Skip to main content
Erschienen in: Forensic Toxicology 1/2017

04.08.2016 | Original Article

Urinary cannabinoid levels during nabiximols (Sativex®)-medicated inpatient cannabis withdrawal

verfasst von: Richard C. Kevin, David J. Allsop, Nicholas Lintzeris, Adrian J. Dunlop, Jessica Booth, Iain S. McGregor

Erschienen in: Forensic Toxicology | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Nabiximols (Sativex®) is a buccal spray containing both ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD). It has shown promise as an agonist substitution therapy for treating cannabis withdrawal and dependence. Monitoring urinary cannabinoid levels during treatment is important for determination of cannabinoid pharmacokinetics and for treatment adherence during clinical trials. Here, we use a recently described hydrolysis method to liberate urinary CBD from its glucuronide conjugate, and describe the trajectory of urinary CBD, THC, 11-nor-9-carboxy-THC (THC-COOH), and 11-hydroxy-THC (11-OH-THC) in patients receiving nabiximols treatment (or placebo) during cannabis withdrawal. Urine and plasma samples were taken before and during a 6-day inpatient treatment regime and during a 3-day drug-free washout. Urine was hydrolysed with red abalone β-glucuronidase, and CBD, THC, THC-COOH, and 11-OH-THC were quantified in daily urine using liquid chromatography-tandem mass spectrometry. Overall, urine and plasma cannabinoid levels followed similar trajectories and closely reflected the dosing schedule. During nabiximols treatment, CBD levels in urine and plasma rose markedly, while concentrations of THC and its metabolites remained at, or slightly above, pre-treatment levels. Following hydrolysis, urinary CBD was detected at levels 50 and 200 times as high as those in non-hydrolysed plasma and non-hydrolysed urine, respectively. THC, THC-COOH, and 11-OH-THC concentrations were also amplified by urinary hydrolysis. This method allows sensitive assessment of urinary CBD, and may prove useful in clinical studies involving nabiximols or other cannabinoid therapies.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Panlilio LV, Goldberg SR, Justinova Z (2015) Cannabinoid abuse and addiction: clinical and preclinical findings. Clin Pharmacol Ther 97:616–627CrossRefPubMedPubMedCentral Panlilio LV, Goldberg SR, Justinova Z (2015) Cannabinoid abuse and addiction: clinical and preclinical findings. Clin Pharmacol Ther 97:616–627CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Degenhardt L, Ferrari AJ, Calabria B, Hall WD, Norman RE, McGrath J, Flaxman AD, Engell RE, Freedman GD, Whiteford HA, Vos T (2013) The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: results from the GBD 2010 study. PLoS One 8:e76635. doi:10.1371/journal.pone.0076635 CrossRefPubMedPubMedCentral Degenhardt L, Ferrari AJ, Calabria B, Hall WD, Norman RE, McGrath J, Flaxman AD, Engell RE, Freedman GD, Whiteford HA, Vos T (2013) The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: results from the GBD 2010 study. PLoS One 8:e76635. doi:10.​1371/​journal.​pone.​0076635 CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Budney AJ, Hughes JR (2006) The cannabis withdrawal syndrome. Curr Opin Psychiatry 19:233–238CrossRefPubMed Budney AJ, Hughes JR (2006) The cannabis withdrawal syndrome. Curr Opin Psychiatry 19:233–238CrossRefPubMed
4.
Zurück zum Zitat Allsop DJ, Norberg MM, Copeland J, Fu S, Budney AJ (2011) The cannabis withdrawal scale development: patterns and predictors of cannabis withdrawal and distress. Drug Alcohol Depend 119:123–129CrossRefPubMed Allsop DJ, Norberg MM, Copeland J, Fu S, Budney AJ (2011) The cannabis withdrawal scale development: patterns and predictors of cannabis withdrawal and distress. Drug Alcohol Depend 119:123–129CrossRefPubMed
5.
Zurück zum Zitat Levin KH, Copersino ML, Heishman SJ, Liu F, Kelly DL, Boggs DL, Gorelick DA (2010) Cannabis withdrawal symptoms in non-treatment-seeking adult cannabis smokers. Drug Alcohol Depend 111:120–127CrossRefPubMedPubMedCentral Levin KH, Copersino ML, Heishman SJ, Liu F, Kelly DL, Boggs DL, Gorelick DA (2010) Cannabis withdrawal symptoms in non-treatment-seeking adult cannabis smokers. Drug Alcohol Depend 111:120–127CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Budney AJ, Vandrey RG, Hughes JR, Thostenson JD, Bursac Z (2008) Comparison of cannabis and tobacco withdrawal: severity and contribution to relapse. J Subst Abuse Treat 35:362–368CrossRefPubMedPubMedCentral Budney AJ, Vandrey RG, Hughes JR, Thostenson JD, Bursac Z (2008) Comparison of cannabis and tobacco withdrawal: severity and contribution to relapse. J Subst Abuse Treat 35:362–368CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Haney M, Ward AS, Comer SD, Hart CL, Foltin RW, Fischman MW (2001) Bupropion SR worsens mood during marijuana withdrawal in humans. Psychopharmacology 155:171–179CrossRefPubMed Haney M, Ward AS, Comer SD, Hart CL, Foltin RW, Fischman MW (2001) Bupropion SR worsens mood during marijuana withdrawal in humans. Psychopharmacology 155:171–179CrossRefPubMed
11.
Zurück zum Zitat Allsop DJ, Lintzeris N, Copeland J, Dunlop A, McGregor IS (2015) Cannabinoid replacement therapy (CRT): nabiximols (Sativex) as a novel treatment for cannabis withdrawal. Clin Pharmacol Ther 97:571–574CrossRefPubMed Allsop DJ, Lintzeris N, Copeland J, Dunlop A, McGregor IS (2015) Cannabinoid replacement therapy (CRT): nabiximols (Sativex) as a novel treatment for cannabis withdrawal. Clin Pharmacol Ther 97:571–574CrossRefPubMed
12.
Zurück zum Zitat Budney AJ, Vandrey RG, Hughes JR, Moore BA, Bahrenburg B (2007) Oral delta-9-tetrahydrocannabinol suppresses cannabis withdrawal symptoms. Drug Alcohol Depend 86:22–29CrossRefPubMed Budney AJ, Vandrey RG, Hughes JR, Moore BA, Bahrenburg B (2007) Oral delta-9-tetrahydrocannabinol suppresses cannabis withdrawal symptoms. Drug Alcohol Depend 86:22–29CrossRefPubMed
13.
Zurück zum Zitat Haney M, Cooper ZD, Bedi G, Vosburg SK, Comer SD, Foltin RW (2013) Nabilone decreases marijuana withdrawal and a laboratory measure of marijuana relapse. Neuropsychopharmacology 38:1557–1565CrossRefPubMedPubMedCentral Haney M, Cooper ZD, Bedi G, Vosburg SK, Comer SD, Foltin RW (2013) Nabilone decreases marijuana withdrawal and a laboratory measure of marijuana relapse. Neuropsychopharmacology 38:1557–1565CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R, Seal M, Surguladze SA, O’Carrol C, Atakan Z, Zuardi AW, McGuire PK (2009) Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry 66:95–105CrossRefPubMed Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R, Seal M, Surguladze SA, O’Carrol C, Atakan Z, Zuardi AW, McGuire PK (2009) Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry 66:95–105CrossRefPubMed
16.
Zurück zum Zitat Morgan CJ, Schafer G, Freeman TP, Curran HV (2010) Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study. Br J Psychiatry 197:285–290CrossRefPubMed Morgan CJ, Schafer G, Freeman TP, Curran HV (2010) Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study. Br J Psychiatry 197:285–290CrossRefPubMed
17.
Zurück zum Zitat Zuardi AW, Crippa JA, Hallak JE, Bhattacharyya S, Atakan Z, Martin-Santos R, McGuire PK, Guimaraes FS (2012) A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation. Curr Pharm Des 18:5131–5140CrossRefPubMed Zuardi AW, Crippa JA, Hallak JE, Bhattacharyya S, Atakan Z, Martin-Santos R, McGuire PK, Guimaraes FS (2012) A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation. Curr Pharm Des 18:5131–5140CrossRefPubMed
18.
Zurück zum Zitat Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM (2015) Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol 172:4790–4805CrossRefPubMedPubMedCentral Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM (2015) Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol 172:4790–4805CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkötter J, Hellmich M, Koethe D (2012) Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatr 2:e94. doi:10.1038/tp.2012.15 CrossRef Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkötter J, Hellmich M, Koethe D (2012) Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatr 2:e94. doi:10.​1038/​tp.​2012.​15 CrossRef
20.
Zurück zum Zitat O’Sullivan SE, Kendall DA (2010) Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology 215:611–616CrossRefPubMed O’Sullivan SE, Kendall DA (2010) Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology 215:611–616CrossRefPubMed
21.
Zurück zum Zitat Iannotti FA, Hill CL, Leo A, Alhusaini A, Soubrane C, Mazzarella E, Russo E, Whalley BJ, Di Marzo V, Stephens GJ (2014) Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem Neurosci 5:1131–1141CrossRefPubMed Iannotti FA, Hill CL, Leo A, Alhusaini A, Soubrane C, Mazzarella E, Russo E, Whalley BJ, Di Marzo V, Stephens GJ (2014) Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem Neurosci 5:1131–1141CrossRefPubMed
22.
Zurück zum Zitat Hassan S, Eldeeb K, Millns PJ, Bennett AJ, Alexander SPH, Kendall DA (2014) Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation. Br J Pharmacol 171:2426–2439CrossRefPubMedPubMedCentral Hassan S, Eldeeb K, Millns PJ, Bennett AJ, Alexander SPH, Kendall DA (2014) Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation. Br J Pharmacol 171:2426–2439CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Stout SM, Cimino NM (2014) Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev 46:86–95CrossRefPubMed Stout SM, Cimino NM (2014) Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev 46:86–95CrossRefPubMed
24.
Zurück zum Zitat Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I (2007) Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci 80:1415–1419CrossRefPubMed Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I (2007) Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci 80:1415–1419CrossRefPubMed
25.
Zurück zum Zitat Williams PL, Moffat AC (1980) Identification in human urine of Δ9-tetrahydrocannabinol-11-oic acid glucuronide: a tetrahydrocannabinol metabolite. J Pharm Pharmacol 32:445–448CrossRefPubMed Williams PL, Moffat AC (1980) Identification in human urine of Δ9-tetrahydrocannabinol-11-oic acid glucuronide: a tetrahydrocannabinol metabolite. J Pharm Pharmacol 32:445–448CrossRefPubMed
26.
Zurück zum Zitat Mazur A, Lichti CF, Prather PL, Zielinska AK, Bratton SM, Gallus-Zawada A, Finel M, Miller GP, Radominska-Pandya A, Moran JH (2009) Characterization of human hepatic and extrahepatic UDP-glucuronosyltransferase enzymes involved in the metabolism of classic cannabinoids. Drug Metab Dispos 37:1496–1504CrossRefPubMedPubMedCentral Mazur A, Lichti CF, Prather PL, Zielinska AK, Bratton SM, Gallus-Zawada A, Finel M, Miller GP, Radominska-Pandya A, Moran JH (2009) Characterization of human hepatic and extrahepatic UDP-glucuronosyltransferase enzymes involved in the metabolism of classic cannabinoids. Drug Metab Dispos 37:1496–1504CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Harvey DJ, Mechoulam R (1990) Metabolites of cannabidiol identified in human urine. Xenobiotica 20:303–320CrossRefPubMed Harvey DJ, Mechoulam R (1990) Metabolites of cannabidiol identified in human urine. Xenobiotica 20:303–320CrossRefPubMed
28.
Zurück zum Zitat Bergamaschi MM, Barnes A, Queiroz RH, Hurd YL, Huestis MA (2013) Impact of enzymatic and alkaline hydrolysis on CBD concentration in urine. Anal Bioanal Chem 405:4679–4689CrossRefPubMedPubMedCentral Bergamaschi MM, Barnes A, Queiroz RH, Hurd YL, Huestis MA (2013) Impact of enzymatic and alkaline hydrolysis on CBD concentration in urine. Anal Bioanal Chem 405:4679–4689CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Allsop DJ, Copeland J, Lintzeris N, Dunlop AJ, Montebello M, Sadler C, Rivas GR, Holland RM, Muhleisen P, Norberg MM, Booth J, McGregor IS (2014) Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial. JAMA Psychiatry 71:281–291CrossRefPubMed Allsop DJ, Copeland J, Lintzeris N, Dunlop AJ, Montebello M, Sadler C, Rivas GR, Holland RM, Muhleisen P, Norberg MM, Booth J, McGregor IS (2014) Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial. JAMA Psychiatry 71:281–291CrossRefPubMed
30.
Zurück zum Zitat Bell ML, Fairclough DL (2014) Practical and statistical issues in missing data for longitudinal patient-reported outcomes. Stat Methods Med Res 23:440–459CrossRefPubMed Bell ML, Fairclough DL (2014) Practical and statistical issues in missing data for longitudinal patient-reported outcomes. Stat Methods Med Res 23:440–459CrossRefPubMed
31.
Zurück zum Zitat Hedges LV (1981) Distribution theory for Glass’s estimator of effect size and related estimators. J Educ Behav Stat 6:107–128CrossRef Hedges LV (1981) Distribution theory for Glass’s estimator of effect size and related estimators. J Educ Behav Stat 6:107–128CrossRef
32.
Zurück zum Zitat Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224CrossRefPubMed Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224CrossRefPubMed
34.
Zurück zum Zitat Desrosiers NA, Himes SK, Scheidweiler KB, Concheiro-Guisan M, Gorelick DA, Huestis MA (2014) Phase I and II cannabinoid disposition in blood and plasma of occasional and frequent smokers following controlled smoked cannabis. Clin Chem 60:631–643CrossRefPubMed Desrosiers NA, Himes SK, Scheidweiler KB, Concheiro-Guisan M, Gorelick DA, Huestis MA (2014) Phase I and II cannabinoid disposition in blood and plasma of occasional and frequent smokers following controlled smoked cannabis. Clin Chem 60:631–643CrossRefPubMed
35.
Zurück zum Zitat Grauwiler SB, Scholer A, Drewe J (2007) Development of a LC/MS/MS method for the analysis of cannabinoids in human EDTA-plasma and urine after small doses of Cannabis sativa extracts. J Chromatogr B 850:515–522CrossRef Grauwiler SB, Scholer A, Drewe J (2007) Development of a LC/MS/MS method for the analysis of cannabinoids in human EDTA-plasma and urine after small doses of Cannabis sativa extracts. J Chromatogr B 850:515–522CrossRef
36.
Zurück zum Zitat Bergamaschi MM, Karschner EL, Goodwin RS, Scheidweiler KB, Hirvonen J, Queiroz RH, Huestis MA (2013) Impact of prolonged cannabinoid excretion in chronic daily cannabis smokers’ blood on per se drugged driving laws. Clin Chem 59:519–526CrossRefPubMedPubMedCentral Bergamaschi MM, Karschner EL, Goodwin RS, Scheidweiler KB, Hirvonen J, Queiroz RH, Huestis MA (2013) Impact of prolonged cannabinoid excretion in chronic daily cannabis smokers’ blood on per se drugged driving laws. Clin Chem 59:519–526CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Lemberger L, Tamarkin NR, Axelrod J, Kopin IJ (1971) Delta-9-tetrahydrocannabinol: metabolism and disposition in long-term marihuana smokers. Science 173:72–74CrossRefPubMed Lemberger L, Tamarkin NR, Axelrod J, Kopin IJ (1971) Delta-9-tetrahydrocannabinol: metabolism and disposition in long-term marihuana smokers. Science 173:72–74CrossRefPubMed
38.
39.
Zurück zum Zitat Wong A, Keats K, Rooney K, Hicks C, Allsop DJ, Arnold JC, McGregor IS (2014) Fasting and exercise increase plasma cannabinoid levels in THC pre-treated rats: an examination of behavioural consequences. Psychopharmacology 231:3987–3996CrossRefPubMed Wong A, Keats K, Rooney K, Hicks C, Allsop DJ, Arnold JC, McGregor IS (2014) Fasting and exercise increase plasma cannabinoid levels in THC pre-treated rats: an examination of behavioural consequences. Psychopharmacology 231:3987–3996CrossRefPubMed
40.
Zurück zum Zitat Johansson E, Noren K, Sjovall J, Halldin MM (1989) Determination of Δ1-tetrahydrocannabinol in human fat biopsies from marihuana users by gas chromatography-mass spectrometry. Biomed Chromatogr 3:35–38CrossRefPubMed Johansson E, Noren K, Sjovall J, Halldin MM (1989) Determination of Δ1-tetrahydrocannabinol in human fat biopsies from marihuana users by gas chromatography-mass spectrometry. Biomed Chromatogr 3:35–38CrossRefPubMed
42.
Zurück zum Zitat Blessing EM, Steenkamp MM, Manzanares J, Marmar CR (2015) Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics 12:825–836CrossRefPubMedPubMedCentral Blessing EM, Steenkamp MM, Manzanares J, Marmar CR (2015) Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics 12:825–836CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Scheidweiler KB, Desrosiers NA, Huestis MA (2012) Simultaneous quantification of free and glucuronidated cannabinoids in human urine by liquid chromatography tandem mass spectrometry. Clin Chim Acta 413:1839–1847CrossRefPubMedPubMedCentral Scheidweiler KB, Desrosiers NA, Huestis MA (2012) Simultaneous quantification of free and glucuronidated cannabinoids in human urine by liquid chromatography tandem mass spectrometry. Clin Chim Acta 413:1839–1847CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Huestis MA, Cone EJ (1998) Urinary excretion half-life of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in humans. Ther Drug Monit 20:570–576CrossRefPubMed Huestis MA, Cone EJ (1998) Urinary excretion half-life of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in humans. Ther Drug Monit 20:570–576CrossRefPubMed
45.
Zurück zum Zitat Friedman D, Devinsky O (2015) Cannabinoids in the treatment of epilepsy. N Engl J Med 373:1048–1058CrossRefPubMed Friedman D, Devinsky O (2015) Cannabinoids in the treatment of epilepsy. N Engl J Med 373:1048–1058CrossRefPubMed
46.
Zurück zum Zitat Trigo JM, Lagzdins D, Rehm J, Selby P, Gamaleddin I, Fischer B, Barnes AJ, Huestis MA, Le Foll B (2016) Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings. Drug Alcohol Depend 161:298–306CrossRefPubMed Trigo JM, Lagzdins D, Rehm J, Selby P, Gamaleddin I, Fischer B, Barnes AJ, Huestis MA, Le Foll B (2016) Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings. Drug Alcohol Depend 161:298–306CrossRefPubMed
47.
Zurück zum Zitat Lee D, Karschner EL, Milman G, Barnes AJ, Goodwin RS, Huestis MA (2013) Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration? Drug Alcohol Depend 130:68–76CrossRefPubMed Lee D, Karschner EL, Milman G, Barnes AJ, Goodwin RS, Huestis MA (2013) Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration? Drug Alcohol Depend 130:68–76CrossRefPubMed
48.
Zurück zum Zitat Bruci Z, Papoutsis I, Athanaselis S, Nikolaou P, Pazari E, Spiliopoulou C, Vyshka G (2012) First systematic evaluation of the potency of Cannabis sativa plants grown in Albania. Forensic Sci Int 222:40–46CrossRefPubMed Bruci Z, Papoutsis I, Athanaselis S, Nikolaou P, Pazari E, Spiliopoulou C, Vyshka G (2012) First systematic evaluation of the potency of Cannabis sativa plants grown in Albania. Forensic Sci Int 222:40–46CrossRefPubMed
49.
50.
Zurück zum Zitat Tsumura Y, Aoki R, Tokieda Y, Akutsu M, Kawase Y, Kataoka T, Takagi T, Mizuno T, Fukada M, Fujii H, Kurahashi K (2012) A survey of the potency of Japanese illicit cannabis in fiscal year 2010. Forensic Sci Int 221:77–83CrossRefPubMed Tsumura Y, Aoki R, Tokieda Y, Akutsu M, Kawase Y, Kataoka T, Takagi T, Mizuno T, Fukada M, Fujii H, Kurahashi K (2012) A survey of the potency of Japanese illicit cannabis in fiscal year 2010. Forensic Sci Int 221:77–83CrossRefPubMed
51.
Zurück zum Zitat Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, Gasperini C, Pozzilli C, Cefaro L, Comi G, Rossi P, Ambler Z, Stelmasiak Z, Erdmann A, Montalban X, Klimek A, Davies P, Sativex Spasticity Study Group (2011) A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol 18:1122–1131CrossRefPubMed Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, Gasperini C, Pozzilli C, Cefaro L, Comi G, Rossi P, Ambler Z, Stelmasiak Z, Erdmann A, Montalban X, Klimek A, Davies P, Sativex Spasticity Study Group (2011) A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol 18:1122–1131CrossRefPubMed
Metadaten
Titel
Urinary cannabinoid levels during nabiximols (Sativex®)-medicated inpatient cannabis withdrawal
verfasst von
Richard C. Kevin
David J. Allsop
Nicholas Lintzeris
Adrian J. Dunlop
Jessica Booth
Iain S. McGregor
Publikationsdatum
04.08.2016
Verlag
Springer Japan
Erschienen in
Forensic Toxicology / Ausgabe 1/2017
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-016-0330-0

Weitere Artikel der Ausgabe 1/2017

Forensic Toxicology 1/2017 Zur Ausgabe

Neu im Fachgebiet Rechtsmedizin