Chronic pain is an oppressive human health problem and a significant cause of morbidity. In 2011 alone, the direct (drug prescription, hospitalization) and indirect (loss of productivity and work force) costs of chronic pain were at $600 billion dollars in the USA alone. This outweighs the costs related to heart disease, cancer, and diabetes combined. Sadly, current pharmacological treatments for chronic pain are also burdened with severe sides effects, including non-steroidal anti-inflammatory drugs and opioids. Rise in opioid prescription over the past decade has led to what is currently referred to as the opioid epidemics. Although prescription opioids are not the leading cause of this epidemics, the treatment of chronic pain is nonetheless linked to the opioid crisis. It is therefore imperative the novel, effective, non-opioid therapies be brought forth for these chronic pain patients.
Among these patients are the nearly 8 million women and 4 million men suffering from interstitial cystitis (IC), commonly referred to as chronic bladder pain. The symptoms of this chronic disease include pelvic pain, urinary storage dysfunctions such as urinary frequency, urgency, and nocturia. All of which lead to a major reduction in patients’ quality of life. There are unfortunately no adequate treatments for chronic bladder pain and new therapeutic approaches are desperately needed.
A growing body of evidence suggests that cannabinoids are beneficial for a range of clinical conditions, including chronic pain and inflammation, and the formulation of novel preparations of cannabinoids is progressing rapidly. One novel formulation, developed by Desert Harvest Inc., packages cannabidiol with aloe vera to increase its bioavailability. Whether such formulation can improve its analgesic properties and alleviate the symptoms of IC remains unknown.
Through an international collaboration with the group of Dr. Reza Sharif Naeini at the McGill University Research Center for Cannabis, Montreal, Canada, Desert Harvest Inc. aimed to validate whether their new formulation could alleviate the pain symptoms in a preclinical model of IC.
Several preclinical models of IC have been developed, with the aim of understanding the underlying mechanisms of the disease and devise better analgesic approaches. One such model is the cyclophosphamide (CYP)-induced bladder inflammation. The compound is metabolized to acrolein in the liver, which then accumulates in the bladder and causes tissue damage. The symptoms are similar to human IC, including bladder inflammation, pain-related behaviors, and bladder overactivity.
The data obtained by the Sharif lab are very encouraging, as they demonstrate that treatment with this cannabidiol-aloe vera formulation significantly reduced the pain symptoms. The effect of urinary frequency, however, were not significant. Pain is sensed in the bladder by pain-sensing nerve fibers, also called nociceptors. The signal emitted by these nociceptors is then conveyed to the spinal cord, where it is processed by other nerve cells before relaying it to the brain for interpretation. Cannabinoids can produce their analgesic effect on at least three different sites along the pain transmission pathway: they can reduce (1) the activity of nociceptors that innervate the bladder, (2) the activity of spinal cord neurons involved in relaying the pain signal, or (3) the activity of brain neurons involved in interpreting the pain signals. The second phase of this collaboration will involve testing the effect of this cannabidiol formulation on the excitability of neurons obtained from human donors. This will indicate whether part of the action of this drug is mediated by reducing the activity of nociceptors.
Both groups are very hopeful of the outcome of these experiments, as they will be the first to examine, in human nociceptors, the analgesic properties of cannabidiol. Findings from this collaboration will confirm the analgesic effect of cannabidiol on nociceptors and increase support for non-opioid pain management strategies.