Pharmacopsychiatry 2001; 34(1): 19-24
DOI: 10.1055/s-2001-15191
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Influence of Treatment of Tourette Syndrome with Δ9-Tetrahydrocannabinol (Δ9-THC) on Neuropsychological Performance

K. R. Müller-Vahl1 , A. Koblenz1 , M. Jöbges2 , H. Kolbe2 , H. M. Emrich1 , U. Schneider1
  • 1Department of Clinical Psychiatry and Psychotherapy
  • 2Department of Neurology
  • Medical School Hannover, Germany
Further Information

Publication History

Publication Date:
31 December 2001 (online)

Previous studies have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient of marijuana, are effective in the therapy of tics and associated behavioral disorders in Tourette Syndrome (TS). Because there is also evidence that cannabis sativa may cause cognitive impairment in healthy users, we performed a randomized double-blind placebo-controlled crossover trial for Δ9-THC in 12 adult TS patients to investigate whether treatment of TS with a single dose of Δ9-THC at 5.0 to 10.0 mg causes significant side effects on neuropsychological performance. Using a variety of neuropsychological tests, we found no significant differences after treatment with Δ9-THC compared to placebo treatment in verbal and visual memory, reaction time, intelligence, sustained attention, divided attention, vigilance, or mood. Only when using the Symptom Checklist 90-R (SCL-90-R) did our data provide evidence for a deterioration of obsessive-compulsive behavior (OCB) and a trend towards an increase in phobic anxiety. However, these results should be interpreted with caution as SCL-90-R has known limitations on measuring OCB. We suggest that the increase in phobic anxiety is mainly due to the fact that a single-dose treatment rules out the possibility of administering the dosage slowly. In contrast to results obtained from healthy marijuana users, a single-dose treatment with Δ9-THC in patients suffering from TS does not cause cognitive impairment. We therefore suggest that further investigations should concentrate on the effects of a longer-term therapy of TS with Δ9-THC.


  • 1 Arnold W. Der Pauli-Test. Berlin; Springer 1975
  • 2 Benton A L. A visual retention test for clinical use.  Arch Neurol Psychol. 1945;  59 273-291
  • 3 Block R I, Farinpour R, Braverman K. Acute effects of marijuana on cognition: relationships to chronic effects and smoking techniques.  Pharmacol Biochem Behav. 1992;  43 907-917
  • 4 Block R I, Ghoneim M M. Effects of chronic marijuana use on human cognition.  Psychopharmacology (Berl.). 1993;  110 219-228
  • 5 Brito G N O. A neurobiological model for Tourette syndrome centered on the nucleus accumbens.  Med Hypothesis. 1997;  49 133-142
  • 6 Chan P K, Chan S C, Yung W H. Presynaptic inhibition of GABAergic inputs to rat substantia nigra pars reticulata neurons by cannabinoid agonist.  Neuroreport. 1998;  9 671-675
  • 7 Clifford D B. Tetrahydrocannabinol for tremor in multiple sclerosis.  Ann Neurol. 1983;  13 669-671
  • 8 Comings D E, Comings B G. Comorbid behavioral disorders. In: Kurlan R (ed.) Handbook of Tourette Syndrome and related tic and behavioral disorders. New York, Basel, Hong Kong; Marcel Dekker, Inc. 1993: 111-147
  • 9 Consroe P, Musty R, Rein J, Tillery W, Pertwee R. The perceived effects of smoked cannabis on patients with multiple sclerosis.  Eur Neurol. 1997;  38 44-48
  • 10 Consroe P, Sandyk R, Snider S R. Open label evaluation of cannabidiol in dystonic movement disorders.  Int J Neurosci. 1986;  30 277-282
  • 11 Crawley J N, Corwin R L, Robinson J K, Felder C C, Devane W A, Axelrod J. Anandamide, an endogenous ligand of the cannabinoid receptor, induces hypomotility and hypothermia in vivo in rodents.  Pharmacol Biochem Behav. 1993;  46 967-972
  • 12 Derogatis L R, Lipman R S, Covi L. SCL-90: an outpatient psychiatric rating scale - preliminary report.  Psychopharmacol Bull. 1973;  9 13-28
  • 13 Derogatis L R. SCL 90. Administration, scoring and procedures. Manual-I for the R(evised) version and other instruments of the psychopathology rating scale series. John Hopkins University School of Medicine 1977
  • 14 Devane W A, Hanus L, Breuer A, Pertwee R G, Stevenson L A, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor.  Science. 1992;  258 1946-1949
  • 15 Emrich H M, Leweke F M, Schneider U. Towards a cannabinoid hypothesis of schizophrenia: cognitive impairments due to dysregulation of the endogenous cannabinoid system.  Pharmacol Biochem Behav. 1997;  56 803-807
  • 16 Gessa G L, Melis M, Muntoni A L, Diana M. Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors.  Eur J Pharmacol. 1998;  341 39-44
  • 17 Golden G S. Psychologic and neuropsychologic aspects of Tourette Syndrome.  Neurologic Clin. 1984;  2 91-102
  • 18 Gorriti M A, Rodriguez de Fonseca F, Navarro M, Palomo T. Chronic (-)-delta9-tetrahydrocannabinol treatment induces sensitization to the psychomotor effects of amphetamine in rats.  Eur J Pharmacol. 1999;  365 133-142
  • 19 Grotenhermen F, Karus M. Marihuana: Die rechtliche Situation in Deutschland. Der Stand der medizinischen Forschung. In Marihuana, die verbotene Medizin. Zweitausendeins, Frankfurt am Main 1994 1. Aufl: 211-272
  • 20 Hamilton M. A rating scale for depression.  J Neurol Neurosurg Psychiatry. 1960;  23 56-62
  • 21 Hamilton M. Development of rating scale for primary depressive illness.  Br J Soc Clin Psychol. 1967;  6 278-296
  • 22 Hampson R E, Deadwyler S A. Role of cannabinoid receptors in memory storage.  Neurobiol Dis. 1998;  5 474-482
  • 23 Helmstadter C, Durwen H F. VLMT. Verbaler Lern- und Merkfähigkeitstest.  Schweiz Arch Neurol Psychiatr. 1990;  141 21-30
  • 24 Hemming M, Yellowlees P M. Effective treatment of Tourette Syndrome with marijuana.  J Psychopharmacol. 1993;  7 389-391
  • 25 Herkenham M, Lynn A B, Little M D, Johnson M R, Melvin L S, de Costa B R, Rice K C. Cannabinoid receptor localization in brain.  Proc Natl Acad Sci USA. 1990;  87 1932-1936
  • 26 Hill M, Armitage P. The two period cross-over clinical trial.  Br J Clin Pharmacol. 1979;  8 7-20
  • 27 Hollister L E. Health aspects of cannabis.  Pharmacol Rev. 1986;  38 1-20
  • 28 Jentsch J D, Andrusiak E, Tran A, Bowers M B, Roth R H. Delta 9-tetrahydrocannabinol increases prefrontal cortical catecholaminergic utilization and impairs spatial working memory in the rat: blockade of dopaminergic effects with HA966.  Neuropsychopharmacology. 1997;  16 426-432
  • 29 Johannes S, Weber A, Müller-Vahl K R, Kolbe H, Dengler R, Münte T F. Event-related brain potentials show changed attentional mechanisms in Gilles de la Tourette syndrome.  Eur J Neurology. 1997;  4 152-161
  • 30 Kim S W, Dysken M W, Kuskowski M. The Symptom Checklist-90: Obsessive-Compulsive Subscale: A reliability and validity study.  Psychiatry Res. 1992;  41 37-44
  • 31 Kimura T, Ohta T, Watanabe K, Yoshimura H, Yamamoto I. Anandamide, an endogenous cannabinoid receptor ligand, also interacts with 5-hydroxytryptamine (5-HT) receptor.  Biol Pharm Bull. 1998;  21 224-226
  • 32 Kleiber D, Kovar K-A. Psychische und soziale Konsequenzen des Cannabiskonsums. In: Kleiber D, Kovar K-A (ed.) Auswirkungen des Cannabiskonsums: eine Expertise zu pharmakologischen und psychosozialen Konsequenzen. Stuttgart; Wissenschaftliche Verlagsgesellschaft mbH 1998: 88-225
  • 33 Korzyn A D. Future therapies. In: Kurlan R (ed.) Handbook of Tourette Syndrome and related tic and behavioral disorders. New York, Basel, Hong Kong; Marcel Dekker, Inc 1993: 199-220
  • 34 Leckman J F, Towbin K E, Ort S I, Cohen D J. Clinical assessment of tic disorder severity. In: Cohen DJ, Bruun RD, Leckman JF Tourette Syndrome and tic disorders. New York; John Wiley 1988: 55-78
  • 35 Mailleux P, Vanderhaeghen J-J. Localization of cannabinoid receptor in the human developing and adult basal ganglia. Higher levels in the striatonigral neurons.  Neurosci Lett. 1992;  148 173-176
  • 36 Maneuf Y P, Nash J E, Crossman A R, Brotchie J M. Activation of the cannabinoid receptor by delta 9-tetrahydrocannabinol reduces gamma-aminobutyric acid uptake in the globus pallidus.  Eur J Pharmacol. 1996;  308 161-164
  • 37 Marsden C D. Treatment of torsion dystonia. Barbeau, A. (ed.) Disorders of Movement. Current status of modern therapy. Philadelphia; Lippincott 1981 8: 81-104
  • 38 Merz J, Lehrl S, Galster J V, Erzigkeit H. MWT-B - ein Intelligenzkurztest.  Psychiatr Neurol Med Psychol. 1975;  27 423-428
  • 39 Miller A S, Sanudo-Pena M C, Walker J M. Ipsilateral turning behavior induced by unilateral microinjections of a cannabinoid into the rat subthalamic nucleus.  Brain Res. 1998;  793 7-11
  • 40 Miller A S, Walker J M. Effects of a cannabinoid on spontaneous and evoked neuronal activity in the substantia nigra pars reticulata.  Eur J Pharmacol. 1995;  279 179-185
  • 41 Molina-Holgado F, Amaro A, Gonzalez M I, Alvarez F J, Leret M L. Effect of maternal delta 9-tetrahydrocannabinol on developing serotonergic system.  Eur J Pharmacol. 1996;  316 39-42
  • 42 Müller-Vahl K R, Kolbe H, Schneider U, Emrich H M. Cannabinoids: Possible role in pathophysiology of Gilles de la Tourette-syndrome.  Acta Psychiat Scand. 1998;  98 502-506
  • 43 Müller-Vahl K R, Schneider U, Koblenz A, Jöbges M, Kolbe H, Dahltrup T, Emrich H M. Treatment of Tourette-Syndrome with delta-9-Tetrahydrocannabinol (THC): a randomized crossover trial. (submitted)
  • 44 Müller-Vahl K R, Schneider U, Kolbe H, Emrich H M. Treatment of Tourette-Syndrome with delta-9-Tetrahydrocannabinol.  Am J Psychiatry. 1999;  156 495
  • 45 Palumbo D, Maughan A, Kurlan R. Hypothesis III. Tourette syndrome is only one of several causes of a developmental basal ganglia syndrome.  Arch Neurol. 1997;  54 475-483
  • 46 Pope H G, Gruber A J, Yurgelun-Todd D. The residual neuropsychological effects of cannabis: the current status of research.  Drug Alcohol Depend. 1995;  38 25-34
  • 47 Pope H G, Yurgelun-Todd D. The residual cognitive effects of heavy marijuana use in college students.  JAMA. 1996;  275 521-527
  • 48 Sandyk R, Awerbuch G. Marijuana and Tourette Syndrome.  J Clin Psychopharmacol. 1988;  8 444-445
  • 49 Sandyk R, Snider S R, Consroe P, Elias S M. Cannabidiol in dystonic movement disorders.  Psychiatry Res. 1986;  18 291
  • 50 Sanudo-Pena M C, Walker J M. Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat.  J Neurophysiol. 1997;  77 1635-1638
  • 51 Schneider U, Leweke F M, Müller-Vahl K R, Emrich H M. Cannabinoid/anandamide system and schizophrenia: is there evidence for association?.  Pharmacopsychiatry. 1998;  31 (Suppl. 2) 110-113
  • 52 Schwartz R H, Gruenewald P J, Klitzner M, Fedio P. Short-term memory impairment in cannabis-dependent adolescents.  Am J Dis Child. 1989;  143 1214-1219
  • 53 Shapiro A K, Shapiro E, Young J G, Feinberg T E. Gilles de la Tourette Syndrome. Raven Press, New York 2d ed 1988
  • 54 Shen M, Piser T M, Seybold V S, Thayer S A. Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission in rat hippocampal cultures.  J Neurosci. 1996;  16 4322-4334
  • 55 Shen M, Thayer S A. Delta9-tetrahydrocannabinol acts as a partial agonist to modulate glutamatergic synaptic transmission between rat hippocampal neurons in culture.  Mol Pharmacol. 1999;  55 8-13
  • 56 Sieradzan K A, Fox S H, Dick J, Brotchie J M. The effects of the cannabinoid receptor agonist nabilone on L-DOPA induced dyskinesia in patients with idiopathic Parkinson's disease (PD).  Mov Disord. 1998;  13 (Suppl. 2) 29
  • 57 Solowij N, Michie P T, Fox A M. Differential impairments of selective attention due to frequency and duration of cannabis use.  Biol Psychiatry. 1995;  37 731-739
  • 58 Swets J A, Green D M, Getty D J, Swets J B. Signal detection and identification at successive stages of observation.  Percept Psychopsy. 1978;  23 275-289
  • 59 Varma V K, Malhotra A K, Dang R, Das K, Nehra R. Cannabis and cognitive functions: a prospective study.  Drug Alcohol Depend. 1988;  21 147-152
  • 60 Wechsler D. A standardized memory scale for clinical use.  J Psychol. 1945;  19 87-95
  • 61 Wechsler D. Die Messung der Intelligenz Erwachsener. Bern; Huber Verlag 1956
  • 62 Weeks R A, Turjanski N, Brooks D J. Tourette Syndrome: a disorder of cingulate and orbitofrontal function?.  QJM. 1996;  89 401-408
  • 63 Woody S R, Steketee G, Chambless D L. The usefulness of the Obsessive Compulsive Scale of the Symptom Checklist-90-Revised.  Behav Res Ther. 1995;  33 607-611
  • 64 Yordanova J, Dumais-Huber C, Rothenberger A, Woerner W. Frontocortical activity in children with comorbidity of tic disorder and attention-deficit hyperactivity disorder.  Biol Psychiatry. 1997;  41 585-594
  • 65 Ziemann U, Paulus W, Rothenberger A. Decreased motor inhibition in Tourette's disorder: evidence from transcranial magnetic stimulation.  Am J Psychiatry. 1997;  154 1277-1284
  • 66 Zimmermann P, Fimm B. Neuropsychologische Testbatterie zur Erfassung von Aufmerksamkeitsdefiziten. Psychologisches Institut der Universität Freiburg 1989

Dr. med. Kirsten R. Müller-Vahl

Department of Clinical Psychiatry and Psychotherapy
Medical School Hannover

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30625 Hannover


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