1.9 million euros for research into neuropathic pain

The Dutch government is supporting research into the use of medicinal cannabis in the treatment of neuropathic pain with € 1.9 million. The grant has been awarded to a joint project of the Centre for Human Drug Research (CHDR), a Dutch independent institute that specializes in clinical drug research, and the Leiden University Medical Center (LUMC). Neurologist Geert Jan Groeneveld (CSO / CMO at CHDR and professor of Clinical Neuropharmacology at the LUMC) and Albert Dahan (professor of Anesthesiology at the LUMC) will conduct the research.

The research intends to lead to a specific recommendation of an optimal delta-9-tetrahydrocannabinol (THC) –  cannabidiol (CBD) dosage for the treatment of neuropathic pain in a particular subgroup of patients. In addition, it contributes to evidence for the effectiveness of medicinal cannabis. Bedrocan’s raw materials will be used for the production of the research material.

Geert Jan Groeneveld
Geert Jan Groeneveld


The research does not look at the entire plant, but purely at the pharmacological effect of THC and CBD. Groeneveld: “We want to approach this research exactly as a drug developer would. As a clinical pharmacologist, you extract the proven pharmacological components from a plant and do research with it. That is also innovative in this research”.

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

“We are going to isolate the THC and CBD from Bedrocan cannabis and administer them in tablet form in different proportions. We will then look at the influence of CBD on the effects of THC , and investigate which THC-CBD combination is best for the treatment of neuropathic pain”, said Groeneveld.  The Dutch company Echo Pharmaceuticals from Leiden will produce the tablets for the research.

Healthy subjects

The study consists of two parts. In the first part, healthy subjects will be administered the tablets with different THC and CBD ratios. The first part of the research will show whether the adverse effects of THC, such as getting high or feeling anxious, can be reduced by administering CBD simultaneously. According to Groeneveld, the scientific literature has so far provided conflicting results about this: “To be honest, I do not expect much from CBD alone as a treatment for neuropathic pain. From a pharmacological point of view, it is likely that THC affects pain, but this is less the case for CBD. CBD could have an effect on inflammation, but there is no reason  to use CBD as a treatment for inflammatory pain. We already have Ibuprofen for that. It will only become interesting if the adverse effects of THC, such as feelings of anxiety, can be alleviated by administering CBD at the same time. “

Search for the ideal ratio between THC and CBD

THC (9-tetrahydrocannabinol) and CBD (cannabidiol) are the two most studied active ingredients of the cannabis plant. THC is known for its analgesic effect, but it also causes psychoactive side effects. CBD could lead to pain-relieving effects through other mechanisms. It is believed that CBD may also influence the psychotropic effects of THC by modulating THC binding to the CB1 receptor. However, it is still unclear what the ideal ratio of THC to CBD would be to take advantage of the CB1 modulating effects of CBD while preserving the positive effects of THC on pain. In addition, it is still unclear whether the analgesic effects that some patients experience as a result of CBD use are due to a pharmacological action of CBD, or simply because CBD prevents the metabolism of concomitantly used pain killers. The latter will also be investigated in these studies.

Patients with neuropathic pain conditions

The effects on pain in patients will not be investigated until the second part of the study, after the results of the first study are known. This will provide information on which THC:CBD ratio works best. The second part of the study will take place among a diverse group of 200 patients with different neuropathic pain conditions. Groeneveld: “We are going to phenotype this group very well in advance. This means that we want to know exactly how the 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? All these are variables that we are going to map.”

Subsequently, the participants in a crossover study will receive placebo for five weeks, and after a wash-out period, they will receive five weeks of cannabinoid treatment or vice versa. Pain will be measured in each treatment period. Groeneveld: “In patients with clear pain relief, we want to further investigate whether there is a correlation between their variables, such as sleeping problems, anxiety or peripheral nerve damage, and the response to treatment with THC.”

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

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