Skip to main content
SpringerLink
Log in

Pharmacological and Toxicological Effects of Synthetic Cannabinoids and Their Metabolites

  • Chapter
  • First Online:
Neuropharmacology of New Psychoactive Substances (NPS)

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 32))

Abstract

Commercial preparations containing synthetic cannabinoids (SCBs) are rapidly emerging as drugs of abuse. Although often assumed to be “safe” and “legal” alternatives to cannabis, reports indicate that SCBs induce toxicity not often associated with the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). This chapter will summarize the evidence that use of SCBs poses greater health risks relative to marijuana and suggest that distinct pharmacological properties and metabolism of SCBs relative to Δ9-THC may contribute to this increased toxicity. Studies reviewed will indicate that in contrast to partial agonist properties of Δ9-THC typically observed in vitro, SCBs act as full CB1 and CB2 receptor agonists both in cellular assays and animal studies. Furthermore, unlike Δ9-THC metabolism, several SCB metabolites retain high affinity for and exhibit a range of intrinsic activities at CB1 and CB2 receptors. Finally, the potential for SCBs to cause adverse drug–drug interactions with other drugs of abuse, as well as with common therapeutic agents, will be discussed. Collectively, the evidence provided in this chapter indicates that SCBs should not be considered safe and legal alternatives to marijuana. Instead, the enhanced toxicity of SCBs relative to marijuana, perhaps resulting from the combined actions of a complex mixture of different SCBs present and their active metabolites that retain high affinity for CB1 and CB2 receptors, highlights the inherent danger that may accompany use of these substances.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Wiley JL, Marusich JA, Huffman JW, Balster RL, Thomas BF (2011) Hijacking of basic research: the case of synthetic cannabinoids. Methods Rep RTI Press 2011:17971

    PubMed  PubMed Central  Google Scholar 

  2. Tai S, Fantegrossi W (2014) Synthetic cannabinoids: pharmacology, behavioral effects, and abuse potential. Curr Addict Rep:1–8

    Google Scholar 

  3. Aung MM, Griffin G, Huffman JW, Wu M, Keel C, Yang B, Showalter VM, Abood ME, Martin BR (2000) Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB(1) and CB(2) receptor binding. Drug Alcohol Depend 60:133–140

    CAS  PubMed  Google Scholar 

  4. Brents LK, Gallus-Zawada A, Radominska-Pandya A, Vasiljevik T, Prisinzano TE, Fantegrossi WE, Moran JH, Prather PL (2012) Monohydroxylated metabolites of the K2 synthetic cannabinoid JWH-073 retain intermediate to high cannabinoid 1 receptor (CB1R) affinity and exhibit neutral antagonist to partial agonist activity. Biochem Pharmacol 83:952–961

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Brents LK, Reichard EE, Zimmerman SM, Moran JH, Fantegrossi WE, Prather PL (2011) Phase I hydroxylated metabolites of the K2 synthetic cannabinoid JWH-018 retain in vitro and in vivo cannabinoid 1 receptor affinity and activity. PLoS One 6:e21917

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Chin CN, Murphy JW, Huffman JW, Kendall DA (1999) The third transmembrane helix of the cannabinoid receptor plays a role in the selectivity of aminoalkylindoles for CB2, peripheral cannabinoid receptor. J Pharmacol Exp Ther 291:837–844

    CAS  PubMed  Google Scholar 

  7. Rajasekaran M, Brents LK, Franks LN, Moran JH, Prather PL (2013) Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors. Toxicol Appl Pharmacol 269:100–108

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Atwood BK, Huffman J, Straiker A, Mackie K (2010) JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious cannabinoid CB receptor agonist. Br J Pharmacol 160:585–593

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Huestis MA (2005) Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Handb Exp Pharmacol (168):657–690

    Google Scholar 

  10. 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 80:1415–1419

    CAS  PubMed  Google Scholar 

  11. Bornheim LM, Lasker JM, Raucy JL (1992) Human hepatic microsomal metabolism of delta 1-tetrahydrocannabinol. Drug Metab Dispos 20:241–246

    CAS  PubMed  Google Scholar 

  12. Watanabe K, Matsunaga T, Yamamoto I, Funae Y, Yoshimura H (1995) Involvement of CYP2C in the metabolism of cannabinoids by human hepatic microsomes from an old woman. Biol Pharm Bull 18:1138–1141

    CAS  PubMed  Google Scholar 

  13. Yamamoto I, Watanabe K, Kuzuoka K, Narimatsu S, Yoshimura H (1987) The pharmacological activity of cannabinol and its major metabolite, 11-hydroxycannabinol. Chem Pharm Bull 35:2144–2147

    CAS  Google Scholar 

  14. Zhang Q, Ma P, Iszard M, Cole RB, Wang W, Wang G (2002) In vitro metabolism of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate, a cannabinoid receptor agonist. Drug Metab Dispos 30:1077–1086

    CAS  PubMed  Google Scholar 

  15. Zhang Q, Ma P, Wang W, Cole RB, Wang G (2004) Characterization of rat liver microsomal metabolites of AM-630, a potent cannabinoid receptor antagonist, by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. J Mass Spectrom 39:672–681

    CAS  PubMed  Google Scholar 

  16. Zhang Q, Ma P, Cole RB, Wang G (2006) Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS. Anal Bioanal Chem 386:1345–1355

    CAS  PubMed  Google Scholar 

  17. Sobolevsky T, Prasolov I, Rodchenkov G (2010) Detection of JWH-018 metabolites in smoking mixture post-administration urine. Forensic Sci Int 200:141–147

    CAS  PubMed  Google Scholar 

  18. Chimalakonda KC, Bratton SM, Le VH, Yiew KH, Dineva A, Moran CL, James LP, Moran JH, Radominska-Pandya A (2011) Conjugation of synthetic cannabinoids JWH-018 and JWH-073, metabolites by human UDP-glucuronosyltransferases. Drug Metab Dispos 39:1967–1976

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Wintermeyer A, Moller I, Thevis M, Jubner M, Beike J, Rothschild MA, Bender K (2010) In vitro phase I metabolism of the synthetic cannabimimetic JWH-018. Anal Bioanal Chem 398:2141–2153

    CAS  PubMed  Google Scholar 

  20. Grigoryev A, Melnik A, Savchuk S, Simonov A, Rozhanets V (2011) Gas and liquid chromatography-mass spectrometry studies on the metabolism of the synthetic phenylacetylindole cannabimimetic JWH-250, the psychoactive component of smoking mixtures. J Chromatogr B Analyt Technol Biomed Life Sci 879:2519–2526

    CAS  PubMed  Google Scholar 

  21. Moller I, Wintermeyer A, Bender K, Jubner M, Thomas A, Krug O, Schanzer W, Thevis M (2011) Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls. Drug Test Anal 3:609–620

    PubMed  Google Scholar 

  22. Grigoryev A, Savchuk S, Melnik A, Moskaleva N, Dzhurko J, Ershov M, Nosyrev A, Vedenin A, Izotov B, Zabirova I, Rozhanets V (2011) Chromatography-mass spectrometry studies on the metabolism of synthetic cannabinoids JWH-018 and JWH-073, psychoactive components of smoking mixtures. J Chromatogr B Analyt Technol Biomed Life Sci 879:1126–1136

    CAS  PubMed  Google Scholar 

  23. Chimalakonda KC, Seely KA, Bratton SM, Brents LK, Moran CL, Endres GW, James LP, Hollenberg PF, Prather PL, Radominska-Pandya A, Moran JH (2012) Cytochrome P450-mediated oxidative metabolism of abused synthetic cannabinoids found in K2/Spice: identification of novel cannabinoid receptor ligands. Drug Metab Dispos 40:2174–2184

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Moran CL, Le VH, Chimalakonda KC, Smedley AL, Lackey FD, Owen SN, Kennedy PD, Endres GW, Ciske FL, Kramer JB, Kornilov AM, Bratton LD, Dobrowolski PJ, Wessinger WD, Fantegrossi WE, Prather PL, James LP, Radominska-Pandya A, Moran JH (2011) Quantitative measurement of JWH-018 and JWH-073 metabolites excreted in human urine. Anal Chem 83:4228–4236

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Beuck S, Moller I, Thomas A, Klose A, Schlorer N, Schanzer W, Thevis M (2011) Structure characterisation of urinary metabolites of the cannabimimetic JWH-018 using chemically synthesised reference material for the support of LC-MS/MS-based drug testing. Anal Bioanal Chem 401:493–505

    CAS  PubMed  Google Scholar 

  26. de Jager AD, Warner JV, Henman M, Ferguson W, Hall A (2012) LC-MS/MS method for the quantitation of metabolites of eight commonly-used synthetic cannabinoids in human urine – an Australian perspective. J Chromatogr B Analyt Technol Biomed Life Sci 897:22–31

    PubMed  Google Scholar 

  27. Dowling G, Regan L (2011) A method for CP 47, 497 a synthetic non-traditional cannabinoid in human urine using liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 879:253–259

    CAS  PubMed  Google Scholar 

  28. ElSohly MA, Gul W, Elsohly KM, Murphy TP, Madgula VL, Khan SI (2011) Liquid chromatography-tandem mass spectrometry analysis of urine specimens for K2 (JWH-018) metabolites. J Anal Toxicol 35:487–495

    CAS  PubMed  Google Scholar 

  29. Hutter M, Broecker S, Kneisel S, Auwarter V (2012) Identification of the major urinary metabolites in man of seven synthetic cannabinoids of the aminoalkylindole type present as adulterants in ‘herbal mixtures’ using LC-MS/MS techniques. J Mass Spectrom 47:54–65

    CAS  PubMed  Google Scholar 

  30. Sobolevsky T, Prasolov I, Rodchenkov G (2012) Detection of urinary metabolites of AM-2201 and UR-144, two novel synthetic cannabinoids. Drug Test Anal 4:745–753

    CAS  PubMed  Google Scholar 

  31. Paine MF, Hart HL, Ludington SS, Haining RL, Rettie AE, Zeldin DC (2006) The human intestinal cytochrome P450 “pie”. Drug Metab Dispos 34:880–886

    CAS  PubMed  Google Scholar 

  32. Pavanello S, Fedeli U, Mastrangelo G, Rota F, Overvad K, Raaschou-Nielsen O, Tjonneland A, Vogel U (2012) Role of CYP1A2 polymorphisms on lung cancer risk in a prospective study. Cancer Genet 205:278–284

    CAS  PubMed  Google Scholar 

  33. Dresen S, Ferreiros N, Putz M, Westphal F, Zimmermann R, Auwarter V (2010) Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds. J Mass Spectrom 45:1186–1194

    CAS  PubMed  Google Scholar 

  34. Kacinko SL, Xu A, Homan JW, McMullin MM, Warrington DM, Logan BK (2011) 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. J Anal Toxicol 35:386–393

    CAS  PubMed  Google Scholar 

  35. Chimalakonda KC, Moran CL, Kennedy PD, Endres GW, Uzieblo A, Dobrowolski PJ, Fifer EK, Lapoint J, Nelson LS, Hoffman RS, James LP, Radominska-Pandya A, Moran JH (2011) Solid-phase extraction and quantitative measurement of omega and omega-1 metabolites of JWH-018 and JWH-073 in human urine. Anal Chem 83:6381–6388

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Seely KA, Prather PL, James LP, Moran JH (2011) Marijuana-based drugs: innovative therapeutics or designer drugs of abuse? Mol Interv 11:36–51

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Huffman JW, Thompson AL, Wiley JL, Martin BR (2008) Synthesis and pharmacology of 1-deoxy analogs of CP-47,497 and CP-55,940. Bioorg Med Chem 16:322–335

    CAS  PubMed  Google Scholar 

  38. Huffman JW, Padgett LW (2005) Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes. Curr Med Chem 12:1395–1411

    CAS  PubMed  Google Scholar 

  39. Frost JM, Dart MJ, Tietje KR, Garrison TR, Grayson GK, Daza AV, El-Kouhen OF, Yao BB, Hsieh GC, Pai M, Zhu CZ, Chandran P, Meyer MD (2010) Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity. J Med Chem 53:295–315

    CAS  PubMed  Google Scholar 

  40. Griffin G, Atkinson PJ, Showalter VM, Martin BR, Abood ME (1998) Evaluation of cannabinoid receptor agonists and antagonists using the guanosine-5′-O-(3-[35S]thio)-triphosphate binding assay in rat cerebellar membranes. J Pharmacol Exp Ther 285:553–560

    CAS  PubMed  Google Scholar 

  41. Huffman JW, Szklennik PV, Almond A, Bushell K, Selley DE, He H, Cassidy MP, Wiley JL, Martin BR (2005) 1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles. Bioorg Med Chem Lett 15:4110–4113

    CAS  PubMed  Google Scholar 

  42. Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y (2013) URB-754: a new class of designer drug and 12 synthetic cannabinoids detected in illegal products. Forensic Sci Int 227:21–32

    CAS  PubMed  Google Scholar 

  43. Jankovics P, Varadi A, Tolgyesi L, Lohner S, Nemeth-Palotas J, Balla J (2012) Detection and identification of the new potential synthetic cannabinoids 1-pentyl-3-(2-iodobenzoyl)indole and 1-pentyl-3-(1-adamantoyl)indole in seized bulk powders in Hungary. Forensic Sci Int 214:27–32

    CAS  PubMed  Google Scholar 

  44. Atwood BK, Lee D, Straiker A, Widlanski TS, Mackie K (2011) CP47,497-C8 and JWH073, commonly found in ‘Spice’ herbal blends, are potent and efficacious CB(1) cannabinoid receptor agonists. Eur J Pharmacol 659:139–145

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Howlett AC, Champion TM, Wilken GH, Mechoulam R (1990) Stereochemical effects of 11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl to inhibit adenylate cyclase and bind to the cannabinoid receptor. Neuropharmacology 29:161–165

    CAS  PubMed  Google Scholar 

  46. Lindigkeit R, Boehme A, Eiserloh I, Luebbecke M, Wiggermann M, Ernst L, Beuerle T (2009) Spice: a never ending story? Forensic Sci Int 191:58–63

    CAS  PubMed  Google Scholar 

  47. Hoffman AF, Lycas MD, Kaczmarzyk JR, Spivak CE, Baumann MH, Lupica CR (2016) Disruption of hippocampal synaptic transmission and long-term potentiation by psychoactive synthetic cannabinoid ‘Spice’ compounds: comparison with Δ9-tetrahydrocannabinol. Addict Biol. doi:10.1111/adb.12334/full (in press)

  48. Fan F, Compton DR, Ward S, Melvin L, Martin BR (1994) Development of cross-tolerance between delta-9-tetrahydrocannabinol, CP 55,940 and WIN 55,212. J Pharmacol Exp Ther 271:1383–1390

    CAS  PubMed  Google Scholar 

  49. Hirvonen J, Goodwin RS, Li CT, Terry GE, Zoghbi SS, Morse C, Pike VW, Volkow ND, Huestis MA, Innis RB (2012) Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Mol Psychiatry 17:642–649

    CAS  PubMed  Google Scholar 

  50. Sim-Selley LJ, Schechter NS, Rorrer WK, Dalton GD, Hernandez J, Martin BR, Selley DE (2006) Prolonged recovery rate of CB1 receptor adaptation after cessation of long-term cannabinoid administration. Mol Pharmacol 70:986–996

    CAS  PubMed  Google Scholar 

  51. Villares J (2007) Chronic use of marijuana decreases cannabinoid receptor binding and mRNA expression in the human brain. Neuroscience 145:323–334

    CAS  PubMed  Google Scholar 

  52. Zimmermann US, Winkelmann PR, Pilhatsch M, Nees JA, Spanagel R, Schulz K (2009) Withdrawal phenomena and dependence syndrome after the consumption of “spice gold”. Dtsch Arztebl Int 106:464–467

    PubMed  PubMed Central  Google Scholar 

  53. Kochanowski M, Kala M (2005) Tetrahydrocannabinols in clinical and forensic toxicology. Przegl Lek 62:576–580

    PubMed  Google Scholar 

  54. Brents LK, Zimmerman SM, Saffell AR, Prather PL, Fantegrossi WE (2013) Differential drug-drug interactions of the synthetic cannabinoids JWH-018 and JWH-073: implications for drug abuse liability and pain therapy. J Pharmacol Exp Ther 346:350–361

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Fattore L, Fratta W (2011) Beyond THC: the new generation of cannabinoid designer drugs. Front Behav Neurosci 5:60

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Lapoint J, James LP, Moran CL, Nelson LS, Hoffman RS, Moran JH (2011) Severe toxicity following synthetic cannabinoid ingestion. Clin Toxicol 49:760–764

    CAS  Google Scholar 

  57. Patton AL, Chimalakonda KC, Moran CL, McCain KR, Radominska-Pandya A, James LP, Kokes C, Moran JH (2013) K2 toxicity: fatal case of psychiatric complications following AM2201 exposure. J Forensic Sci 58:1676–1680

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Seely KA, Lapoint J, Moran JH, Fattore L (2012) Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuropsychopharmacol Biol Psychiatry 39:234–243

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Seely KA, Patton AL, Moran CL, Womack ML, Prather PL, Fantegrossi WE, Radominska-Pandya A, Endres GW, Channell KB, Smith NH, McCain KR, James LP, Moran JH (2013) Forensic investigation of K2, Spice, and “bath salt” commercial preparations: a three-year study of new designer drug products containing synthetic cannabinoid, stimulant, and hallucinogenic compounds. Forensic Sci Int 233(1–3):416–422

    CAS  PubMed  Google Scholar 

  60. Klein TW, Newton C, Larsen K, Lu L, Perkins I, Nong L, Friedman H (2003) The cannabinoid system and immune modulation. J Leukoc Biol 74:486–496

    CAS  PubMed  Google Scholar 

  61. Patel KD, Davison JS, Pittman QJ, Sharkey KA (2010) Cannabinoid CB(2) receptors in health and disease. Curr Med Chem 17:1393–1410

    PubMed  Google Scholar 

  62. Onaivi ES, Ishiguro H, Gong JP, Patel S, Meozzi PA, Myers L, Perchuk A, Mora Z, Tagliaferro PA, Gardner E, Brusco A, Akinshola BE, Hope B, Lujilde J, Inada T, Iwasaki S, Macharia D, Teasenfitz L, Arinami T, Uhl GR (2008) Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects. PLoS One 3:e1640

    PubMed  PubMed Central  Google Scholar 

  63. Gamaleddin I, Zvonok A, Makriyannis A, Goldberg SR, Le Foll B (2012) Effects of a selective cannabinoid CB2 agonist and antagonist on intravenous nicotine self administration and reinstatement of nicotine seeking. PLoS One 7:e29900

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Xi ZX, Peng XQ, Li X, Song R, Zhang HY, Liu QR, Yang HJ, Bi GH, Li J, Gardner EL (2011) Brain cannabinoid CB(2) receptors modulate cocaine’s actions in mice. Nat Neurosci 14:1160–1166

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Haj-Dahmane S, Shen RY (2011) Modulation of the serotonin system by endocannabinoid signaling. Neuropharmacology 61:414–420

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Franklin JM, Carrasco GA (2013) G-protein receptor kinase 5 regulates the cannabinoid receptor 2-induced up-regulation of serotonin 2A receptors. J Biol Chem 288:15712–15724

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Franklin JM, Vasiljevik T, Prisinzano TE, Carrasco GA (2013) Cannabinoid 2 receptor- and beta arrestin 2-dependent upregulation of serotonin 2A receptors. Eur Neuropsychopharmacol 23:760–767

    CAS  PubMed  Google Scholar 

  68. Ghisleni G, Kazlauckas V, Both FL, Pagnussat N, Mioranzza S, Rocha JB, Souza DO, Porciuncula LO (2008) Diphenyl diselenide exerts anxiolytic-like effect in Wistar rats: putative roles of GABAA and 5HT receptors. Prog Neuropsychopharmacol Biol Psychiatry 32:1508–1515

    CAS  PubMed  Google Scholar 

  69. Morgan D, Kondabolu K, Kuipers A, Sakhuja R, Robertson KL, Rowland NE, Booth RG (2013) Molecular and behavioral pharmacology of two novel orally-active 5HT2 modulators: potential utility as antipsychotic medications. Neuropharmacology 72:274–281

    CAS  PubMed  Google Scholar 

  70. Fantegrossi WE, Murnane KS, Reissig CJ (2008) The behavioral pharmacology of hallucinogens. Biochem Pharmacol 75:17–33

    CAS  PubMed  Google Scholar 

  71. Gunderson EW, Haughey HM, Ait-Daoud N, Joshi AS, Hart CL (2012) “Spice” and “K2” herbal highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans. Am J Addict 21:320–326

    PubMed  Google Scholar 

  72. Celofiga A, Koprivsek J, Klavz J (2014) Use of synthetic cannabinoids in patients with psychotic disorders: case series. J Dual Diagn 10(3):168–173

    PubMed  Google Scholar 

  73. Seng KC, Seng CK (2008) The success of the genome-wide association approach: a brief story of a long struggle. Eur J Hum Genet 16(5):554–564

    CAS  PubMed  Google Scholar 

  74. Shirley KL, Hon YY, Penzak SR, Lam YW, Spratlin V, Jann MW (2003) Correlation of cytochrome P450 (CYP) 1A2 activity using caffeine phenotyping and olanzapine disposition in healthy volunteers. Neuropsychopharmacology 28(5):961–966

    CAS  PubMed  Google Scholar 

  75. Hiratsuka M (2012) In vitro assessment of the allelic variants of cytochrome P450. Drug Metab Pharmacokinet 27(1):68–84

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences College of Medicine, Mail Slot 638, 4301 West Markham Street, Little Rock, AR, 72207, USA

    Sherrica Tai & William E. Fantegrossi

  2. Department of Pharmacology, University of Michigan Medical School, 2301 MSRB III, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA

    Sherrica Tai

Authors
  1. Sherrica Tai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William E. Fantegrossi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William E. Fantegrossi .

Editor information

Editors and Affiliations

  1. Designer Drug Research Unit (DDRU), National Institute on Drug Abuse, Baltimore, MD, USA

    Michael H. Baumann

  2. Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA

    Richard A. Glennon

  3. RTI International, Research Triangle Park, NC, USA

    Jenny L. Wiley

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing AG

About this chapter

Cite this chapter

Tai, S., Fantegrossi, W.E. (2016). Pharmacological and Toxicological Effects of Synthetic Cannabinoids and Their Metabolites. In: Baumann, M.H., Glennon, R.A., Wiley, J.L. (eds) Neuropharmacology of New Psychoactive Substances (NPS). Current Topics in Behavioral Neurosciences, vol 32. Springer, Cham. https://doi.org/10.1007/7854_2016_60

Download citation

Publish with us

Policies and ethics

Search

Navigation