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Dopaminerge Störungen mit Endocannabinoid-Beteiligung

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Dopaminerge Störungen mit Endocannabinoid-Beteiligung

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Endocannabinoide sind in eine Vielzahl von Störungsbildern involviert, darunter etliche, die typischerweise mit einem erhöhten (fett) oder verringerten (kursiv) oder verringerten oder erhöhten (kursiv und fett) Dopaminspiegel korrelieren:123

1. Endocannabinoide bei verschiedenen Störungsbildern

Störung Dopamin AEA 2-AG CB1R CB2R
ADHS DA verringert AEA erhöht4 CB1R-Agonist verbesserte Hyperaktivität/Impulsivität5
Cardiovaskuläre Störungen6
ASS789101112131415 AEA verringert16, Endocannabinoide verringert17
Parkinson1819 DA verringert AEA erhöht20 2-AG erhöht21 CB1R-Expression in Basalganglien erhöht222324 CB2R erhöht2526
Alzheimer2728 AEA-Erhöhung hilfreich2930 CB1R verringert31 CB2R erhöht32
Huntington28 verringerte bis völlig verlorene CB1R und D1R33
Multiple Sklerose34 AEA erhöht in Liquor und peripheren Lymphozyten erhöht35 2-AG unverändert in Liquor und peripheren Lymphozyten35
Fragiles-X-Syndrom34 2-AG-Erhöhung in Tiermodell hilfreich36 CB1R aufgrund Überstimulation verringert. CBD könnte hilfreich sein.37
amyotrophe Lateralsklerose
traumatische Hirnverletzungen
Schlaganfall
Epilepsie DA verringert AEA erhöht nach Krampfanfällen 2-AG erhöht nach Krampfanfällen
Glioblastom DA verringert
Angststörungen AEA verringert3839 AEA-Erhöhung hilfreich40 2-AG-Erhöhung hilfreich40 CB2R-Antagonisten hilfreich41
PTSD und fehlerhafte Löschung aversiver Erinnerungen42 verringert AEA verringert4344 AEA unverändert45 AEA-Stressantwort unverändert4647 2-AG verringert45 2-AG-Stressantwort verringert4647 CB1R erhöht4344
Depression4849 DA verringert AEA bei leichter Depression erhöht, bei schwerer eher unverändert39 AEA-Erhöhung hilfreich50 Fluoxetin verringerte AEA in limbischen Regionen50 Tianeptin erhöhte AEA im Hippocampus und dorsalen Striatum50 Imipramin erhöht Endocannabinoide im dorsalen Striatum50 Escitalopram erhöhte Endocannabinoide im Hippocampus und dorsalen Striatum ODER verringerte sie im Cortex und Cerebellum50 2-AG verringert50 bei Frauen mit schwerer Depression3938 2-AG tendenziell erhöht bei leichter Depression39 Fluoxetin erhöhte 2-AG im PFC50 Tianeptin erhöhte 2-AG im dorsalen Striatum und PFC50 Imipramin erhöht Endocannabinoide im dorsalen Striatum50 Escitalopram erhöhte Endocannabinoide im Hippocampus und dorsalen Striatum{ ODER verringerte sie im Cortex und Cerebellum50
Bipolare Störung51
Essstörungen525354
Psychose55 DA erhöht AEA verringert in CSF56 und Blut57
Schizophrenie Negativsymptome: DA verringert im PFC / Positivsymptome: DA erhöht im dorsomedialen Striatum58596061626364 AEA im Gehirn 8-fach erhöht65 bis 10-fach66 CB1R erhöht65

2. Cannabinoide bei Parkinson

Cannabinoide bei Parkinson

Parkinson entsteht durch eine schrittweise Degeneration dopaminerger Neuronen der Substantia nigra, was die dopaminerge Neurotransmission im Striatum immer weiter einschränkt.67
Möglicherweise ist eine gestörte Endocannabinoid-Signalübertragung in den Basalganglien Ursache für Parkinson. Cannabinoide werden zur Behandlung von Parkinson-Symptomen und zur Verzögerung der Parkinson-Entstehung diskutiert und getestet.68697071

  • CB1R-Agonisten
    • verringern den Tremor, der durch eine übermäßige Stimulation der subthalamischen Neuronen entsteht727374 über Cannabinoidrezeptoren auf Astrozyten im ventralen Horn des Rückenmarks75
      • auch im Tiermodell76
    • lindern Levodopa-induzierte Dyskinesien7778
  • Antioxidative Phytocannabinoide scheinen in Parkinson-Tiermodellen die Degeneration dopaminerger Neuronen von Parkinson zu hemmen79
    • andere Studien faden keine starke antioxidative Wirkung von Cannabinoiden80
  • CB2Rs sind an der Kontrolle motorischer Effekte beteiligt8182
  • Cannabinoide wirken neuroprotektiv838485 und hemmen die Parkinson-Entwicklung bei Parkinson-Tiermodellen86

Cannabiskonsum zeigte bei Parkinson in Studien

  • bei 45,9 %87 bis 78 %88 Verbesserungen durch Cannabis-Konsum
  • Motorik
    • verringerten Ruhetremor89 bei 31 %87
    • verringerte Bradykinesie89 bei 45 %87
    • geringere Steifheit89
    • keine verbesserte Motorik90 in Doppelblindstudien9192
    • keine Verbesserung in Bezug auf Levodopa-induzierte Dyskinesien in Doppelblindstudien9291
  • weniger Schmerzen89
  • verbesserten Schlaf89 durch Nabilon93
  • verringerte Angst durch Nabilon93

CBD bewirkte bei Parkinson

  • eine Verringerung der Parkinson-Gesamtwerte94
  • eine signifikante Verringerung psychotischer Symptome94
  • keine Verbesserung motorischer oder allgemeiner Symptome in Doppelblindstudie9594

In einem Parkinson-Tiermodell fanden sich deutlich erhöhte Mengen an TRPV1, was die erhöhte Schmerzempfindlichkeit bei Parkinson erklären könnte.96

3. Psychose-Risikofaktoren bei Cannabiskonsum

Besondere Psychose-Risikofaktoren bei Cannabis-Konsum:9798

  • häufiger Konsum
  • Konsum von Cannabis mit hohem Δ9-THC-Gehalt
  • früher Konsum (Adoleszenz)
  • familiäre Vorgeschichte von Psychosen
  • Psychose-Prodromalsymptome
    • Nervosität
    • Ängstlichkeit
    • Unruhe
    • Ängste oder Depressionen
    • Rückzug aus sozialen Bindungen
    • verringerte Lebensfreude und Leistungsfähigkeit
    • Bewältigung von Ausbildung oder Beruf eingeschränkt gegenüber früher
  • Träger des Val-Allels von COMT
  • Halluzinationen bei Cannabiskonsum99

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