Cannabinoide bei (Tumor-)Schmerzen

Zusammenfassung

Mit der Entdeckung des Endocannabinoidsystems in den 90er-Jahren des vorigen Jahrhunderts sind die Forschungsaktivitäten zu Effekten und Wirkmechanismen von Cannabinoiden intensiviert worden. Dies hat zu klinischen Studien mit ca. 3000 Patienten geführt, in denen sich Schmerz lindernde Effekte von Cannabinoiden vor allem bei Patienten mit neuropathischen Schmerzen und Spastikbeschwerden zeigten sowie bei Patienten mit einem hohen Ausmaß an Disstress und solchen, die anderweitig (z. B. mit Opioiden) nicht ausreichend behandelt werden können. Die oromucosale Kombination aus Delta9-Tetrahydrocannabinol (THC) und Cannabidiol (CBD) wurde zwischenzeitlich zur Behandlung von neuropathischen Schmerzen und Spastik bei Patienten mit Multipler Sklerose in verschiedenen Ländern zugelassen und zur Behandlung von Tumorschmerzen, die unzureichend mit Opioiden behandelt werden können. Cannabinoide, die überwiegend an peripheren Cannabinoidrezeptoren binden und Rezeptor-unabhängige Effekte aufweisen (z. B. ajulämische Säure), und Substanzen, die Endocannabinoid metabolisierende Enzyme inhibieren, könnten analgetische Effekte von cannabimimetischen Effekten weiter differenzieren.

Summary

In the early 1990s, cannabinoid (CB) receptors of the subtypes CB1 and CB2 were discovered and described in both the CNS and the peripheral nervous system and on keratinocytes, immune cells, cells of the peripheral nervous system and microglia, as well as on spinal cord dorsal horn neurons, respectively. Together with the subsequently characterized endogenous ligands and the ligand-metabolizing enzymes, these receptors form the endocannabinoid system (ECS). Both the discovery of ECS and its role in the control of pain and habituation to stress, as well as the significant analgesic and antihyperalgesic effects in animal studies, suggest the usefulness of cannabinoids in pain conditions. The data from clinical studies on more than 3000 patients allow the conclusion that cannabinoids are efficacious in the treatment of chronic pain, especially in neuropathic pain and (painful) spasticity and in a patient group whose therapy success is otherwise unsatisfactory and who are characterized by failed stress adaptation.

Several countries have approved the oromucosal combination of delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) (trade name Sativex®) for the symptomatic relief of central neuropathic pain and spasticity associated with multiple sclerosis (MS) and intractable cancer pain unresponsive to optimized opioid therapy.

Since with the available cannabinoid preparations the relationship of benefit to harm seems not to be optimally balanced, efforts are warranted to investigate the ideal method of administration and to develop cannabinoids with a more favourable therapeutic index.

Cannabinoids, which primarily stimulate peripheral CB1 receptors or selectively CB2 receptors, can further separate analgesic activity from cannabimimetic activity. Local or topical modes of application are another attempt aiming in the same direction. Modulating the endogenous cannabinoid tone (via the inhibition of endocannabinoid-metabolising enzymes) is another strategy.

Schlüsselwörter

Cannabinoide - Endocannabinoidsystem - chronische Schmerzen - klinische Evidenz - therapeutische Breite

Key words

Cannabinoids - endocannabinoid system - chronic pain - clinical evidence - therapeutic index

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