Cannabinoids and Pain: New Insights From Old Molecules

Abstract

Cannabis has been used for medicinal purposes for thousands of years. The prohibition of cannabis in the middle of the 20th century has arrested cannabis research. In recent years there is a growing debate about the use of cannabis for medical purposes. The term ‘medical cannabis’ refers to physician-recommended use of the cannabis plant and its components, called cannabinoids, to treat disease or improve symptoms. Chronic pain is the most commonly cited reason for using medical cannabis. Cannabinoids act via cannabinoid receptors, but they also affect the activities of many other receptors, ion channels and enzymes. Preclinical studies in animals using both pharmacological and genetic approaches have increased our understanding of the mechanisms of cannabinoid-induced analgesia and provided therapeutical strategies for treating pain in humans. The mechanisms of the analgesic effect of cannabinoids include inhibition of the release of neurotransmitters and neuropeptides from presynaptic nerve endings, modulation of postsynaptic neuron excitability, activation of descending inhibitory pain pathways, and reduction of neural inflammation. Recent meta-analyses of clinical trials that have examined the use of medical cannabis in chronic pain present a moderate amount of evidence that cannabis/cannabinoids exhibit analgesic activity, especially in neuropathic pain. The main limitations of these studies are short treatment duration, small numbers of patients, heterogeneous patient populations, examination of different cannabinoids, different doses, the use of different efficacy endpoints, as well as modest observable effects. Adverse effects in the short-term medical use of cannabis are generally mild to moderate, well tolerated and transient. However, there are scant data regarding the long-term safety of medical cannabis use. Larger well-designed studies of longer duration are mandatory to determine the long-term efficacy and long-term safety of cannabis/cannabinoids and to provide definitive answers to physicians and patients regarding the risk and benefits of its use in the treatment of pain. In conclusion, the evidence from current research supports the use of medical cannabis in the treatment of chronic pain in adults. Careful follow-up and monitoring of patients using cannabis/cannabinoids are mandatory.

<p>A Review of Scientific Evidence for THC:CBD Oromucosal Spray (Nabiximols) in the Management of Chronic Pain</p>

“…As a discussion of the full range of cannabis and cannabis-based products is beyond the scope of this review, interested readers are directed to recent comprehensive reviews on the subject. 58,59 Plant-derived (ie phytocannabinoids) and synthetic cannabinoids currently available for medicinal use are described briefly before the focus is turned specifically to THC:CBD oromucosal spray (nabiximols) for management of chronic pain conditions. Sativex ® (USAN name: nabiximols) oromucosal spray is a phytocannabinoid extract containing THC and CBD (1:1 ratio) as its principal components.…”

Cannabinoids, Blood–Brain Barrier, and Brain Disposition

“…Research on cannabinoids shows that these compounds have a number of pharmacobiological effects, such as hypothermia, catalepsy, anti-inflammatory activity, analgesia, induction of cell proliferation, growth arrest, or apoptosis [1,2]. More than one hundred cannabinoids have been identified in the plant cannabis.…”

CB2/miR-124 signaling down-regulate the expression of purinergic P2X4 and P2X7 receptor in dorsal spinal cord of CCI rats

“…It is well known that chronic neuropathic pain is often induced by peripheral nerve injury or dysfunction of the sensory nervous system in a large number of patients. Cannabinoids-mediate analgesia effect has been observed in various types of neuropathic pain in animals, including chronic constriction nerve injury, trigeminal neuralgia, chemotherapy-and streptozotocin-induced neuropathy [1]. More recent studies have suggested that cannabinoid CB1 and CB2 receptors, expressed in dorsal spinal cord, play an important role in spinal nociception [2][3][4][5].…”