Dronabinol for the Treatment of Paraneoplastic Night Sweats in Cancer Patients: A Report of Five Cases.

Posted on February 14, 2019 by David

View details for Journal of Palliative Medicine cover image “Night sweats significantly impact the quality of life for cancer patients and are often resistant to treatment.

Cannabinoids have been shown to modulate cytokine activity and produce hypothermia in animal models, suggesting that they may be a promising candidate for palliation of night sweats in patients with oncologic disease.

A retrospective record search identified five cancer patients who had tried oral dronabinol for palliation of their night sweats between 2013 and 2016 and subjectively reported on its efficacy.

RESULTS:

Treatment of five patients with advanced cancer with synthetic orally administered dronabinol resulted in the successful management of persistent symptomatic paraneoplastic night sweats.

CONCLUSION:

Dronabinol and/or medicinal cannabis are promising therapies for palliation of night sweats in cancer patients.”

https://www.ncbi.nlm.nih.gov/pubmed/30759037

https://www.liebertpub.com/doi/10.1089/jpm.2018.0551

miRNA expression profiles and molecular networks in resting and LPS-activated BV-2 microglia-Effect of cannabinoids.

Posted on February 12, 2019 by David

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“Mammalian microRNAs (miRNAs) play a critical role in modulating the response of immune cells to stimuli.

Cannabinoids are known to exert beneficial actions such as neuroprotection and immunosuppressive activities. However, the underlying mechanisms which contribute to these effects are not fully understood.

We previously reported that the psychoactive cannabinoid Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signaling pathways.

Using lipopolysaccharide (LPS) to stimulate BV-2 microglial cells, we examined the role of cannabinoids on the expression of miRNAs. Expression was analyzed by performing deep sequencing, followed by Ingenuity Pathway Analysis to describe networks and intracellular pathways.

miRNA sequencing analysis revealed that 31 miRNAs were differentially modulated by LPS and by cannabinoids treatments. In addition, we found that at the concentration tested, CBD has a greater effect than THC on the expression of most of the studied miRNAs.

The results clearly link the effects of both LPS and cannabinoids to inflammatory signaling pathways. LPS upregulated the expression of pro-inflammatory miRNAs associated to Toll-like receptor (TLR) and NF-κB signaling, including miR-21, miR-146a and miR-155, whereas CBD inhibited LPS-stimulated expression of miR-146a and miR-155. In addition, CBD upregulated miR-34a, known to be involved in several pathways including Rb/E2f cell cycle and Notch-Dll1 signaling.

Our results show that both CBD and THC reduced the LPS-upregulated Notch ligand Dll1 expression. MiR-155 and miR-34a are considered to be redox sensitive miRNAs, which regulate Nrf2-driven gene expression. Accordingly, we found that Nrf2-mediated expression of redox-dependent genes defines a Mox-like phenotype in CBD treated BV-2 cells.

In summary, we have identified a specific repertoire of miRNAs that are regulated by cannabinoids, in resting (surveillant) and in LPS-activated microglia. The modulated miRNAs and their target genes are controlled by TLR, Nrf2 and Notch cross-talk signaling and are involved in immune response, cell cycle regulation as well as cellular stress and redox homeostasis.”

https://www.ncbi.nlm.nih.gov/pubmed/30742662

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212039

Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases

Posted on February 11, 2019 by David

British Journal of Dermatology banner

“Epidermolysis bullosa (EB) is a genetic blistering disorder characterized by intense pain related to disease pathology and care‐based interventions.

Opioid‐based therapies underpin pain care in EB; however, they are unable to provide adequate analgesia in a significant proportion of patients.

Cannabinoid‐based medicines (CBMs) have been studied increasingly for pain conditions of various aetiologies and pose as a novel dimension for pain care in EB.

We present three patients with EB who were prescribed pharmaceutical‐grade sublingually administered CBMs comprising tetrahydrocannabinol and cannabidiol.

All three patients reported improved pain scores, reduced pruritus and reduction in overall analgesic drug intake.”

https://www.ncbi.nlm.nih.gov/pubmed/30347109

https://onlinelibrary.wiley.com/doi/full/10.1111/bjd.17341

“Cannabinoids Could Help Manage EB-related Pain, Study Suggests” https://epidermolysisbullosanews.com/2019/02/08/cannabinoids-could-help-manage-eb-related-pain-study-suggests/

WHO proposes rescheduling cannabis to allow medical applications

Posted on February 9, 2019 by David

“The World Health Organization has proposed rescheduling cannabis within international law to take account of the growing evidence for medical applications of the drug, reversing its position held for the past 60 years that cannabis should not be used in legitimate medical practice.”

https://www.bmj.com/content/364/bmj.l574

“WHO RECOMMENDS RESCHEDULING #CANNABIS IN INTERNATIONAL LAW FOR FIRST TIME IN HISTORY. The World Health Organization has suggested that cannabis should be downgraded, or “rescheduled,” given the mounting evidence showing that the drug could prove beneficial in treating a number of health problems. This marks a significant change in WHO’s position, which for the last 60 years has said that cannabis should not be used in medicine, according to an article in the BMJ.” https://www.newsweek.com/who-recommends-rescheduling-cannabis-international-law-first-time-history-1324613

Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer.

Posted on February 9, 2019 by David

Proceedings of the National Academy of Sciences: 116 (6)

“Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New therapeutic approaches and diagnostic tools for identification, stratification, and treatment of patients at higher risk of resistance and recurrence are therefore warranted.

Here, we unveil a mechanism controlling the oncogenic activity of HER2: heteromerization with the cannabinoid receptor CB₂R. We show that HER2 physically interacts with CB₂R in breast cancer cells, and that the expression of these heteromers correlates with poor patient prognosis.

The cannabinoid Δ⁹-tetrahydrocannabinol (THC) disrupts HER2-CB₂R complexes by selectively binding to CB₂R, which leads to (i) the inactivation of HER2 through disruption of HER2-HER2 homodimers, and (ii) the subsequent degradation of HER2 by the proteasome via the E3 ligase c-CBL. This in turn triggers antitumor responses in vitro and in vivo. Selective targeting of CB₂R transmembrane region 5 mimicked THC effects.

Together, these findings define HER2-CB₂R heteromers as new potential targets for antitumor therapies and biomarkers with prognostic value in HER2-positive breast cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/30733293

https://www.pnas.org/content/early/2019/02/06/1815034116

“Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different cancer models. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer” http://www.ncbi.nlm.nih.gov/pubmed/25855725

“Extensive preclinical research has demonstrated that cannabinoids, the active ingredients of Cannabis sativa, trigger antitumor responses in different models of cancer. Together, our results suggest that standardized cannabis drug preparations, rather than pure cannabinoids, could be considered as part of the therapeutic armamentarium to manage breast cancer.” https://www.ncbi.nlm.nih.gov/pubmed/29940172

http://www.thctotalhealthcare.com/category/breast-cancer/

Cannabinoids Reduce Inflammation but Inhibit Lymphocyte Recovery in Murine Models of Bone Marrow Transplantation.

Posted on February 6, 2019 by David

“Cannabinoids, the biologically active constituents of Cannabis, have potent neuronal and immunological effects. However, the basic and medical research dedicated to medical cannabis and cannabinoids is limited. The influence of these treatments on hematologic reconstitution and on the development of graft versus host disease (GVHD) after bone marrow transplantation (BMT) is largely unknown.

In this research, we compared the influence of D9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on lymphocyte activation in vitro and in murine BMT models.

Our in vitro results demonstrate that these treatments decrease activated lymphocyte proliferation and affect cytokine secretion. We also discovered that CBD and THC utilize different receptors to mediate these effects. In vivo, in a syngeneic transplantation model, we demonstrate that all treatments inhibit lymphocyte reconstitution and show the inhibitory role of the cannabinoid receptor type 2 (CB2) on lymphocyte recovery.

Although pure cannabinoids exhibited a superior effect in vitro, in an allogeneic (C57BL/6 to BALB/c) BMT mouse model, THC-high and CBD-high cannabis extracts treatment reduced the severity of GVHD and improved survival significantly better than the pure cannabinoids.

Our results highlights the complexity of using cannabinoids-based treatments and the need for additional comparative scientific results.”

https://www.ncbi.nlm.nih.gov/pubmed/30720730

https://www.mdpi.com/1422-0067/20/3/668

An Update of Current Cannabis-Based Pharmaceuticals in Pain Medicine.

Posted on February 6, 2019 by David

“Cannabis users have long reported therapeutic properties of the plant for a variety of conditions, some of which include nausea, emesis, seizures, cancer, neurogenic diseases and pain control. Research has elucidated many cannabinoid pharmacodynamic and pharmacokinetic properties, expanding the potential use of cannabinoids as a medical therapy.

Due to the inconsistent delivery and control of the active components involved with smoking, pharmaceutical companies are investigating and prioritizing routes other than smoke inhalation for therapeutic use of cannabinoids. In this relatively new field of pharmaceutical development, ongoing drug development promises great benefit from targeted endocannabinoid receptor agonism.

Available in Canada and Europe, nabiximols, a specific extract from the Cannabis plant, has demonstrated great benefit in the treatment of pain related to spasticity in multiple sclerosis, cancer and otherwise chronic pain conditions.

The cannabidiol oral solution Epidiolex®, which is available in the USA, is indicated for management of refractory epilepsy but may offer therapeutic relief to chronic pain conditions as well.

Current investigative drugs, such as those developed by Cara Therapeutics and Zynerba Pharmaceuticals, are synthetic cannabinoids which show promise to specifically target neuropsychiatric conditions and chronic pain symptoms such as neuropathy and allodynia.

The objective of this review is to provide clinicians with an update of currently available and promising developmental cannabis pharmaceutical derivatives which may stand to greatly benefit patients with otherwise difficult-to-treat chronic conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/30721403

https://link.springer.com/article/10.1007%2Fs40122-019-0114-4

Cannabinoids: the lows and the highs of chemotherapy-induced nausea and vomiting.

Posted on February 6, 2019 by David

“Despite remaining one of the most widely abused drugs worldwide, Cannabis sativa exhibits remarkable medicinal properties. The phytocannabinoids, cannabidiol and Δ-9-tetrahydrocannabinol, reduce nausea and vomiting, particularly during chemotherapy. This is attributed to their ability to reduce the release of serotonin from enterochromaffin cells in the small intestine, which would otherwise orchestrate the vomiting reflex. Although there are many preclinical and clinical studies on the effects of Δ-9-tetrahydrocannabinol during nausea and vomiting, little is known about the role that cannabidiol plays in this scenario. Since cannabidiol does not induce psychotropic effects, in contrast to other cannabinoids, its use as an anti-emetic is of great interest. This review aims to summarize the available literature on cannabinoid use, with a specific focus on the nonpsychotropic drug cannabidiol, as well as the roles that cannabinoids play in preventing several other adverse side effects of chemotherapy including organ toxicity, pain and loss of appetite.”

https://www.ncbi.nlm.nih.gov/pubmed/30720344

https://www.futuremedicine.com/doi/10.2217/fon-2018-0530

New Prospect for Cancer Cachexia: Medical Cannabinoid.

Posted on February 6, 2019 by David

Image result for journal of cancer

“Cachexia is a common term for the wasting symptoms which may appear in almost every chronic illness, such as AIDS, tuberculosis, and cancer. Cancer cachexia (CCA) is a result of the interaction between the host and the tumor, mainly manifested in short-term wasting, malnutrition, and so on. Due to the chronic food shortages, absorption dysfunction and metabolic disorders, all of these eventually lead to hypoimmunity, organ failure, and higher susceptibility to pathogenic microorganisms. And then increased morbidity and mortality rates as well as reduced tolerance to anti-cancer treatments will be resulted in patients with CCA. Up to now, no standard guidelines have been established for cachexia treatment. Moreover, progestagens, the only drugs approved by FDA for cancer-related cachexia, can only increase adipose tissue and have not been confirmed to augment lean body mass. Cannabinoid, such as Δ-9-tetrahydrocannabinol (THC) and cannabidiol, is one of a class of diverse chemical compounds. Previous studies have showed that cannabinoid had considerable potential to improve the appetite, body weight, body fat level, caloric intake, mood, quality of life in kinds of diseases. This review will elaborate the anti-CCA role of cannabinoid and explore that whether cannabinoid is effective for CCA and provide a basis for guiding clinical drug use.”

https://www.ncbi.nlm.nih.gov/pubmed/30719170

http://www.jcancer.org/v10p0716.htm

Marijuana smoking and markers of testicular function among men from a fertility centre

Posted on February 6, 2019 by David

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“Men who had ever smoked marijuana had significantly higher sperm concentration than men who had never smoked marijuana after adjusting for potential confounders.

These findings are not consistent with a deleterious effect of marijuana on testicular function.”

https://www.ncbi.nlm.nih.gov/pubmed/30726923

https://academic.oup.com/humrep/advance-article-abstract/doi/10.1093/humrep/dez002/5307080?redirectedFrom=fulltext