Blends in the United States
Journal of forensic sciences, 2012Co-Authors: Barry K. Logan, Lindsay E. Reinhold, Francis X. DiamondAbstract:Synthetic cannabinoid agonists are chemically diverse with multiple analogs gaining popularity as drugs of abuse. We report on the use of thin layer chromatography, gas chromatography mass spectrometry, high-performance liquid chromatography, and liquid chromatography time of flight mass spectrometry for the identification and quantitation of these pharmacologically active chemicals in street drug dosage forms. Using these approaches, we have identified the synthetic cannabinoids JWH-018, JWH-019, JWH-073, JWH-081, JWH-200, JWH-210, JWH-250, CP47,497 (C=8) (cannabicyclohexanol), RCS-4, RCS-8, AM-2201, and AM-694 in various commercially available products. Other noncannabinoid drugs including mitragynine have also been detected. Typical concentrations of drug in the materials are in the range 5-20 mg/g, or 0.5-2% by weight for each compound, although many products contained more than one drug.
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Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Identification and Quantification of JWH-018, JWH-073, JWH-019, and JWH-250 in Human Whole Blood
Journal of Analytical Toxicology, 2011Co-Authors: Sherri L. Kacinko, Allan Xu, Matthew Mcmullin, Joseph W. Homan, Donna M. Warrington, Barry K. LoganAbstract:A sensitive and specific method for the quantification of JWH-018, JWH-073, and JWH-250 and the qualitative identification of JWH-019 in whole blood was developed and validated. Samples fortified with JWH-018-d₉ and JWH-073-d₉ underwent liquid-liquid extraction and were analyzed by liquid chromatography-positive ion electrospray ionization-tandem mass spectrometry. Two transitions were monitored for all analytes except JWH-250, for which there was only one available transition. JWH-019 did not meet the stringent requirements for quantitative analysis, and thus this method is only appropriate for the qualitative identification of this compound in whole blood. The linear range was 0.1-20 μg/L for all quantitative analytes. The maximum average within and between-run imprecision was 7.9% and 10.2%, respectively, and all controls quantified within 8.2% of target concentrations. Process efficiency, a measurement that takes into effect extraction efficiency and matrix effect, was ≥ 32.0% for all quantitative analytes; similar results were obtained for the deuterated internal standards. All analytes were stable at room, refrigerated, and frozen temperatures for at least 30 days. The method was used to quantify JWH-018 and JWH-073 in a blood specimen collected from a person known to have used an herbal incense blend containing these substances.
