Cannabinoids and cancer pain: A new hope or a false dawn?

Matthew R.D. Brown and W. Paul Farquhar-Smith  (March 2018)

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There are a wealth of preclinical data in a number of acute, chronic, neuropathic and cancer pain models that have demonstrated a potent analgesic potential for cannabinoids, especially in patients with cancer. However, although there are some positive results in pain of cancer patients, the clinical evidence for cannabinoids as analgesics has not been convincing and their use can only be weakly recommended. The efficacy of cannabinoids seems to have been ‘lost in translation’ which may in part be related to using extracts of herbal cannabis rather than targeted selective full agonists at the cannabinoid CB1 and CB2 receptors.

Use of cannabinoids in cancer care: palliative care

S.K. Aggarwal, MD PhD  (July 2014) 

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Integrating cim into oncologic palliative care promises to improve overall health-related quality of life, to provide further relief from distressing symptoms and spiritual suffering, and to bring hope to patients and families facing terminal illness.

Cannabinoids as therapeutic agents in cancer: current status and future implications

Bandana Chakravarti, Janani Ravi, and Ramesh K. Ganju  (July 2014)

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Though cannabinoids are clinically used for anti-palliative effects, recent studies open a promising possibility as anti-cancer agents. They have been shown to possess anti-proliferative and anti-angiogenic effects in vitro as well as in vivo in different cancer models. Cannabinoids regulate key cell signaling pathways that are involved in cell survival, invasion, angiogenesis, metastasis, etc. There is more focus on CB1 and CB2, the two cannabinoid receptors which are activated by most of the cannabinoids. In this review article, we will focus on a broad range of cannabinoids, their receptor dependent and receptor independent functional roles against various cancer types with respect to growth, metastasis, energy metabolism, immune environment, stemness and future perspectives in exploring new possible therapeutic opportunities.

The endocannabinoid signaling system in cancer

SimonaPisantiPaolaPicardiAlbaD’AlessandroChiaraLaezzaMaurizioBifulco  (May 2013)

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The endocannabinoid system, comprising lipid-derived endocannabinoids, their G-protein-coupled receptors (GPCRs), and the enzymes for their metabolism, is emerging as a promising therapeutic target in cancer. This report highlights the main signaling pathways for the antitumor effects of the endocannabinoid system in cancer and its basic role in cancer pathogenesis, and discusses the alternative view of cannabinoid receptors as tumor promoters. We focus on new players in the antitumor action of the endocannabinoid system and on emerging crosstalk among cannabinoid receptors and other membrane or nuclear receptors involved in cancer. We also discuss the enzyme MAGL, a key player in endocannabinoid metabolism that was recently recognized as a marker of tumor lipogenic phenotype.

Increasing 2-arachidonoyl glycerol signaling in the periphery attenuates mechanical hyperalgesia in a model of bone cancer pain

Iryna A.KhasabovaAnishaChandiramaniCatherineHarding-RoseDonald A.SimoneVirginia S.Seybold  (July 2011)

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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. The present study determined that a local, peripheral increase in the endocannabinoid 2-arachidonoyl glycerol (2-AG) reduced mechanical hyperalgesia evoked by the growth of a fibrosarcoma tumor in and around the calcaneous bone. Intraplantar (ipl) injection of 2-AG attenuated hyperalgesia (ED50 of 8.2 μg) by activation of peripheral CB2 but not CB1 receptors and had an efficacy comparable to that of morphine.

Reduction of Bone Cancer Pain by Activation of Spinal Cannabinoid Receptor 1 and Its Expression in the Superficial Dorsal Horn of the Spinal Cord in a Murine Model of Bone Cancer Pain

Shingo Furuse, M.D.Tomoyuki Kawamata, M.D., Ph.D.Jun Yamamoto, M.D., Ph.D.Yukitoshi Niiyama, M.D., Ph.D.Keiichi Omote, M.D., Ph.D.; et al  (July 2009)

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The results of our study demonstrate that spinal CB1 activation by an exogenously administered CB1 agonist reduced bone cancer–related pain behaviors, including behaviors related to spontaneous pain and movement-evoked pain. Presynaptic inhibition of spinal neurons and/or descending fibers may contribute to spinal CB1 activation–induced analgesia. In addition, MOR expression in the superficial dorsal horn ipsilateral to the site of implantation of sarcoma cells was decreased compared to that contralateral to the site of implantation, whereas CB1 expression in the superficial dorsal horn was preserved. The findings of this study may lead to novel strategies for the treatment of bone cancer pain.

A Decrease in Anandamide Signaling Contributes to the Maintenance of Cutaneous Mechanical Hyperalgesia in a Model of Bone Cancer Pain

Iryna A. KhasabovaSergey G. KhasabovCatherine Harding-RoseLia G. CoicouBryan A. SeyboldAmy E. LindbergChristopher D. SteevensDonald A. Simone and Virginia S. Seybold  (October 2008)

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Tumors in bone are associated with pain in humans. Data generated in a murine model of bone cancer pain suggest that a disturbance of local endocannabinoid signaling contributes to the pain. When tumors formed after injection of osteolytic fibrosarcoma cells into the calcaneus bone of mice, cutaneous mechanical hyperalgesia was associated with a decrease in the level of anandamide (AEA) in plantar paw skin ipsilateral to tumors. The decrease in AEA occurred in conjunction with increased degradation of AEA by fatty acid amide hydrolase (FAAH). Intraplantar injection of AEA reduced the hyperalgesia, and intraplantar injection of URB597, an inhibitor of FAAH, increased the local level of AEA and also reduced hyperalgesia. An increase in FAAH mRNA and enzyme activity in dorsal root ganglia (DRG) L3–L5 ipsilateral to the affected paw suggests DRG neurons contribute to the increased FAAH activity in skin in tumor-bearing mice.

Cannabinoids in pancreatic cancer: Correlation with survival and pain

Christoph W. Michalski, Florian E. Oti, Mert Erkan, Danguole Sauliunaite, Frank Bergmann, Pal Pacher, Sandor Batkai, Michael W. Müller, Nathalia A. Giese, Helmut Friess, Jörg Kleeff  (October 2007)
There was a significant relationship between low CB1 receptor immunoreactivity or mRNA expression levels (p = 0.0011 and p = 0.026, respectively), or high FAAH and MGLL cancer cell immunoreactivity (p = 0.036 and p = 0.017, respectively) and longer survival of PDAC patients. These results are underlined by a significant correlation of high pain scores and increased survival (p = 0.0343). CB2 receptor immunoreactivity, CB2 receptor, FAAH and MGLL mRNA expression levels did not correlate with survival. Therefore, changes in the levels of endocannabinoid metabolizing enzymes and cannabinoid receptors on pancreatic cancer cells may affect prognosis and pain status of PDAC patients.