To explore the effects of cannabinoid 2 receptor (CB2) in the development of bone cancer pain in mice.”
The cannabinoid 2 receptor plays an important role in the formation of bone cancer pain.”
“The endocannabinoid system plays a key role in regulating a variety of physiological processes such as appetite control and energy balance, pain perception, and immune responses. Recent studies have implicated the endocannabinoid system in the regulation of bone cell activity and bone remodeling. These studies showed that endogenous cannabinoid ligands, cannabinoid receptors, and the enzymes responsible for ligand synthesis and breakdown all play important roles in bone mass and in the regulation of bone disease. These findings suggest that the endocannabinoid pathway could be of value as a therapeutic target for the prevention and treatment of bone diseases. Here, we review the role of the skeletal endocannabinoid system in the regulation of bone remodeling in health and disease.”
“Metastatic and primary bone cancers are usually accompanied by severe pain that is difficult to manage. In light of the adverse side effects of opioids, manipulation of the endocannabinoid system may provide an effective alternative for the treatment of cancer pain…
These data extend our previous findings with anandamide in the same model and suggest that the peripheral endocannabinoid system is a promising target for the management of cancer pain.
Taken together, the data demonstrate that peripheral 2-AG signaling may be a significant target to exploit for the management of cancer pain. In contrast to AEA, which inhibits nociception through CB1 receptors… Dual pharmacological modulation of peripheral AEA and 2-AG signaling that directly and indirectly affects DRG neurons may be a novel approach to reducing cancer pain without the side effects…”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104059/
“…a great body of evidence demonstrates the analgesic efficacy of systemically administered CB2 agonists in acute and chronic experimental pain….
The activation of CB2 receptors induces analgesia in experimental models of chronic pain. The present experiments were designed to study whether the activation of peripheral or spinal CB2 receptors relieves thermal hyperalgesia and mechanical allodynia in two models of bone cancer pain.
Spinal CB2 receptors are involved in the antiallodynic effect… in two neoplastic models while peripheral and spinal receptors participate in the antihyperalgesic effects… The use of drugs that activate CB2 receptors could be a useful strategy to counteract bone cancer-induced pain symptoms.”
“CB2 agonists not only produce antinociceptive and anti-inflammatory effects, but also have been shown to increase bone density.”
“Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB(2) selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB(2) agonist administered over a 7day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation.”
“Based on the antihyperalgesic effects of CB2 agonists, the lack of potential CNS-induced side effects and their propensity to stimulated bone growth, we addressed whether the sustained selective CB2 agonists… has the potential to alleviate bone cancer-induced pain while maintaining bone integrity in a murine model of bone cancer”.
“These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871326/
“Pain associated with cancer and tumor growth is often difficult to manage.”
“Cannabis sativa has a long history of use for management of pain.”
“In light of the adverse side effects of opioids, cannabinoid (CB) receptor agonists may provide an effective alternative for the treatment of cancer pain. The present study examined the potency and efficacy of synthetic CB1 and CB2 receptor agonists in a murine model of tumor pain.”
“Together these data support the use of combined CB1 and CB2 receptor agonists in the development of strategies for the treatment of tumor related pain.”
“These data extend our previous findings that the peripheral cannabinoid receptors are a promising target for the management of cancer pain and mixed cannabinoid receptor agonists may have a therapeutic advantage over selective agonists.”
“When 7-year-old Mykayla Comstock was diagnosed with leukemia in July, it was less than three days before her mother filed Oregon medical marijuana paperwork so the child could take lime-flavored capsules filled with cannabis oil.
The decision to give Mykayla the capsules came naturally to Erin Purchase, MyKayla’s mother, who believes marijuana has healing power, but doctors aren’t so sure it’s a good idea.
“The first doctor was not for it at all,” Purchase told ABCNews.com. “She was rude and she told us it was inappropriate. “Basically she blew up at us and told us to transfer to another facility.”
They found a new doctor, who knows that Mykayla takes about a gram of cannabis oil a day — half in the morning and half at night — but he doesn’t talk about it with them.
“This is our daughter,” Purchase, 25, said. “If they don’t agree with our personal choices, we’d rather they not say anything at all.””
.””At first, Mykayla wasn’t responding well to her treatment, and doctors said she might need a bone marrow transplant. Then she started taking the cannabis oil pills. her mother said. By early August, Mykayla was in remission and the transplant was no longer necessary.”
“I don’t think it’s just a coincidence,” Purchase said. “I credit it with helping — at least helping — her ridding the cancer from her body.””
Read more: http://abcnews.go.com/Health/medical-marijuana-year-sparks-controversy/story?id=17814636
https://www.facebook.com/BraveMyKayla
“Like some cancer patients in states where it’s allowed, Mykayla Comstock uses cannabis as part of her treatment. Comstock is 7-years old. Her mother, a long time advocate for medical use of the illegal drug, has been giving her a gram of oral cannabis oil every day. Despite the fact that medical marijuana is legal in Oregon, where Comstock lives, the idea of giving it to a child still gives pause to many adults who associate the drug with recreational use that breaks the law.
As reported by ABC News, Mykayla was diagnosed with acute lymphoblastic leukemia in July. Against her doctor’s wishes, her mother, Erin Purchase, began giving her lime-flavored capsules filled with cannabis oil after she had a poor response to her initial chemotherapy treatment.
Her doctors suggested a bone marrow transplant, but while she was taking the medical marijuana, she went into remission in August. She continues to rely on cannabis to ease pain and nausea and her mother plans to continue giving her the drug during the additional two to three years of chemotherapy she still faces.
Purchase believes that certain components in marijuana, which show anti-cancer activity in many early studies, helped spark the remission. Mykayla’s current doctor knows she takes the capsules, but doesn’t discuss the marijuana as part of her medical therapy.” http://www.cnn.com/2012/11/30/health/medical-marijuana-children-time/
“Like synthetic CB1R agonists, AEA attenuates hyperalgesia in models of neuropathic, inflammatory and tumor pain.”
“Collectively, these results suggest that pharmacological facilitation of AEA signaling is a promising strategy for attenuating cisplatin-associated sensory neuropathy.”
We have shown that cisplatin produces hyperalgesia and toxicity to sensory neurons as indicated by neurochemical, morphological and functional measures. Increasing AEA signaling at CB1 receptors not only reduced the hyperalgesia but reduced the neurotoxicity of cisplatin as well. Although the mechanisms by which AEA reduce neurotoxicity remain to be resolved, the present studies underscore the dual utility in exploiting the endocannabinoid system for management of neuropathic pain produced by chemotherapy.”
“Cannabinoids-endocannaboids are possible preventatives of common diseases including cancers. Cannabinoid receptors (CB(½), TRPV1) are central components of the system. Many disease-ameliorating effects of cannabinoids-endocannabinoids are receptor mediated, but many are not, indicating non-CBR signaling pathways.
Cannabinoids-endocannabinoids are anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic in most cancers, in vitro and in vivo in animals.
They signal through p38, MAPK, JUN, PI3, AKT, ceramide, caspases, MMPs, PPARs, VEGF, NF-κB, p8, CHOP, TRB3 and pro-apoptotic oncogenes (p53,p21 waf1/cip1) to induce cell cycle arrest, autophagy, apoptosis and tumour inhibition. Paradoxically they are pro-proliferative and anti-apoptotic in some cancers. Differences in receptor expression and concentrations of cannabinoids in cancer and immune cells can elicit anti- or pro-cancer effects through different signal cascades (p38MAPK or PI3/AKT).
Similarities between effects of cannabinoids-endocannabinoids, omega-3 LCPUFA and CLAs/CLnAs as anti-inflammatory, antiangiogenic, anti-invasive anti-cancer agents indicate common signaling pathways.
Evidence in vivo and in vitro shows EPA and DHA can form endocannabinoids that: (i) are ligands for CB(½) receptors and possibly TRPV-1, (ii) have non-receptor mediated bioactivity, (iii) induce cell cycle arrest, (iii) increase autophagy and apoptosis, and (iv) augment chemotherapeutic actions in vitro. They can also form bioactive, eicosanoid-like products that appear to be non-CBR ligands but have effects on PPARs and NF-kB transcription factors. The use of cannabinoids in cancer treatment is currently limited to chemo- and radio-therapy-associated nausea and cancer-associated pain apart from one trial on brain tumours in patients. Further clinical studies are urgently required to determine the true potential of these intriguing, low toxicity compounds in cancer therapy. Particularly in view of their synergistic effects with chemotherapeutic agents similar to that observed for n-3 LCPUFA.” https://www.ncbi.nlm.nih.gov/pubmed/23103355
http://www.sciencedirect.com/science/article/pii/S0163782712000537
“Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge. Nabiximols (Nabiximols is the U.S. Adopted Name [USAN] for Sativex [GW Pharma Ltd, Wiltshire, U.K.], which does not yet have an INN), a novel cannabinoid formulation, is undergoing investigation as add-on therapy…
This study supports the efficacy and safety of nabiximols at the 2 lower-dose levels and provides important dose information for future trials.
PERSPECTIVE: Nabiximols, a novel cannabinoid formulation, may be a useful add-on analgesic for patients with opioid-refractory cancer pain. A randomized, double-blind, placebo-controlled, graded-dose study demonstrated efficacy and safety at low and medium doses.”