Tripping with Synthetic Cannabinoids (“Spice”): Anecdotal and Experimental Observations in Animals and Man

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


The phenomenon of consuming synthetic cannabinoids (“Spice”) for recreational purposes is a fairly recent trend. However, consumption of cannabis dates back millennia, with numerous accounts written on the experience of its consumption, and thousands of scientific reports published on the effects of its constituents in laboratory animals and humans. Here, we focus on consolidating the scientific literature on the effects of “Spice” compounds in various behavioral assays, including assessing abuse liability, tolerance, dependence, withdrawal, and potential toxicity. In most cases, the behavioral effects of “Spice” compounds are compared with those of Δ9-tetrahydrocannabinol. Methodological aspects, such as modes of administration and other logistical issues, are also discussed. As the original “Spice” molecules never were intended for human consumption, scientifically based information about potential toxicity and short- and long-term behavioral effects are very limited. Consequently, preclinical behavioral studies with “Spice” compounds are still in a nascent stage. Research is needed to address the addiction potential and other effects, including propensity for producing tissue/organ toxicity, of these synthetic cannabimimetic “Spice” compounds.


Cannabinoid Cannabinoid receptor 1 Marijuana ‘Spice’ Synthetic marijuana THC 





2-Arachidonoyl glycerol


Alexandros Makriyannis


Cannabinoid receptor type-1


Cannabinoid receptor type-2




Compound Pfizer


Conditioned place preference


Endocannabinoid system


Emergency room


Hebrew University






Intra-cranial self-stimulation


John W. Huffman


medial forebrain bundle






  1. 1.
    Hanus LO (2009) Pharmacological and therapeutic secrets of plant and brain (endo)cannabinoids. Med Res Rev 29:213–271CrossRefPubMedGoogle Scholar
  2. 2.
    Badiani A (2010) History of psychopharmacology. In: Stolerman IP (ed) Encyclopedia of psychopharmacology. Springer, Berlin, Heidelberg, pp 593–603Google Scholar
  3. 3.
    Baruk H (1970) The Society Moreau de Tours and Psychopharmacology. Med Klin 65:1803–1805PubMedGoogle Scholar
  4. 4.
    Mora G (1989) Historical antecedents of modern psychopharmacology. Psychiatr J Univ Ott 14:279–281PubMedGoogle Scholar
  5. 5.
    Järbe TUC, Gifford RS, Zvonok A, Makriyannis A (2015) Δ9-Tetrahydrocannabinol discriminative stimulus effects of AM2201 and related aminoalkylindole analogs in rats. Behav PharmacolGoogle Scholar
  6. 6.
    Gatch MB, Forster MJ (2014) Delta9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice. Behav Pharmacol 25:750–757CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Banister SD, Moir M, Stuart J, Kevin RC, Wood KE, Longworth M, Wilkinson SM, Beinat C, Buchanan AS, Glass M, Connor M, McGregor IS, Kassiou M (2015) Pharmacology of indole and indazole synthetic cannabinoid designer drugs AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, and 5F-ADBICA. ACS Chem Neurosci 6:1546–1559CrossRefPubMedGoogle Scholar
  8. 8.
    Banister SD, Stuart J, Kevin RC, Edington A, Longworth M, Wilkinson SM, Beinat C, Buchanan AS, Hibbs DE, Glass M, Connor M, McGregor IS, Kassiou M (2015) Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135. ACS Chem NeurosciGoogle Scholar
  9. 9.
    Fattore L, Fratta W (2011) Beyond THC: the new generation of cannabinoid designer drugs. Front Behav Neurosci 5:60 (1-12)CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Baumann MH, Solis E Jr, Watterson LR, Marusich JA, Fantegrossi WE, Wiley JL (2014) Baths salts, spice, and related designer drugs: the science behind the headlines. J Neurosci 34:15150–15158CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA (2014) Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend 144:12–41CrossRefPubMedGoogle Scholar
  12. 12.
    Martin BR, Compton DR, Thomas BF, Prescott WR, Little PJ, Razdan RK, Johnson MR, Melvin LS, Mechoulam R, Ward SJ (1991) Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs. Pharmacol Biochem Behav 40:471–478CrossRefPubMedGoogle Scholar
  13. 13.
    Wiley JL, Razdan RK, Martin BR (2006) Evaluation of the role of the arachidonic acid cascade in anandamide’s in vivo effects in mice. Life Sci 80:24–35CrossRefPubMedGoogle Scholar
  14. 14.
    Järbe TUC, Gifford RS (2014) “Herbal incense”: designer drug blends as cannabimimetics and their assessment by drug discrimination and other in vivo bioassays. Life Sci 97:64–71CrossRefPubMedGoogle Scholar
  15. 15.
    Järbe TUC, Swedberg MDB (1982) A conceptualization of drug discrimination learning. In: Colpaert FC, Slangen JL (eds) Drug discrimination: application in CNS pharmacology. Elsevier/North-Holland Biomed Press, Amsterdam, pp 327–341Google Scholar
  16. 16.
    Solinas M, Panlilio LV, Justinova Z, Yasar S, Goldberg SR (2006) Using drug-discrimination techniques to study the abuse-related effects of psychoactive drugs in rats. Nat Protoc 1:1194–1206CrossRefPubMedGoogle Scholar
  17. 17.
    Järbe TUC (2011) Perceptual drug discriminative aspects of the endocannabinoid signaling system in animals and man. In: Glennon RA, Young R (eds) Drug discrimination: applications to medicinal chemistry and drug studies. Wiley, Hoboken, pp 241–285CrossRefGoogle Scholar
  18. 18.
    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 346:350–361CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Gatch MB, Forster MJ (2015) Delta9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids found on the gray market. Behav Pharmacol 26:460–468CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gatch MB, Forster MJ (2016) Delta-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids in mice and rats. Psychopharmacology 233(10):1901–10CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Järbe TUC, Deng H, Vadivel SK, Makriyannis A (2011) Cannabinergic aminoalkylindoles, including AM678=JWH018 found in ‘Spice’, examined using drug (Δ9-THC) discrimination for rats. Behav Pharmacol 22:498–507CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Samano KL, Poklis A, Lichtman AH (2013) Preclinical investigation of the abused synthetic cannabinoid CP47,497. College on Problems of Drug Dependence 75th Annual Meeting. College on Problems of Drug Dependence, San Diego, CA, abstract # 555Google Scholar
  23. 23.
    Wiley JL, Marusich JA, Lefever TW, Antonazzo KR, Wallgren MT, Cortes RA, Patel PR, Grabenauer M, Moore KN, Thomas BF (2015) AB-CHMINACA, AB-PINACA, and FUBIMINA: affinity and potency of novel synthetic cannabinoids in producing Delta9-tetrahydrocannabinol-like effects in mice. J Pharmacol Exp Ther 354:328–339CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Wiley JL, Marusich JA, Lefever TW, Grabenauer M, Moore KN, Thomas BF (2013) Cannabinoids in disguise: Delta9-tetrahydrocannabinol-like effects of tetramethylcyclopropyl ketone indoles. Neuropharmacology 75:145–154CrossRefPubMedGoogle Scholar
  25. 25.
    Rodriguez JS, McMahon LR (2014) JWH-018 in rhesus monkeys: differential antagonism of discriminative stimulus, rate-decreasing, and hypothermic effects. Eur J Pharmacol 740:151–159CrossRefPubMedGoogle Scholar
  26. 26.
    Wiley JL, Lefever TW, Cortes RA, Marusich JA (2014) Cross-substitution of Delta9-tetrahydrocannabinol and JWH-018 in drug discrimination in rats. Pharmacol Biochem Behav 124:123–128CrossRefPubMedGoogle Scholar
  27. 27.
    Muller HH, Kornhuber J, Sperling W (2015) The behavioral profile of spice and synthetic cannabinoids in humans. Brain Res Bull S0361–9230(15):30052–6Google Scholar
  28. 28.
    Tyndall JA, Gerona R, De Portu G, Trecki J, Elie MC, Lucas J, Slish J, Rand K, Bazydlo L, Holder M, Ryan MF, Myers P, Iovine N, Plourde M, Weeks E, Hanley JR, Endres G, Germaine DS, Dobrowolski PJ, Schwartz M (2015) An outbreak of acute delirium from exposure to the synthetic cannabinoid AB-CHMINACA. Clin Toxicol 53(10):950–6CrossRefGoogle Scholar
  29. 29.
    Ginsburg BC, McMahon LR, Sanchez JJ, Javors MA (2012) Purity of synthetic cannabinoids sold online for recreational use. J Anal Toxicol 36:66–68CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Lu H-C, Mackie K (2016) An introduction to the endogenous cannabinoid system. Biol Psychiatry 79(7):516–25CrossRefPubMedGoogle Scholar
  31. 31.
    Huestis MA (2007) Human cannabinoid pharmacokinetics. Chem Biodivers 4:1770–1804CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564CrossRefPubMedGoogle Scholar
  33. 33.
    Su MK, Seely KA, Moran JH, Hoffman RS (2015) Metabolism of classical cannabinoids and the synthetic cannabinoid JWH-018. Clin Pharmacol Ther 97:562–564CrossRefPubMedGoogle Scholar
  34. 34.
    Erratico C, Negreira N, Norouzizadeh H, Covaci A, Neels H, Maudens K, van Nuijs AL (2015) In vitro and in vivo human metabolism of the synthetic cannabinoid AB-CHMINACA. Drug Test Anal 7:866–876CrossRefPubMedGoogle Scholar
  35. 35.
    Gurney SM, Scott KS, Kacinko SL, Presley BC, Logan BK (2014) Pharmacology, toxicology, and adverse effects of synthetic cannabinoid drugs. Forensic Sci Rev 26:53–78PubMedGoogle Scholar
  36. 36.
    Pertwee RG (2010) Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr Med Chem 17:1360–1381CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    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 40:2174–2184CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Wiebelhaus JM, Poklis JL, Poklis A, Vann RE, Lichtman AH, Wise LE (2012) Inhalation exposure to smoke from synthetic “marijuana” produces potent cannabimimetic effects in mice. Drug Alcohol Depend 126:316–323CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Marshell R, Kearney-Ramos T, Brents LK, Hyatt WS, Tai S, Prather PL, Fantegrossi WE (2014) In vivo effects of synthetic cannabinoids JWH-018 and JWH-073 and phytocannabinoid Delta9-THC in mice: inhalation versus intraperitoneal injection. Pharmacol Biochem Behav 124:40–47CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Donohue K, Steiner R (2012) JWH-018 and JWH-022 as combustion products of AM2201. Microgram J 9:52–56Google Scholar
  41. 41.
    Järbe TUC, Li C, Vadivel SK, Makriyannis A (2010) Discriminative stimulus functions of methanandamide and Δ9-THC in rats: tests with aminoalkylindoles (WIN55,212-2 and AM678) and ethanol. Psychopharmacology (Berl) 208:87–98CrossRefGoogle Scholar
  42. 42.
    Ginsburg BC, Schulze DR, Hruba L, McMahon LR (2012) JWH-018 and JWH-073: Delta(9)-tetrahydrocannabinol-like discriminative stimulus effects in monkeys. J Pharmacol Exp Ther 340:37–45CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Vann RE, Walentiny DM (2011) Preclinical evaluation of marijuana’s appetitive, rewarding and psychoactive properties. The 21st Annual Symposium of the International Cannabinoid Research Society. International Cannabinoid Research Society, Research Triangle Park, NC, USA, Pheasant Run, St. Charles, IL, USAGoogle Scholar
  44. 44.
    Hruba L, McMahon LR (2014) The cannabinoid agonist HU-210: pseudo-irreversible discriminative stimulus effects in rhesus monkeys. Eur J Pharmacol 727:35–42CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Järbe TUC, Hiltunen AJ, Mechoulam R (1989) Stereospecificity of the discriminative stimulus functions of the dimethylheptyl homologs of 11-hydroxy-Δ8-tetrahydrocannabinol in rats and pigeons. J Pharmacol Exp Ther 250:1000–1005PubMedGoogle Scholar
  46. 46.
    Devane WA, Breuer A, Sheskin T, Järbe TUC, Eisen MS, Mechoulam R (1992) A novel probe for the cannabinoid receptor. J Med Chem 35:2065–2069CrossRefPubMedGoogle Scholar
  47. 47.
    Järbe TUC, Swedberg MD, Mechoulam R (1981) A repeated test procedure to assess onset and duration of the cue properties of (-) Δ9-THC, (-) Δ8-THC-DMH and (+) Δ8-THC. Psychopharmacology (Berl) 75:152–157CrossRefGoogle Scholar
  48. 48.
    Järbe TUC, Tai S, Lemay BJ, Nikas SP, Shukla VG, Zvonok A, Makriyannis A (2012) AM2389, a high-affinity, in vivo potent CB(1)-receptor-selective cannabinergic ligand as evidenced by drug discrimination in rats and hypothermia testing in mice. Psychopharmacology (Berl) 220:417–426CrossRefGoogle Scholar
  49. 49.
    Hancock-Allen JB, Barker L, VanDyke M, Holmes DB (2015) Notes from the field: death following ingestion of an Edible Marijuana Product--Colorado, March 2014. MMWR Morb Mortal Wkly Rep 64:771–772CrossRefPubMedGoogle Scholar
  50. 50.
    Zanettini C, Panlilio LV, Alicki M, Goldberg SR, Haller J, Yasar S (2011) Effects of endocannabinoid system modulation on cognitive and emotional behavior. Front Behav Neurosci 5:57CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Tan H, Ahmad T, Loureiro M, Zunder J, Laviolette SR (2014) The role of cannabinoid transmission in emotional memory formation: implications for addiction and schizophrenia. Front Psychiatry 5:73PubMedPubMedCentralGoogle Scholar
  52. 52.
    Panlilio LV, Goldberg SR, Justinova Z (2015) Cannabinoid abuse and addiction: clinical and preclinical findings. Clin Pharmacol Ther 97:616–627CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Panagis G, Mackey B, Vlachou S (2014) Cannabinoid regulation of brain reward processing with an emphasis on the role of CB1 receptors: a step back into the future. Front Psychiatry 5:92CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    De Luca MA, Valentini V, Bimpisidis Z, Cacciapaglia F, Caboni P, Di Chiara G (2014) Endocannabinoid 2-arachidonoylglycerol self-administration by Sprague-Dawley rats and stimulation of in vivo dopamine transmission in the nucleus accumbens shell. Front Psychiatry 5:140PubMedPubMedCentralGoogle Scholar
  55. 55.
    De Luca MA, Bimpisidis Z, Melis M, Marti M, Caboni P, Valentini V, Margiani G, Pintori N, Polis I, Marsicano G, Parsons LH, Di Chiara G (2015) Stimulation of in vivo dopamine transmission and intravenous self-administration in rats and mice by JWH-018, a Spice cannabinoid. Neuropharmacology 99:705–714CrossRefPubMedGoogle Scholar
  56. 56.
    Cha HJ, Lee KW, Song MJ, Hyeon YJ, Hwang JY, Jang CG, Ahn JI, Jeon SH, Kim HU, Kim YH, Seong WK, Kang H, Yoo HS, Jeong HS (2014) Dependence potential of the synthetic cannabinoids JWH-073, JWH-081, and JWH-210: in vivo and in vitro approaches. Biomol Ther (Seoul) 22:363–369CrossRefGoogle Scholar
  57. 57.
    Lefever TW, Marusich JA, Antonazzo KR, Wiley JL (2014) Evaluation of WIN 55,212-2 self-administration in rats as a potential cannabinoid abuse liability model. Pharmacol Biochem Behav 118:30–35CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Braida D, Iosue S, Pegorini S, Sala M (2004) Delta9-tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats. Eur J Pharmacol 506:63–69CrossRefPubMedGoogle Scholar
  59. 59.
    Braida D, Pozzi M, Parolaro D, Sala M (2001) Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940 in the rat: interaction with the opioid system. Eur J Pharmacol 413:227–234CrossRefPubMedGoogle Scholar
  60. 60.
    Schindler CW, Scherma M, Redhi GH, Vadivel SK, Makriyannis A, Goldberg SR, Justinova Z (2016) Self-administration of the anandamide transport inhibitor AM404 by squirrel monkeys. Psychopharmacology 233(10):1867–77CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Vlachou S, Panagis G (2014) Regulation of brain reward by the endocannabinoid system: a critical review of behavioral studies in animals. Curr Pharm Des 20:2072–2088CrossRefPubMedGoogle Scholar
  62. 62.
    Li JX, Koek W, France CP (2012) Interactions between Delta(9)-tetrahydrocannabinol and heroin: self-administration in rhesus monkeys. Behav Pharmacol 23:754–761CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Panlilio LV, Justinova Z, Goldberg SR (2010) Animal models of cannabinoid reward. Br J Pharmacol 160:499–510CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Cooper ZD, Haney M (2008) Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor. Addict Biol 13:188–195CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Justinova Z, Goldberg SR, Heishman SJ, Tanda G (2005) Self-administration of cannabinoids by experimental animals and human marijuana smokers. Pharmacol Biochem Behav 81:285–299CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Bardo MT, Bevins RA (2000) Conditioned place preference: what does it add to our preclinical understanding of drug reward? Psychopharmacology (Berl) 153:31–43CrossRefGoogle Scholar
  67. 67.
    Tzschentke TM (2007) Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 12:227–462CrossRefPubMedGoogle Scholar
  68. 68.
    Lepore M, Vorel SR, Lowinson J, Gardner EL (1995) Conditioned place preference induced by delta 9-tetrahydrocannabinol: comparison with cocaine, morphine, and food reward. Life Sci 56:2073–2080CrossRefPubMedGoogle Scholar
  69. 69.
    Valjent E, Maldonado R (2000) A behavioural model to reveal place preference to delta 9-tetrahydrocannabinol in mice. Psychopharmacology (Berl) 147:436–438CrossRefGoogle Scholar
  70. 70.
    Pandolfo P, Vendruscolo LF, Sordi R, Takahashi RN (2009) Cannabinoid-induced conditioned place preference in the spontaneously hypertensive rat-an animal model of attention deficit hyperactivity disorder. Psychopharmacology (Berl) 205:319–326CrossRefGoogle Scholar
  71. 71.
    Hyatt WS, Fantegrossi WE (2014) Delta9-THC exposure attenuates aversive effects and reveals appetitive effects of K2/‘Spice’ constituent JWH-018 in mice. Behav Pharmacol 25:253–257CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Tampus R, Yoon SS, de la Pena JB, Botanas CJ, Kim HJ, Seo JW, Jeong EJ, Jang CG, Cheong JH (2015) Assessment of the abuse liability of synthetic cannabinoid agonists JWH-030, JWH-175, and JWH-176. Biomol Ther (Seoul) 23:590–596CrossRefGoogle Scholar
  73. 73.
    Negus SS, Miller LL (2014) Intracranial self-stimulation to evaluate abuse potential of drugs. Pharmacol Rev 66:869–917CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Desai RI, Thakur GA, Vemuri VK, Bajaj S, Makriyannis A, Bergman J (2013) Analysis of tolerance and behavioral/physical dependence during chronic CB1 agonist treatment: effects of CB1 agonists, antagonists, and noncannabinoid drugs. J Pharmacol Exp Ther 344:319–328CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Singh H, Schulze DR, McMahon LR (2011) Tolerance and cross-tolerance to cannabinoids in mice: schedule-controlled responding and hypothermia. Psychopharmacology (Berl) 215:665–675CrossRefGoogle Scholar
  76. 76.
    Fan F, Tao Q, Abood M, Martin BR (1996) Cannabinoid receptor down-regulation without alteration of the inhibitory effect of CP 55,940 on adenylyl cyclase in the cerebellum of CP 55,940-tolerant mice. Brain Res 706:13–20CrossRefPubMedGoogle Scholar
  77. 77.
    D’Souza DC, Cortes-Briones JA, Ranganathan M, Thurnauer H, Creatura G, Surti T, Planeta B, Neumeister A, Pittman B, Normandin M, Kapinos M, Ropchan J, Huang Y, Carson RE, Skosnik PD (2016) Rapid changes in CB1 receptor availability in cannabis dependent males after abstinence from cannabis. Biol Psychiatry Cogn Neurosci Neuroimaging 1:60–67CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Gifford RS, Raghav JG, Järbe TUC (2016) Does agonist efficacy alter the in vivo effects of cannabinoids: girl, could we get much “higher”? In: Preedy VR (ed) Neuropathology of drug addictions and substance misuse, vol 1. Elsevier Inc. doi:10.1016/B978-0-12-800213-1.00067-5
  79. 79.
    Tai S, Fantegrossi WE (2014) Synthetic cannabinoids: pharmacology, behavioral effects, and abuse potential. Curr Addict Rep 1:129–136CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Tai S, Nikas SP, Shukla VG, Vemuri K, Makriyannis A, Jarbe TU (2015) Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist. Psychopharmacology (Berl) 232:2751–2761CrossRefGoogle Scholar
  81. 81.
    Tai S, Hyatt WS, Gu C, Franks LN, Vasiljevik T, Brents LK, Prather PL, Fantegrossi WE (2015) Repeated administration of phytocannabinoid Delta-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner. Pharmacol Res 102:22–32CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Ossato A, Vigolo A, Trapella C, Seri C, Rimondo C, Serpelloni G, Marti M (2015) JWH-018 impairs sensorimotor functions in mice. Neuroscience 300:174–188CrossRefPubMedGoogle Scholar
  83. 83.
    Vigolo A, Ossato A, Trapella C, Vincenzi F, Rimondo C, Seri C, Varani K, Serpelloni G, Marti M (2015) Novel halogenated derivates of JWH-018: behavioral and binding studies in mice. Neuropharmacology 95:68–82CrossRefPubMedGoogle Scholar
  84. 84.
    Cha HJ, Seong YH, Song MJ, Jeong HS, Shin J, Yun J, Han K, Kim YH, Kang H, Kim HS (2015) Neurotoxicity of synthetic cannabinoids JWH-081 and JWH-210. Biomol Ther (Seoul) 23:597–603CrossRefGoogle Scholar
  85. 85.
    Basavarajappa BS, Subbanna S (2014) CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and memory deficits following treatment with JWH-081, a new component of spice/K2 preparations. Hippocampus 24:178–188CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Wiley JL, Marusich JA, Huffman JW, Balster RL, Thomas BF (2011) Hijacking of basic research: the case of synthetic cannabinoids. Methods Rep RTI Press. doi:10.3768/rtipress.2011.op.0007.1111

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Torbjörn U. C. Järbe
    • 1
  • Jimit Girish Raghav
    • 1
  1. 1.Department of Pharmaceutical Sciences, Center for Drug Discovery (CDD)Northeastern UniversityBostonUSA

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