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.
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.
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.
What types of pain can cannabidiol (CBD) treat?
Pain, when used as an umbrella term, is more vast than the Pacific Ocean. Using CBD to treat pain can be effective only under the pretense that the type of pain is well-understood and properly diagnosed.
Most of us have crossed paths with the loud, piercing, cuss-worthy persona of acute pain: an elbow dings the edge of the table or a pinky toe that has found the bed frame yet again at 3 a.m. Other types of pain produce less shock value but are no less odious in nature.
For the sake of this article, I’ll simply go into the types of pain that CBD has shown to treat effectively: neuropathic and inflammatory pain.
Types of pain
CBD treats neuropathic pain like Cinderella’s foot fit the magic shoe—a blissful, but unexpected, union. Neuropathic pain is largely created and sustained due to the glutamenergic system, which is a major excitatory neuronal pathway. Glutamate is the neurotransmitter that is responsible for turning neurons on, which is great, sometimes.
Inflammatory pain is related to neuropathic pain, except it is not limited to neurons. Examples of inflammatory pain include all types of arthritis, a few autoimmune diseases such as Crohn’s and ulcerative colitis, and simple conditions like headaches, cramps, muscle aches, and pains.
For humans, communication is key, not only interpersonally but also molecularly. Problems arise in paradise when cells become damaged due to injury or chronic illness. When the body senses this damage, it cranks inflammation to HIGH and begins pumping inflammatory agents on its cells.
The point is to promote death of the damaged cell, otherwise called apoptosis. Our bodies don’t enjoy malfunctioning cells and would prefer that they throw in the towel—this is important in ridding ourselves of possible cancer and maintaining optimal functioning. However, when this becomes a chronic condition, it is named inflammatory pain.
How CBD works for pain
CBD inhibits glutamate release and other inflammatory agents, which makes it ‘neuroprotective’ and excellent at dulling the prickling, tingling and burning sensations that neuropathic pain is characterized for. CBD can be used as a supplement to help manage neuropathic pain, alongside other natural supplements such as magnesium glycinate.
Pain due to inflammation is not as easily characterized as other types of pain, mostly because its origins of pain vary and so does the experience. On the bright side, CBD is good at calming inflammation, no matter what the root cause.
The anti-inflammatory mechanism of cannabidiol is unique to cannabis. It doesn’t work like other anti-inflammatory drugs by inhibiting COX-1 and COX-2 receptors, which means you don’t run the risk of developing gastrointestinal ulcers or heart attacks, hooray! Some studies have shown that cannabinoids (CBD and THC) are up to twenty times more potent anti-inflammatory agents when compared to NSAIDs (eg. ibuprofen).
When taken regularly alongside other natural anti-inflammatory supplements (eg. curcumin, Omega-3), CBD can provide systemic relief of inflammation. Usually taken three times per day, dosing at each interval depends on your unique needs. Typically patients start with 0.5 mg per dose and increase until maximum relief.
Cannabidiol can be an effective, non-psychotropic alternative to THC when used correctly. However, we are still in the infancy stage of incorporating CBD into health and medicine, so it is important to consult your physician when contemplating the use of CBD to treat pain.
It’s important to remember that CBD, like other nutraceuticals, can interact with medications.
The takeaway? CBD isn’t effective in treating all types of pain—for that reason, it’s important to understand your pain: does it worsen with the weather, cause swelling, or is it persistent and stabbing? If you feel that you experience inflammatory or neuropathic pain, talk to your doctor. CBD supplementation could be right for you.