Targeting CB 2 receptors and the endocannabinoid system for the treatment of pain
Brain Research Reviews, ISSN: 0165-0173, Vol: 60, Issue: 1, Page: 255-266
2009
- 189Citations
- 294Captures
- 1Mentions
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Metrics Details
- Citations189
- Citation Indexes186
- 186
- CrossRef153
- Policy Citations2
- Policy Citation2
- Patent Family Citations1
- Patent Families1
- Captures294
- Readers294
- 294
- Mentions1
- Blog Mentions1
- Blog1
Review Description
The endocannabinoid system consists of the cannabinoid (CB) receptors, CB 1 and CB 2, the endogenous ligands anandamide (AEA, arachidonoylethanolamide) and 2-arachidonoylglycerol (2-AG), and their synthetic and metabolic machinery. The use of cannabis has been described in classical and recent literature for the treatment of pain, but the potential for psychotropic effects as a result of the activation of central CB 1 receptors places a limitation upon its use. There are, however, a number of modern approaches being undertaken to circumvent this problem, and this review represents a concise summary of these approaches, with a particular emphasis upon CB 2 receptor agonists. Selective CB 2 agonists and peripherally restricted CB 1 or CB 1 /CB 2 dual agonists are being developed for the treatment of inflammatory and neuropathic pain, as they demonstrate efficacy in a range of pain models. CB 2 receptors were originally described as being restricted to cells of immune origin, but there is evidence for their expression in human primary sensory neurons, and increased levels of CB 2 receptors reported in human peripheral nerves have been seen after injury, particularly in painful neuromas. CB 2 receptor agonists produce antinociceptive effects in models of inflammatory and nociceptive pain, and in some cases these effects involve activation of the opioid system. In addition, CB receptor agonists enhance the effect of μ-opioid receptor agonists in a variety of models of analgesia, and combinations of cannabinoids and opioids may produce synergistic effects. Antinociceptive effects of compounds blocking the metabolism of anandamide have been reported, particularly in models of inflammatory pain. There is also evidence that such compounds increase the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs), raising the possibility that a combination of suitable agents could, by reducing the NSAID dose needed, provide an efficacious treatment strategy, while minimizing the potential for NSAID-induced gastrointestinal and cardiovascular disturbances. Other potential “partners” for endocannabinoid modulatory agents include α 2 -adrenoceptor modulators, peroxisome proliferator-activated receptor α agonists and TRPV1 antagonists. An extension of the polypharmacological approach is to combine the desired pharmacological properties of the treatment within a single molecule. Hopefully, these approaches will yield novel analgesics that do not produce the psychotropic effects that limit the medicinal use of cannabis.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0165017308001410; http://dx.doi.org/10.1016/j.brainresrev.2008.12.003; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=63749099041&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/19150370; https://linkinghub.elsevier.com/retrieve/pii/S0165017308001410; https://dx.doi.org/10.1016/j.brainresrev.2008.12.003
Elsevier BV
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