Endocannabinoidsystem und Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung im Erwachsenenalter

ZUSAMMENFASSUNG

ADHS ist eine entwicklungspsychiatrische Erkrankung, die im Erwachsenenalter häufig unerkannt und unbehandelt bleibt. Die Folgen für die Betroffenen sind neben häufigeren Arbeitsplatzverlusten, ein erhöhtes Unfallrisiko und Schwierigkeiten in der sozialen Interaktion. Häufig präsentiert sich die ADHS im Erwachsenenalter sehr heterogen und ist in ca. 80 % der Fälle mit psychiatrischen Komorbiditäten, wie Depressionen, bipolare Störung, Angststörung, Borderline- und dissoziale Persönlichkeitsstörung sowie Suchterkrankungen vergesellschaftet. Letztere führt zu der hohen Inzidenz von Cannabismissbrauch von Patienten mit ADHS. Auf der anderen Seite wird vermutet, dass Cannabis von den Betroffenen als leichtes Sedativum im Sinne einer Selbstmedikation gegen einige Symptome des ADHS wie innere Unruhe, Rastlosigkeit und Schlafstörungen eingesetzt wird. Seit den frühen 1990er-Jahren sind zahlreiche Studien erschienen, die den Zusammenhang zwischen einer Störung des physiologischen endogenen Cannabinoidsystems und der Genese psychiatrischer Erkrankungen wie Depressionen, Angststörungen, posttraumatischer Belastungsstörung (PTBS), Schizophrenie, Suchterkrankungen und Schlafstörungen beschreiben und im Endocannabinoidsystem eine potenzielle Möglichkeit neuer pharmakologischer Behandlungsmöglichkeiten, z. B. durch den Einsatz von synthetischen Cannabinoiden, sehen. In diesem Artikel sollen grundlegende Mechanismen des Endocannabinoidsystems erklärt und die Zusammenhänge mit der Genese des ADHS anhand der Studienlage beleuchtet werden. Zudem soll ein Ausblick auf mögliche Therapieoptionen mit Cannabinoiden gegeben werden.

ABSTRACT

ADHD is a developmental psychiatric disorder that often goes unnoticed and untreated in adulthood. The consequences for affected individuals include frequent school drop-outs, job losses, more frequent accidents, and difficulties in social interaction. ADHD presents in adult life in about 80 % of cases comorbid with other psychiatric disorders, like major depression, bipolar disorder, anxiety disorder, borderline personality disorder, antisocial disorder and substance abuse. Especially cannabis use, and misuse has a high incidence in patients with ADHD. They use cannabis as a light sedative in the sense of a self-medication for ADHD symptoms such as inner restlessness, motor restlessness and sleep disorders. Since the early 1990 s frequent studies investigated a potential role of the endocannabinoid system in the genesis of psychiatric disorders such as depression, anxiety disorders, post-traumatic stress disorder (PTSD), schizophrenia, and sleep disorders. In targeting the endocannabinoid system with synthetical cannabinoids new opportunities for treatment of these mental disorders are discussed. In this article mechanisms of the endocannabinoid system are explained and the connections with ADHD are mentioned. In addition, an outlook on possible treatment options with cannabinoids is given.

Schlüsselwörter

Endocannabinoide - ADHS - Dopamin - Cannabidiol

Key words

Endocannabinoids - adhd - dopamine - cannabidiol

• Literatur

• 1 Katzman MA, Bilkey TS, Chokka PR. et al Adult ADHD and comorbid disorders: Clinical implications of a dimensional approach. BMC Psychiatry 2017; 17 (01) 302 doi: 10.1186/s12888-017-1463-3
• 2 Faraone SV, Larsson H. Genetics of attention deficit hyperactivity disorder. Mol Psychiatry 2018; 24 (04) 562-575
• 3 Asherson P, Buitelaar J, Faraone S. et al Adult attention-deficit hyperactivity disorder: Key conceptual issues. The Lancet Psychiatry 2016; 3 (06) 568-78
• 4 Hillard CJ. Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?. Neuropsychopharmacology 2018; 43 (01) 155-172
• 5 Katzman MA, Furtado M, Anand L. Targeting the Endocannabinoid System in Psychiatric Illness. Journal of Clinical Psychopharmacology 2016; 36 (06) 691-703
• 6 Devane WA, Dysarz FA, Johnson MR. et al Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 1988; 34 (05) 605-13
• 7 Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365 6441 61-5
• 8 Mechoulam R, Parker L. The Endocannabinoid System and the Brain. Ssrn 2013; 5 (04) E107 doi: 10.3390/medicines5040107
• 9 Howlett AC. International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors. Pharmacol Rev 2003; 54 (02) 161-202
• 10 Scherma M, Masia P, Deidda M. et al New Perspectives on the Use of Cannabis in the Treatment of Psychiatric Disorders. Medicines 2018; 5 (04) E107
• 11 Pertwee RG. The diverse CB 1 and CB 2 receptor pharmacology of three plant cannabinoids: Δ 9-tetrahydrocannabinol, cannabidiol and Δ 9-tetrahydrocannabivarin. Br J Pharmacol 2008; 153 (02) 199-215
• 12 Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 1997; 74 (02) 129-80
• 13 Di Marzo V. Biosynthesis and inactivation of endocannabinoids: Relevance to their proposed role as neuromodulators. Life Sci 1999; 65 6-7 645-55
• 14 Mechoulam R, Peters M, Murillo-Rodriguez E. et al Cannabidiol – Recent advances. Chemistry and Biodiversity 2007; 4 (08) 1678-92
• 15 Hillard CJ. NIH Public Access. Changes 2009; 14 (023) 2347-61
• 16 Hill MN, Miller GE, Carrier EJ. et al Exposure to Social Stress. 2010; 34 (08) 1257-62
• 17 Hill MN, Liu Q, Pan B. et al Recruitment of Prefrontal Cortical Endocannabinoid Signaling by Glucocorticoids Contributes to Termination of the Stress Response. J Neurosci 2011; 31 (029) 10506-15
• 18 Lu AT, Ogdie MN, Järvelin MR. et al Association of the Cannabinoid Receptor Gene (CNR1) With ADHD and Post-Traumatic Stress Disorder. Am J Med Genet B Neuropsychiatr Genet 2008; 147B (08) 1488-94
• 19 Curatolo P, D’Agati E, Moavero R. The neurobiological basis of ADHD. Italian Journal of Pediatrics 2010; 6 (01) 79
• 20 Nieoullon A. Dopamine and the regulation of cognition and attention. Progress in Neurobiology 2002; 67 (01) 53-83
• 21 Mortimer N, Ganster T, O’Leary A. et al Dissociation of impulsivity and aggression in mice deficient for the ADHD risk gene Adgrl3: Evidence for dopamine transporter dysregulation. Neuropharmacology 2019 www.sciencedirect.com/science/article/pii/S0028390819300784?dgcid=raven_sd_aip_email
• 22 El Khoury MA, Gorgievski V, Moutsimilli L. et al Interactions between the cannabinoid and dopaminergic systems: Evidence from animal studies. Prog Neuro-Psychopharmacology Biol Psychiatry 2012; 38 (01) 36-50 http://dx.doi.org/10.1016/j.pnpbp.2011.12.005
• 23 Gardner EL. Endocannabinoid signaling system and brain reward: Emphasis on dopamine. Pharmacol Biochem Behav 2005; 81 (02) 263-84
• 24 Bossong MG, Mehta MA, Van Berckel BNM. et al Further human evidence for striatal dopamine release induced by administration of δ9-tetrahydrocannabinol (THC): Selectivity to limbic striatum. Psychopharmacology 2015; 232 (015) 2723-9
• 25 Giuffrida A, Parsons LH, Kerr TM. et al Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 1999; 2 (04) 358-63
• 26 Castelli M, Federici M, Rossi S. et al Loss of striatal cannabinoid CB1 receptor function in attention-deficit/hyperactivity disorder mice with point-mutation of the dopamine transporter. Eur J Neurosci 2011; 34 (09) 1369-77 doi: 10.1111/j.1460-9568.2011.07876.x
• 27 Klassen LJ, Katzman MA, Chokka P. Adult ADHD and its comorbidities, with a focus on bipolar disorder. J Affect Disord 2010; 124 1–2 1-8
• 28 Young J. Common comorbidities seen in adolescents with attention-deficit/hyperactivity disorder. Adolesc Med State Art Rev 2008; 19 (02) 216-28 vii
• 29 Antshel KM, Barkley RA. Attention Deficit/Hyperactivity Disorder. Bern: Springer International Publishing Switzerland; 2016
• 30 Centonze D, Bari M, Di Michele B. et al Altered anandaminde degradation in ADHD. Neurology 2009; 72 (017) 1526-7
• 31 Lee SS, Humphreys KL, Flory K. et al Prospective association of childhood attention-deficit/hyperactivity disorder (ADHD) and substance use and abuse/dependence: a meta-analytic review. Clin Psychol Rev 2011; 31 (03) 328-41
• 32 Wallace AL, Wade NE, Hatcher KF. et al Effects of Cannabis Use and Subclinical ADHD Symptomology on Attention Based Tasks in Adolescents and Young Adults. 2018 Oct 6. doi: 10.1093/arclin/acy080
• 33 Tamm L, Epstein JN, Lisdahl KM. et al Impact of ADHD and cannabis use on executive functioning in young adults. Drug Alcohol Depend 2013; 133 (02) 607-14
• 34 Kahn S, Bossong MG, Jansma JM. et al Default Mode Network in the Effects of D 9- Tetrahydrocannabinol (THC) on Human Executive Function. 2013; 8 (07) 1-10
• 35 Wiersema JR, Gasthuys R, Verguts T. et al Dysfunctional modulation of default mode network activity in attention-deficit/hyperactivity disorder. J Abnorm Psychol 2015; 124 (01) 208-214
• 36 Kelly C, Castellanos FX, Tomaselli O. et al NU SC. YNICL 2016 http://dx.doi.org/10.1016/j.nicl.2016.09.012
• 37 Cooper RE, Williams E, Seegobin S. et al Cannabinoids in attention-deficit/hyperactivity disorder: A randomised-controlled trial. Eur Neuropsychopharmacol 2017; 27 (08) 795-808
• 38 Castellano C, Rossi-Arnaud C, Cestari V. et al Cannabinoids and memory: animal studies. Curr Drug Targets CNS Neurol Disord 2003; 2 (06) 389-402
• 39 Di Forti M, Marconi A, Carra E. et al Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: A case-control study. Lancet Psychiatry 2015; 2 (03) 233-8
• 40 Englund A, Morrison PD, Nottage J. et al Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J Psychopharmacol 2013; 27 (01) 19-27