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Cannabinoids and Cancer
1. Rimonabant Kills Colon Cancer Stem Cells without Inducing Toxicity in Normal Colon Organoids. Fiore D(1), Ramesh P(2), Proto MC(1), Piscopo C(1), Franceschelli S(1), Anzelmo S(1), Medema JP(2), Bifulco M(3), Gazzerro P(1). Author information: (1)Department of Pharmacy, University of Salerno, Fisciano, Italy. (2)Laboratory of Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Academisch Medisch Centrum, University of Amsterdam, Amsterdam, Netherlands. (3)Department of Molecular Medicine and Medical Biotechnologies, University of Naples "Federico II", Naples, Italy. Colorectal cancer (CRC), like other tumor types, is a highly heterogeneous disease. Within the tumor bulk, intra-tumoral heterogeneity is also ascribable to Cancer Stem Cells (CSCs) subpopulation, characterized by high chemoresistance and the unique ability to retain tumorigenic potential, thus associated to tumor recurrence. High dynamic plasticity of CSCs, makes the development of winning therapeutic strategies even more complex to completely eradicate tumor fuel. Rimonabant, originally synthesized as antagonist/inverse agonist of Cannabinoid Receptor 1, is able to inactivate Wnt signaling, both in vitro and in vivo, in CRC models, through inhibition of p300-histone acetyltransferase activity. Since Wnt/β-Catenin pathway is the main player underlying CSCs dynamic, this finding candidates Rimonabant as potential modulator of cancer stemness, in CRC. In this work, using established 3D cultures of primary colon CSCs, taking into account the tumor heterogeneity through monitoring of Wnt activity, we demonstrated that Rimonabant was able to reduces both tumor differentiated cells and colon CSCs proliferation and to control their survival in long term cultures. Interestingly, in ex vivo model of wild type human organoids, retaining both architecture and heterogeneity of original tissue, Rimonabant showed no toxicity against cells from healthy colon epithelium, suggesting its potential selectivity toward cancer cells. Overall, results from this work provided new insights on anti-tumor efficacy of Rimonabant, strongly suggesting that it could be a novel lead compound for CRC treatment. 2. The role of cannabinoids in pain control: the good, the bad, and the ugly. Pergolizzi JV Jr(1), Lequang JA(2), Taylor R Jr(1), Raffa RB(1), Colucci D(3); NEMA Research Group. Author information: (1)NEMA Research, Inc., Naples, Italy. (2)NEMA Research, Inc., Naples, Italy - Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.. (3)Department of Bioengineering, Northeastern University, Boston, MA, USA. Cannabinoids appear to possess many potential medical uses, which may extend to pain control. A narrative review of the literature has found a variety of studies testing botanical and synthetic cannabinoids in different pain syndromes (acute pain, cancer pain, chronic noncancer pain, fibromyalgia pain, migraine, neuropathic pain, visceral pain, and others). Results from these studies are mixed; cannabinoids appear to be most effective in controlling neuropathic pain, allodynia, medication-rebound headache, and chronic noncancer pain, but do not seem to offer any advantage over nonopioid analgesics for acute pain. Cannabinoids seem to work no better than placebo for visceral pain and conferred only modest analgesic effect in cancer pain. Cannabinoids do many good things-they appear to be effective in treating certain types of pain without the issues of tolerance associated with opioids. Negatively, marijuana currently has a very murky legal status all over the world-laws regulating its use are inconsistent and in flux. Thus, both patients and prescribers may be unsure about whether or not it is an appropriate form of pain control. Cannabinoid-based analgesia has been linked to potential memory deficits and cognitive impairment. A great deal more remains to be elucidated about cannabinoids which may emerge to play an important role in the treatment of neuropathic and possibly other painful conditions. There remains a great deal more to learn about the role of cannabinoids in pain management. 3. The therapeutic effects of Cannabis and cannabinoids: An update from the National Academies of Sciences, Engineering and Medicine report. Abrams DI(1). Author information: (1)Hematology-Oncology, Zuckerberg San Francisco General Hospital, Professor of Clinical Medicine, University of California San Francisco Ward 84, 995 Potrero Avenue, San Francisco, CA 94110, USA. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.. The National Academies of Sciences, Engineering and Medicine conducted a rapid turn-around comprehensive review of recent medical literature on The Health Effects of Cannabis and Cannabinoids. The 16-member committee adopted the key features of a systematic review process, conducting an extensive search of relevant databases and considered 10,000 recent abstracts to determine their relevance. Primacy was given to recently published systematic reviews and primary research that studied one of the committee's 11 prioritized health endpoints- therapeutic effects; cancer incidence; cardiometabolic risk; respiratory disease; immune function; injury and death; prenatal, perinatal and postnatal outcomes; psychosocial outcomes; mental health; problem Cannabis use; and Cannabis use and abuse of other substances. The committee developed standard language to categorize the weight of evidence regarding whether Cannabis or cannabinoids use for therapeutic purposes are an effective or ineffective treatment for the prioritized health endpoints of interest. In the Therapeutics chapter reviewed here, the report concluded that there was conclusive or substantial evidence that Cannabis or cannabinoids are effective for the treatment of pain in adults; chemotherapy-induced nausea and vomiting and spasticity associated with multiple sclerosis. Moderate evidence was found for secondary sleep disturbances. The evidence supporting improvement in appetite, Tourette syndrome, anxiety, posttraumatic stress disorder, cancer, irritable bowel syndrome, epilepsy and a variety of neurodegenerative disorders was described as limited, insufficient or absent. A chapter of the NASEM report enumerated multiple barriers to conducting research on Cannabis in the US that may explain the paucity of positive therapeutic benefits in the published literature to date. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. 4. Cannabinoid Disposition After Human Intraperitoneal Use: An Insight Into Intraperitoneal Pharmacokinetic Properties in Metastatic Cancer. Lucas CJ(1), Galettis P(2), Song S(3), Solowij N(4), Reuter SE(5), Schneider J(6), Martin JH(2). Author information: (1)Discipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..au. (2)Discipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia. (3)Drug/Trace Metal Lab, Chemistry Department, Pathology North Hunter, New South Wales, Australia. (4)School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia. (5)Discipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia. (6)School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia. BACKGROUND: Medicinal cannabis is prescribed under the provision of a controlled drug in the Australian Poisons Standard. However, multiple laws must be navigated in order for patients to obtain access and imported products can be expensive. Dose-response information for both efficacy and toxicity pertaining to medicinal cannabis is lacking. The pharmacokinetic properties of cannabis administered by traditional routes has been described but to date, there is no literature on the pharmacokinetic properties of an intraperitoneal cannabinoid emulsion. CASE DESCRIPTION: A cachectic 56-year-old female with stage IV ovarian cancer and peritoneal metastases presented to hospital with fevers, abdominal distension and severe pain, vomiting, anorexia, dehydration and confusion. The patient reported receiving an intraperitoneal injection, purported to contain 12 g of mixed cannabinoid (administered by a deregistered medical practitioner) two days prior to presentation. Additionally, cannabis oil oral capsules were administered in the hours prior to hospital admission. RESULTS: THC concentrations were consistent with the clinical state but not with the known pharmacokinetic properties of cannabis nor of intraperitoneal absorption. THC concentrations at the time of presentation were predicted to be ~60 ng/mL. Evidence suggests that blood THC concentrations >5 ng/mL are associated with substantial cognitive and psychomotor impairment. The predicted time for concentrations to drop <5 ng/mL was 49 days after administration. DISCUSSION: The unusual pharmacokinetic properties of the case suggest that there is a large amount unknown about cannabis pharmacokinetic properties. The pharmacokinetic properties of a large amount of a lipid soluble compound given intraperitoneally gave insights into the absorption and distribution of cannabinoids, particularly in the setting of metastatic malignancy. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved. 5. Practical considerations in medical cannabis administration and dosing. MacCallum CA(1), Russo EB(2). Author information: (1)Faculty of Medicine, University of British Columbia, BC, Canada. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.. (2)International Cannabis and Cannabinoids Institute, Prague, Czech Republic. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.. Cannabis has been employed medicinally throughout history, but its recent legal prohibition, biochemical complexity and variability, quality control issues, previous dearth of appropriately powered randomised controlled trials, and lack of pertinent education have conspired to leave clinicians in the dark as to how to advise patients pursuing such treatment. With the advent of pharmaceutical cannabis-based medicines (Sativex/nabiximols and Epidiolex), and liberalisation of access in certain nations, this ignorance of cannabis pharmacology and therapeutics has become untenable. In this article, the authors endeavour to present concise data on cannabis pharmacology related to tetrahydrocannabinol (THC), cannabidiol (CBD) et al., methods of administration (smoking, vaporisation, oral), and dosing recommendations. Adverse events of cannabis medicine pertain primarily to THC, whose total daily dose-equivalent should generally be limited to 30mg/day or less, preferably in conjunction with CBD, to avoid psychoactive sequelae and development of tolerance. CBD, in contrast to THC, is less potent, and may require much higher doses for its adjunctive benefits on pain, inflammation, and attenuation of THC-associated anxiety and tachycardia. Dose initiation should commence at modest levels, and titration of any cannabis preparation should be undertaken slowly over a period of as much as two weeks. Suggestions are offered on cannabis-drug interactions, patient monitoring, and standards of care, while special cases for cannabis therapeutics are addressed: epilepsy, cancer palliation and primary treatment, chronic pain, use in the elderly, Parkinson disease, paediatrics, with concomitant opioids, and in relation to driving and hazardous activities. Copyright © 2018. Published by Elsevier B.V.
