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Fortschritte in der Cannabis-Forschung aus pharmazeutisch-chemischer Sicht

Progress in cannabis research from a pharmaceutical chemist’s point of view

Zusammenfassung

Zubereitungen aus der Hanfpflanze Cannabis sativa werden seit Jahrtausenden als Genussdrogen und Arzneimittel eingesetzt. Die wichtigsten Inhaltsstoffe sind das psychoaktive (−)‑trans-∆9-Tetrahydrocannabinol (THC), das als Partialagonist an den Cannabinoid (CB)-Rezeptoren CB1 und CB2 fungiert, und das nicht psychoaktive, pleiotrop wirkende Cannabidiol (CBD). Beide Verbindungen sind hoch lipophil wie die endogenen CB-Rezeptor-Agonisten, die Arachidonsäure-Derivate Anandamid und Arachidonoylglycerol. Die CB-Rezeptoren gehören zur Familie der G‑Protein-gekoppelten Rezeptoren und in den letzten Jahren konnten die ersten Röntgenstrukturen beider Rezeptor-Subtypen erhalten werden, die das rationale Design neuer synthetischer Liganden erleichtern werden. Neben den bereits weitgehend etablierten Indikationen wie chronischer Schmerz, Chemotherapie-induziertem Erbrechen, Spasmen bei multipler Sklerose und Kachexie gibt es Hinweise auf eine Reihe weiterer Cannabinoid-Wirkungen, die noch durch klinische Studien bestätigt werden müssen.

Abstract

Preparations of hemp, Cannabis sativa, have been used for thousands of years as recreational and therapeutic drugs. The most important constituents are the psychoactive (−)-trans-∆9-tetrahydrocannabinol (THC), a partial agonist at cannabinoid (CB) receptors CB1 and CB2, and the non-psychoactive pleiotropic cannabidiol (CBD). Both compounds are highly lipophilic, like the endogenous CB receptor agonists, the arachidonic acid derivatives anandamide and arachidonoyl glycerol. The CB receptors belong to the family of G protein-coupled receptors, and the first X‑ray crystal structures of both CB receptors subtypes have recently been obtained, which will facilitate the rational design of novel synthetic ligands. Besides the already largely established indications such as chronic pain, chemotherapy-induced vomiting, multiple sclerosis-associated spasms, and cachexia, there is preliminary evidence for several further cannabinoid effects, which will have to be confirmed by clinical studies.

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Danksagung

Unsere Forschungsarbeiten auf dem Gebiet der CB-Rezeptoren und Cannabinoid-aktivierten G‑Protein-gekoppelten Rezeptoren werden durch die Deutsche Forschungsgemeinschaft im Rahmen des Graduiertenkollegs GRK1873 gefördert.

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Correspondence to Christa E. Müller.

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C.E. Müller gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Müller, C.E. Fortschritte in der Cannabis-Forschung aus pharmazeutisch-chemischer Sicht. Bundesgesundheitsbl 62, 818–824 (2019). https://doi.org/10.1007/s00103-019-02964-4

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  • DOI: https://doi.org/10.1007/s00103-019-02964-4

Schlüsselwörter

  • Cannabidiol
  • Cannabinoide
  • Cannabinoid-Rezeptoren
  • Endocannabinoide
  • Tetrahydrocannabinol

Keywords

  • Cannabidiol
  • Cannabinoids
  • Cannabinoid receptors
  • Endocannabinoids
  • Tetrahydrocannabinol