Psychomotor performance in relation to acute oral administration of Δ9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects

  • Patrik Roser
  • Jürgen Gallinat
  • Gordon Weinberg
  • Georg Juckel
  • Inge Gorynia
  • Andreas M. Stadelmann


Abnormalities in psychomotor performance are a consistent finding in schizophrenic patients as well as in chronic cannabis users. The high levels of central cannabinoid (CB1) receptors in the basal ganglia, the cerebral cortex and the cerebellum indicate their implication in the regulation of motor activity. Based on the close relationship between cannabis use, the endogenous cannabinoid system and motor disturbances found in schizophrenia, we expected that administration of cannabinoids may change pattern of psychomotor activity like in schizophrenic patients. This prospective, double-blind, placebo-controlled cross-over study investigated the acute effects of cannabinoids on psychomotor performance in 24 healthy right-handed volunteers (age 27.9 ± 2.9 years, 12 male) by comparing Δ9-tetrahydrocannabinol (Δ9-THC) and standardized cannabis extract containing Δ9-THC and cannabidiol. Psychomotor performance was assessed by using a finger tapping test series. Cannabis extract, but not Δ9-THC, revealed a significant reduction of right-hand tapping frequencies that was also found in schizophrenia. As to the pure Δ9-THC condition, left-hand tapping frequencies were correlated with the plasma concentrations of the Δ9-THC metabolite 11-OH-THC. These effects are thought to be related to cannabinoid actions on CB1 receptors in the basal ganglia, the cerebral cortex and the cerebellum. Our data further demonstrate that acute CB1 receptor activation under the cannabis extract condition may also affect intermanual coordination (IMC) as an index of interhemispheric transfer. AIR-Scale scores as a measure of subjective perception of intoxication were dose-dependently related to IMC which was shown by an inverted U-curve. This result may be due to functional changes involving GABAergic and glutamatergic neurotransmission within the corpus callosum.


cannabinoids psychomotor performance interhemispheric transfer 



This study was supported by the Institute for Clinical Research, Berlin, Germany.


  1. 1.
    Andreasson S, Allebeck P, Engstrom A, Rydberg U (1987) Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 2:1483–1486PubMedCrossRefGoogle Scholar
  2. 2.
    Bisogno T, Hanus L, De Petrocelis L, Tehilibon S, Ponde DE, Brandi I, Moriello AS, Davies JB, Mechoulam R, Di Marzo V (2001) Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol 134:845–852PubMedCrossRefGoogle Scholar
  3. 3.
    Bloom JS, Hynd GW (2005) The role of the corpus callosum in interhemispheric transfer of information: excitation or inhibition? Neuropsychol Rev 15:59–71PubMedCrossRefGoogle Scholar
  4. 4.
    Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218Google Scholar
  5. 5.
    Bornheim LM, Grillo MP (1998) Characterization of cytochrome P450 3A inactivation by cannabidiol: possible involvement of cannabidiol-hydroxyquinone as a P450 inactivator. Chem Res Toxicol 11:1209–1216PubMedCrossRefGoogle Scholar
  6. 6.
    Breivogel CS, Griffin G, Di Marzo V, Martin BR (2001) Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol 60:155–163PubMedGoogle Scholar
  7. 7.
    Chan PK, Chan SC, Yung WH (1998) Presynaptic inhibition of GABAergic inputs to rat substantia nigra pars reticulata neurones by a cannabinoid agonist. Neuroreport 9:671–675PubMedCrossRefGoogle Scholar
  8. 8.
    Crow TJ, Colter N, Frith CD, Johnstone EC, Owens DGC (1989) Developmental arrest of cerebral asymmetries in early onset schizophrenia. Psychiatry Res 29:247–253PubMedCrossRefGoogle Scholar
  9. 9.
    Dean B, Sundram S, Bradbury R, Scarr E, Copolov D (2001) Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use. Neuroscience 103:9–15PubMedCrossRefGoogle Scholar
  10. 10.
    Doty RW (1989) Schizophrenia: a disease of interhemispheric processes at forebrain and brainstem levels? Behav Brain Res 34:1–33PubMedCrossRefGoogle Scholar
  11. 11.
    D’Souza DC (2007) Cannabinoids and psychosis. Int Rev Neurobiol 78:289–326PubMedCrossRefGoogle Scholar
  12. 12.
    Emrich HM, Leweke FM, Schneider U (1997) Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to dysregulation of the endogenous cannabinoid system. Pharmacol Biochem Behav 56:803–807PubMedCrossRefGoogle Scholar
  13. 13.
    Flyckt L, Sydow O, Bjerkenstedt L, Edman G, Rydin E, Wiesel FA (1999) Neurological signs and psychomotor performance in patients with schizophrenia, their relatives and healthy controls. Psychiatry Res 86:113–129PubMedCrossRefGoogle Scholar
  14. 14.
    Gold S, Arndt S, Nopoulos P, O’Leary DS, Andreasen NC (1999) Longitudinal study of cognitive function in first-episode and recent-onset schizophrenia. Am J Psychiatry 156:1342–1348PubMedGoogle Scholar
  15. 15.
    Goode DJ, Manning AA (1988) Specific imbalance of right and left sided motor neuron excitability in schizophrenia. J Neurol Neurosurg Psychiatry 51:626–629PubMedCrossRefGoogle Scholar
  16. 16.
    Goode DJ, Manning AA, Middleton JF, Williams B (1981) Fine motor performance before and after treatment in schizophrenic and schizoaffective patients. Psychiatry Res 5:247–255PubMedCrossRefGoogle Scholar
  17. 17.
    Gorynia I, Campman V, Uebelhack R (2003) Intermanual coordination in relation to different clinical subgroups in right-handed patients with schizophrenic and other psychotic disorders. Eur Arch Psychiatry Clin Neurosci 253:53–59PubMedCrossRefGoogle Scholar
  18. 18.
    Gorynia I, Dudeck U, Neumärker KJ (1994) Instability in functional motor laterality of children and adolescents with endogenous psychosis and predominantly motor disturbances. Eur Arch Psychiatry Clin Neurosci 244:33–38PubMedCrossRefGoogle Scholar
  19. 19.
    Gorynia I, Egenter D (2000) Intermanual coordination in relation to handedness, familial sinistrality and lateral preferences. Cortex 36:1–18PubMedCrossRefGoogle Scholar
  20. 20.
    Gorynia I, Uebelhack R (1992) Functional motor asymmetries correlated with clinical findings in unmedicated schizophrenic patients. Eur Arch Psychiatry Clin Neurosci 242:39–45PubMedCrossRefGoogle Scholar
  21. 21.
    Grotenhermen F (2005) Cannabinoids. Curr Drug Targets CNS Neurol Disord 4:507–530PubMedCrossRefGoogle Scholar
  22. 22.
    Günther W, Günther R, Eich FX, Eben E (1986) Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy. II. Cross validation study on schizophrenic patients: persistence of a “psychotic motor syndrome” as possible evidence of an independent biological marker syndrome for schizophrenia. Eur Arch Psychiatry Neurol Sci 235:301–308PubMedCrossRefGoogle Scholar
  23. 23.
    Gupta S, Andreasen NC, Arndt S, Flaum M, Schultz SK, Hubbard WC, Smith M (1995) Neurological soft signs in neuroleptic-naive and neuroleptic treated schizophrenic patients and in normal comparison subjects. Am J Psychiatry 152:191–196PubMedGoogle Scholar
  24. 24.
    Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87:1932–1936PubMedCrossRefGoogle Scholar
  25. 25.
    Hokama H, Shenton ME, Nestor PG, Kikinis R, Levitt JJ, Metcalf D, Wible CG, O’Donnell BF, Jolesz FA, McCarley RW (1995) Caudate, putamen, and globus pallidus volume in schizophrenia: a quantitative MRI study. Psychiatry Res 61:209–229PubMedCrossRefGoogle Scholar
  26. 26.
    Iversen L (2003) Cannabis and the brain. Brain 126:1252– 1270PubMedCrossRefGoogle Scholar
  27. 27.
    Johns A (2001) Psychiatric effects of cannabis. Br J Psychiatry 178:116–122PubMedCrossRefGoogle Scholar
  28. 28.
    Juckel G, Roser P, Nadulski T, Stadelmann AM, Gallinat J (2007) Acute effects of delta-9-tetrahydrocannabinol and standardized cannabis extract on the auditory evoked mismatch negativity. Schizophr Res 97:109–117PubMedCrossRefGoogle Scholar
  29. 29.
    Levander SE, Bartfai A, Schalling D (1985) Regional cortical dysfunction in schizophrenic patients studied by computerized neuropsychological methods. Percept Mot Skills 61:479–495PubMedGoogle Scholar
  30. 30.
    Leweke FM, Giuffrida A, Wurster U, Emrich HM, Piomelli D (1999) Elevated endogenous cannabinoids in schizophrenia. Neuroreport 10:1665–1669PubMedCrossRefGoogle Scholar
  31. 31.
    Lezak MD (1995) Neuropsychological assessments, 3rd edn. Oxford University Press, New YorkGoogle Scholar
  32. 32.
    Martinez-Arevalo MJ, Calcedo-Ordonez A, Varo-Prieto JR (1994) Cannabis consumption as a prognostic factor in schizophrenia. Br J Psychiatry 164:679–681PubMedCrossRefGoogle Scholar
  33. 33.
    Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564PubMedCrossRefGoogle Scholar
  34. 34.
    Mechoulam R, Gaoni Y (1965) A total synthesis of delta-1-tetrahydrocannabinol, the active constituent of hashish. J Am Chem Soc 87:3273–3275PubMedCrossRefGoogle Scholar
  35. 35.
    Mechoulam R, Parker LA, Gallily R (2002) Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol 42:11S–19SPubMedGoogle Scholar
  36. 36.
    Nadulski T, Pragst F, Weinberg G, Roser P, Schnelle M, Fronk EM, Stadelmann AM (2005) Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract. Ther Drug Monit 27:799–810PubMedCrossRefGoogle Scholar
  37. 37.
    Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113PubMedCrossRefGoogle Scholar
  38. 38.
    Pelletier J, Suchet L, Witjas T, Habib M, Guttmann CR, Salamon G, Lyon-Caen O, Chérif AA (2001) A longitudinal study of callosal atrophy and interhemispheric dysfunction in relapsing-remitting multiple sclerosis. Arch Neurol 58:105–111PubMedCrossRefGoogle Scholar
  39. 39.
    Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215PubMedCrossRefGoogle Scholar
  40. 40.
    Pycock CJ, Kilpatric IC (1989) Motor asymmetries and drug effects: behavioral analyses of receptor activation. In: Boulton AA, Baker GB, Greenshaw AJ (eds) Neuromethods, vol 13: psychopharmacology. Human Press, Clifton, pp 1–93Google Scholar
  41. 41.
    Rodriguez de Fonseca F, Del Arco I, Martin-Calderon JL, Gorriti MA, Navarro M (1998) Role of the endogenous cannabinoid system in the regulation of motor activity. Neurobiol Dis 5:483–501PubMedCrossRefGoogle Scholar
  42. 42.
    Rodriguez de Fonseca F, Gorriti MA, Bilbao A, Escuredo L, Garcia-Segura LM, Piomelli D, Navarro M (2001) Role of the endogenous cannabinoid system as a modulator of dopamine transmission: implications for Parkinson’s disease and schizophrenia. Neurotox Res 3:23–35PubMedGoogle Scholar
  43. 43.
    Roser P, Vollenweider FX, Kawohl W (2008) Potential antipsychotic properties of central cannabinoid (CB1) receptor antagonists. World J Biol Psychiatry 7:1–12. DOI: 10.1080/15622970801908047Google Scholar
  44. 44.
    Roser P, Juckel G, Rentzsch J, Nadulski T, Gallinat J, Stadelmann AM (2008) Effects of acute oral Delta(9)-tetrahydrocannabinol and standardized cannabis extract on the auditory P300 event-related potential in healthy volunteers. Eur Neuropsychopharmacol 18:569–577PubMedCrossRefGoogle Scholar
  45. 45.
    Roser P, Stadelmann AM, Arning L, Gallinat J, Epplen JT, Juckel G (2008) Acute effects of Δ9-tetrahydrocannabinol on the auditory event-related mismatch negativity depending on genetic variations in the dysbindin, neuregulin and G72 gene. Int J Neuropsychopharmacol 11(Suppl 1):256Google Scholar
  46. 46.
    Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101PubMedCrossRefGoogle Scholar
  47. 47.
    Sañudo-Peña MC, Romero J, Seale GE, Fernandez-Ruiz JJ, Walker JM (2000) Activational role of cannabinoids on movement. Eur J Pharmacol 391:269–274PubMedCrossRefGoogle Scholar
  48. 48.
    Sañudo-Peña MC, Tsou K, Walker JM (1999) Motor actions of cannabinoids in the basal ganglia output nuclei. Life Sci 65:703–713PubMedCrossRefGoogle Scholar
  49. 49.
    Sauerwein HC, Lassonde M (1994) Cognitive and sensori-motor functioning in the absence of the corpus callosum: neuropsychological studies in callosal agenesis and callosotomized patients. Behav Brain Res 64:229–240PubMedCrossRefGoogle Scholar
  50. 50.
    Schmidt SL, Oliveira RM, Krahe TE, Filgueiras CC (2000) The effects of hand preference and gender on finger tapping performance asymmetry by the use of an infra-red light measurement device. Neuropsychologia 38:529–534PubMedCrossRefGoogle Scholar
  51. 51.
    Shakow D, Huston PE (1936) Studies on motor function in schizophrenia: I. Speed of tapping. J Gen Psychol 15:63–106Google Scholar
  52. 52.
    Shaw JC, Colter N, Resek G (1983) EEG coherence, lateral preference and schizophrenia. Psychol Med 13:299–306PubMedCrossRefGoogle Scholar
  53. 53.
    Shimoyama I, Ninchoji T, Uemura K (1990) The finger-tapping test. A quantitative analysis. Arch Neurol 47:681–684PubMedGoogle Scholar
  54. 54.
    Solowij N (1998) Cannabis and cognitive functioning. Cambridge University Press, CambridgeGoogle Scholar
  55. 55.
    Stratta P, Rossi A, Gallucci M, Amicarelli I, Passariello R, Casacchia M (1989) Hemispheric asymmetries and schizophrenia: a preliminary magnetic resonance imaging study. Biol Psychiatry 25:275–284PubMedCrossRefGoogle Scholar
  56. 56.
    Strik W, Dierks T (2008) Neurophysiological mechanisms of psychotic symptoms. Eur Arch Psychiatry Clin Neurosci 258(Suppl 5):66–70PubMedCrossRefGoogle Scholar
  57. 57.
    Struve FA, Straumanis JJ, Patrick G (1994) Persistent topographic quantitative EEG sequelae of chronic marihuana use: a replication study and initial discriminant function analysis. Clin Electroencephalogr 25:63–75PubMedGoogle Scholar
  58. 58.
    Struve FA, Straumanis JJ, Patrick G, Leavitt J, Manno JE, Manno BR (1999) Topographic quantitative EEG sequelae of chronic marihuana use: a replication using medically and psychiatrically screened normal subjects. Drug Alcohol Depend 56:167–179PubMedCrossRefGoogle Scholar
  59. 59.
    Szabo B, Wallmichrath I, Mathonia P, Pfreundtner C (2000) Cannabinoids inhibit excitatory neurotransmission in the substantia nigra pars reticulata. Neuroscience 97:89–97PubMedCrossRefGoogle Scholar
  60. 60.
    Torrey E (1980) Neurological abnormalities in schizophrenic patients. Biol Psychiatry 15:381–388PubMedGoogle Scholar
  61. 61.
    Turner WM, Tsuang MT (1990) Impact of substance abuse on the course and outcome of schizophrenia. Schizophr Bull 16:87–95PubMedGoogle Scholar
  62. 62.
    Wobrock T, Sittinger H, Behrendt B, D’Amelio R, Falkai P, Caspari D (2007) Comorbid substance abuse and neurocognitive function in recent-onset schizophrenia. Eur Arch Psychiatry Clin Neurosci 257:203–210PubMedCrossRefGoogle Scholar
  63. 63.
    Woodruff PW, McManus IC, David AS (1995) Meta-analysis of corpus callosum size in schizophrenia. J Neurol Neurosurg Psychiatry 58:457–461PubMedCrossRefGoogle Scholar
  64. 64.
    Zavitsanou K, Garrick T, Huang XF (2004) Selective antagonist [3H] SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 28:355–360PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff Verlag Darmstadt 2009

Authors and Affiliations

  • Patrik Roser
    • 1
  • Jürgen Gallinat
    • 2
  • Gordon Weinberg
    • 2
  • Georg Juckel
    • 1
  • Inge Gorynia
    • 2
  • Andreas M. Stadelmann
    • 2
  1. 1.Department of PsychiatryRuhr-University BochumBochumGermany
  2. 2.Department of PsychiatryCharité University HospitalBerlinGermany

Personalised recommendations