Clinical study

A randomized, double-blind, placebo-controlled, parallel-group, 4-arm trial of cannabis formulations with THC, CBD, and combined THC and CBD effects and flexible dosing.

This study is based on OUH / SDU.

Treatment of peripheral neuropathic pain is unsatisfactory, as less than half of the patients achieve good pain relief by using the usual drugs (Finnerup et al. 2015). Peripheral neuropathic pain is one of the types of pain that cannabis is claimed to work on, but the evidence is sparse and ambiguous. The various active components of cannabis act via receptors. The natural ligands for these receptors are endo-cannabinoids. Cannabinoid receptors are widespread in the body, with CB1 receptors present in large numbers in the central nervous system and CB2 receptors present in immune cells and peripheral nerves. Activation of CB1 receptors is responsible for the many psychotropic effects of cannabis, while the consequence of CB2 receptor activation may include pain relief. CB1 and CB2 receptors are the targets of the component 9-delta-tetra-hydro-cannabinoid in cannabis, and this component is a partial agonist at these receptors. Cannabidiol is another component of cannabis, and it acts indirectly antagonistically on CB1 and CB2 receptors. However, the cannabidiol may potentiate the effect of agonists by increasing the number of CB1 receptors. Cannabidiol is also an agonist for the serotonin 5-HT1a receptor, which may explain the possible antidepressant and anti-anxiety effects of cannabis. It is important to note that natural cannabis contains more than 400 components, and of these, more than 70 are classified as phyto-cannabinoids. With natural cannabis, therefore, the picture is much more complex than just assessing the effects of tetra-hydro-cannabinol and cannabidiol. This project aims to clarify whether the main active components in cannabis can provide clinically significant pain relief in peripheral neuropathic pain and whether the treatment can be used without clinically significant mental side effects. The primary effect variable will be the weekly average of daily total pain measured with a 0-10 point numerical scale (NRS) and mental function Trail Making Test A and B. The project hypothesizes that THC and the combination of THC and CBD, but not CBD alone, can relieve neuropathic pain and that treatment including THC will cause clinically significant impairment of mental function. This is a randomized, double-blind, placebo-controlled, parallel-group, 4-arm trial of cannabis formulations with THC, CBD, and combined THC and CBD effects and flexible dosing. The treatment periods will be of 8 weeks, preceded by 1 week for baseline observations and followed by 1 week for dose reduction and cessation of treatment. Patients will be able to continue their current treatment of neuropathic pain except for solid opioids, or they may be without treatment (no treatment for neuropathic pain either because conventional treatments have failed or because they could not be tolerated – at least one treatment tried). If the patient chooses to continue with regular treatment, this must not be changed in dose or product during the study period.