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

Abstract

Rationale

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  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 38:21–43

    PubMed  CAS  Google Scholar 

  2. Allman MJ, Meck WH (2012) Pathophysiological distortions in time perception and timed performance. Brain 135:656–677

    PubMed  Article  Google 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 46:908–920

    PubMed  CAS  Article  Google 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 261:114–122

    PubMed  CAS  Google Scholar 

  5. Azorlosa JL, Greenwald MK, Stitzer ML (1995) Marijuana smoking: effects of varying puff volume and breathhold duration. J Pharmacol Exp Ther 272:560–569

    PubMed  CAS  Google 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 62:1053–1057

    PubMed  CAS  Article  Google Scholar 

  7. Bech P, Rafaelsen L, Rafaelsen OJ (1973) Cannabis and alcohol: effects on estimation of time and distance. Psychopharmacologia 32:373–381

    PubMed  CAS  Article  Google Scholar 

  8. Borg J, Gershon S, Alpert M (1975) Dose effects of smoked marihuana on human cognitive and motor functions. Psychopharmacologia 42:211–218

    PubMed  CAS  Article  Google Scholar 

  9. Brown TM, Brotchie JM, Fitzjohn SM (2003) Cannabinoids decrease corticostriatal synaptic transmission via an effect on glutamate uptake. J Neurosci 23:11073–11077

    PubMed  CAS  Google Scholar 

  10. Buonomano DV (2007) The biology of time across different scales. Nat Chem Biol 3:594–597

    PubMed  CAS  Article  Google 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 182:195–203

    PubMed  CAS  Google 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) 219:885–896

    CAS  Article  Google Scholar 

  13. Carlini EA, Karniol IG, Renault PF, Schuster CR (1974) Effects of marihuana in laboratory animals and in man. Br J Pharmacol 50:299–309

    PubMed  CAS  Article  Google 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 18:53–64

    PubMed  Article  Google 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 70:181–190

    PubMed  Article  Google Scholar 

  16. Chait LD, Burke KA (1994) Preference for high- versus low-potency marijuana. Pharmacol Biochem Behav 49:643–647

    PubMed  CAS  Article  Google Scholar 

  17. Chait LD, Zacny JP (1992) Reinforcing and subjective effects of oral delta 9-THC and smoked marijuana in humans. Psychopharmacology (Berlin) 107:255–262

    CAS  Article  Google 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 190:259–262

    PubMed  CAS  Article  Google 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 102:156–162

    PubMed  CAS  Article  Google 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 85:114–122

    PubMed  CAS  Article  Google 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 88:149–159

    PubMed  CAS  Article  Google Scholar 

  22. Chevaleyre V, Takahashi KA, Castillo PE (2006) Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 29:37–76

    PubMed  CAS  Article  Google Scholar 

  23. Clark LD, Hughes R, Nakashima EN (1970) Behavioral effects of marihuana. Experimental studies. Arch Gen Psychiatry 23:193–198

    PubMed  CAS  Article  Google Scholar 

  24. Cohen J (1973) Eta-squared and partial eta-squared in communication science. Hum Commun Res 28:473–490

    Google Scholar 

  25. Conrad DG, Elsmore TF, Sodetz FJ (1972) 9-tetrahydrocannabinol: dose-related effects on timing behavior in chimpanzee. Science 175:547–550

    PubMed  CAS  Article  Google Scholar 

  26. Coull JT, Cheng RK, Meck WH (2011a) Neuroanatomical and neurochemical substrates of timing. Neuropsychopharmacology 36:3–25

    PubMed  Article  Google 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) 218:543–556

    CAS  Article  Google 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 71:17–32

    PubMed  CAS  Google Scholar 

  29. Davalos DB, Kisley MA, Ross RG (2003) Effects of interval duration on temporal processing in schizophrenia. Brain Cogn 52:295–301

    PubMed  Article  Google Scholar 

  30. de Souza MR, Karniol IG, Ventura DF (1974) Human tonal preferences as a function of frequency under delta8-tetrahydrocannabinol. Pharmacol Biochem Behav 2:607–611

    PubMed  Article  Google 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 282:313–322

    PubMed  CAS  Article  Google 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 115–128

    Google 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 62:73–87

    PubMed  CAS  Article  Google 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 29:1558–1572

    PubMed  Article  CAS  Google 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) 198:587–603

    Article  CAS  Google 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 33:2505–2516

    PubMed  Article  CAS  Google 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 37:1632–1646

    PubMed  Article  CAS  Google Scholar 

  38. Egerton A, Allison C, Brett RR, Pratt JA (2006) Cannabinoids and prefrontal cortical function: insights from preclinical studies. Neurosci Biobehav Rev 30:680–695

    PubMed  CAS  Article  Google 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 17:1629–1632

    PubMed  CAS  Article  Google 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 York

    Google Scholar 

  41. French ED (1997) Delta9-Tetrahydrocannabinol excites rat VTA dopamine neurons through activation of cannabinoid CB1 but not opioid receptors. Neurosci Lett 226:159–162

    PubMed  CAS  Article  Google Scholar 

  42. French ED, Dillon K, Wu X (1997) Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra. Neuroreport 8:649–652

    PubMed  CAS  Article  Google 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 13:1189–1215

    PubMed  CAS  Article  Google Scholar 

  44. Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066

    PubMed  CAS  Google Scholar 

  45. Gardner EL (2005) Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol Biochem Behav 81:263–284

    PubMed  CAS  Article  Google 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 341:39–44

    PubMed  CAS  Article  Google Scholar 

  47. Gibbon J, Church RM, Meck WH (1984) Scalar timing in memory. Ann N Y Acad Sci 423:52–77

    PubMed  CAS  Article  Google Scholar 

  48. Grotenhermen F (2003) Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 42:327–360

    PubMed  CAS  Article  Google 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 469:411–415

    PubMed  CAS  Article  Google Scholar 

  50. Han CJ, Robinson JK (2001) Cannabinoid modulation of time estimation in the rat. Behav Neurosci 115:243–246

    PubMed  CAS  Article  Google Scholar 

  51. Heishman SJ, Arasteh K, Stitzer ML (1997) Comparative effects of alcohol and marijuana on mood, memory, and performance. Pharmacol Biochem Behav 58:93–101

    PubMed  CAS  Article  Google 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 547:267–274

    PubMed  CAS  Article  Google 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 109:451–460

    PubMed  CAS  Article  Google Scholar 

  54. Hicks RE, Gualtieri CT, Mayo JP Jr, Perez-Reyes M (1984) Cannabis, atropine, and temporal information processing. Neuropsychobiology 12:229–237

    PubMed  CAS  Article  Google 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 17:642–649

    PubMed  CAS  Article  Google Scholar 

  56. Ivry RB, Schlerf JE (2008) Dedicated and intrinsic models of time perception. Trends Cogn Sci 12:273–280

    PubMed  Article  Google Scholar 

  57. Ivry RB, Spencer RM (2004) The neural representation of time. Curr Opin Neurobiol 14:225–232

    PubMed  CAS  Article  Google Scholar 

  58. Johnson JE, Petzel TP (1971) Temporal orientation and time estimation in chronic schizophrenics. J Clin Psychol 27:194–196

    PubMed  CAS  Article  Google Scholar 

  59. Jones RT, Stone GC (1970) Psychological studies of marijuana and alcohol in man. Psychopharmacologia 18:108–117

    PubMed  CAS  Article  Google Scholar 

  60. Kagerer FA, Wittmann M, Szelag E, Steinbuchel N (2002) Cortical involvement in temporal reproduction: evidence for differential roles of the hemispheres. Neuropsychologia 40:357–366

    PubMed  Article  Google Scholar 

  61. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89:309–380

    PubMed  CAS  Article  Google Scholar 

  62. Karniol IG, Carlini EA (1973) Comparative studies in man and in laboratory animals on 8- and 9-trans-tetrahydrocannabinol. Pharmacology 9:115–126

    PubMed  CAS  Article  Google Scholar 

  63. Karniol IG, Shirakawa I, Takahashi RN, Knobel E, Musty RE (1975) Effects of delta9-tetrahydrocannabinol and cannabinol in man. Pharmacology 13:502–512

    PubMed  CAS  Article  Google 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 26:5628–5637

    PubMed  CAS  Article  Google Scholar 

  65. Kelland MD, Chiodo LA, Freeman AS (1991) Dissociative anesthesia and striatal neuronal electrophysiology. Synapse 9:75–78

    PubMed  CAS  Article  Google 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 262:413–427

    CAS  Article  Google Scholar 

  67. Kheirbek MA (2007) A molecular switch for induction of long-term depression of corticostriatal transmission. J Neurosci 27:9824–9825

    PubMed  CAS  Article  Google 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 109:601–606

    PubMed  CAS  Article  Google 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 26:6458–6468

    PubMed  CAS  Article  Google 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 63:1597–1613

    PubMed  CAS  Article  Google Scholar 

  71. Lemberger L, Axelrod J, Kopin IJ (1971) Metabolism and disposition of delta-9-tetrahydrocannabinol in man. Pharmacol Rev 23:371–380

    PubMed  CAS  Google Scholar 

  72. Lewis PA, Miall RC (2003) Distinct systems for automatic and cognitively controlled time measurement: evidence from neuroimaging. Curr Opin Neurobiol 13:250–255

    PubMed  CAS  Article  Google Scholar 

  73. Lewis PA, Miall RC (2006) A right hemispheric prefrontal system for cognitive time measurement. Behav Process 71:226–234

    CAS  Article  Google Scholar 

  74. Lichtman AH, Martin BR (2005) Cannabinoid tolerance and dependence. Handb Exp Pharmacol (168):691–717

  75. Lieving LM, Lane SD, Cherek DR, Tcheremissine OV (2006) Effects of marijuana on temporal discriminations in humans. Behav Pharmacol 17:173–183

    PubMed  Article  Google 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) 74:208–212

    CAS  Article  Google Scholar 

  77. MacDonald CJ, Meck WH (2005) Differential effects of clozapine and haloperidol on interval timing in the supraseconds range. Psychopharmacology (Berlin) 182:232–244

    CAS  Article  Google Scholar 

  78. Madison G (2001) Variability in isochronous tapping: higher order dependencies as a function of intertap interval. J Exp Psychol Hum Percept Perform 27:411–422

    PubMed  CAS  Article  Google Scholar 

  79. Martin GW, Wilkinson DA, Kapur BM (1988) Validation of self-reported cannabis use by urine analysis. Addict Behav 13:147–150

    PubMed  CAS  Article  Google Scholar 

  80. Matell MS, Meck WH (2004) Cortico-striatal circuits and interval timing: coincidence detection of oscillatory processes. Cogn Brain Res 21:139–170

    Article  Google Scholar 

  81. Matell MS, King GR, Meck WH (2004) Differential modulation of clock speed by the administration of intermittent versus continuous cocaine. Behav Neurosci 118:150–156

    PubMed  CAS  Article  Google 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) 188:201–212

    CAS  Article  Google Scholar 

  83. Mathew RJ, Wilson WH, Turkington TG, Coleman RE (1998) Cerebellar activity and disturbed time sense after THC. Brain Res 797:183–189

    PubMed  CAS  Article  Google Scholar 

  84. McClure GY, McMillan DE (1997) Effects of drugs on response duration differentiation. J Pharmacol Exp Ther 281:1368–1380

    PubMed  CAS  Google Scholar 

  85. McDonald J, Schleifer L, Richards JB, de Wit H (2003) Effects of THC on behavioral measures of impulsivity in humans. Neuropsychopharmacology 28:1356–1365

    PubMed  CAS  Article  Google Scholar 

  86. Meck WH (1983) Selective adjustment of the speed of internal clock and memory processes. J Exp Psychol Anim Behav Process 9:171–201

    PubMed  CAS  Article  Google Scholar 

  87. Meck WH (1996) Neuropharmacology of timing and time perception. Brain Res Cogn Brain Res 3:227–242

    PubMed  CAS  Article  Google Scholar 

  88. Meck WH (2005) Neuropsychology of timing and time perception. Brain Cogn 58:1–8

    PubMed  Article  Google Scholar 

  89. Meck WH, Benson AM (2002) Dissecting the brain’s internal clock: how frontal-striatal circuitry keeps time and shifts attention. Brain Cogn 48:195–211

    PubMed  Article  Google Scholar 

  90. Meck WH, Church RM (1983) A mode control model of counting and timing processes. J Exp Psychol Anim Behav Process 9:320–334

    PubMed  CAS  Article  Google Scholar 

  91. Menhiratta SS, Wig NN, Verma SK (1978) Some psychological correlates of long-term heavy cannabis users. Br J Psychiatry 132:482–486

    PubMed  CAS  Article  Google Scholar 

  92. Meschler JP, Howlett AC (2001) Signal transduction interactions between CB1 cannabinoid and dopamine receptors in the rat and monkey striatum. Neuropharmacology 40:918–926

    PubMed  CAS  Article  Google Scholar 

  93. Meyer RE, Pillard RC, Shapiro LM, Mirin SM (1971) Administration of marijuana to heavy and casual marijuana users. Am J Psychiatry 128:198–204

    PubMed  CAS  Google 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 York

  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, MD

  96. Office of National Drug Control Policy (2008) Marijuana: the greatest cause of illegal drug abuse. The marijuana factbook. ONDCP, Washington, DC

    Google 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 28:409–416

    PubMed  CAS  Article  Google 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 14:1145–1151

    PubMed  Article  Google 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 21:491–502

    PubMed  CAS  Article  Google Scholar 

  100. Perez-Reyes M, Burstein SH, White WR, McDonald SA, Hicks RE (1991) Antagonism of marihuana effects by indomethacin in humans. Life Sci 48:507–515

    PubMed  CAS  Article  Google 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 948:155–158

    PubMed  CAS  Article  Google 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 189:173–179

    PubMed  CAS  Article  Google Scholar 

  103. Rabin AI (1957) Time estimation of schizophrenics and nonotics. J Clin Psychol 13:88–90

    PubMed  CAS  Article  Google Scholar 

  104. Rammsayer TH (1999) Neuropharmacological evidence for different timing mechanisms in humans. Q J Exp Psychol B 52:273–286

    PubMed  CAS  Google Scholar 

  105. Rammsayer TH, Vogel WH (1992) Pharmacologic properties of the internal clock underlying time perception in humans. Neuropsychobiology 26:71–80

    PubMed  CAS  Article  Google Scholar 

  106. Ranganathan M, D’Souza DC (2006) The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology (Berlin) 188:425–444

    CAS  Article  Google 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) 203:737–744

    CAS  Article  Google 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 15:1251–1264

    PubMed  CAS  Article  Google 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 245:178–186

    PubMed  CAS  Google 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–S30

    PubMed  Google 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 98:408–419

    PubMed  CAS  Article  Google Scholar 

  112. Stone JM, Pilowsky LS (2006) Antipsychotic drug action: targets for drug discovery with neurochemical imaging. Expert Rev Neurother 6:57–64

    PubMed  CAS  Article  Google 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 43:236–237

    PubMed  CAS  Article  Google 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 30:228–235

    PubMed  CAS  Article  Google 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 276:2048–2050

    PubMed  CAS  Article  Google Scholar 

  116. Tart CT (1970) Marijuana intoxication common experiences. Nature 226:701–704

    PubMed  CAS  Article  Google Scholar 

  117. Tinklenberg JR, Kopell BS, Melges FT, Hollister LE (1972) Marihuana and alcohol, time production and memory functions. Arch Gen Psychiatry 27:812–815

    PubMed  CAS  Article  Google Scholar 

  118. Tinklenberg JR, Roth WT, Kopell BS (1976) Marijuana and ethanol: differential effects on time perception, heart rate, and subjective response. Psychopharmacology (Berlin) 49:275–279

    CAS  Article  Google 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 47:52–57

    Article  Google Scholar 

  120. Tysk L (1983) Time estimation by healthy subjects and schizophrenic patients: a methodological study. Percept Mot Ski 56:983–988

    CAS  Article  Google Scholar 

  121. Vachon L, Sulkowski A, Rich E (1974) Marihuana effects on learning, attention and time estimation. Psychopharmacologia 39:1–11

    PubMed  CAS  Article  Google Scholar 

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

    PubMed  CAS  Article  Google 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 536

    Google Scholar 

  124. Wearden JH, Lejeune H (2008) Scalar properties in human timing: conformity and violations. Q J Exp Psychol (Hove) 61:569–587

    CAS  Article  Google 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, DC

    Google Scholar 

  126. Weil AT, Zinberg NE, Nelsen JM (1968) Clinical and psychological effects of marihuana in man. Science 162:1234–1242

    PubMed  CAS  Article  Google 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 1:203–212

    PubMed  Article  Google Scholar 

  128. Wittmann M, Paulus MP (2008) Decision making, impulsivity and time perception. Trends Cogn Sci 12:7–12

    PubMed  Article  Google Scholar 

  129. Wittmann M, Leland DS, Churan J, Paulus MP (2007) Impaired time perception and motor timing in stimulant-dependent subjects. Drug Alcohol Depend 90:183–192

    PubMed  Article  Google 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 109:143–157

    Article  Google Scholar 

Download references

Acknowledgments

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.

Author information

Affiliations

Authors

Corresponding author

Correspondence to R. Andrew Sewell.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 42 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sewell, R.A., Schnakenberg, A., Elander, J. et al. Acute effects of THC on time perception in frequent and infrequent cannabis users. Psychopharmacology 226, 401–413 (2013). https://doi.org/10.1007/s00213-012-2915-6

Download citation

Keywords

  • Cannabinoids
  • Δ9-tetrahydrocannabinol
  • Time perception
  • Temporal processing