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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Vaporized Delta-9-tetrahydrocannabinol Inhalation in Female Sprague Dawley Rats: A Pharmacokinetic and Behavioral Assessment

Author(s): Samantha L. Penman, Erin C. Berthold, Abrianna Mihalkovic, Nikki Hammond, Christopher R. McCurdy, Kenneth Blum, Rina D. Eiden, Abhisheak Sharma and Panayotis K. Thanos*

Volume 29, Issue 27, 2023

Published on: 03 May, 2023

Page: [2149 - 2160] Pages: 12

DOI: 10.2174/1381612829666230419093809

Price: $65

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Abstract

Background: Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of cannabis. Historically, rodent studies examining the effects of THC have used intraperitoneal injection as the route of administration, heavily focusing on male subjects. However, human cannabis use is often through inhalation rather than injection.

Objective: We sought to characterize the pharmacokinetic and phenotypic profile of acutely inhaled THC in female rats, compared to intraperitoneal injection, to identify any differences in exposure of THC between routes of administration.

Methods: Adult female rats were administered THC via inhalation or intraperitoneal injection. Serum samples from multiple time points were analyzed for THC and metabolites 11-hydroxy-delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol using ultra-performance liquid chromatography-tandem mass spectrometry. Rats were similarly treated for locomotor activity analysis.

Results: Rats treated with 2 mg/kg THC intraperitoneally reached a maximum serum THC concentration of 107.7 ± 21.9 ng/mL. Multiple THC inhalation doses were also examined (0.25 mL of 40 or 160 mg/mL THC), achieving maximum concentrations of 43.3 ± 7.2 and 71.6 ± 22.5 ng/mL THC in serum, respectively. Significantly reduced vertical locomotor activity was observed in the lower inhaled dose of THC and the intraperitoneal injected THC dose compared to vehicle treatment.

Conclusion: This study established a simple rodent model of inhaled THC, demonstrating the pharmacokinetic and locomotor profile of acute THC inhalation, compared to an i.p. injected THC dose in female subjects. These results will help support future inhalation THC rat research which is especially important when researching behavior and neurochemical effects of inhaled THC as a model of human cannabis use.

Keywords: Delta-9-tetrahydrocannabinol (THC), cannabis, liquid-chromatography/mass-spectrometry, rodent, serum, locomotor activity.

« Previous Next »
[1]
Marijuana DrugFacts 2019. Available from: https://nida.nih.gov/publications/drugfacts/cannabis-marijuana
[2]
Yu B, Chen X, Chen X, Yan H. Marijuana legalization and historical trends in marijuana use among US residents aged 12-25: Results from the 1979-2016 National Survey on drug use and health. BMC Public Health 2020; 20(1): 156.
[http://dx.doi.org/10.1186/s12889-020-8253-4] [PMID: 32013937]
[3]
Laaris N, Good CH, Lupica CR. Δ9-tetrahydrocannabinol is a full agonist at CB1 receptors on GABA neuron axon terminals in the hippocampus. Neuropharmacology 2010; 59(1-2): 121-7.
[http://dx.doi.org/10.1016/j.neuropharm.2010.04.013] [PMID: 20417220]
[4]
Pertwee RG, Howlett AC, Abood ME, et al. International union of basic and clinical pharmacology. lxxix. cannabinoid receptors and their ligands: Beyond CB₁ and CB₂. Pharmacol Rev 2010; 62(4): 588-631.
[http://dx.doi.org/10.1124/pr.110.003004] [PMID: 21079038]
[5]
Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006; 58(3): 389-462.
[http://dx.doi.org/10.1124/pr.58.3.2] [PMID: 16968947]
[6]
Mackie K. Cannabinoid receptors: Where they are and what they do. J Neuroendocrinol 2008; 20(S1): 10-4.
[http://dx.doi.org/10.1111/j.1365-2826.2008.01671.x] [PMID: 18426493]
[7]
Crean RD, Crane NA, Mason BJ. An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. J Addict Med 2011; 5(1): 1-8.
[http://dx.doi.org/10.1097/ADM.0b013e31820c23fa] [PMID: 21321675]
[8]
Broyd SJ, van Hell HH, Beale C, Yücel M, Solowij N. Acute and chronic effects of cannabinoids on human cognition-A systematic review. Biol Psychiatry 2016; 79(7): 557-67.
[http://dx.doi.org/10.1016/j.biopsych.2015.12.002] [PMID: 26858214]
[9]
Elikkottil J, Gupta P, Gupta K. The analgesic potential of cannabinoids. J Opioid Manag 2009; 5(6): 341-57.
[http://dx.doi.org/10.5055/jom.2009.0034] [PMID: 20073408]
[10]
Farokhnia M, McDiarmid GR, Newmeyer MN, et al. Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: A randomized, double-blind, placebo-controlled, human laboratory study. Transl Psychiatry 2020; 10(1): 71.
[http://dx.doi.org/10.1038/s41398-020-0756-3] [PMID: 32075958]
[11]
Cohen K, Weinstein A. The effects of cannabinoids on executive functions: Evidence from cannabis and synthetic cannabinoids-A systematic review. Brain Sci 2018; 8(3): 40.
[http://dx.doi.org/10.3390/brainsci8030040] [PMID: 29495540]
[12]
Harris HM, Rousseau MA, Wanas AS, et al. Role of cannabinoids and terpenes in cannabis-mediated analgesia in rats. Cannabis Cannabinoid Res 2019; 4(3): 177-82.
[http://dx.doi.org/10.1089/can.2018.0054] [PMID: 31579834]
[13]
Farrimond JA, Mercier MS, Whalley BJ, Williams CM. Cannabis sativa and the endogenous cannabinoid system: Therapeutic potential for appetite regulation. Phytother Res 2011; 25(2): 170-88.
[http://dx.doi.org/10.1002/ptr.3375] [PMID: 21213357]
[14]
Ohlsson A, Lindgren J-E, Wahlen A, Agurell S, Hollister LE, Gillespie HK. Plasma delta-9-tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther 1980; 28(3): 409-16.
[http://dx.doi.org/10.1038/clpt.1980.181] [PMID: 6250760]
[15]
Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers 2007; 4(8): 1770-804.
[http://dx.doi.org/10.1002/cbdv.200790152] [PMID: 17712819]
[16]
Huestis MA, Henningfield JE, Cone EJ. Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J Anal Toxicol 1992; 16(5): 276-82.
[http://dx.doi.org/10.1093/jat/16.5.276] [PMID: 1338215]
[17]
Lee D, Bergamaschi MM, Milman G, et al. Plasma cannabinoid pharmacokinetics after controlled smoking and ad libitum cannabis smoking in chronic frequent users. J Anal Toxicol 2015; 39(8): 580-7.
[http://dx.doi.org/10.1093/jat/bkv082] [PMID: 26378131]
[18]
Spindle TR, Cone EJ, Schlienz NJ, et al. Acute pharmacokinetic profile of smoked and vaporized cannabis in human blood and oral fluid. J Anal Toxicol 2019; 43(4): 233-58.
[http://dx.doi.org/10.1093/jat/bky104] [PMID: 30615181]
[19]
Hartman RL, Brown TL, Milavetz G, et al. Controlled Cannabis vaporizer administration: Blood and plasma cannabinoids with and without alcohol. Clin Chem 2015; 61(6): 850-69.
[http://dx.doi.org/10.1373/clinchem.2015.238287] [PMID: 26019183]
[20]
Meyer P, Langos M, Brenneisen R. Human pharmacokinetics and adverse effects of pulmonary and intravenous THC-CBD formulations. Med Cannabis Cannabinoids 2018; 1(1): 36-43.
[http://dx.doi.org/10.1159/000489034] [PMID: 34676320]
[21]
Nguyen JD, Aarde SM, Vandewater SA, et al. Inhaled delivery of Δ9-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology. Neuropharmacology 2016; 109: 112-20.
[http://dx.doi.org/10.1016/j.neuropharm.2016.05.021] [PMID: 27256501]
[22]
Manwell LA, Charchoglyan A, Brewer D, Matthews BA, Heipel H, Mallet PE. A vapourized Δ9-tetrahydrocannabinol (Δ9-THC) delivery system part I: Development and validation of a pulmonary cannabinoid route of exposure for experimental pharmacology studies in rodents. J Pharmacol Toxicol Methods 2014; 70(1): 120-7.
[http://dx.doi.org/10.1016/j.vascn.2014.06.006] [PMID: 24973534]
[23]
Taffe MA, Creehan KM, Vandewater SA, Kerr TM, Cole M. Effects of Δ9-tetrahydrocannabinol (THC) vapor inhalation in Sprague-Dawley and Wistar rats. Exp Clin Psychopharmacol 2021; 29(1): 1-13.
[http://dx.doi.org/10.1037/pha0000373] [PMID: 32297788]
[24]
Baglot SL, Hume C, Petrie GN, et al. Pharmacokinetics and central accumulation of delta-9-tetrahydrocannabinol (THC) and its bioactive metabolites are influenced by route of administration and sex in rats. Sci Rep 2021; 11(1): 23990.
[http://dx.doi.org/10.1038/s41598-021-03242-7] [PMID: 34907248]
[25]
Wiley JL, O’Connell MM, Tokarz ME, Wright MJ Jr. Pharmacological effects of acute and repeated administration of Delta(9)-tetrahydrocannabinol in adolescent and adult rats. J Pharmacol Exp Ther 2007; 320(3): 1097-105.
[http://dx.doi.org/10.1124/jpet.106.108126] [PMID: 17172531]
[26]
Harte-Hargrove LC, Dow-Edwards DL. Withdrawal from THC during adolescence: Sex differences in locomotor activity and anxiety. Behav Brain Res 2012; 231(1): 48-59.
[http://dx.doi.org/10.1016/j.bbr.2012.02.048] [PMID: 22421367]
[27]
Taffe MA, Creehan KM, Vandewater SA. Cannabidiol fails to reverse hypothermia or locomotor suppression induced by Δ 9 -tetrahydrocannabinol in Sprague-Dawley rats. Br J Pharmacol 2015; 172(7): 1783-91.
[http://dx.doi.org/10.1111/bph.13024] [PMID: 25425111]
[28]
Bruijnzeel AW, Qi X, Guzhva LV, et al. Behavioral characterization of the effects of Cannabis smoke and anandamide in rats. PLoS One 2016; 11(4): e0153327.
[http://dx.doi.org/10.1371/journal.pone.0153327] [PMID: 27065006]
[29]
Katsidoni V, Kastellakis A, Panagis G. Biphasic effects of Δ9-tetrahydrocannabinol on brain stimulation reward and motor activity. Int J Neuropsychopharmacol 2013; 16(10): 2273-84.
[http://dx.doi.org/10.1017/S1461145713000709] [PMID: 23830148]
[30]
Metna-Laurent M, Mondésir M, Grel A, Vallée M, Piazza P-V. Cannabinoid-induced tetrad in mice. Curr Protoc Neurosci 2017; 80(1): 9.59.1-10.
[http://dx.doi.org/10.1002/cpns.31]
[31]
Martin BR, Compton DR, Thomas BF, et al. Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs. Pharmacol Biochem Behav 1991; 40(3): 471-8.
[http://dx.doi.org/10.1016/0091-3057(91)90349-7] [PMID: 1666911]
[32]
Ravula A, Chandasana H, Setlow B, Febo M, Bruijnzeel AW, Derendorf H. Simultaneous quantification of cannabinoids tetrahydrocannabinol, cannabidiol and CB1 receptor antagonist in rat plasma: An application to characterize pharmacokinetics after passive Cannabis smoke inhalation and co-administration of rimonabant. J Pharm Biomed Anal 2018; 160: 119-25.
[http://dx.doi.org/10.1016/j.jpba.2018.07.004] [PMID: 30077950]
[33]
Hložek T, Uttl L, Kadeřábek L, et al. Pharmacokinetic and behavioural profile of THC, CBD, and THC+CBD combination after pulmonary, oral, and subcutaneous administration in rats and confirmation of conversion in vivo of CBD to THC. Eur Neuropsychopharmacol 2017; 27(12): 1223-37.
[http://dx.doi.org/10.1016/j.euroneuro.2017.10.037] [PMID: 29129557]
[34]
Berthold EC, Yang R, Sharma A, et al. Regulatory sampling of industrial hemp plant samples (Cannabis sativa L.) using UPLC-MS/MS method for detection and quantification of twelve cannabinoids. J Cannabis Res 2020; 2(1): 42.
[http://dx.doi.org/10.1186/s42238-020-00050-0] [PMID: 33526142]
[35]
Bioanalytical Method Validation. Guidance for Industry. FDA 2018.
[36]
Robison LS, Michaelos M, Gandhi J, et al. Sex differences in the physiological and behavioral effects of chronic oral methylphenidate treatment in rats. Front Behav Neurosci 2017; 11: 53.
[http://dx.doi.org/10.3389/fnbeh.2017.00053] [PMID: 28400722]
[37]
Sharma A, Jaiswal S, Shukla M, et al. HPLC–MS-MS method development and validation of antileishmanial agent, S010-0269, in hamster serum. J Chromatogr Sci 2015; 53(9): 1542-8.
[http://dx.doi.org/10.1093/chromsci/bmv050] [PMID: 25935158]
[38]
OEHHA. Calculation of Rat Breathing Rate Based on Bodyweight. California Environmental Protection Agency 2018.
[39]
Hazekamp A, Ruhaak R, Zuurman L, van Gerven J, Verpoorte R. Evaluation of a vaporizing device (Volcano®) for the pulmonary administration of tetrahydrocannabinol. J Pharm Sci 2006; 95(6): 1308-17.
[http://dx.doi.org/10.1002/jps.20574] [PMID: 16637053]
[40]
Nair A, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 2016; 7(2): 27-31.
[http://dx.doi.org/10.4103/0976-0105.177703] [PMID: 27057123]
[41]
Miladinovic T, Manwell LA, Raaphorst E, Malecki SL, Rana SA, Mallet PE. Effects of chronic nicotine exposure on Δ9-tetrahydrocannabinol-induced locomotor activity and neural activation in male and female adolescent and adult rats. Pharmacol Biochem Behav 2020; 194: 172931.
[http://dx.doi.org/10.1016/j.pbb.2020.172931] [PMID: 32353393]
[42]
Abela AR, Rahbarnia A, Wood S, Lê AD, Fletcher PJ. Adolescent exposure to Δ9-tetrahydrocannabinol delays acquisition of paired-associates learning in adulthood. Psychopharmacology 2019; 236(6): 1875-86.
[http://dx.doi.org/10.1007/s00213-019-5171-1] [PMID: 30694374]
[43]
Cha YM, White AM, Kuhn CM, Wilson WA, Swartzwelder HS. Differential effects of delta9-THC on learning in adolescent and adult rats. Pharmacol Biochem Behav 2006; 83(3): 448-55.
[http://dx.doi.org/10.1016/j.pbb.2006.03.006] [PMID: 16631921]
[44]
Ruiz CM, Torrens A, Castillo E, et al. Pharmacokinetic, behavioral, and brain activity effects of Δ9-tetrahydrocannabinol in adolescent male and female rats. Neuropsychopharmacology 2021; 46(5): 959-69.
[http://dx.doi.org/10.1038/s41386-020-00839-w] [PMID: 32927465]
[45]
Vozella V, Zibardi C, Ahmed F, Piomelli D. Fast and sensitive quantification of Δ9-tetrahydrocannabinol and its main oxidative metabolites by liquid chromatography/tandem mass spectrometry. Cannabis Cannabinoid Res 2019; 4(2): 110-23.
[http://dx.doi.org/10.1089/can.2018.0075] [PMID: 31236476]
[46]
Karschner EL, Schwilke EW, Lowe RH, et al. Do Δ9-tetra-hydrocannabinol concentrations indicate recent use in chronic cannabis users? Addiction 2009; 104(12): 2041-8.
[http://dx.doi.org/10.1111/j.1360-0443.2009.02705.x] [PMID: 19804462]
[47]
Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 2003; 42(4): 327-60.
[http://dx.doi.org/10.2165/00003088-200342040-00003] [PMID: 12648025]
[48]
Martignoni M, Groothuis GMM, de Kanter R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol 2006; 2(6): 875-94.
[http://dx.doi.org/10.1517/17425255.2.6.875] [PMID: 17125407]
[49]
Harvey DJ, Brown NK. Comparative in vitro metabolism of the cannabinoids. Pharmacol Biochem Behav 1991; 40(3): 533-40.
[http://dx.doi.org/10.1016/0091-3057(91)90359-A] [PMID: 1806943]
[50]
Nguyen JD, Creehan KM, Grant Y, Vandewater SA, Kerr TM, Taffe MA. Explication of CB1 receptor contributions to the hypothermic effects of Δ9-tetrahydrocannabinol (THC) when delivered by vapor inhalation or parenteral injection in rats. Drug Alcohol Depend 2020; 214: 108166.
[http://dx.doi.org/10.1016/j.drugalcdep.2020.108166] [PMID: 32717503]
[51]
Fokos S, Panagis G. Effects of Δ9-tetrahydrocannabinol on reward and anxiety in rats exposed to chronic unpredictable stress. J Psychopharmacol 2010; 24(5): 767-77.
[http://dx.doi.org/10.1177/0269881109104904] [PMID: 19406854]
[52]
Rubino T, Sala M, Viganò D, et al. Cellular mechanisms underlying the anxiolytic effect of low doses of peripheral Δ9-tetrahydrocannabinol in rats. Neuropsychopharmacology 2007; 32(9): 2036-45.
[http://dx.doi.org/10.1038/sj.npp.1301330] [PMID: 17287821]
[53]
Berrendero F, Maldonado R. Involvement of the opioid system in the anxiolytic-like effects induced by Δ9-tetrahydrocannabinol. Psychopharmacology 2002; 163(1): 111-7.
[http://dx.doi.org/10.1007/s00213-002-1144-9] [PMID: 12185408]
[54]
Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: A review. Eur J Pharmacol 2003; 463(1-3): 3-33.
[http://dx.doi.org/10.1016/S0014-2999(03)01272-X] [PMID: 12600700]
[55]
Breit KR, Rodriguez CG, Lei A, Thomas JD. Combined vapor exposure to THC and alcohol in pregnant rats: Maternal outcomes and pharmacokinetic effects. Neurotoxicol Teratol 2020; 82: 106930.
[http://dx.doi.org/10.1016/j.ntt.2020.106930] [PMID: 33086086]
[56]
Moore CF, Davis CM, Harvey EL, Taffe MA, Weerts EM. Appetitive, antinociceptive, and hypothermic effects of vaped and injected Δ9-tetrahydrocannabinol (THC) in rats: Exposure and dose-effect comparisons by strain and sex. Pharmacol Biochem Behav 2021; 202: 173116.
[http://dx.doi.org/10.1016/j.pbb.2021.173116] [PMID: 33493547]
[57]
Nguyen JD, Grant Y, Kerr TM, Gutierrez A, Cole M, Taffe MA. Tolerance to hypothermic and antinoceptive effects of ∆9-tetrahydrocannabinol (THC) vapor inhalation in rats. Pharmacol Biochem Behav 2018; 172: 33-8.
[http://dx.doi.org/10.1016/j.pbb.2018.07.007] [PMID: 30031028]
[58]
Lankenau SE, Fedorova EV, Reed M, Schrager SM, Iverson E, Wong CF. Marijuana practices and patterns of use among young adult medical marijuana patients and non-patient marijuana users. Drug Alcohol Depend 2017; 170: 181-8.
[http://dx.doi.org/10.1016/j.drugalcdep.2016.10.025] [PMID: 27987475]
[59]
Steigerwald S, Wong PO, Cohen BE, et al. Smoking, vaping, and use of edibles and other forms of marijuana among U.S. adults. Ann Intern Med 2018; 169(12): 890-2.
[http://dx.doi.org/10.7326/M18-1681] [PMID: 30167665]
[60]
McLaren J, Swift W, Dillon P, Allsop S. Cannabis potency and contamination: A review of the literature. Addiction 2008; 103(7): 1100-9.
[http://dx.doi.org/10.1111/j.1360-0443.2008.02230.x] [PMID: 18494838]
[61]
ElSohly MA, Mehmedic Z, Foster S, Gon C, Chandra S, Church JC. Changes in cannabis potency over the last 2 decades (1995-2014): Analysis of current data in the United States. Biol Psychiatry 2016; 79(7): 613-9.
[http://dx.doi.org/10.1016/j.biopsych.2016.01.004] [PMID: 26903403]
[62]
Ramaekers JG, van Wel JH, Spronk DB, et al. Cannabis and tolerance: Acute drug impairment as a function of cannabis use history. Sci Rep 2016; 6(1): 26843.
[http://dx.doi.org/10.1038/srep26843] [PMID: 27225696]
[63]
Lukas G, Brindle SD, Greengard P. The route of absorption of intraperitoneally administered compounds. J Pharmacol Exp Ther 1971; 178(3): 562-4.
[PMID: 5571904]
[64]
Al Shoyaib A, Archie SR, Karamyan VT. Intraperitoneal route of drug administration: Should it be used in experimental animal studies? Pharm Res 2020; 37(1): 12.
[http://dx.doi.org/10.1007/s11095-019-2745-x] [PMID: 31873819]
[65]
Wiley JL, Taylor SI, Marusich JA. Δ9-Tetrahydrocannabinol discrimination: Effects of route of administration in rats. Drug Alcohol Depend 2021; 225: 108827.
[http://dx.doi.org/10.1016/j.drugalcdep.2021.108827] [PMID: 34186444]
[66]
Wiley JL, Barrus DG, Farquhar CE, Lefever TW, Gamage TF. Sex, species and age: Effects of rodent demographics on the pharmacology of Δ9-tetrahydrocanabinol. Prog Neuropsychopharmacol Biol Psychiatry 2021; 106: 110064.
[http://dx.doi.org/10.1016/j.pnpbp.2020.110064] [PMID: 32810571]
[67]
Wiley JL, Burston JJ. Sex differences in Δ9-tetrahydrocannabinol metabolism and in vivo pharmacology following acute and repeated dosing in adolescent rats. Neurosci Lett 2014; 576: 51-5.
[http://dx.doi.org/10.1016/j.neulet.2014.05.057] [PMID: 24909619]
[68]
Farquhar CE, Breivogel CS, Gamage TF, et al. Sex, THC, and hormones: Effects on density and sensitivity of CB1 cannabinoid receptors in rats. Drug Alcohol Depend 2019; 194: 20-7.
[http://dx.doi.org/10.1016/j.drugalcdep.2018.09.018] [PMID: 30391834]
[69]
Johansson E, Agurell S, Hollister LE, Halldin MM. Prolonged apparent half-life of Δ1-tetrahydrocannabinol in plasma of chronic marijuana users. J Pharm Pharmacol 2011; 40(5): 374-5.
[http://dx.doi.org/10.1111/j.2042-7158.1988.tb05272.x] [PMID: 2899638]
[70]
Desrosiers NA, Himes SK, Scheidweiler KB, Concheiro-Guisan M, Gorelick DA, Huestis MA. Phase I and II cannabinoid disposition in blood and plasma of occasional and frequent smokers following controlled smoked cannabis. Clin Chem 2014; 60(4): 631-43.
[http://dx.doi.org/10.1373/clinchem.2013.216507] [PMID: 24563491]
[71]
Newmeyer MN, Swortwood MJ, Barnes AJ, Abulseoud OA, Scheidweiler KB, Huestis MA. Free and glucuronide whole blood cannabinoids’ pharmacokinetics after controlled smoked, vaporized, and oral cannabis administration in frequent and occasional cannabis users: Identification of recent cannabis intake. Clin Chem 2016; 62(12): 1579-92.
[http://dx.doi.org/10.1373/clinchem.2016.263475] [PMID: 27899456]

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