, Volume 226, Issue 2, pp 401–413 | Cite as

Acute effects of THC on time perception in frequent and infrequent cannabis users

  • R. Andrew SewellEmail author
  • Ashley Schnakenberg
  • Jacqueline Elander
  • Rajiv Radhakrishnan
  • Ashley Williams
  • Patrick D. Skosnik
  • Brian Pittman
  • Mohini Ranganathan
  • D. Cyril D’Souza
Original Investigation



Cannabinoids have been shown to alter time perception, but existing literature has several limitations. Few studies have included both time estimation and production tasks, few control for subvocal counting, most had small sample sizes, some did not record subjects’ cannabis use, many tested only one dose, and used either oral or inhaled administration of Δ9-tetrahydrocannabinol (THC), leading to variable pharmacokinetics, and some used whole-plant cannabis containing cannabinoids other than THC. Our study attempted to address these limitations.


This study aims to characterize the acute effects of THC and frequent cannabis use on seconds-range time perception. THC was hypothesized to produce transient, dose-related time overestimation and underproduction. Frequent cannabis smokers were hypothesized to show blunted responses to these alterations.


IV THC was administered at doses from 0.015 to 0.05 mg/kg to 44 subjects who participated in several double-blind, randomized, counterbalanced, crossover, placebo-controlled studies. Visual time estimation and production tasks in the seconds range were presented to subjects three times on each test day.


All doses induced time overestimation and underproduction. Chronic cannabis use had no effect on baseline time perception. While infrequent/nonsmokers showed temporal overestimation at medium and high doses and temporal underproduction at all doses, frequent cannabis users showed no differences. THC effects on time perception were not dose related.


A psychoactive dose of THC increases internal clock speed as indicated by time overestimation and underproduction. This effect is not dose related and is blunted in chronic cannabis smokers who did not otherwise have altered baseline time perception.


Cannabinoids Δ9-tetrahydrocannabinol Time perception Temporal processing 



The authors wish to acknowledge support from the (1) Department of Veterans Affairs, (2) National Institute of Mental Health, (3) National Institute of Drug Abuse, (4) National Institute of Alcoholism and Alcohol Abuse (NIAAA) and (5) the Yale Center for Clinical Investigation (YCCI). This research project was funded in part by grants from NIH (R01 DA012382, R21 DA020750, R21 MH086769, R21 AA016311 to DCD). The authors also thank Angelina Genovese, R.N.C., M.B.A.; Michelle San Pedro, R.N.; Elizabeth O’Donnell, R.N.; Brenda Breault, R.N., B.S.N.; Sonah Yoo, R.Ph.; Rachel Galvan, R.Ph.; and Willie Ford of the Neurobiological Studies Unit at the VA Connecticut Healthcare System, West Haven Campus for their central contributions to the success of this project. The experiments comply with the current laws of the USA.

Funding and Conflict of Interest

The authors wish to acknowledge support from the (1) Department of Veterans Affairs, (2) National Institute of Mental Health, (3) National Institute of Drug Abuse, (4) National Institute of Alcoholism and Alcohol Abuse (NIAAA) and (5) the Yale Center for Clinical Investigation (YCCI). This research project was funded in part by grants from NIH (R01 DA012382, R21 DA020750, R21 MH086769, R21 AA016311 to DCD). Patrick Skosnik, Ashley Williams, Ashley Schnakenberg, Rajiv Radhakrishnan, Brian Pittman, and R. Andrew Sewell report no financial relationships with commercial interests. Mohini Ranganathan has in the past three years and currently receives research grant support administered through Yale University School of Medicine from Eli Lilly Inc. Deepak Cyril D’Souza has in the past three years and currently receives research grant support administered through Yale University School of Medicine from Astra Zeneca, Abbott Laboratories, Eli Lilly Inc., Organon, Pfizer Inc., and Sanofi; he is also a consultant for Bristol Meyers Squibb.

Supplementary material

213_2012_2915_MOESM1_ESM.pdf (42 kb)
ESM 1 (PDF 42 kb)


  1. Agurell S, Halldin M, Lindgren JE, Ohlsson A, Widman M, Gillespie H, Hollister L (1986) Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacol Rev 38:21–43PubMedGoogle Scholar
  2. Allman MJ, Meck WH (2012) Pathophysiological distortions in time perception and timed performance. Brain 135:656–677PubMedCrossRefGoogle Scholar
  3. Andreasen NC, Nopoulos P, O’Leary DS, Miller DD, Wassink T, Flaum M (1999) Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms. Biol Psychiatry 46:908–920PubMedCrossRefGoogle Scholar
  4. 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 261:114–122PubMedGoogle Scholar
  5. Azorlosa JL, Greenwald MK, Stitzer ML (1995) Marijuana smoking: effects of varying puff volume and breathhold duration. J Pharmacol Exp Ther 272:560–569PubMedGoogle Scholar
  6. Ball SA, Carroll KM, Rounsaville BJ (1994) Sensation seeking, substance abuse, and psychopathology in treatment-seeking and community cocaine abusers. J Consult Clin Psychol 62:1053–1057PubMedCrossRefGoogle Scholar
  7. Bech P, Rafaelsen L, Rafaelsen OJ (1973) Cannabis and alcohol: effects on estimation of time and distance. Psychopharmacologia 32:373–381PubMedCrossRefGoogle Scholar
  8. Borg J, Gershon S, Alpert M (1975) Dose effects of smoked marihuana on human cognitive and motor functions. Psychopharmacologia 42:211–218PubMedCrossRefGoogle Scholar
  9. Brown TM, Brotchie JM, Fitzjohn SM (2003) Cannabinoids decrease corticostriatal synaptic transmission via an effect on glutamate uptake. J Neurosci 23:11073–11077PubMedGoogle Scholar
  10. Buonomano DV (2007) The biology of time across different scales. Nat Chem Biol 3:594–597PubMedCrossRefGoogle Scholar
  11. Cappell H, Webster CD, Herring BS, Ginsberg R (1972) Alcohol and marihuana: a comparison of effects on a temporally controlled operant in humans. J Pharmacol Exp Ther 182:195–203PubMedGoogle Scholar
  12. Carbuto M, Sewell RA, Williams A, Forselius-Bielen K, Braley G, Elander J, Pittman B, Schnakenberg A, Bhakta S, Perry E, Ranganathan M, D’Souza DC (2012) The safety of studies with intravenous delta(9)-tetrahydrocannabinol in humans, with case histories. Psychopharmacology (Berl) 219:885–896CrossRefGoogle Scholar
  13. Carlini EA, Karniol IG, Renault PF, Schuster CR (1974) Effects of marihuana in laboratory animals and in man. Br J Pharmacol 50:299–309PubMedCrossRefGoogle Scholar
  14. Carpenter KM, McDowell D, Brooks DJ, Cheng WY, Levin FR (2009) A preliminary trial: double-blind comparison of nefazodone, bupropion-SR, and placebo in the treatment of cannabis dependence. Am J Addict 18:53–64PubMedCrossRefGoogle Scholar
  15. Carroll CA, O’Donnell BF, Shekhar A, Hetrick WP (2009) Timing dysfunctions in schizophrenia span from millisecond to several-second durations. Brain Cogn 70:181–190PubMedCrossRefGoogle Scholar
  16. Chait LD, Burke KA (1994) Preference for high- versus low-potency marijuana. Pharmacol Biochem Behav 49:643–647PubMedCrossRefGoogle Scholar
  17. Chait LD, Zacny JP (1992) Reinforcing and subjective effects of oral delta 9-THC and smoked marijuana in humans. Psychopharmacology (Berlin) 107:255–262CrossRefGoogle Scholar
  18. Chen J, Paredes W, Lowinson JH, Gardner EL (1990a) Delta 9-tetrahydrocannabinol enhances presynaptic dopamine efflux in medial prefrontal cortex. Eur J Pharmacol 190:259–262PubMedCrossRefGoogle Scholar
  19. Chen JP, Paredes W, Li J, Smith D, Lowinson J, Gardner EL (1990b) Delta 9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacology 102:156–162PubMedCrossRefGoogle Scholar
  20. Cheng RK, MacDonald CJ, Meck WH (2006) Differential effects of cocaine and ketamine on time estimation: implications for neurobiological models of interval timing. Pharmacol Biochem Behav 85:114–122PubMedCrossRefGoogle Scholar
  21. Cheng RK, Ali YM, Meck WH (2007) Ketamine “unlocks” the reduced clock-speed effects of cocaine following extended training: evidence for dopamine–glutamate interactions in timing and time perception. Neurobiol Learn Mem 88:149–159PubMedCrossRefGoogle Scholar
  22. Chevaleyre V, Takahashi KA, Castillo PE (2006) Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 29:37–76PubMedCrossRefGoogle Scholar
  23. Clark LD, Hughes R, Nakashima EN (1970) Behavioral effects of marihuana. Experimental studies. Arch Gen Psychiatry 23:193–198PubMedCrossRefGoogle Scholar
  24. Cohen J (1973) Eta-squared and partial eta-squared in communication science. Hum Commun Res 28:473–490Google Scholar
  25. Conrad DG, Elsmore TF, Sodetz FJ (1972) 9-tetrahydrocannabinol: dose-related effects on timing behavior in chimpanzee. Science 175:547–550PubMedCrossRefGoogle Scholar
  26. Coull JT, Cheng RK, Meck WH (2011a) Neuroanatomical and neurochemical substrates of timing. Neuropsychopharmacology 36:3–25PubMedCrossRefGoogle Scholar
  27. Coull JT, Morgan H, Cambridge VC, Moore JW, Giorlando F, Adapa R, Corlett PR, Fletcher PC (2011b) Ketamine perturbs perception of the flow of time in healthy volunteers. Psychopharmacology (Berlin) 218:543–556CrossRefGoogle Scholar
  28. Cowan RL, Wilson CJ (1994) Spontaneous firing patterns and axonal projections of single corticostriatal neurons in the rat medial agranular cortex. J Neurophysiol 71:17–32PubMedGoogle Scholar
  29. Davalos DB, Kisley MA, Ross RG (2003) Effects of interval duration on temporal processing in schizophrenia. Brain Cogn 52:295–301PubMedCrossRefGoogle Scholar
  30. de Souza MR, Karniol IG, Ventura DF (1974) Human tonal preferences as a function of frequency under delta8-tetrahydrocannabinol. Pharmacol Biochem Behav 2:607–611PubMedCrossRefGoogle Scholar
  31. Dornbush RL, Kokkevi A (1976) Acute effects of cannabis on cognitive, perceptual, and motor performance in chronic hashish users. Ann N Y Acad Sci 282:313–322PubMedCrossRefGoogle Scholar
  32. Dornbush R, Clare G, Zaks A, Crown P, Volavka J, Fink M (1971) 21-day administration of marijuana in male volunteers. In: Lewis M (ed) Current research in marijuana. Academic, New York, pp 115–128Google Scholar
  33. Dougherty DM, Cherek DR, Roache JD (1994) The effects of smoked marijuana on progressive-interval schedule performance in humans. J Exp Anal Behav 62:73–87PubMedCrossRefGoogle Scholar
  34. D’Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT, Braley G, Gueorguieva R, Krystal JH (2004) The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 29:1558–1572PubMedCrossRefGoogle Scholar
  35. D’Souza DC, Braley G, Blaise R, Vendetti M, Oliver S, Pittman B, Ranganathan M, Bhakta S, Zimolo Z, Cooper T, Perry E (2008a) Effects of haloperidol on the behavioral, subjective, cognitive, motor, and neuroendocrine effects of Delta-9-tetrahydrocannabinol in humans. Psychopharmacology (Berlin) 198:587–603CrossRefGoogle Scholar
  36. D’Souza DC, Ranganathan M, Braley G, Gueorguieva R, Zimolo Z, Cooper T, Perry E, Krystal J (2008b) Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology 33:2505–2516PubMedCrossRefGoogle Scholar
  37. D’Souza DC, Fridberg DJ, Skosnik PD, Williams A, Roach B, Singh N, Carbuto M, Elander J, Schnakenberg A, Pittman B, Sewell RA, Ranganathan M, Mathalon D (2012) Dose-related modulation of event-related potentials to novel and target stimuli by intravenous delta(9)-THC in humans. Neuropsychopharmacology 37:1632–1646PubMedCrossRefGoogle Scholar
  38. Egerton A, Allison C, Brett RR, Pratt JA (2006) Cannabinoids and prefrontal cortical function: insights from preclinical studies. Neurosci Biobehav Rev 30:680–695PubMedCrossRefGoogle Scholar
  39. Fadda P, Scherma M, Spano MS, Salis P, Melis V, Fattore L, Fratta W (2006) Cannabinoid self-administration increases dopamine release in the nucleus accumbens. Neuroreport 17:1629–1632PubMedCrossRefGoogle Scholar
  40. First M, Spitzer R, Gibbon M, Williams J (2007) Structured Clinical Interview for Axis I DSM-IV Disorders, Research Version. B.R. Department, New York State Psychiatric Institute, New YorkGoogle Scholar
  41. French ED (1997) Delta9-Tetrahydrocannabinol excites rat VTA dopamine neurons through activation of cannabinoid CB1 but not opioid receptors. Neurosci Lett 226:159–162PubMedCrossRefGoogle Scholar
  42. French ED, Dillon K, Wu X (1997) Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra. Neuroreport 8:649–652PubMedCrossRefGoogle Scholar
  43. Freund TF, Powell JF, Smith AD (1984) Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines. Neuroscience 13:1189–1215PubMedCrossRefGoogle Scholar
  44. Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066PubMedGoogle Scholar
  45. Gardner EL (2005) Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol Biochem Behav 81:263–284PubMedCrossRefGoogle Scholar
  46. Gessa GL, Melis M, Muntoni AL, Diana M (1998) Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors. Eur J Pharmacol 341:39–44PubMedCrossRefGoogle Scholar
  47. Gibbon J, Church RM, Meck WH (1984) Scalar timing in memory. Ann N Y Acad Sci 423:52–77PubMedCrossRefGoogle Scholar
  48. Grotenhermen F (2003) Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 42:327–360PubMedCrossRefGoogle Scholar
  49. Gutyrchik E, Churan J, Meindl T, Bokde AL, von Bernewitz H, Born C, Reiser M, Poppel E, Wittmann M (2010) Functional neuroimaging of duration discrimination on two different time scales. Neurosci Lett 469:411–415PubMedCrossRefGoogle Scholar
  50. Han CJ, Robinson JK (2001) Cannabinoid modulation of time estimation in the rat. Behav Neurosci 115:243–246PubMedCrossRefGoogle Scholar
  51. Heishman SJ, Arasteh K, Stitzer ML (1997) Comparative effects of alcohol and marijuana on mood, memory, and performance. Pharmacol Biochem Behav 58:93–101PubMedCrossRefGoogle Scholar
  52. Herkenham M, Lynn AB, de Costa BR, Richfield EK (1991) Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Res 547:267–274PubMedCrossRefGoogle Scholar
  53. Hermann H, Marsicano G, Lutz B (2002) Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain. Neuroscience 109:451–460PubMedCrossRefGoogle Scholar
  54. Hicks RE, Gualtieri CT, Mayo JP Jr, Perez-Reyes M (1984) Cannabis, atropine, and temporal information processing. Neuropsychobiology 12:229–237PubMedCrossRefGoogle Scholar
  55. 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 CB(1) receptors in chronic daily cannabis smokers. Mol Psychiatry 17:642–649PubMedCrossRefGoogle Scholar
  56. Ivry RB, Schlerf JE (2008) Dedicated and intrinsic models of time perception. Trends Cogn Sci 12:273–280PubMedCrossRefGoogle Scholar
  57. Ivry RB, Spencer RM (2004) The neural representation of time. Curr Opin Neurobiol 14:225–232PubMedCrossRefGoogle Scholar
  58. Johnson JE, Petzel TP (1971) Temporal orientation and time estimation in chronic schizophrenics. J Clin Psychol 27:194–196PubMedCrossRefGoogle Scholar
  59. Jones RT, Stone GC (1970) Psychological studies of marijuana and alcohol in man. Psychopharmacologia 18:108–117PubMedCrossRefGoogle Scholar
  60. Kagerer FA, Wittmann M, Szelag E, Steinbuchel N (2002) Cortical involvement in temporal reproduction: evidence for differential roles of the hemispheres. Neuropsychologia 40:357–366PubMedCrossRefGoogle Scholar
  61. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89:309–380PubMedCrossRefGoogle Scholar
  62. Karniol IG, Carlini EA (1973) Comparative studies in man and in laboratory animals on 8- and 9-trans-tetrahydrocannabinol. Pharmacology 9:115–126PubMedCrossRefGoogle Scholar
  63. Karniol IG, Shirakawa I, Takahashi RN, Knobel E, Musty RE (1975) Effects of delta9-tetrahydrocannabinol and cannabinol in man. Pharmacology 13:502–512PubMedCrossRefGoogle Scholar
  64. Katona I, Urban GM, Wallace M, Ledent C, Jung KM, Piomelli D, Mackie K, Freund TF (2006) Molecular composition of the endocannabinoid system at glutamatergic synapses. J Neurosci 26:5628–5637PubMedCrossRefGoogle Scholar
  65. Kelland MD, Chiodo LA, Freeman AS (1991) Dissociative anesthesia and striatal neuronal electrophysiology. Synapse 9:75–78PubMedCrossRefGoogle Scholar
  66. Kemp JM, Powell TP (1971) The site of termination of afferent fibres in the caudate nucleus. Philos Trans R Soc B Biol Sci 262:413–427CrossRefGoogle Scholar
  67. Kheirbek MA (2007) A molecular switch for induction of long-term depression of corticostriatal transmission. J Neurosci 27:9824–9825PubMedCrossRefGoogle Scholar
  68. Kitai ST, Kocsis JD, Preston RJ, Sugimori M (1976) Monosynaptic inputs to caudate neurons identified by intracellular injection of horseradish peroxidase. Brain Res 109:601–606PubMedCrossRefGoogle Scholar
  69. Laviolette SR, Grace AA (2006a) Cannabinoids potentiate emotional learning plasticity in neurons of the medial prefrontal cortex through basolateral amygdala inputs. J Neurosci 26:6458–6468PubMedCrossRefGoogle Scholar
  70. Laviolette SR, Grace AA (2006b) The roles of cannabinoid and dopamine receptor systems in neural emotional learning circuits: implications for schizophrenia and addiction. Cell Mol Life Sci 63:1597–1613PubMedCrossRefGoogle Scholar
  71. Lemberger L, Axelrod J, Kopin IJ (1971) Metabolism and disposition of delta-9-tetrahydrocannabinol in man. Pharmacol Rev 23:371–380PubMedGoogle Scholar
  72. Lewis PA, Miall RC (2003) Distinct systems for automatic and cognitively controlled time measurement: evidence from neuroimaging. Curr Opin Neurobiol 13:250–255PubMedCrossRefGoogle Scholar
  73. Lewis PA, Miall RC (2006) A right hemispheric prefrontal system for cognitive time measurement. Behav Process 71:226–234CrossRefGoogle Scholar
  74. Lichtman AH, Martin BR (2005) Cannabinoid tolerance and dependence. Handb Exp Pharmacol (168):691–717Google Scholar
  75. Lieving LM, Lane SD, Cherek DR, Tcheremissine OV (2006) Effects of marijuana on temporal discriminations in humans. Behav Pharmacol 17:173–183PubMedCrossRefGoogle Scholar
  76. 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 (Berlin) 74:208–212CrossRefGoogle Scholar
  77. MacDonald CJ, Meck WH (2005) Differential effects of clozapine and haloperidol on interval timing in the supraseconds range. Psychopharmacology (Berlin) 182:232–244CrossRefGoogle Scholar
  78. Madison G (2001) Variability in isochronous tapping: higher order dependencies as a function of intertap interval. J Exp Psychol Hum Percept Perform 27:411–422PubMedCrossRefGoogle Scholar
  79. Martin GW, Wilkinson DA, Kapur BM (1988) Validation of self-reported cannabis use by urine analysis. Addict Behav 13:147–150PubMedCrossRefGoogle Scholar
  80. Matell MS, Meck WH (2004) Cortico-striatal circuits and interval timing: coincidence detection of oscillatory processes. Cogn Brain Res 21:139–170CrossRefGoogle Scholar
  81. Matell MS, King GR, Meck WH (2004) Differential modulation of clock speed by the administration of intermittent versus continuous cocaine. Behav Neurosci 118:150–156PubMedCrossRefGoogle Scholar
  82. Matell MS, Bateson M, Meck WH (2006) Single-trials analyses demonstrate that increases in clock speed contribute to the methamphetamine-induced horizontal shifts in peak-interval timing functions. Psychopharmacology (Berlin) 188:201–212CrossRefGoogle Scholar
  83. Mathew RJ, Wilson WH, Turkington TG, Coleman RE (1998) Cerebellar activity and disturbed time sense after THC. Brain Res 797:183–189PubMedCrossRefGoogle Scholar
  84. McClure GY, McMillan DE (1997) Effects of drugs on response duration differentiation. J Pharmacol Exp Ther 281:1368–1380PubMedGoogle Scholar
  85. McDonald J, Schleifer L, Richards JB, de Wit H (2003) Effects of THC on behavioral measures of impulsivity in humans. Neuropsychopharmacology 28:1356–1365PubMedCrossRefGoogle Scholar
  86. Meck WH (1983) Selective adjustment of the speed of internal clock and memory processes. J Exp Psychol Anim Behav Process 9:171–201PubMedCrossRefGoogle Scholar
  87. Meck WH (1996) Neuropharmacology of timing and time perception. Brain Res Cogn Brain Res 3:227–242PubMedCrossRefGoogle Scholar
  88. Meck WH (2005) Neuropsychology of timing and time perception. Brain Cogn 58:1–8PubMedCrossRefGoogle Scholar
  89. Meck WH, Benson AM (2002) Dissecting the brain’s internal clock: how frontal-striatal circuitry keeps time and shifts attention. Brain Cogn 48:195–211PubMedCrossRefGoogle Scholar
  90. Meck WH, Church RM (1983) A mode control model of counting and timing processes. J Exp Psychol Anim Behav Process 9:320–334PubMedCrossRefGoogle Scholar
  91. Menhiratta SS, Wig NN, Verma SK (1978) Some psychological correlates of long-term heavy cannabis users. Br J Psychiatry 132:482–486PubMedCrossRefGoogle Scholar
  92. Meschler JP, Howlett AC (2001) Signal transduction interactions between CB1 cannabinoid and dopamine receptors in the rat and monkey striatum. Neuropharmacology 40:918–926PubMedCrossRefGoogle Scholar
  93. Meyer RE, Pillard RC, Shapiro LM, Mirin SM (1971) Administration of marijuana to heavy and casual marijuana users. Am J Psychiatry 128:198–204PubMedGoogle Scholar
  94. Morrow R (1944) Psychophysical and other functions. In: Mayor’s Committee on Marihuana (ed) The Marihuana Problem in the City of New York, City of New YorkGoogle Scholar
  95. Office of Applied Studies (2006) (Office of Applied Studies 2006; Office of National Drug Control Policy 2008) Results from the 2005 National Survey on Drug Use and Health: National findings. Substance Abuse and Mental Health Services Administration, Rockville, MDGoogle Scholar
  96. Office of National Drug Control Policy (2008) Marijuana: the greatest cause of illegal drug abuse. The marijuana factbook. ONDCP, Washington, DCGoogle Scholar
  97. 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 28:409–416PubMedCrossRefGoogle Scholar
  98. O’Leary DS, Block RI, Turner BM, Koeppel J, Magnotta VA, Ponto LB, Watkins GL, Hichwa RD, Andreasen NC (2003) Marijuana alters the human cerebellar clock. Neuroreport 14:1145–1151PubMedCrossRefGoogle Scholar
  99. Paule MG, Meck WH, McMillan DE, McClure GY, Bateson M, Popke EJ, Chelonis JJ, Hinton SC (1999) The use of timing behaviors in animals and humans to detect drug and/or toxicant effects. Neurotoxicol Teratol 21:491–502PubMedCrossRefGoogle Scholar
  100. Perez-Reyes M, Burstein SH, White WR, McDonald SA, Hicks RE (1991) Antagonism of marihuana effects by indomethacin in humans. Life Sci 48:507–515PubMedCrossRefGoogle Scholar
  101. Pistis M, Ferraro L, Pira L, Flore G, Tanganelli S, Gessa GL, Devoto P (2002) Delta(9)-tetrahydrocannabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the rat prefrontal cortex: an in vivo microdialysis study. Brain Res 948:155–158PubMedCrossRefGoogle Scholar
  102. Pomarol-Clotet E, Honey GD, Murray GK, Corlett PR, Absalom AR, Lee M, McKenna PJ, Bullmore ET, Fletcher PC (2006) Psychological effects of ketamine in healthy volunteers. Phenomenological study. Br J Psychiatry 189:173–179PubMedCrossRefGoogle Scholar
  103. Rabin AI (1957) Time estimation of schizophrenics and nonotics. J Clin Psychol 13:88–90PubMedCrossRefGoogle Scholar
  104. Rammsayer TH (1999) Neuropharmacological evidence for different timing mechanisms in humans. Q J Exp Psychol B 52:273–286PubMedGoogle Scholar
  105. Rammsayer TH, Vogel WH (1992) Pharmacologic properties of the internal clock underlying time perception in humans. Neuropsychobiology 26:71–80PubMedCrossRefGoogle Scholar
  106. Ranganathan M, D’Souza DC (2006) The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology (Berlin) 188:425–444CrossRefGoogle Scholar
  107. Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J, D’Souza DC (2009) The effects of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology (Berlin) 203:737–744CrossRefGoogle Scholar
  108. Ranganathan M, Carbuto M, Braley G, Elander J, Perry E, Pittman B, Radhakrishnan R, Sewell RA, D’Souza DC (2012) Naltrexone does not attenuate the effects of intravenous Delta9-tetrahydrocannabinol in healthy humans. Int J Neuropsychopharmacol 15:1251–1264PubMedCrossRefGoogle Scholar
  109. Schulze GE, McMillan DE, Bailey JR, Scallet A, Ali SF, Slikker W Jr, Paule MG (1988) Acute effects of delta-9-tetrahydrocannabinol in rhesus monkeys as measured by performance in a battery of complex operant tests. J Pharmacol Exp Ther 245:178–186PubMedGoogle Scholar
  110. Sewell RA, Skosnik PD, Garcia-Sosa I, Ranganathan M, D’Souza DC (2010) Behavioral, cognitive and psychophysiological effects of cannabinoids: relevance to psychosis and schizophrenia. Rev Bras Psiquiatr 32(Suppl 1):S15–S30PubMedGoogle Scholar
  111. Solinas M, Justinova Z, Goldberg SR, Tanda G (2006) Anandamide administration alone and after inhibition of fatty acid amide hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in rats. J Neurochem 98:408–419PubMedCrossRefGoogle Scholar
  112. Stone JM, Pilowsky LS (2006) Antipsychotic drug action: targets for drug discovery with neurochemical imaging. Expert Rev Neurother 6:57–64PubMedCrossRefGoogle Scholar
  113. Stone JM, Morrison PD, Nottage J, Bhattacharyya S, Feilding A, McGuire PK (2010) Delta-9-tetrahydrocannabinol disruption of time perception and of self-timed actions. Pharmacopsychiatry 43:236–237PubMedCrossRefGoogle Scholar
  114. Surmeier DJ, Ding J, Day M, Wang Z, Shen W (2007) D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci 30:228–235PubMedCrossRefGoogle Scholar
  115. Tanda G, Pontieri FE, Di Chiara G (1997) Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science 276:2048–2050PubMedCrossRefGoogle Scholar
  116. Tart CT (1970) Marijuana intoxication common experiences. Nature 226:701–704PubMedCrossRefGoogle Scholar
  117. Tinklenberg JR, Kopell BS, Melges FT, Hollister LE (1972) Marihuana and alcohol, time production and memory functions. Arch Gen Psychiatry 27:812–815PubMedCrossRefGoogle Scholar
  118. Tinklenberg JR, Roth WT, Kopell BS (1976) Marijuana and ethanol: differential effects on time perception, heart rate, and subjective response. Psychopharmacology (Berlin) 49:275–279CrossRefGoogle Scholar
  119. Troche S, Rammsayer T (2009) Temporal and non-temporal sensory discrimination and their predictions of capacity- and speed-related aspects of psychometric intelligence. Personal Individ Differ 47:52–57CrossRefGoogle Scholar
  120. Tysk L (1983) Time estimation by healthy subjects and schizophrenic patients: a methodological study. Percept Mot Ski 56:983–988CrossRefGoogle Scholar
  121. Vachon L, Sulkowski A, Rich E (1974) Marihuana effects on learning, attention and time estimation. Psychopharmacologia 39:1–11PubMedCrossRefGoogle Scholar
  122. Villares J (2007) Chronic use of marijuana decreases cannabinoid receptor binding and mRNA expression in the human brain. Neuroscience 145:323–334PubMedCrossRefGoogle Scholar
  123. Wall M, Brine D, Perez-Reyes M (1976) Metabolism of cannabinoids in man. In: Braude M, Szara S (eds) Pharmacology of marihuana. Raven, New York, p 536Google Scholar
  124. Wearden JH, Lejeune H (2008) Scalar properties in human timing: conformity and violations. Q J Exp Psychol (Hove) 61:569–587CrossRefGoogle Scholar
  125. Webb P, Strube F, Leavitt J, Norris G, Fitz-Gerald M, Nixon F, Straumanis J (1993) Time distortion as a persistent sequelae of chronic THC use. In: Harris L (ed) NIDA Research Monograph 132, Problems of Drug Dependence. US Government Printing Office, Washington, DCGoogle Scholar
  126. Weil AT, Zinberg NE, Nelsen JM (1968) Clinical and psychological effects of marihuana in man. Science 162:1234–1242PubMedCrossRefGoogle Scholar
  127. Williamson LL, Cheng RK, Etchegaray M, Meck WH (2008) “Speed” warps time: methamphetamine’s interactive roles in drug abuse, habit formation, and the biological clocks of circadian and interval timing. Curr Drug Abuse Rev 1:203–212PubMedCrossRefGoogle Scholar
  128. Wittmann M, Paulus MP (2008) Decision making, impulsivity and time perception. Trends Cogn Sci 12:7–12PubMedCrossRefGoogle Scholar
  129. Wittmann M, Leland DS, Churan J, Paulus MP (2007) Impaired time perception and motor timing in stimulant-dependent subjects. Drug Alcohol Depend 90:183–192PubMedCrossRefGoogle Scholar
  130. Zelanti PS, Droit-Volet S (2012) Cognitive abilities explaining age-related changes in time perception of short and long durations. J Exp Child Psychol 109:143–157CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA) 2012

Authors and Affiliations

  • R. Andrew Sewell
    • 1
    • 2
    • 3
    Email author
  • Ashley Schnakenberg
    • 1
    • 2
    • 3
  • Jacqueline Elander
    • 1
    • 2
    • 3
  • Rajiv Radhakrishnan
    • 1
    • 2
    • 3
  • Ashley Williams
    • 1
    • 2
    • 3
  • Patrick D. Skosnik
    • 1
    • 2
    • 3
  • Brian Pittman
    • 1
    • 3
  • Mohini Ranganathan
    • 1
    • 2
    • 3
  • D. Cyril D’Souza
    • 1
    • 2
    • 3
  1. 1.Department of Psychiatry, Yale School of MedicineYale UniversityNew HavenUSA
  2. 2.VA Connecticut Healthcare SystemWest HavenUSA
  3. 3.Clinical Neuroscience Research Unit, Yale School of MedicineYale UniversityNew HavenUSA

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