Cannabinoid and Cancer / FEBRERO 2018

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Cannabinoids and Cancer


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.

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.

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.

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
(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.

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.