Netherlands: €1.9 million research to find the right THC:CBD ratio for neuropathic pain

The Dutch government is to fund €1.9 million of research into the optimal dosage of THC and CBD for the treatment of neuropathic pain.

The project is supported by Center for Human Drug Research (CHDR), a Dutch institute for clinical drug research and the Leiden University Medical Center (LUMC). Bedrocan will supply the raw material for the study, and Echo Pharmaceuticals will produce the tablets containing THC and/or CBD.

«We will isolate THC and CBD and administer them in tablet form in different proportions. We will then examine the influence of CBD on the effects of THC and study which THC:CBD combination is best for the treatment of neuropathic pain,» said Geert Jan Groeneveld, neurologist at CHDR.

«We want to approach this research exactly as a drug developer would,» said Geert Jan Groeneveld. «As a clinical pharmacologist, you extract known pharmacological components from a plant and do research with it. It's also innovative in this research.»

The researchers will measure the pharmacodynamics and THC pharmacokinetics and CBD, the effects of both substances on pain and brain function, and how the substances behave in the human body.

What does science have to say about the effect of THC:CBD on neuropathic pain?

THC and CBD are the two most important active cannabinoids of the cannabis plant. THC is known for its analgesic effect, and also causes psychoactive side-effects. CBD, on the other hand, may have analgesic effects via other mechanisms, and modulates the psychoactive effects of THC.

In the first part of the study, healthy subjects will be given tablets with different ratios of THC and CBD to show whether the anxiety-inducing effects of THC can be reduced by simultaneously administering CBD, the scientific literature having so far provided contradictory results on the subject.

«To be honest, I don't expect much from CBD alone as a treatment for neuropathic pain. From a pharmacological point of view, THC is likely to affect pain, but this is less the case for CBD. The CBD may have an effect on inflammation, But there's no reason to use CBD as a treatment for inflammatory pain. We already have ibuprofen for that. It will only become interesting if the undesirable effects of THC, such as feelings of anxiety, can be mitigated by administering CBD at the same time,» explained Geert Jan Groeneveld.

Some patients are already using CBD to relieve inflammatory pain. L’exact effect of CBD on pain is uncertain: is it directly a pharmacological action of CBD or simply that CBD prevents the metabolism used by analgesics?

Once the results of the first study are known, a second study will examine the effects on pain and explore the best THC:CBD dosage. The second study will be carried out among a group of 200 patients suffering from various types of neuropathic pain.

Exploring sources of pain

«We're going to phenotype this group a long time in advance,» said Groeneveld. «This means we want to know exactly how neuropathic pain manifests itself specifically in this group. Do patients have demonstrable nerve damage, do they have a personality disorder, are they depressed or do they have sleep disorders? It's all these variables that we're going to map.»

Upon completion of the first two studies, participants in a crossover study will receive placebo for five weeks and, after a period of cannabis withdrawal, will receive five weeks cannabinoid treatment or THC. Pain will be measured at each treatment period.

«In patients with clear pain relief, we want to investigate further whether there is a correlation between their variables, such as sleep problems, anxiety or peripheral nerve damage, and response to THC treatment,» said Groeneveld.

The first part of the study will start in spring 2021 and Groeneveld expects the first results this summer. The second part of the study with pain patients will start in autumn 2021 and last at least two years.