Fortschr Neurol Psychiatr 2005; 73(8): 463-469
DOI: 10.1055/s-2004-830119
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Cannabinoide bei Multipler Sklerose - therapeutisch sinnvoll?

Cannabinoids in Multiple Sclerosis - Therapeutically Reasonable?C.  Trebst1 , M.  Stangel1
  • 1Neurologische Klinik mit Klinischer Neurophysiologie (Prof. Dr. R. Dengler), Medizinische Hochschule Hannover
Further Information

Publication History

Publication Date:
15 December 2004 (online)

Zusammenfassung

Seit Jahrhunderten werden Extrakte aus der Pflanze Cannabis sativa als Rausch- und Heilmittel gebraucht. Berichte von Patienten mit Multipler Sklerose (MS), die Marihuana rauchten und über eine positive Wirkung auf MS-assoziierte Symptome wie Spastik und Schmerz berichteten, haben Cannabis-Präparate wiederholt in die Diskussion als mögliche Therapie bei der MS gebracht. Allerdings sind nach vielen kleineren z. T. sehr heterogenen Studien erst kürzlich die Ergebnisse einer großen, multizentrischen, doppelblinden, plazebokontrollierten Studie zum Einsatz von Cannabinoiden in der Behandlung der Spastik und anderer Symptome bei der MS veröffentlicht worden. Basierend auf diesen Studien sowie auf Erkenntnissen aus der Grundlagenforschung und aus Experimenten in Tiermodellen ergeben sich Hinweise, dass Cannabinoide in der symptomatischen Therapie der MS sinnvoll sein könnten. Allerdings kann derzeit der breite Einsatz außerhalb von klinischen Studien nicht empfohlen werden. Darüber hinaus gibt es Hinweise auf immunmodulatorische und neuroprotektive Wirkmechanismen der Cannabinoide. Dieser Übersichtsartikel fasst den derzeitigen Stand der experimentellen und klinischen Forschung zum Einsatz von Cannabinoiden bei der Therapie der MS zusammen.

Abstract

For centuries extracts from the Cannabis sativa plant have been used for recreational use and as remedies. Anecdotal reports from patients with multiple sclerosis (MS) experiencing relief of their spasticity and pain after smoking marihuana have prompted discussions about a potential therapeutic application of cannabis preparations in MS. Only recently the first large, multicenter, double-blind, placebo controlled study was conducted evaluating the use of cannabinoids for treatment of spasticity and other symptoms related to MS. Based on this trial and previous uncontrolled observations together with insights from basic research and animal experiments there is reasonable evidence for the therapeutical employment of cannabinoids in the treatment of MS related symptoms. Furthermore, data are arising that cannabinoids have immunomodulatory and neuroprotective properties. However, results from clinical trials do not allow the recommendation for the general use of cannabinoids in MS. This article summarizes the present knowledge of clinical and experimental research regarding the therapeutic potential of cannabinoids for the treatment of MS.

Literatur

  • 1 Frohne D, Jensen U. Systematik des Pflanzenreichs unter besonderer Berücksichtigung chemischer Merkmale und pflanzlicher Drogen. Stuttgart-New York: Gustav Fischer Verlag 1985
  • 2 Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish.  Ann Chem Soc. 1964;  86 1646-1647
  • 3 Matsuda L A, Lolait S J, Brownstein M J, Young A C, Bonner T I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA.  Nature. 1990;  346 561-564
  • 4 Munro S, Thomas K L, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids.  Nature. 1993;  365 61-65
  • 5 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 U S A. 1990;  87 1932-1936
  • 6 Howlett A C, Barth F, Bonner T I, Cabral G, Casellas P, Devane W A, Felder C C, Herkenham M, Mackie K, Martin B R, Mechoulam R, Pertwee R G. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors.  Pharmacol Rev. 2002;  54 161-202
  • 7 Grotenhermen F. Some practice-relevant aspects of the pharmacokinetics of THC.  Forsch Komplementarmed. 1999;  6 Suppl 3 37-39
  • 8 Lyman W D, Sonett J R, Brosnan C F, Elkin R, Bornstein M B. Delta 9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis.  J Neuroimmunol. 1989;  23 73-81
  • 9 Wirguin I, Mechoulam R, Breuer A, Schezen E, Weidenfeld J, Brenner T. Suppression of experimental autoimmune encephalomyelitis by cannabinoids.  Immunopharmacology. 1994;  28 209-214
  • 10 Achiron A, Miron S, Lavie V, Margalit R, Biegon A. Dexanabinol (HU-211) effect on experimental autoimmune encephalomyelitis: implications for the treatment of acute relapses of multiple sclerosis.  J Neuroimmunol. 2000;  102 26-31
  • 11 Arevalo-Martin A, Vela J M, Molina-Holgado E, Borrell J, Guaza C. Therapeutic action of cannabinoids in a murine model of multiple sclerosis.  J Neurosci. 2003;  23 2511-2516
  • 12 Croxford J L, Miller S D. Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212.  J Clin Invest. 2003;  111 1231-1240
  • 13 Killestein J, Uitdehaag B M, Polman C H. Cannabinoids in multiple sclerosis: do they have a therapeutic role?.  Drugs. 2004;  64 1-11
  • 14 Killestein J, Hoogervorst E L, Reif M, Blauw B, Smits M, Uitdehaag B M, Nagelkerken L, Polman C H. Immunomodulatory effects of orally administered cannabinoids in multiple sclerosis.  J Neuroimmunol. 2003;  137 140-143
  • 15 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
  • 16 Baker D, Pryce G. The therapeutic potential of cannabis in multiple sclerosis.  Expert Opin Investig Drugs. 2003;  12 561-567
  • 17 Trapp B D, Peterson J, Ransohoff R M, Rudick R, Mork S, Bo L. Axonal transection in the lesions of multiple sclerosis.  N Engl J Med. 1998;  338 278-285
  • 18 Bjartmar C, Kidd G, Mork S, Rudick R, Trapp B D. Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients.  Ann Neurol. 2000;  48 893-901
  • 19 Grundy R I. The therapeutic potential of the cannabinoids in neuroprotection.  Expert Opin Investig Drugs. 2002;  11 1365-1374
  • 20 Molina-Holgado E, Vela J M, Arevalo-Martin A, Almazan G, Molina-Holgado F, Borrell J, Guaza C. Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling.  J Neurosci. 2002;  22 9742-9753
  • 21 Guzman M, Sanchez C, Galve-Roperh I. Control of the cell survival/death decision by cannabinoids.  J Mol Med. 2001;  78 613-625
  • 22 Hampson A J, Grimaldi M, Axelrod J, Wink D. Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants.  Proc Natl Acad Sci U S A. 1998;  95 8268-8273
  • 23 Stelt M van der, Veldhuis W B, Bar P R, Veldink G A, Vliegenthart J F, Nicolay K. Neuroprotection by Delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity.  J Neurosci. 2001;  21 6475-6479
  • 24 Hansen H H, Azcoitia I, Pons S, Romero J, Garcia-Segura L M, Ramos J A, Hansen H S, Fernandez-Ruiz J. Blockade of cannabinoid CB(1) receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity.  J Neurochem. 2002;  82 154-158
  • 25 Molina-Holgado F, Pinteaux E, Moore J D, Molina-Holgado E, Guaza C, Gibson R M, Rothwell N J. Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia.  J Neurosci. 2003;  23 6470-6474
  • 26 Pryce G, Ahmed Z, Hankey D J, Jackson S J, Croxford J L, Pocock J M, Ledent C, Petzold A, Thompson A J, Giovannoni G, Cuzner M L, Baker D. Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.  Brain. 2003;  126 2191-2202
  • 27 Baker D, Pryce G, Croxford J L, Brown P, Pertwee R G, Makriyannis A, Khanolkar A, Layward L, Fezza F, Bisogno T, Di M V. Endocannabinoids control spasticity in a multiple sclerosis model.  FASEB J. 2001;  15 300-302
  • 28 Baker D, Pryce G, Croxford J L, Brown P, Pertwee R G, Huffman J W, Layward L. Cannabinoids control spasticity and tremor in a multiple sclerosis model.  Nature. 2000;  404 84-87
  • 29 Petro D J. Marihuana as a therapeutic agent for muscle spasm or spasticity.  Psychosomatics. 1980;  21 81-85
  • 30 Meinck H M, Schonle P W, Conrad B. Effect of cannabinoids on spasticity and ataxia in multiple sclerosis.  J Neurol. 1989;  236 120-122
  • 31 Brenneisen R, Egli A, Elsohly M A, Henn V, Spiess Y. The effect of orally and rectally administered delta 9-tetrahydrocannabinol on spasticity: a pilot study with 2 patients.  Int J Clin Pharmacol Ther. 1996;  34 446-452
  • 32 Petro D J, Ellenberger Jr C. Treatment of human spasticity with delta 9-tetrahydrocannabinol.  J Clin Pharmacol. 1981;  21 413S-416S
  • 33 Ungerleider J T, Andyrsiak T, Fairbanks L, Ellison G W, Myers L W. Delta-9-THC in the treatment of spasticity associated with multiple sclerosis.  Adv Alcohol Subst Abuse. 1987;  7 39-50
  • 34 Greenberg H S, Werness S A, Pugh J E, Andrus R O, Anderson D J, Domino E F. Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers.  Clin Pharmacol Ther. 1994;  55 324-328
  • 35 Killestein J, Hoogervorst E L, Reif M, Kalkers N F, Van Loenen A C, Staats P G, Gorter R W, Uitdehaag B M, Polman C H. Safety, tolerability, and efficacy of orally administered cannabinoids in MS.  Neurology. 2002;  58 1404-1407
  • 36 Wade D T, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms.  Clin Rehabil. 2003;  17 21-29
  • 37 Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, Thompson A. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial.  Lancet. 2003;  362 1517-1526
  • 38 Campbell F A, Tramer M R, Carroll D, Reynolds D J, Moore R A, McQuay H J. Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review.  BMJ. 2001;  323 13-16
  • 39 Clifford D B. Tetrahydrocannabinol for tremor in multiple sclerosis.  Ann Neurol. 1983;  13 669-671
  • 40 Fox P, Bain P G, Glickman S, Carroll C, Zajicek J. The effect of cannabis on tremor in patients with multiple sclerosis.  Neurology. 2004;  62 1105-1109
  • 41 Schon F, Hart P E, Hodgson T L, Pambakian A L, Ruprah M, Williamson E M, Kennard C. Suppression of pendular nystagmus by smoking cannabis in a patient with multiple sclerosis.  Neurology. 1999;  53 2209-2210

Dr. med. Corinna Trebst

Neurologische Klinik, OE 7210 · Medizinische Hochschule Hannover

Carl-Neuberg-Straße 1

30625 Hannover

Email: trebst.corinna@mh-hannover.de

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