A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss

Posted on November 29, 2012 by David

“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/

CB1 and CB2 receptor agonists promote analgesia through synergy in a murine model of tumor pain

Posted on November 29, 2012 by David

“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.”

“Co-administering both CB receptor agonists attenuated mechanical hyperalgesia through a synergistic mechanism.”

“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.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155626/

Cannabis Oil Pills Helped Child Go Into Cancer Remission, Mom Says – ABCNews

Posted on November 29, 2012 by David

“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.””

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/

http://www.thctotalhealthcare.com/category/leukemia/

Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy

Posted on November 29, 2012 by David

“Painful peripheral neuropathy is a dose-limiting complication of chemotherapy. Cisplatin produces a cumulative toxic effect on peripheral nerves…”

“Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy”

“Clinically, the synthetic cannabinoid agonist nabilone reduces chemotherapy-induced pain”

“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.”

“Conclusion

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.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366638/

Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators.

Posted on November 29, 2012 by David

Cover image

“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

Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial.

Posted on November 29, 2012 by David

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/22483680

Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain.

Posted on November 29, 2012 by David

“This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.” http://www.ncbi.nlm.nih.gov/pubmed/19896326

“In conclusion, THC:CBD extract, a nonopioid analgesic, endocannabinoid system modulator, has been shown to be a useful adjunctive treatment for relief of pain in patients with advanced cancer who experience inadequate analgesia despite chronic opioid therapy. The reductions in pain scores were neither because of a change in opioid background medications nor because of an increase in use of breakthrough medication. Therefore, we can conclude that the observed reduction in pain scores is attributable to the positive analgesic effects of THC:CBD extract.” http://www.jpsmjournal.com/article/S0885-3924(09)00787-8/fulltext

An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to Strong Opioid Analgesics.

Posted on November 29, 2012 by David

“Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group.

OBJECTIVES:

This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer.

CONCLUSION:

This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.”

http://www.ncbi.nlm.nih.gov/pubmed/23141881

Smoking Marijuana Eases Chronic Neuropathic Pain.

Posted on November 25, 2012 by David

“Smoking cannabis reduces chronic neuropathic pain and also improves sleep, according to new research published today in the Canadian Medical Association Journal.

A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis 3 times a day for 5 days was sufficient to achieve these outcomes, lead study author Mark A. Ware, MBBS, from McGill University Health Center, Montreal, Canada, told Medscape Medical News in an interview.

“Patients have been reporting that cannabis helps control their pain, and they have been saying so for a long time,” Dr. Ware said. “At the time that we had secured the funding and began the trial, there had been no clinical trials that had established this or investigated it.”

In addition, a large body of scientific knowledge is emerging abound the role of cannabinoid receptors and cannabinoid ligands in the human body, providing a potential scientific explanation as to why cannabinoids would be analgesic, he added. “So the 2 main supports came together, and in Canada at the time, there was an environment where we were able to secure funding sufficient for studies of this.”

Posttraumatic and Postsurgical Neuropathy

The study included 21 individuals older than 18 years (mean age, 45.4 years) with posttraumatic or postsurgical neuropathic pain lasting for at least 3 months. They were randomly assigned to receive cannabis at 4 potencies — 0%, 2.5%, 6%, and 9.4% tetrahydrocannabinol — during 4 periods in a crossover design. Each period lasted 14 days and began with 5 days of cannabis use followed by a 9-day washout period.

The cannabis doses were delivered in a single smoked inhalation using a titanium pipe. Patients self-administered the first dose of each period under supervision and were instructed to inhale for 5 seconds while the cannabis was lit, hold the smoke in their lungs for 10 seconds, and then exhale. They self-administered the remaining doses for each period at home.

The participants were allowed to continue their routine medications, and the use of acetaminophen as breakthrough analgesia was also permitted.

Pain intensity was measured using an 11-item numeric rating scale that used “no pain” and “worst pain possible” as anchors.

The study found that the higher dose of cannabis was the most efficient in reducing pain. The average daily pain intensity was 5.4 with the 9.4% tetrahydrocannabinol cannabis dose compared with 6.1 with the 0% or placebo dose (95% confidence interval, 0.02 – 1.4; P = .023).

In addition, participants reported significantly more drowsiness and reported getting to sleep more easily, faster, and with fewer periods of wakefulness when taking the 9.4% dose than when taking the 0% dose ( P < .05). The higher dose also improved anxiety and depression compared with the placebo dose.

Blind Held; Studies Feasible

“It was feared that participants would know right away if they were smoking cannabis because of the acute psychoactive effects of the drug, but our results do not support this,” Dr. Ware noted. “They do show that short-term placebo-controlled trials of smoked cannabis are feasible.”

He would like his study to act as a stimulus for other studies on cannabis and pain relief.

“Studies of this kind can be done. Ours was difficult to do because it was the first time we had done anything like this. We were breaking new ground with regard to regulations and so on, but it is possible. Having done it once, it’s not as difficult to do it again. So our results raise the possibility of extending the study for a longer duration, or being able to look at safety issues, and so on. It is possible to do a scientific trial with this compound. Your political views shouldn’t matter. This is just good science,” Dr. Ware said.

In a related commentary, Henry J. McQuay, DM, from Balliol College, Oxford, United Kingdom, writes that the study authors should be congratulated for tackling the question of whether cannabis helps in neuropathic pain, “particularly given that the regulatory hurdles for their trial must have been a nightmare.”

He concludes that the study “adds to the trickle of evidence that cannabis may help some of the patients who are struggling at present.””

http://www.medscape.com/viewarticle/727702

Marijuana component could ease pain from chemotherapy drugs

Posted on November 25, 2012 by David

“A chemical component of the marijuana plant could prevent the onset of pain associated with drugs used in chemo therapy, particularly in breast cancer patients, according to researchers at Temple University’s School of Pharmacy.

“We found that cannabidiol completely prevented the onset of the neuropathic, or nerve pain caused by the chemo drug Paclitaxel, which is used to treat breast cancer,” said Ward, who is also a research associate professor in Temple’s Center for Substance Abuse Research.

Ward said that one of cannabidiol’s major benefits is that, unlike other chemicals found in marijuana such as THC, it does not produce psycho-active effects such as euphoria, increased appetite or cognitive deficits. “Cannabidiol has the therapeutic qualities of marijuana but not the side effects,” she said.”