Dutch government funds €1.9m research into THC/CBD balance

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The Dutch government is providing €1.9 million ($2.25 million) in research funding for a study aimed at finding an optimal balance between THC and CBD dosages in medical cannabis for the treatment of neuropathic pain.

The grant has been awarded to a joint project of the Centre for Human Drug Research (CHDR), a Dutch clinical drug research institute, and the Leiden University Medical Center (LUMC).


Take this pill

“We are going to isolate the THC and CBD . . . 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 Neurologist Geert Jan Groeneveld of CHDR. Groeneveld is CSO, CMO at CHDR, and professor of Clinical Neuropharmacology at the LUMC. He is conducting the research with and Albert Dahan, professor of Anesthesiology at the LUMC.

Dutch company Bedrocan’s raw materials will be used for the production of the research material; Echo Pharmaceuticals, Leiden, Netherlands, will produce the tablets for the research, Bedrocan said in a press release.

Drug developer approach

“We want to approach this research exactly as a drug developer would,” Groeneveld said. “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 measure the pharmacodynamics and pharmacokinetics of THC and CBD, the effects of both substances have on pain and brain function, and how the substances behave in the human body.

Literature is conflicting

THC and CBD are the two most studied active cannabinioids 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. But it is also believed that CBD may modulate the psychotropic effects of THC.

In the first part of the study, healthy subjects will be administered the tablets with different THC and CBD ratios to show whether the anxiety-inducing effects of THC can be reduced by administering CBD simultaneously. Groeneveld said the scientific literature has so far provided conflicting results

Does CBD affect pain?

“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,” Groeneveld said, “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.”

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 used pain killers, the researchers said. That latter question also be investigated in the studies.

Once results of the first study are known, a second study will look at the effects on pain in patients, and inform the question of which THC:CBD ratio works best. The second study will take place among a diverse group of 200 patients with different neuropathic pain conditions.

Drilling down on pain sources

“We are going to phenotype this group very well in advance,” Groeneveld said. “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.”

Once the first two studies are complete, participants in a crossover study will receive a placebo for five weeks, and after a wash-out period, get five weeks of cannabinoid or THC treatment. Pain will be measured in each treatment period.

Other variables

“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,” Groeneveld said.

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 2021 and last at least two years.


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