Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside

Abstract

Summary:Neuropathic pain is a debilitating form of chronic pain resulting from nerve injury, disease states, or toxic insults. Neuropathic pain is often refractory to conventional pharmacotherapies, necessitating validation of novel analgesics. Cannabinoids, drugs that share the same target as ⌬ 9 -tetrahydrocannabinol (⌬ 9 -THC), the psychoactive ingredient in cannabis, have the potential to address this unmet need. Here, we review studies evaluating cannabinoids for neuropathic pain management in the clinical and preclinical literature. Neuropathic pain associated with nerve injury, diabetes, chemotherapeutic treatment, human immunodeficiency virus, multiple sclerosis, and herpes zoster infection is considered. In animals, cannabinoids attenuate neuropathic nociception produced by traumatic nerve injury, disease, and toxic insults. Effects of mixed cannabinoid CB 1 /CB 2 agonists, CB 2 selective agonists, and modulators of the endocannabinoid system (i.e., inhibitors of transport or degradation) are compared. Effects of genetic disruption of cannabinoid receptors or enzymes controlling endocannabinoid degradation on neuropathic nociception are described. Specific forms of allodynia and hyperalgesia modulated by cannabinoids are also considered. In humans, effects of smoked marijuana, synthetic ⌬ 9 -THC analogs (e.g., Marinol, Cesamet) and medicinal cannabis preparations containing both ⌬ 9 -THC and cannabidiol (e.g., Sativex, Cannador) in neuropathic pain states are reviewed. Clinical studies largely affirm that neuropathic pain patients derive benefits from cannabinoid treatment. Subjective (i.e., rating scales) and objective (i.e., stimulusevoked) measures of pain and quality of life are considered. Finally, limitations of cannabinoid pharmacotherapies are discussed together with directions for future research.

The Impact of Marijuana Policies on Youth: Clinical, Research, and Legal Update

“…47,48 Research has demonstrated that cannabinoids are useful in treating anorexia associated with cancer, nausea and vomiting associated with chemotherapy, chronic pain, and multiple sclerosis. [49][50][51][52] A recently published study also demonstrated that current marijuana use was associated with lower levels of fasting insulin, lower homeostasis model assessmentestimated insulin resistance, and smaller waist circumference. 53 Two recently published review articles on medical marijuana for digestive disorders and select neurologic disorders generally noted small numbers of studies and mixed results.…”

Comparison of the Analgesic Effects of Dronabinol and Smoked Marijuana in Daily Marijuana Smokers

“…The potential use of cannabinoids to treat pain and their limitations have been widely discussed in review and opinion publications (eg, Rahn and Hohmann, 2009). Adverse effects of cannabinoids that can limit their therapeutic use are negative subjective effects and impaired cognition (as discussed in Haney, 2007).…”

Clinical laboratory testing for smoking toxicity: implications for early identification of respiratory diseases

“…40,41 Cannabis contains δ-9-tetrahydrocannabinol that is associated with alleviation of pain and has been used therapeutically in various cultures for medicinal purposes.…”

“…43 Further, the smoker"s paradox acknowledges the substantial benefits of therapeutic smoking, which has contributed to adoption of therapeutic smoking and development of new drugs. [40][41][42][43][44][45] Therefore, there are justifiable reasons for clinical laboratory testing of smoking toxicity not limited to evidence-based pathology for early identification and intervention of subclinical pathology in smokers but also laboratory monitoring of therapeutic smoking.…”