Cannabis bei Parkinson – Hype oder Heilmittel?

Zusammenfassung

In Deutschland können seit März 2017 Patienten mit einer schwerwiegenden Erkrankung Cannabisblüten und -extrakte sowie synthetische Cannabinoide zu Lasten der Krankenkassen verordnet werden. Die Zulassung von medizinischem Cannabis beinhaltet keine Festlegung auf eine Indikation und ist somit auch für Parkinson-Patienten relevant. Laut Gesetz haben schwerbetroffene Patienten sogar einen Anspruch auf Versorgung mit medizinischem Cannabis, wenn übliche Maßnahmen nicht erfolgreich waren oder nicht vertragen wurden oder „eine nicht ganz entfernte Aussicht auf eine spürbare positive Einwirkung auf schwerwiegenden Symptome besteht“.

Vor diesem Hintergrund und verstärkt durch Medienberichte fragen zunehmend Parkinson Patienten nach Verordnung von Cannabis. Dies stellt die behandelnden Neurologen vor eine neue Herausforderung.

Dieser Artikel gibt einen Überblick über die verschreibungsfähigen Cannabisprodukte und Applikationsformen sowie die Datenlage für Cannabis bei motorischen- und nicht-motorischen Parkinson Symptomen. Ferner werden aus Sicht der Autoren Indikationen definiert, für welche im Einzelfall Cannabis bei Parkinson-Patienten hilfreich sein könnte und ggf. dem Wunsch des Patienten nach Verordnung stattgegeben werden sollte. Es werden praxisrelevante Empfehlungen für die Verordnung von Cannabinoiden sowie die Beratung des Patienten, einschließlich hinsichtlich der Fahrfähigkeit ausgesprochen.

Abstract

Cannabis buds and extracts as well as synthetic cannabinoids have been available on prescription to patients with severe diseases since March 2017, with the costs covered by health insurance companies.

The prescription of medical marihuana is not restricted to specific symptoms and is therefore also valid for patients with Parkinson‘s disease. From a legal perspective, patients who are seriously ill even have the right to be treated with cannabis if standard treatment methods are unsuccessful or result in unbearable side effects. This also applies even if only a slight chance of noticeable improvement is predicted as a result of the cannabis treatment.

Bearing this in mind and due to an intense media coverage of this topic, more and more patients with Parkinson‘s disease are requesting cannabis prescription, which is a challenging situation to their neurologists.

This article provides an overview of the various cannabis products that can be prescribed, the different modes of administration and the available literature regarding motor- and non-motor symptoms in Parkinson‘s disease. Furthermore, the authors state their opinion on which indications cannabinoids could be useful in treating patients with Parkinson‘s disease or in which situation the patient could or even should be prescribed cannabinoids. Additionally, this article presents practical recommendations for the prescription of cannabinoids and patient counseling, e. g., on the effects of medical marijuana on driving capacity.

Schlüsselwörter

Cannabis - Cannabinoide - Parkinson - Therapie - THC

Key words

cannabis - cannabinoids - therapy - THC - Parkinson’s Disease

• Literatur

• 1 Deutscher Bundestag. Gesetz zur Änderung betäubungsmittelrechtlicher und anderer Vorschriften (06. März 2017). Im Internet: https://www.bgbl.de/xaver/bgbl/start.xav?startbk=Bundesanzeiger_BGBl&jumpTo=bgbl117s0403.pdf#__bgbl__%2F%2F*%5B%40attr_id%3D%27bgbl117s0403.pdf%27%5D__1496759835851 Stand 2017
• 2 Müller-Vahl K, Grotenhermen F. Medizinisches Cannabis: Die wichtigsten Änderungen. Dtsch Arztebl 2017; 114 A-352–6
• 3 Whiting PF, Wolff RF, Deshpande S. et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA 2015; 313: 2456-73
• 4 Petzke F, Enax-Krumova EK, Hauser W. Wirksamkeit, Verträglichkeit und Sicherheit von Cannabinoiden bei neuropathischen Schmerzsyndromen. Schmerz 2016; 30: 62-88
• 5 Deutscher Bundestag. Antwort der Bundesregierung auf die Kleine Anfrage der Abgeordneten Frank Tempel, Ulla Jelpe, Jan Korte, Dr. Petra Sitte und der Fraktion DIE LINKE. – Drucksache 18/11485 – Cannabismedizin und Straßenverkehr (27.03.2017). Im Internet: http://dip21.bundestag.de/dip21/btd/18/117/1811701.pdf Stand 2017
• 6 Deutscher Bundestag. Versorgung mit Cannabis als Medizin (28.06.2016). Im Internet: http://dipbt.bundestag.de/doc/btd/18/089/1808953.pdf Stand 2017
• 7 Solimini R, Rotolo MC, Pichini S. et al. Neurological Disorders in Medical Use Of Cannabis: an Update. CNS Neurol Disord Drug Targets. doi: 10.2174/1871527316666170413105421. [Epub ahead of print]
• 8 Fife TD, Moawad H, Moschonas C. et al. Clinical perspectives on medical marijuana (cannabis) for neurologic disorders. Neurology: Clinical Practice 2015; 5: 344-351
• 9 Kluger B, Triolo P, Jones W. et al. The therapeutic potential of cannabinoids for movement disorders. Mov Disord 2015; 30: 313-27
• 10 Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 2008; 153: 199-215
• 11 Mandelbaum DE, de la Monte SM. Adverse Structural and Functional Effects of Marijuana on the Brain: Evidence Reviewed. Pediatr Neurol 2017; 66: 12-20
• 12 Etges T, Karolia K, Grint T. et al. An observational postmarketing safety registry of patients in the UK, Germany, and Switzerland who have been prescribed Sativex(®) (THC:CBD, nabiximols) oromucosal spray. Ther Clin Risk Manag 2016; 12: 1667-1675
• 13 Karschner EL, Darwin WD, Goodwin RS. et al. Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin Chem 2011; 57: 66-75
• 14 Patti F, Messina S, Solaro C. et al. Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity. J Neurol Neurosurg Psychiatry 2016; 87: 944-51
• 15 Russo M, De Luca R, Torrisi M. et al. Should we care about sativex-induced neurobehavioral effects? A 6-month follow-up study. Eur Rev Med Pharmacol Sci 2016; 20: 3127-33
• 16 Venderová K, Růzicka E, Vorísek V. et al. Survey on cannabis use in Parkinson‘s disease: subjective improvement of motor symptoms. Mov Disord 2004; 19: 1102-6
• 17 Zuardi AW, Crippa JA, Hallak JE. et al. Cannabidiol for the treatment of psychosis in Parkinson’s disease. J Psychopharmacol 2009; 23: 979-983
• 18 Lotan I, Treves TA, Roditi Y. et al. Cannabis (medical marijuana) treatment for motor and non-motor symptoms of Parkinson disease: an open-label observational study. Clin Neuropharmacol 2014; 37: 41-4
• 19 Frankel JP, Hughes A, Lees AJ. et al. Marijuana for parkinsonian tremor. J Neurol Neurosurg Psychiatry 1990; 53: 436
• 20 Carroll CB, Bain PG, Teare L. et al. Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Neurology 2004; 63: 1245-50
• 21 Sieradzan KA, Fox SH, Hill M. et al. Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: a pilot study. Neurology 2001; 57: 2108-11
• 22 Koppel BS, Brust JC, Fife T. et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014; 82: 1556-63
• 23 Russo EB, Guy GW, Robson PJ. Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis-based medicine. Chem Biodivers 2007; 4: 1729-43
• 24 Hsiao YT, Yi PL, Li CL. et al. Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats. Neuropharmacology 2012; 62: 373-84
• 25 Pava MJ, Makriyannis A, Lovinger DM. Endocannabinoid Signaling Regulates Sleep Stability. PLoS One 2016; 11: e0152473
• 26 Chagas MH, Eckeli AL, Zuardi AW. et al. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson’s disease patients: a case series. J Clin Pharm Ther 2014; 39: 564-6
• 27 Yust Katz S, Hershkovitz R, Gurevich T. et al. Pain in Extrapyramidal. Neurodegenerative Diseases. Clin J Pain 2017; 33: 635-639
• 28 Buhmann C, Wrobel N, Grashorn W. et al. Pain in Parkinson disease: a cross-sectional survey of its prevalence, specifics, and therapy. J Neurol 2017; 264: 758-769
• 29 Mendlin A, Martín FJ, Jacobs BL. Dopaminergic input is required for increases in serotonin output produced by behavioral activation: an in vivo microdialysis study in rat forebrain. Neuroscience 1999; 93: 897-905
• 30 Rüb U, Del Tredici K, Schultz C. et al. Parkinson’s disease: the thalamic components of the limbic loop are severely impaired by alpha-synuclein immunopositive inclusion body pathology. Neurobiol Aging 2002; 23: 245-54
• 31 Chagas MH, Zuardi AW, Tumas V. et al. Effects of cannabidiol in the treatment of patients with Parkinson’s disease: an exploratory double-blind trial. J Psychopharmacol 2014; 28: 1088-98
• 32 Pharmazeutische Zeitung online. Cannabis als Medizin – Was kommt auf die Apotheken zu? (Ausgabe 08/2017). Im Internet: http://www.pharmazeutische-zeitung.de/index.php?id=67762 Stand 2017
• 33 TÜV Süd. Information zu MPU und Fahreignung. Im Internet: http://www.tuev-sued.de/uploads/images/1455711433332422611403/information-mpu-november-2015.pdf Stand 2017
• 34 Buhmann C, Gerloff C. Autofahren bei Morbus Parkinson. Akt Neurol 2013; 40: 315-320
• 35 Malek N, Grosset DG. Medication adherence in patients with Parkinson’s disease. CNS Drugs 2015; 29: 47-53
• 36 Pezzella FR, Colosimo C, Vanacore N. et al. Prevalence and clinical features of hedonistic homeostatic dysregulation in Parkinson’s disease. Mov Disord 2005; 20: 77-81
• 37 Giovannoni G, O’Sullivan JD, Turner K. et al. Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies. J Neurol Neurosurg Psychiatry 2000; 68: 423-8
• 38 Roland CL, Lake J, Oderda GM. Prevalence of Prescription Opioid Misuse/ Abuse as Determined by International Classification of Diseases Codes: A Systematic Review. J Pain Palliat Care Pharmacother 2016; 30: 258-268
• 39 Wortmann M. Cannabisarzneimittel – Fahrverbot auch Tage nach THC Konsum. DNP 2017; 18: 56
• 40 Freidel M, Tiel-Wilck K, Schreiber H. et al. Drug-resistant MS spasticity treatment with Sativex(®) add-on and driving ability. Acta Neurol Scand 2015; 131: 9-16
• 41 Ford B. Pain in Parkinson’s disease. Clin Neurosci 1998; 5: 63-72
• 42 Bureau voor Medicinale Cannabis. Medicinal Cannabis – patients’ guide (Februar 2011). www.cannabisbureau.nl/Media/Default/PDF/Medicinale%20Cannabis%20informa tiebrochure%20voor%20artsen%20en%20apothekers.pdf Stand 2017
• 43 Izzo AA, Borrelli F, Capasso R. et al. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 2009; 30: 515-27
• 44 Ablin J, Ste-Marie PA, Schäfer M. et al. Medical use of cannabis products: Lessons to be learned from Israel and Canada. Schmerz 2016; 30: 3-13
• 45 Health Canada. Information for Health Care Professionals – Cannabis (marihuana, marijuana) and the cannabinoids (Februar 2013). http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/marihuana/med/infoprof-eng.pdf Stand 2017
• 46 Mallat A, Hezode C, Lotersztajn S. Environmental factors as disease accelerators during chronic hepatitis C. J Hepatol 2008; 48: 657-65
• 47 Broyd SJ, van Hell HH, Beale C. et al. Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic Review. Biol Psychiatry 2016; 79: 557-67
• 48 Bagot KS, Milin R, Kaminer Y. Adolescent Initiation of Cannabis Use and Early-Onset Psychosis. Subst Abus 2015; 36: 524-33
• 49 American College of Obstetricians and Gynecologists Committee on Obstetric Practice. Committee Opinion No. 637: Marijuana Use During Pregnancy and Lactation. Obstet Gynecol 2015; 126: 234-8
• 50 Robson P. Abuse potential and psychoactive effects of δ-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine. Expert Opin Drug Saf 2011; 10: 675-85
• 51 Tsang CC, Giudice MG. Nabilone for the Management of Pain. Pharmacotherapy 2016; 36: 273-86
• 52 Schoedel KA, Chen N, Hilliard A. et al. A randomized, double-blind, placebo-controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use. Hum Psychopharmacol 2011; 26: 224-36
• 53 Bundesinstitut für Arzneimittel und Medizinprodukte. Bundesopiumstelle. Cannabis als Medizin. Begleiterhebung.. Im Internet: http://www.bfarm.de/DE/Bundesopiumstelle/Cannabis/Begleiterhebung/_node.html Stand 2017
• 54 Chaudhuri KR, Rizos A, Trenkwalder C. et al. King’s Parkinson’s disease pain scale, the first scale for pain in PD: An international validation. Mov Disord 2015; 30: 1623-31
• 55 Jost WH, Rizos A, Odin P. et al. King’s Parkinson’s disease pain scale: Intercultural adaptation in the German language. Nervenarzt. 2017 [Epub ahead of print]
• 56 Buhmann C, Rizos A, Emmans D. et al. Intercultural adaptation of the AIMS in German language: A scale for abnormal involuntary movements. Nervenarzt 2016; 87: 411-7
• 57 Goetz CG, Tilley BC, Shaftman SR. et al. Movement Disorder Society-sponsored revision of the Unified Parkinson‘s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 2008; 23: 2129-70
• 58 Trenkwalder C, Kohnen R, Högl B. et al. Parkinson’s disease sleep scale – validation of the revised version PDSS-2. Mov Disord 2011; 26: 644-52
• 59 Peto V, Jenkinson C, Fitzpatrick R. et al. The development and validation of a short measure of functioning and well being for individuals with Parkinson’s disease. Qual Life Res 1995; 4: 241-8
• 60 Bundesinstitut für Arzneimittel und Medizinprodukte. Erklärung der/ des betreuenden/ begleitenden Ärztin/ Arztes im Zusammenhang mit dem Antrag auf Erteilung einer Erlaubnis (§ 3 Abs. 2 BtMG) zum Erwerb von Cannabis-Extrakt bzw. Medizinal-Cannabisblüten im Rahmen einer medizinisch betreuten und begleiteten Selbsttherapie. Im Internet: http://www.bfarm.de/SharedDocs/Formulare/DE/Bundesopiumstelle/BtM/Cannabis_Erklaerung_Arzt.pdf?__blob=publicationFile&v=11 Stand 2017