Abstract
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.
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References
Andreasson S, Allebeck P, Engstrom A, Rydberg U (1987) Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 2:1483–1486
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 134:845–852
Bloom JS, Hynd GW (2005) The role of the corpus callosum in interhemispheric transfer of information: excitation or inhibition? Neuropsychol Rev 15:59–71
Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218
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 11:1209–1216
Breivogel CS, Griffin G, Di Marzo V, Martin BR (2001) Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol 60:155–163
Chan PK, Chan SC, Yung WH (1998) Presynaptic inhibition of GABAergic inputs to rat substantia nigra pars reticulata neurones by a cannabinoid agonist. Neuroreport 9:671–675
Crow TJ, Colter N, Frith CD, Johnstone EC, Owens DGC (1989) Developmental arrest of cerebral asymmetries in early onset schizophrenia. Psychiatry Res 29:247–253
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 103:9–15
Doty RW (1989) Schizophrenia: a disease of interhemispheric processes at forebrain and brainstem levels? Behav Brain Res 34:1–33
D’Souza DC (2007) Cannabinoids and psychosis. Int Rev Neurobiol 78:289–326
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 56:803–807
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 86:113–129
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 156:1342–1348
Goode DJ, Manning AA (1988) Specific imbalance of right and left sided motor neuron excitability in schizophrenia. J Neurol Neurosurg Psychiatry 51:626–629
Goode DJ, Manning AA, Middleton JF, Williams B (1981) Fine motor performance before and after treatment in schizophrenic and schizoaffective patients. Psychiatry Res 5:247–255
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 253:53–59
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 244:33–38
Gorynia I, Egenter D (2000) Intermanual coordination in relation to handedness, familial sinistrality and lateral preferences. Cortex 36:1–18
Gorynia I, Uebelhack R (1992) Functional motor asymmetries correlated with clinical findings in unmedicated schizophrenic patients. Eur Arch Psychiatry Clin Neurosci 242:39–45
Grotenhermen F (2005) Cannabinoids. Curr Drug Targets CNS Neurol Disord 4:507–530
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 235:301–308
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 152:191–196
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 87:1932–1936
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 61:209–229
Iversen L (2003) Cannabis and the brain. Brain 126:1252– 1270
Johns A (2001) Psychiatric effects of cannabis. Br J Psychiatry 178:116–122
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 97:109–117
Levander SE, Bartfai A, Schalling D (1985) Regional cortical dysfunction in schizophrenic patients studied by computerized neuropsychological methods. Percept Mot Skills 61:479–495
Leweke FM, Giuffrida A, Wurster U, Emrich HM, Piomelli D (1999) Elevated endogenous cannabinoids in schizophrenia. Neuroreport 10:1665–1669
Lezak MD (1995) Neuropsychological assessments, 3rd edn. Oxford University Press, New York
Martinez-Arevalo MJ, Calcedo-Ordonez A, Varo-Prieto JR (1994) Cannabis consumption as a prognostic factor in schizophrenia. Br J Psychiatry 164:679–681
Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564
Mechoulam R, Gaoni Y (1965) A total synthesis of delta-1-tetrahydrocannabinol, the active constituent of hashish. J Am Chem Soc 87:3273–3275
Mechoulam R, Parker LA, Gallily R (2002) Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol 42:11S–19S
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 27:799–810
Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113
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 58:105–111
Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215
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 1–93
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 5:483–501
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 3:23–35
Roser P, Vollenweider FX, Kawohl W (2008) Potential antipsychotic properties of central cannabinoid (CB1) receptor antagonists. World J Biol Psychiatry 7:1–12. DOI: 10.1080/15622970801908047
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 18:569–577
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):256
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 152:1092–1101
Sañudo-Peña MC, Romero J, Seale GE, Fernandez-Ruiz JJ, Walker JM (2000) Activational role of cannabinoids on movement. Eur J Pharmacol 391:269–274
Sañudo-Peña MC, Tsou K, Walker JM (1999) Motor actions of cannabinoids in the basal ganglia output nuclei. Life Sci 65:703–713
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 64:229–240
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 38:529–534
Shakow D, Huston PE (1936) Studies on motor function in schizophrenia: I. Speed of tapping. J Gen Psychol 15:63–106
Shaw JC, Colter N, Resek G (1983) EEG coherence, lateral preference and schizophrenia. Psychol Med 13:299–306
Shimoyama I, Ninchoji T, Uemura K (1990) The finger-tapping test. A quantitative analysis. Arch Neurol 47:681–684
Solowij N (1998) Cannabis and cognitive functioning. Cambridge University Press, Cambridge
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 25:275–284
Strik W, Dierks T (2008) Neurophysiological mechanisms of psychotic symptoms. Eur Arch Psychiatry Clin Neurosci 258(Suppl 5):66–70
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 25:63–75
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 56:167–179
Szabo B, Wallmichrath I, Mathonia P, Pfreundtner C (2000) Cannabinoids inhibit excitatory neurotransmission in the substantia nigra pars reticulata. Neuroscience 97:89–97
Torrey E (1980) Neurological abnormalities in schizophrenic patients. Biol Psychiatry 15:381–388
Turner WM, Tsuang MT (1990) Impact of substance abuse on the course and outcome of schizophrenia. Schizophr Bull 16:87–95
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 257:203–210
Woodruff PW, McManus IC, David AS (1995) Meta-analysis of corpus callosum size in schizophrenia. J Neurol Neurosurg Psychiatry 58:457–461
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 28:355–360
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This study was supported by the Institute for Clinical Research, Berlin, Germany.
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I. Gorynia and A.M. Stadelmann have equally contributed to this work.
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Roser, P., Gallinat, J., Weinberg, G. et al. Psychomotor performance in relation to acute oral administration of Δ9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects. Eur Arch Psychiatry Clin Neurosci 259, 284–292 (2009). https://doi.org/10.1007/s00406-009-0868-5
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DOI: https://doi.org/10.1007/s00406-009-0868-5