Tag Archives: pain

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

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“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

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“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/

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

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 “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/

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

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 “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.

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“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.

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  “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

[Cannabinoids in the control of pain].

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Abstract

“Hemp (Cannabis sativa L.) has been used since remotes ages as a herbal remedy. Only recently the medical community highlighted the pharmacological scientific bases of its effects. The most important active principle, Delta-9-tetrahydrocannabinol, was identified in the second half of the last century, and subsequently two receptors were identified and cloned: CB1 that is primarily present in the central nervous system, and CB2 that is present on the cells of the immune system. Endogenous ligands, called endocannabinoids, were characterized. The anandamide was the first one to be discovered. The effectiveness of the cannabinoids in the treatment of nausea and vomit due to anti-neoplastic chemotherapy and in the wasting-syndrome during AIDS is recognized. Moreover, the cannabinoids are analgesic, and their activity is comparable to the weak opioids. Furthermore, parallels exist between opioid and cannabinoid receptors, and evidence is accumulating that the two systems sometimes may operate synergistically. The interest of the pharmaceutical companies led to the production of various drugs, whether synthetic or natural derived. The good ratio between the polyunsatured fatty acids omega-3 and omega-6 of the oil of Cannabis seeds led to reduction of the phlogosis and an improvement of the pain symptoms in patients with chronic musculo-skeletal inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/19388223

An analgesic role for cannabinoids.

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Abstract

“Cannabinoids have significant analgesic properties in animal models, particularly for chronic pain states, but there are few human studies. An endogenous cannabinoid system, with specific receptors and transmitters, has recently been discovered. This discovery has led pharmacologists to explore the potential of synthetic cannabinoids to selectively target chronic pain disorders without producing the side effects associated with cannabis. Well-controlled clinical trials on cannabinoids, and cannabinoid delivery systems, are now required.”

http://www.ncbi.nlm.nih.gov/pubmed/11130354

Reassessment of the role of cannabinoids in the management of pain.

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“The aim of this article is to assess the role of cannabinoids in the treatment of acute and chronic pain in humans.

 …to date there is increasing evidence that cannabinoids are safe and effective for refractory chronic pain conditions including neuropathic pain associated with multiple sclerosis, rheumatoid arthritis, and peripheral neuropathy associated with HIV/AIDS.

SUMMARY:

The precise role of cannabinoids in pain treatment still needs further evaluation. Cannabinoid compounds may be more effective in the context of chronic neuropathic pain than for the management of acute pain.”

http://www.ncbi.nlm.nih.gov/pubmed/17873600

Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials.

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“Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required.

In conclusion this systematic review of 18 recent good quality randomized trials demonstrates that cannabinoids are a modestly effective and safe treatment option for chronic non-cancer (predominantly neuropathic) pain. Given the prevalence of chronic pain, its impact on function and the paucity of effective therapeutic interventions, additional treatment options are urgently needed. More large scale trials of longer duration reporting on pain and level of function are required.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243008/