“The hypothesis was tested that THC and anandamide elicit antinociception in the paw pressure test, and that arthritic rats would exhibit a different response.
THC and anandamide appear to release an as yet unknown endogenous opioid, because naloxone significantly blocked their effects.
This study indicates that anandamide and THC may act at different receptor sites to modulate endogenous opioid levels in mechanical nociception.”
“Cannabinoids exhibit medicinal properties including analgesic, anti-inflammatory and immunosuppressive properties. This paper reviews some of the recent findings in the study of cannabinoids in pain and inflammation. Some of the effects of cannabinoids are receptor mediated and others are receptor independent. Endocannabinoids naturally reduce pain and are cerebroprotective. Natural and synthetic cannabinoids have the potential to reduce nociception, reverse the development of allodynia and hyperalgesia, reduce inflammation and inflammatory pain and protect from secondary tissue damage in traumatic head injury.”
“For thousands of years, physicians and their patients employed cannabis as a therapeutic agent.
Despite this extensive historical usage, in the Western world, cannabis fell into disfavor among medical professionals because the technology available in the 1800s and early 1900s did not permit reliable, standardized preparations to be developed.
However, since the discovery and cloning of cannabinoid receptors (CB1 and CB2) in the 1990s, scientific interest in the area has burgeoned, and the complexities of this fascinating receptor system, and its endogenous ligands, have been actively explored.
Recent studies reveal that cannabinoids have a rich pharmacology and may interact with a number of other receptor systems-as well as with other cannabinoids-to produce potential synergies.
Cannabinoids-endocannabinoids, phytocannabinoids, and synthetic cannabinoids-affect numerous bodily functions and have indicated efficacy of varying degrees in a number of serious medical conditions.
Cannabinoid receptor agonists and/or molecules that affect the modulation of endocannabinoid synthesis, metabolism, and transport may, in the future, offer extremely valuable tools for the treatment of a number of currently intractable disorders.”
“Activation of opioid and cannabinoid receptors expressed in nociceptors induces effective antihyperalgesia.
In this study, we examined whether combinations of opioid and cannabinoid receptor agonists directed at the injured site would enhance therapeutic effectiveness.
Our findings showed that MOR and CB1 agonists directed at the inflamed site effectively attenuate mechanical hyperalgesia when administered individually, but exert opposing effects when administered together.
The antagonistic interactions between the two classes of drugs at the inflamed site suggest distinct mechanisms unique to peripheral nociceptors or inflamed tissue, and therefore require further studies to investigate whether the therapeutic utility of the combined drug treatments in chronic pain conditions can be optimized.”
“Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB1 and CB2).
These results suggest that attenuation of mechanically evoked responses of Aδ nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB1 receptors during inflammation.
Several studies have demonstrated that locally administered cannabinoids produce antinociception in animal models of both acute and persistent pain through peripheral mechanisms.
Taken together, our data suggest that peripherally acting cannabinoids could be a potential therapeutic treatment for chronic inflammatory pain.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585399/
“Myrcene, a monoterpene… The results suggest that myrcene is capable of inducing antinociception in mice, probably mediated by alpha 2-adrenoceptor stimulated release of endogenous opioids.” http://www.ncbi.nlm.nih.gov/pubmed/1983154
“Three different medicinal cannabis varieties were investigated Bedrocan, Bedrobinol and Bediol. The top five major compounds in Bedrocan extracts were Delta(9)-THC, cannabigerol (CBG), terpinolene, myrcene, and cis-ocimene in Bedrobinol Delta(9)-THC, myrcene, CBG, cannabichromene (CBC), and camphene in Bediol cannabidiol (CBD), Delta(9)-THC, myrcene, CBC, and CBG. The major components in Bedrocan smoke were Delta(9)-THC, cannabinol (CBN), terpinolene, CBG, myrcene and cis-ocimene in Bedrobinol Delta(9)-THC, CBN and myrcene in Bediol CBD, Delta(9)-THC, CBN, myrcene, CBC and terpinolene. The major components in Bedrocan vapor were Delta(9)-THC, terpinolene, myrcene, CBG, cis-ocimene and CBD in Bedrobinol Delta(9)-THC, myrcene and CBD in Bediol CBD, Delta(9)-THC, myrcene, CBC and terpinolene. ” http://www.ncbi.nlm.nih.gov/pubmed/20118579
“The metabotropic glutamate (mGlu) receptor 5 and the cannabinoid type 1 (CB1) receptor are G-protein-coupled receptors (GPCR) that are widely expressed in the central nervous system (CNS). mGlu5 receptors, present at the postsynaptic site, are coupled to Gαq/11 proteins and display an excitatory response upon activation, while the CB1 receptor, mainly present at presynaptic terminals, is coupled to the Gi/o protein and triggers an inhibitory response. Recent studies suggest that the glutamatergic and endocannabinoid systems exhibit a functional interaction to modulate several neural processes. In this review we discuss possible mechanisms involved in this crosstalk and its relationship with physiological and pathological conditions, including nociception, addiction and fragil X syndrome.”
“Use of marijuana to ease back pain was common among patients at a university spine clinic in Colorado where pot has been legal for medical purposes since 2000, but most of the users did not have a prescription, according to research presented here.
Among 184 patients at a Colorado spine center, 19% said they used marijuana for pain relief, but less than half, 46%, actually had a prescription for the drug, according to study co-author Michael Finn, MD, an assistant professor of neurosurgery at the University of Colorado in Denver.
The most common way to use the drug was smoking it, 90%, followed by oral ingestion, 45%, and vaporization, 29%.
According to the users, marijuana worked. A total of 89% said it greatly or moderately relived their pain, and 81% said it worked as well as or better than narcotic painkillers.”
http://www.medpagetoday.com/MeetingCoverage/AdditionalMeetings/42228
“Cannabinoids and related drugs generate profound behavioral effects (such as analgesic effects) through activating CNR1 (cannabinoid receptor 1 [brain]). However, repeated cannabinoid administration triggers lysosomal degradation of the receptor and rapid development of drug tolerance, limiting the medical use of marijuana in chronic diseases.
Here we show that a protein involved in macroautophagy/autophagy (a conserved lysosomal degradation pathway), BECN2 (beclin 2), mediates cannabinoid tolerance by preventing CNR1 recycling and resensitization after prolonged agonist exposure, and deletion of Becn2 rescues CNR1 activity in mouse brain and conveys resistance to analgesic tolerance to chronic cannabinoids.
Overall, our findings demonstrate the functional link among autophagy, receptor signaling and animal behavior regulated by psychoactive drugs, and develop a new strategy to prevent tolerance and improve medical efficacy of cannabinoids by modulating the BECN2 interactome and autophagy activity.”
“Clinical studies have reported that pan-cannabinoid receptor agonists may have efficacy in neuropathic pain states and that this might be enhanced by co-administration with opioids. While cannabinoid-opioid analgesic synergy has been demonstrated in animal models of acute pain, it has not been examined in neuropathic pain models. We examined the effect of combination treatment with cannabinoid and opioid receptor agonists on allodynia and side-effects in a nerve injury induced neuropathic pain model.
These findings indicate that combination administration of non-selective opioid and cannabinoid receptor agonists synergistically reduces nerve injury induced allodynia, while producing side-effects in an additive manner. This suggests that combination treatment has an improved anti-allodynic potency and therapeutic index in a neuropathic pain model.”