In the past decade, medicinal cannabis has received increasing interest as a treatment for a range of indications, including (neuropathic) pain. However, the results of earlier clinical studies related to the use of medicinal cannabis in neuropathic pain are inconclusive, and it is unclear which patients benefit most from treatment with medicinal cannabis. Therefore, with the €1.9 million subsidy granted by ZonMw, researchers Geert Jan Groeneveld (CSO/CMO at CHDR), Albert Dahan (professor of Anesthesiology at the LUMC) and Linda Klumpers (BIRD Life Sciences Consulting B.V) intend to gain more insight into the use of medicinal cannabis in the treatment of neuropathic pain in a collaborative project.
The two most studied active ingredients derived from the cannabis plant (cannabinoids) to date are delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC induces analgesic effects primarily by stimulating the body's cannabinoid receptors (CB1 and CB2), but stimulating the CB1 receptor also causes psychoactive side effects. CBD induces analgesic effects via different mechanisms, and is thought to be able to modulate the psychotropic effects of THC binding to the CB1 receptor. However, it is still unclear what the ideal ratio between THC and CBD would be to benefit from the CB1 modulating effects of CBD, while retaining the positive effects of THC on pain. In addition, it is still unclear whether the analgesic effects observed due to CBD use are caused by a pharmacological action of CBD, or merely by CBD preventing metabolism of concomitantly used pain medication. For neuropathic pain specifically, it has been challenging to find convincing evidence of analgesic effects of cannabinoids because there are many diverse mechanisms involved in neuropathic pain and within an individual different factors can be involved to a different extent. Therefore, it is reasonable to believe that selecting a trial population with a more homogeneous phenotype may aid in demonstrating significant treatment effects of medicinal cannabis.
In the current project, Geert Jan Groeneveld, Albert Dahan, and Linda Klumpers will address these questions/hypotheses and will evaluate whether CBD attenuates the side-effects of THC and what ratio of THC:CBD results in the best relation between pain attenuating effects and psychotropic effects, whether cannabidiol influences the plasma concentrations of commonly used drugs for treatment of neuropathic pain that are metabolized by CYP3A4 or CYP2D6, and in which phenotypical subgroups of patients with neuropathic pain cannabinoids have the most beneficial effects.
The project (848120001) is part of ZonMw’s “Goed Gebruik Geneesmiddelen” (Rational Pharmacotherapy) program, which has the aim of making use of existing medicines more effectively, efficiently and safely. The results of this project will address the current lack of evidence for the effectiveness of medicinal cannabis and will lead to a specific recommendation of an optimal dose combination of THC:CBD in a specific subgroup of patients with neuropathic pain.