Pharmacokinetics and pharmacodynamics of drugs abused in driving

  • Marilyn A. Huestis
  • Michael L. Smith


Driving under the influence of impairing drugs is a prevalent and preventable worldwide problem. Scientists are conducting pharmacodynamic and pharmacokinetic studies to help officials identify drugged drivers and remove them from the roadways. Current approaches for drugs of abuse other than alcohol first determine an estimate of time of use from concentrations of drugs and metabolites in bodily fluids following controlled drug administration. The degree of driving impairment is then suggested based on the time course of effects from pharmacodynamic studies. Reasonable estimates of impairment can be made based on currently available studies for cannabis, cocaine, amphetamines and opioids. Predictive models were published relating cannabinoid concentrations in plasma and whole blood with time of use following various routes of administration and doses. Results of performance tests and driving simulators after controlled cannabis dosing document impairment at various times after use and show that impairment can last up to eight hours for many tasks and 24 hours for complex divided-attention tasks. A few studies on other drugs report expected plasma or oral fluid concentrations with time after drug administration. Degree of impairment is dependant on dose, route of administration, and tolerance. Further pharmacokinetic and pharmacodynamic studies are needed to guide drug concentration interpretation, to develop predictive models for other drugs, and to guide development of science-based drugged driving legislation.


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  1. 1.
    Walsh JM VA, Huestis MA, Morland J (2007) Guidelines for Drugged Driving Research: Talloires Report, Talloires, FranceGoogle Scholar
  2. 2.
    Huestis MA, Smith ML (2006) Human cannabinoid pharmacokinetics and interpretation of cannabinoid concentrations in biological fluids and tissues. In: MA ElSohly (ed): Marijuana and the Cannabinoids. Humana Press, Totawa, New Jersey, 205–236Google Scholar
  3. 3.
    (2007) The Nation’s Top Strategies to Stop Impaired Driving. In: U S Department of Transportation, National Highway Traffic Safety Administration Report,, accessed 2/7/2008Google Scholar
  4. 4.
    Garriott J (ed) (2003) Medico-Legal Aspects of Alcohol. Lawyers & Judges Publishing Company, Inc., TucsonGoogle Scholar
  5. 5.
    Borkenstein RF (1987) An historical survey of alcohol, drugs and traffic safety — research highlights. In: PC Noordzij, R Roszbach, JJ de Gier, W Neuteboom, PGM Zweipfenning (eds): Alcohol, Drugs and Traffic Safety — T 86. Excerpta Medica, Amsterdam, 51–60Google Scholar
  6. 6.
    Huestis MA, Henningfield JE, Cone EJ (1992) Blood cannabinoids. II. Models for the prediction of time of marijuana exposure from plasma concentrations of delta-9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THCCOOH). J Anal Toxicol 16: 283–290PubMedGoogle Scholar
  7. 7.
    Huestis MA, Barnes A, Smith ML (2005) Estimating the time of last cannabis use from plasma delta9-tetrahydrocannabinol and 11-nor-9-carboxy-delta9-tetrahydrocannabinol concentrations. Clin Chem 51: 2289–2295PubMedGoogle Scholar
  8. 8.
    Huestis MA, Elsohly M, Nebro W, Barnes A, Gustafson RA, Smith ML (2006) Estimating time of last oral ingestion of cannabis from plasma THC and THCCOOH concentrations. Ther Drug Monit 28: 540–544PubMedGoogle Scholar
  9. 9.
    Cone EJ, Holicky BA, Grant TM, Darwin WD, Goldberger BA (1993) Pharmacokinetics and pharmacodynamics of intranasal “snorted” heroin. J Anal Toxicol 17: 327–337PubMedGoogle Scholar
  10. 10.
    Jenkins AJ, Keenan RM, Henningfield JE, Cone EJ (1994) Pharmacokinetics and pharmacodynamics of smoked heroin. J Anal Toxicol 18: 317–330PubMedGoogle Scholar
  11. 11.
    Huestis MA (2007) Human cannabinoid pharmacokinetics. Chem Biodivers 4: 1770–1804PubMedGoogle Scholar
  12. 12.
    Huestis MA, Boyd SJ, Heishman SJ, Preston KL, Bonnet D, Le Fur G, Gorelick DA (2007) Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Psychopharmacology (Berl) Google Scholar
  13. 13.
    Huestis MA, Sampson AH, Holicky BJ, Henningfield JE, Cone EJ (1992) Characterization of the absorption phase of marijuana smoking. Clin Pharmacol Ther 52: 31–41PubMedGoogle Scholar
  14. 14.
    Huestis MA, Henningfield JE, Cone EJ (1992) Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J Anal Toxicol 16: 276–282PubMedGoogle Scholar
  15. 15.
    Huestis MA (2005) Pharmacokinetics and metabolism of the plant cannabinoids, delta-9-tetrahydrocannabinol, cannabidiol and cannabinol. In: RG Pertwee (ed): Handbook of Experimental Pharmacology, Volume 168. Springer, New York, 657–690Google Scholar
  16. 16.
    Turner CE, ElSohly MA, Boeren EG (1980) Constituents of cannabis sativa L. XVII. a review of the natural constituents. J Nat Prod 43: 169–234PubMedGoogle Scholar
  17. 17.
    Claussen U, Korte F (1968) Über das Verhalten von Hanf und von delta-9-6a, 10a-transtetrahydrocannabinol beim Rauchen. Justus Liebigs.Ann.Chem. 713: 162–165PubMedGoogle Scholar
  18. 18.
    ElSohly HN, Boeren EG, Turner CE, ElSohly MA (1984) Constituents of cannabis sativa L. XXIV: Cannabitetrol, a new polyhydroxylated cannabinoid. In: S Agurell, WL Dewey, RE Willette (eds): The Cannabinoids: Chemical, Pharmacologic and Therapeutic Aspects. Academic Press, Inc., Orlando, 89–96Google Scholar
  19. 19.
    Perez-Reyes M, Di Guiseppi S, Davis KH, Schindler VH, Cook CE (1982) Comparison of effects of marijuana cigarettes of three different potencies. Clin Pharmacol Ther 31: 617–624PubMedGoogle Scholar
  20. 20.
    Mechoulam R (1970) Marihuana chemistry. Science 168: 1159–1166PubMedGoogle Scholar
  21. 21.
    Ohlsson A, Lindgren JE, Wahlen A, Agurell S, Hollister LE, Gillespie HK (1980) Plasma delta-9-tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther 28: 409–416PubMedGoogle Scholar
  22. 22.
    Agurell S, Leander K (1971) Stability, transfer and absorption of cannabinoid constituents of cannabis (hashish) during smoking. Acta Pharm Suec 8: 391–402PubMedGoogle Scholar
  23. 23.
    Ohlsson A, Agurell S, Londgren JE, Gillespie HK, Hollister LE (1985) Pharmacokinetic studies of delta-1-tetrahydrocannabinol in man. In: G Barnett, CN Chiang (eds): Pharmacokinetics and Pharmacodynamics of Psychoactive Drugs. Mosby Yearbook, Inc., St. Louis, 75–92Google Scholar
  24. 24.
    Agurell S, Halldin M, Lindgren JE, Ohlsson A, Widman M, Gillespie H, Hollister L (1986) Pharmacokinetics and metabolism of delta-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacol Rev 38: 21–43PubMedGoogle Scholar
  25. 25.
    Ohlsson A, Lindgren JE, Wahlen A, Agurell S, Hollister LE, Gillespie HK (1982) Single dose kinetics of deuterium labelled delta-1-tetrahydrocannabinol in heavy and light cannabis users. Biomed Mass Spectrom 9: 6–10PubMedGoogle Scholar
  26. 26.
    Azorlosa JL, Heishman SJ, Stitzer ML, Mahaffey JM (1992) Marijuana smoking: Effect of varying delta 9-tetrahydrocannabinol content and number of puffs. J Pharmacol Exp Ther 261(1): 114–122PubMedGoogle Scholar
  27. 27.
    Heishman SJ, Stitzer ML, Yingling JE (1989) Effects of tetrahydrocannabinol content on marijuana smoking behavior, subjective reports, and performance. Pharmacol Biochem Behav 34: 173–179PubMedGoogle Scholar
  28. 28.
    Perez-Reyes M (1990) Marijuana smoking: factors that influence the bioavailability of tetrahydrocannabinol. In: CN Chiang, RL Hawks (eds): Research Findings on Smoking of Abused Substances. NIDA Research Monograph #99, Rockville, 42–62Google Scholar
  29. 29.
    Cami J, Guerra D, Ugena B, Segura J, de La Torre R (1991) Effect of subject expectancy on the THC intoxication and disposition from smoked hashish cigarettes. Pharmacol Biochem Behav 40: 115–119PubMedGoogle Scholar
  30. 30.
    Perez-Reyes M, Owens SM, Di Guiseppi S (1981) The clinical pharmacology and dynamics of marijuana cigarette smoking. J Clin Pharmacol 21: 201S–207SPubMedGoogle Scholar
  31. 31.
    Harder S, Rietbrock S (1997) Concentration-effect relationship of delta-9-tetrahydrocannabiol and prediction of psychotropic effects after smoking marijuana. Int J Clin Pharmacol Ther 35: 155–159PubMedGoogle Scholar
  32. 32.
    Law B, Mason PA, Moffat AC, Gleadle RI, King LJ (1984) Forensic aspects of the metabolism and excretion of cannabinoids following oral ingestion of cannabis resin. J Pharm Pharmacol 36: 289–294PubMedGoogle Scholar
  33. 33.
    Ohlsson A, Lindgren JE, Wahlen A, Agurell S, Hollister LE, Gillespie HK (1981) Plasma levels of delta-9-tetrahydrocannabinol after intravenous, oral and smoke administration. NIDA Research Monograph 34: 250–256PubMedGoogle Scholar
  34. 34.
    Perez-Reyes M, Lipton MA, Timmons MC, Wall ME, Brine DR, Davis KH (1973) Pharmacology of orally administered delta-9-tetrahydrocannabinol. Clin Pharmacol Ther 14: 48–55PubMedGoogle Scholar
  35. 35.
    Wall ME, Sadler BM, Brine D, Taylor H, Perez-Reyes M (1983) Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol Ther 34: 352–363PubMedGoogle Scholar
  36. 36.
    Nadulski T, Sporkert F, Schnelle M, Stadelmann AM, Roser P, Schefter T, Pragst F (2005) Simultaneous and sensitive analysis of THC, 11-OH-THC, THC-COOH, CBD, and CBN by GC-MS in plasma after oral application of small doses of THC and cannabis extract. J Anal Toxicol 29: 782–789PubMedGoogle Scholar
  37. 37.
    Binitie A (1975) Psychosis following ingestion of hemp in children. Psychopharmacologia 44: 301–302PubMedGoogle Scholar
  38. 38.
    Meier HJ, Vonesch HJ (1997) Cannabis-intoxikation nach salatgenuss. Schweiz Med Wochenschr 127: 214–218PubMedGoogle Scholar
  39. 39.
    Goodwin RS, Gustafson RA, Barnes A, Nebro W, Moolchan ET, Huestis MA (2006) Delta(9)-tetrahydrocannabinol, 11-hydroxy-delta(9)-tetrahydrocannabinol and 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in human plasma after controlled oral administration of cannabinoids. Ther Drug Monit 28: 545–551PubMedGoogle Scholar
  40. 40.
    Lemberger L, Silberstein SD, Axelrod J, Kopin IJ (1970) Marihuana: studies on the disposition and metabolism of delta-9-tetrahydrocannabinol in man. Science 170: 1320–1322PubMedGoogle Scholar
  41. 41.
    Adams IB, Martin BR (1996) Cannabis: pharmacology and toxicology in animals and humans. Addiction 91(11): 1585–1614PubMedGoogle Scholar
  42. 42.
    Chiang CN, Rapaka RS (1987) Pharmacokinetics and disposition of cannabinoids. In: RS Rapaka, A Makriyannis (eds): NIDA Research Monograph-Structure-Activity Relationships of the Cannabinoids. National Institute on Drug Abuse, Rockville, 173–188Google Scholar
  43. 43.
    Perez-Reyes M, Timmons MC, Lipton MA, Davis KH, Wall ME (1972) Intravenous injection in man of delta-9-tetrahydrocannabinol and 11-OH-delta-9-tetrahydrocannabinol. Science 177: 633–635PubMedGoogle Scholar
  44. 44.
    Hunt CA, Jones RT (1980) Tolerance and disposition of tetrahydrocannabinol in man. J Pharmacol Exp Ther 215: 35–44PubMedGoogle Scholar
  45. 45.
    Kelly P, Jones RT (1992) Metabolism of tetrahydrocannabinol in frequent and infrequent marijuana users. J Anal Toxicol 16: 228–235PubMedGoogle Scholar
  46. 46.
    Grotenhermen F (2003) Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 42: 327–360PubMedGoogle Scholar
  47. 47.
    Harvey DJ (2001) Absorption, distribution, and biotransformation of the cannabinoids. In: GG Nahas, KM Sutin, DJ Harvey, S Agurell (eds): Marijuana and Medicine. Humana Press, Totowa, 91–103Google Scholar
  48. 48.
    Johansson E, Noren K, Sjovall J, Halldin MM (1989) Determination of delta-1-tetrahydrocannabinol in human fat biopsies from marihuana users by gas chromatography-mass spectrometry. Biomed Chromatogr 3: 35–38PubMedGoogle Scholar
  49. 49.
    Kreuz DS, Axelrod J (1973) Delta-9-tetrahydrocannabinol: Localization in body fat. Science 179: 391–393PubMedGoogle Scholar
  50. 50.
    Garrett ER, Hunt CA (1977) Pharmacokinetics of delta-9-tetrahydrocannabinol in dogs. J Pharm Sci 66: 395–406PubMedGoogle Scholar
  51. 51.
    Dewey WL, McMillan DE, Harris LS, Turk RF (1972) Distribution of radioactivity in brain of tolerant and nontolerant pigeons treated with 3-H-delta-9-tetrahydrocannabinol. Biochemical Pharmacology 22: 399–405Google Scholar
  52. 52.
    Matsunaga T, Iwawaki Y, Watanabe K, Yamamoto I, Kageyama T, Yoshimura H (1995) Metabolism of delta-9-tetrahydrocannabinol by cytochrome P450 isozymes purified from hepatic microsomes of monkeys. Life Sci 56: 2089–2095PubMedGoogle Scholar
  53. 53.
    Harvey DJ, Paton WDM (1986) Metabolism of the cannabinoids. Rev Biochem Toxicol 6: 221–264Google Scholar
  54. 54.
    Bornheim LM, Lasker JM, Raucy JL (1992) Human hepatic microsomal metabolism of delta-1-tetrahydrocannabinol. Drug Metab Dispos 20(2): 241–246PubMedGoogle Scholar
  55. 55.
    McBurney LJ, Bobbie BA, Sepp LA (1986) GC/MS and Emit analyses for delta-9-tetrahydrocannabinol metabolites in plasma and urine of human subjects. J Anal Toxicol 10: 56–64PubMedGoogle Scholar
  56. 56.
    Mechoulam R, Zvi ZB, Agurell S, Nilsson IM, Nilsson JLG, Edery H, Grunfeld Y (1973) Delta-6 tetrahydrocannabinol-7-oic acid, a urinary delta-6-THC metabolite: isolation and synthesis. Experientia 29: 1193–1195PubMedGoogle Scholar
  57. 57.
    Halldin MM, Widman M, Bahr CV, Lindgren JE, Martin BR (1982) Identification of in vitro metabolites of delta-tetrahydrocannabinol formed by human livers. Drug Metab Dispos 10: 297–301PubMedGoogle Scholar
  58. 58.
    Mason AP, McBay AJ (1985) Cannabis: Pharmacology and interpretation of effects. J Forensic Sci 30: 615–631PubMedGoogle Scholar
  59. 59.
    Lemberger L, Tamarkin NR, Axelrod J (1971) Delta-9-tetrahydrocannabinol: metabolism and disposition in long-term marihuana smokers. Science 173: 72–74PubMedGoogle Scholar
  60. 60.
    Williams PL, Moffat AC (1980) Identification in human urine of delta-9-tetrahydrocannabinol-11-oic glucuronide: a tetrahydrocannabinol metabolite. J Pharm Pharmacol 32: 445–448PubMedGoogle Scholar
  61. 61.
    Kemp PM, Abukhalaf IK, Manno JE, Manno BR, Alford DD, McWilliams ME, Nixon FE, Fitzgerald MJ, Reeves RR, Wood MJ (1995) Cannabinoids in humans. II. The influence of three methods of hydrolysis on the concentration of THC and two metabolites in urine. J Anal Toxicol 19: 292–298PubMedGoogle Scholar
  62. 62.
    Kemp PM, Abukhalaf IK, Manno JE, Manno BR, Alford DD, Abusada GA (1995) Cannabinoids in humans. I. Analysis of delta-9-tetrahydrocannabinol and six metabolites in plasma and urine using GC-MS. J Anal Toxicol 19: 285–291PubMedGoogle Scholar
  63. 63.
    Johansson E, Agurell S, Hollister LE, Halldin MM (1988) Prolonged apparent half-life of delta-1-tetrahydrocannabinol in plasma of chronic marijuana users. J Pharm Pharmacol 40: 374–375PubMedGoogle Scholar
  64. 64.
    Johansson E, Halldin MM, Agurell S, Hollister LE, Gillespie HK (1989) Terminal elimination plasma half-life of delta-1-tetrahydrocannabinol (delta-1-THC) in heavy users of marijuana. Eur J Clin Pharmacol 37: 273–277PubMedGoogle Scholar
  65. 65.
    Johansson E, Halldin MM (1989) Urinary excretion half-life of delta1-tetrahydrocannabinol-7-oic acid in heavy marijuana users after smoking. J Anal Toxicol 13: 218–223PubMedGoogle Scholar
  66. 66.
    Huestis MA, Mitchell JM, Cone EJ (1996) Urinary excretion profiles of 11-nor-9-carboxydelta9-tetrahydrocannabinol in humans after single smoked doses of marijuana. J Anal Toxicol 20: 441–452PubMedGoogle Scholar
  67. 67.
    Lindgren JE, Ohlsson A, Agurell S, Hollister L, Gillespie H (1981) Clinical effects and plasma levels of delta-9-tetrahydrocannabinol (delta-9-THC) in heavy and light users of cannabis. Psychopharmacology 74: 208–212PubMedGoogle Scholar
  68. 68.
    Wall ME, Perez-Reyes M (1981) The metabolism of delta-9-tetrahydrocannabinol and related cannabinoids in man. J Clin Pharmacol 21: 178S–189SPubMedGoogle Scholar
  69. 69.
    Peat MA (1989) Distribution of delta-9-tetrahydrocannabinol and its metabolites. In: RC Baselt (ed): Advances in Analytical Toxicology II. Year Book Medical Publishers, Chicago, 186–217Google Scholar
  70. 70.
    Schwilke EW, Karschner EL, Lowe RH, Darwin WD, Huestis MA (2007) Whole blood cannabinoids in daily cannabis users during seven days of monitored abstinence: Society of Forensic Toxicologists Annual Meeting — 2007, Durham, NC, S23Google Scholar
  71. 71.
    Lowe RH, Karschner EL, Schwilke EW, Barnes AJ, Huestis MA (2007) Simultaneous quantification of delta-9-tetrahydrocannabinol (THC), 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC), and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in human plasma using two-dimensional gas chromatography, cryofocusing, and electron impact-mass spectrometry. J Chromatogr A 1163: 318–327PubMedGoogle Scholar
  72. 72.
    Huestis MA, Cone EJ (2004) Relationship of delta 9-tetrahydrocannabinol concentrations in oral fluid and plasma after controlled administration of smoked cannabis. J Anal Toxicol 28: 394–399PubMedGoogle Scholar
  73. 73.
    Daldrup T (1996) Cannabis im Strassenverkehr. Ministerium fur Wirtschaft Mittelstand, Technologie und Verkehr NRW Abschlussbericht Z.B. 3.4721: 03-02/93Google Scholar
  74. 74.
    Drasch G, von Meyer L, Roider G (2003) Absolute FahruntÜchtigkeit unter der Wirkung von Cannabis — Vorschlag fur einen Granzwert. Blutalkohol 40: 269–286Google Scholar
  75. 75.
    Musshoff F, Madea B (2006) Review of biologic matrices (urine, blood, hair) as indicators of recent or ongoing cannabis use. Ther Drug Monit 28: 155–163PubMedGoogle Scholar
  76. 76.
    Couper F, Logan B, Corbett MJ, Farrell L, Huestis M, Jeffrey W, Raemakers J, Frank JF (2004) Drugs and Human Performance Fact Sheets. National Highway Traffic Safety Administration DOT HS 809 725: 1–100Google Scholar
  77. 77.
    Chait LD, Perry JL (1994) Acute and residual effects of alcohol and marijuana, alone and in combination, on mood and performance. Psychopharmacology 115: 340–349PubMedGoogle Scholar
  78. 78.
    Hollister LE, Gillespie HK, Ohlsson A, Lindgren JE, Wahlen A, Agurell S (1981) Do plasma concentrations of delta-9-tetrahydrocannabinol reflect the degree of intoxication? J Clin Pharmacol 21: 171S–177SPubMedGoogle Scholar
  79. 79.
    Sharma S, Moskowitz H (1972) Effect of marijuana on the visual autokinetic phenomenon. Percept Mot Skills 35: 891–894PubMedGoogle Scholar
  80. 80.
    Ramaekers JG, Kauert G, van Ruitenbeek P, Theunissen EL, Schneider E, Moeller MR (2006) High-potency marijuana impairs executive function and inhibitory motor control. Neuropsychopharmacology 31: 2296–2303PubMedGoogle Scholar
  81. 81.
    Ramaekers JG, Berghaus G, van Laar M, Drummer OH (2004) Dose related risk of motor vehicle crashes after cannabis use. Drug Alcohol Depend 73: 109–119PubMedGoogle Scholar
  82. 82.
    Drummer OH, Gerostamoulos J, Batziris H, Chu M, Caplehorn J, Robertson MD, Swann P (2004) The involvement of drugs in drivers of motor vehicles killed in Australian road traffic crashes. Accid Anal Prev 36: 239–248PubMedGoogle Scholar
  83. 83.
    Heishman SJ, Huestis MA, Henningfield JE, Cone EJ (1990) Acute and residual effects of marijuana: profiles of plasma THC levels, physiological, subjective, and performance measures. Pharmacol Biochem Behav 37: 561–565PubMedGoogle Scholar
  84. 84.
    Leirer VO, Yesavage JA, Morrow DG (1991) Marijuana carryover effects on aircraft pilot performance. Aviat Space Environ Med 62: 221–227PubMedGoogle Scholar
  85. 85.
    Huestis MA (2002) Cannabis (Marijuana) — Effects on Human Behavior and Performance. In: LJ Farrell, BK Logan, KM Dubowski (eds): The Effects of Drugs on Human Performance and Behavior. Central Police University Press, Taipei, 15–60Google Scholar
  86. 86.
    Theunissen EL KG, Toennes SW, Moeller MR, Ramaekers JG (2007) Cannabis effects on cognition and psychomotor function in daily cannabis users: The International Association of Forensic Toxicologists, International Council on Alcohol, Drugs and Traffic Safety, 8th Ignition Interlock Symposium, Seattle, WA, USAGoogle Scholar
  87. 87.
    Pennings EJ, Leccese AP, Wolff FA (2002) Effects of concurrent use of alcohol and cocaine. Addiction 97: 773–783PubMedGoogle Scholar
  88. 88.
    Baselt R (2002) Disposition of Toxic Drugs and Chemicals in Man. Biomedical Publications, Foster City, CAGoogle Scholar
  89. 89.
    Cone EJ (1995) Pharmacokinetics and pharmacodynamics of cocaine. J Anal Toxicol 19: 459–478PubMedGoogle Scholar
  90. 90.
    Kolbrich E, Barnes A, Gorelick DA, Boyd SJ, Cone EJ, Huestis MA (2006) Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration. J Anal Toxicol 30: 501–510PubMedGoogle Scholar
  91. 91.
    Van Dyke C, Barash PG, Jatlow P, Byck R (1976) Cocaine: plasma concentrations after intranasal application in man. Science 191: 859–861PubMedGoogle Scholar
  92. 92.
    Javaid JI, Fischman MW, Schuster CR, Dekirmenjian H, Davis JM (1978) Cocaine plasma concentration: relation to physiological and subjective effects in humans. Science 202: 227–228PubMedGoogle Scholar
  93. 93.
    Paly D, Jatlow P, Van Dyke C, Jeri FR, Byck R (1982) Plasma cocaine concentrations during cocaine paste smoking. Life Sci 30: 731–738PubMedGoogle Scholar
  94. 94.
    Jufer RA, Wstadik A, Walsh SL, Levine BS, Cone EJ (2000) Elimination of cocaine and metabolites in plasma, saliva, and urine following repeated oral administration to human volunteers. J Anal Toxicol 24: 467–477PubMedGoogle Scholar
  95. 95.
    Moolchan ET, Cone EJ, Wstadik A, Huestis MA, Preston KL (2000) Cocaine and metabolite elimination patterns in chronic cocaine users during cessation: plasma and saliva analysis. J Anal Toxicol 24: 458–466PubMedGoogle Scholar
  96. 96.
    Jeffcoat AR, Perez-Reyes M, Hill JM, Sadler BM, Cook CE (1989) Cocaine disposition in humans after intravenous injection, nasal insufflation (snorting), or smoking. Drug Metab Dispos 17: 153–159PubMedGoogle Scholar
  97. 97.
    Isenschmid D (2006) Cocaine. In: B Levine (ed): Principles of Forensic Toxicology. AACC Press, Washington, 239–260Google Scholar
  98. 98.
    Wilson LD, Jeromin J, Garvey L, Dorbandt A (2001) Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse. Acad Emerg Med 8: 211–222PubMedGoogle Scholar
  99. 99.
    Baker J, Jatlow P, Pade P, Ramakrishnan V, McCance-Katz EF (2007) Acute cocaine responses following cocaethylene infusion. Am J Drug Alcohol Abuse 33: 619–625PubMedGoogle Scholar
  100. 100.
    Perez-Reyes M, Jeffcoat AR, Myers M, Sihler K, Cook CE (1994) Comparison in humans of the potency and pharmacokinetics of intravenously injected cocaethylene and cocaine. Psychopharmacology 116: 428–432PubMedGoogle Scholar
  101. 101.
    Levine B, Smith ML (1995) Stability of Drugs of Abuse in Biological Specimens. In: R Lui, Goldberger, BA (ed): Handbook of Workplace Drug Testing. AACC Press, Washington, 209–224Google Scholar
  102. 102.
    Huestis MA, Darwin WD, Shimomura E, Lalani SA, Trinidad DV, Jenkins AJ, Cone EJ, Jacobs AJ, Smith ML, Paul BD (2007) Cocaine and metabolites urinary excretion after controlled smoked administration. J Anal Toxicol 31: 462–468PubMedGoogle Scholar
  103. 103.
    Cook CE, Jeffcoat AR, Sadler BM, Hill JM, Voyksner RD, Pugh DE, White WR, Perez-Reyes M (1992) Pharmacokinetics of oral methamphetamine and effects of repeated daily dosing in humans. Drug Metab Dispos 20: 856–862PubMedGoogle Scholar
  104. 104.
    Cook CE, Jeffcoat AR, Hill JM, Pugh DE, Patetta PK, Sadler BM, White WR, Perez-Reyes M (1993) Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride. Drug Metab Dispos 21: 717–723PubMedGoogle Scholar
  105. 105.
    Anggard E, Gunne LM, Jonsson LE, Niklasson F (1970) Pharmacokinetic and clinical studies on amphetamine dependent subjects. Eur J Clin Pharmacol 3: 3–11Google Scholar
  106. 106.
    Mitler MM, Hajdukovic R, Erman MK (1993) Treatment of narcolepsy with methamphetamine. Sleep 16: 306–317PubMedGoogle Scholar
  107. 107.
    Perez-Reyes M, White WR, McDonald SA, Hicks RE, Jeffcoat AR, Hill JM, Cook CE (1991) Clinical effects of daily methamphetamine administration. Clin Neuropharmacol 14(4): 352–358PubMedGoogle Scholar
  108. 108.
    Schepers RJF, Oyler JM, Joseph RE, Jr., Cone EJ, Moolchan ET, Huestis MA (2003) Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers. Clin Chem 49: 121–132PubMedGoogle Scholar
  109. 109.
    Logan BK (1996) Methamphetamine and driving impairment. J Forensic Sci 41: 457–464PubMedGoogle Scholar
  110. 110.
    Logan BK GA, Loew S (2007) Blood drug concentrations of frequently encountered drugs in impaired and fatally injured drivers: The International Association of Forensic Toxicologists, International Council on Alcohol, Drugs and Traffic Safety, 8th Ignition Interlock Symposium, Seattle, WA, USAGoogle Scholar
  111. 111.
    Jones AW (2007) Age-and gender-related differences in blood amphetamine concentrations in apprehended drivers: lack of association with clinical evidence of impairment. Addiction 102: 1085–1091PubMedGoogle Scholar
  112. 112.
    Vainio A, Ollila J, Matikainen E, Rosenberg P, Kalso E (1995) Driving ability in cancer patients receiving long-term morphine analgesia. Lancet 346: 667–670PubMedGoogle Scholar
  113. 113.
    Takala A, Kaasalainen V, Seppala T, Kalso E, Olkkola KT (1997) Pharmacokinetic comparison of intravenous and intranasal administration of oxycodone. Acta Anaesthesiol Scand 41: 309–312PubMedGoogle Scholar
  114. 114.
    Berkowitz BA, Ngai SH, Yang JC, Hempstead J, Spector S (1975) The disposition of morphine is surgical patients. Clin Pharmacol Ther 17: 629–635PubMedGoogle Scholar
  115. 115.
    Zacny JP (1995) A review of the effects of opioids on psychomotor and cognitive functioning in humans. Exp Clin Psychopharmacol 3: 432–466Google Scholar
  116. 116.
    Hasselstrom J, Alexander N, Bringel C, Svensson JO, Sawe J (1991) Single-dose and steady-state kinetics of morphine and its metabolites in cancer patients — a comparison of two oral formulations. Eur J Clin Pharmacol 40: 585–591PubMedGoogle Scholar
  117. 117.
    Skopp G, Ganssmann B, Cone EJ, Aderjan R (1997) Plasma concentrations of heroin and morphine-related metabolites after intranasal and intramuscular administration. J Anal Toxicol 21: 105–111PubMedGoogle Scholar
  118. 118.
    Gyr E, Brenneisen R, Bourquin D, Lehmann T, Vonlanthen D, Hug I (2000) Pharmacodynamics and pharmacokinetics of intravenously, orally and rectally administered diacetylmorphine in opioid dependents, a two-patient pilot study within a heroin-assisted treatment program. Int J Clin Pharmacol Ther 38: 486–491PubMedGoogle Scholar
  119. 119.
    Smith ML, Shimomura ET, Summers J, Paul BD, Jenkins AJ, Darwin WD, Cone EJ (2001) Urinary excretion profiles for total morphine, free morphine, and 6-acetylmorphine following smoked and intravenous heroin. J Anal Toxicol 25: 504–514PubMedGoogle Scholar
  120. 120.
    O’Neal CL, Crouch DJ, Rollins DE, Fatah A, Cheever ML (1999) Correlation of saliva codeine concentrations with plasma concentrations after oral codeine administration. J Anal Toxicol 23: 452–459PubMedGoogle Scholar
  121. 121.
    Kim I, Barnes AJ, Oyler JM, Schepers R, Joseph RE, Jr., Cone EJ, Lafko D, Moolchan ET, Huestis MA (2002) Plasma and oral fluid pharmacokinetics and pharmacodynamics after oral codeine administration. Clin Chem 48: 1486–1496PubMedGoogle Scholar
  122. 122.
    Gjerde H, Morland J (1991) A case of high opiate tolerance: implications for drug analyses and interpretations. Int J Legal Med 104: 239–240PubMedGoogle Scholar
  123. 123.
    Findlay JW, Fowle AS, Butz RF, Jones EC, Weatherley BC, Welch RM, Posner J (1986) Comparative disposition of codeine and pholcodine in man after single oral doses. Br J Clin Pharmacol 22: 61–71PubMedGoogle Scholar
  124. 124.
    Hoffman DJ, Leveque MJ, Thomson T (1983) Capillary GLC assay for carbinoxamine and hydrocodone in human serum using nitrogen-sensitive detection. J Pharm Sci 72: 1342–1344PubMedGoogle Scholar
  125. 125.
    Otton SV, Schadel M, Cheung SW, Kaplan HL, Sellers EM (1993) CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone. Clin Pharmacol Ther 54: 463–472PubMedGoogle Scholar
  126. 126.
    Kaplan HL, Busto UE, Baylon GJ, Cheung SW, Otton SV, Somer G, Sellers EM (1997) Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability. J Pharmacol Exp Ther 281: 103–108PubMedGoogle Scholar
  127. 127.
    Smith ML, Hughes RO, Levine B, Dickerson S, Darwin WD, Cone EJ (1995) Forensic drug testing for opiates. VI. Urine testing for hydromorphone, hydrocodone, oxymorphone, and oxycodone with commercial opiate immunoassays and gas chromatography-mass spectrometry. J Anal Toxicol 19: 18–26PubMedGoogle Scholar
  128. 128.
    Vallner JJ, Stewart JT, Kotzan JA, Kirsten EB, Honignerg IL (1981) Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects. J Clin Pharmacol 21: 152–156PubMedGoogle Scholar
  129. 129.
    Hagen N, Thirlwell MP, Dhaliwal HS, Babul N, Harsanyi Z, Darke AC (1995) Steady-state pharmacokinetics of hydromorphone and hydromorphone-3-glucuronide in cancer patients after immediate and controlled-release hydromorphone. J Clin Pharmacol 35: 37–44PubMedGoogle Scholar
  130. 130.
    Oyler JM, Cone EJ, Joseph RE, Jr., Huestis MA (2000) Identification of hydrocodone in human urine following controlled codeine administration. J Anal Toxicol 24: 530–535PubMedGoogle Scholar
  131. 131.
    Cone EJ, Heit HA, Caplan YH, Gourlay D (2006) Evidence of morphine metabolism to hydromorphone in pain patients chronically treated with morphine. J Anal Toxicol 30: 1–5PubMedGoogle Scholar
  132. 132.
    Cone EJ, Fant RV, Rohay JM, Caplan YH, Ballina M, Reder RF, Haddox JD (2004) Oxycodone involvement in drug abuse deaths. II. Evidence for toxic multiple drug-drug interactions. J Anal Toxicol 28: 616–624PubMedGoogle Scholar
  133. 133.
    Renzi NL, Jr., Tam JN (1979) Quantitative GLC determination of oxycodone in human plasma. J Pharm Sci 68: 43–45PubMedGoogle Scholar
  134. 134.
    Mandema JW, Kaiko RF, Oshlack B, Reder RF, Stanski DR (1996) Characterization and validation of a pharmacokinetic model for controlled-release oxycodone. Br J Clin Pharmacol 42: 747–756PubMedGoogle Scholar
  135. 135.
    Kaiko RF, Benziger DP, Fitzmartin RD, Burke BE, Reder RF, Goldenheim PD (1996) Pharmacokinetic-pharmacodynamic relationships of controlled-release oxycodone. Clin Pharmacol Ther 59: 52–61PubMedGoogle Scholar
  136. 136.
    Inturrisi CE, Verebely K (1972) The levels of methadone in the plasma in methadone maintenance. Clin Pharmacol Ther 13: 633–637PubMedGoogle Scholar
  137. 137.
    Preston KL, Epstein DH, Davoudzadeh D, Huestis MA (2003) Methadone and metabolite urine concentrations in patients maintained on methadone. J Anal Toxicol 27: 332–341PubMedGoogle Scholar
  138. 138.
    Stout PR FL (2003) Opioids-Effects on Human Performance and Behavior. Forensic Sci Rev 15: 29–59Google Scholar
  139. 139.
    Heiskanen T, Olkkola KT, Kalso E (1998) Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Clin Pharmacol Ther 64: 603–611PubMedGoogle Scholar
  140. 140.
    Farrell LJ, Kerrigan S, Logan BK (2007) Recommendations for toxicological investigation of drug impaired driving. J Forensic Sci 52: 1214–1218PubMedGoogle Scholar
  141. 141.
    Grotenhermen F, Leson G, Berghaus G, Drummer OH, Kruger HP, Longo M, Moskowitz H, Perrine B, Ramaekers JG, Smiley A et al (2007) Developing limits for driving under cannabis. Addiction 102: 1910–1917PubMedGoogle Scholar
  142. 142.
    Walsh JM (2004) Developing global strategies for identifying, prosecuting, and treating drug-impaired drivers. In: JM Walsh (ed), Bethesda, 1–58Google Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2009

Authors and Affiliations

  • Marilyn A. Huestis
    • 1
  • Michael L. Smith
    • 2
  1. 1.Chemistry and Drug Metabolism, Intramural Research ProgramNational Institute on Drug Abuse, National Institutes of HealthBaltimoreUSA
  2. 2.The Armed Forces Medical Examiner System, Division of Forensic ToxicologyArmed Forces Institute of PathologyRockvilleUSA

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