El uso Medicinal del Cannabis

La planta de cannabis se utilizó por miles de años en distintas culturas alrededor del mundo para distintos fines, entre ellos, la medicina. La planta posee distintos principios activos, denominados Cannabinoides. Estos Cannabinoides, en un número de más de 60, tienen distintas funciones, algunas descubiertas, y en su mayoría sin tener en claro aún cual es propósito. Estos Cannabinoides, por estar dentro de la planta se denominan Fitocannabinoides.

El cuerpo humano posee, en la superficie de muchos tipos de células de nuestro organismo, sitios específicos donde se acoplan estos  principios activos de la planta, los fitocannabinoides. Los más comunes, y de cuales se tiene mayor información son el THC, el CBD, CBG, CBN y algunos más. Los receptores de estos cannabinoides son denominados CB1 y CB2, encontrándose distribuidos por todo el cuerpo.El cuerpo humano también produce moléculas similares a las de la planta de cannabis, llamados endocannabinoides (endo=adentro). 

Los cannabinoides tienen muchas propiedades medicinales, y esto permite que algunas dolencias y patologías puedan ser tratadas con cannabis, tales como cáncer, epilepsia, glaucoma, esclerosis múltiple, fibromialgia, dolor crónico, etc.

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cannabinoids and cancer JUNIO 2018

Cannabinoids and cancer

 

1. Cannabis and Cannabinoids (PDQ®): Health Professional Version.

This PDQ cancer information summary for health professionals provides
comprehensive, peer-reviewed, evidence-based information about the use of
Cannabis and cannabinoids in the treatment of people with cancer. It is intended 
as a resource to inform and assist clinicians who care for cancer patients. It
does not provide formal guidelines or recommendations for making health care
decisions. This summary is reviewed regularly and updated as necessary by the PDQ
Integrative, Alternative, and Complementary Therapies Editorial Board, which is
editorially independent of the National Cancer Institute (NCI). The summary
reflects an independent review of the literature and does not represent a policy 
statement of NCI or the National Institutes of Health (NIH).



2. Biochem Pharmacol.

Appraising the "entourage effect": antitumor action of a pure cannabinoid versus 
a botanical drug preparation in preclinical models of breast cancer.

Blasco-Benito S(1), Seijo-Vila M(2), Caro-Villalobos M(2), Tundidor I(2),
Andradas C(3), García-Taboada E(4), Wade J(5), Smith S(5), Guzmán M(6),
Pérez-Gómez E(2), Gordon M(5), Sánchez C(7).

Author information: 
(1)Complutense University, Madrid, Spain; Instituto de Investigación Hospital 12 
de Octubre, Madrid, Spain. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..
(2)Complutense University, Madrid, Spain; Instituto de Investigación Hospital 12 
de Octubre, Madrid, Spain.
(3)Complutense University, Madrid, Spain; Telethon Kids Institute, Perth,
Australia.
(4)Complutense University, Madrid, Spain.
(5)Aunt Zelda's, California, US.
(6)Complutense University, Madrid, Spain; Instituto Ramón y Cajal de
Investigación Sanitaria, CIBERNED and IUIN, Madrid, Spain.
(7)Complutense University, Madrid, Spain; Instituto de Investigación Hospital 12 
de Octubre, Madrid, Spain. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..

Breast cancer is the second leading cause of death among women. Although early
diagnosis and development of new treatments have improved their prognosis, many
patients present innate or acquired resistance to current therapies. New
therapeutic approaches are therefore warranted for the management of this
disease. Extensive preclinical research has demonstrated that cannabinoids, the
active ingredients of Cannabis sativa, trigger antitumor responses in different
models of cancer. Most of these studies have been conducted with pure compounds, 
mainly Δ9-tetrahydrocannabinol (THC). The cannabis plant, however, produces
hundreds of other compounds with their own therapeutic potential and the
capability to induce synergic responses when combined, the so-called "entourage
effect". Here, we compared the antitumor efficacy of pure THC with that of a
botanical drug preparation (BDP). The BDP was more potent than pure THC in
producing antitumor responses in cell culture and animal models of ER+/PR+, HER2+
and triple-negative breast cancer. This increased potency was not due to the
presence of the 5 most abundant terpenes in the preparation. While pure THC acted
by activating cannabinoid CB2 receptors and generating reactive oxygen species,
the BDP modulated different targets and mechanisms of action. The combination of 
cannabinoids with estrogen receptor- or HER2-targeted therapies (tamoxifen and
lapatinib, respectively) or with cisplatin, produced additive antiproliferative
responses in cell cultures. Combinations of these treatments in vivo showed no
interactions, either positive or negative. 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.

Copyright © 2018. Published by Elsevier Inc.



3. Eur J Med Chem.
Structure-activity relationships of imidazothiazinones and analogs as antagonists of the cannabinoid-activated orphan G protein-coupled receptor GPR18. Schoeder CT(1), Kaleta M(2), Mahardhika AB(1), Olejarz-Maciej A(2), Łażewska D(2), Kieć-Kononowicz K(3), Müller CE(4). Author information: (1)PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, An der Immenburg 4, University of Bonn, D-53121 Bonn, Germany; Research Training Group 1873, University of Bonn, 53127 Bonn, Germany. (2)Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, 9 Medyczna Str., 30-688 Kraków, Poland. (3)Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, 9 Medyczna Str., 30-688 Kraków, Poland. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.. (4)PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, An der Immenburg 4, University of Bonn, D-53121 Bonn, Germany; Research Training Group 1873, University of Bonn, 53127 Bonn, Germany. Electronic address: Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.. GPR18 is a cannabinoid-activated orphan G protein-coupled receptor (GPCR) that is selectively expressed on immune cells. Despite its significant potential as a drug target for inflammatory diseases and cancer immunotherapy, only very few GPR18 ligands have been described to date. In the present study we investigated the structure-activity relationships (SARs) of (Z)-2-(3-(4-chlorobenzyloxy)benzylidene)-6,7-dihydro-2H-imidazo[2,1-b][1,3]thiazi n-3(5H)-one (PSB-CB5, 5), the most potent GPR18 antagonist described to date. Analogs were synthesized that exhibit broad modifications of the heterocyclic core and/or variation of substituents at the benzylidene moiety. The compounds were investigated in β-arrestin recruitment assays as inhibitors of human GPR18 activation by tetrahydrocannabinol (THC). Selectivity was assessed versus the cannabinoid receptors (CB1 and CB2) and versus GPR55, another orphan GPCR that interacts with cannabinoids. Phenyloxyalkyloxy-substituted benzylidenethiazinones with long alkyl chains (optimal length: hexamethylene) efficiently blocked GPR18 with similarly high potency as lead structure 5. (Z)-2-(3-(6-(4-Chlorophenoxy)hexyloxy)benzylidene)-6,7-dihydro-2H-imidazo[2,1-b][ 1,3]thiazin-3(5H)-one (PSB-CB-27, 23) exhibited the best profile: it displayed an IC50 value of 650 nM at GPR18 and showed improved selectivity versus CB receptors as compared to lead structure 5. Importantly, in contrast to 5, which showed only partial inhibition (60%), 23 led to a complete blockade of THC-induced GPR18 activation and is thus a superior tool for target validation. In addition, several compounds, e.g. 18 and 22, were identified as dual GPR18/GPR55 antagonists with similar potency at both targets, and selectivity versus CB receptors. Copyright © 2018 Elsevier Masson SAS. All rights reserved. 4. Iran Biomed J. Assessment of Cannabinoids Agonist and Antagonist in Invasion Potential of K562 Cancer Cells Gholizadeh F(1), Ghahremani MH(1), Aliebrahimi S(2), Shadboorestan A(1), Ostad SN(1). Author information: (1)Department of Toxicology and Pharmacology, Faculty of Pharmacy and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran. (2)Department of Cellular and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. Background: The prominent hallmark of malignancies is the metastatic spread of cancer cells. Recent studies have reported that the nature of invasive cells could be changed after this phenomenon, causing chemotherapy resistance. It has been demonstrated that the up-regulated expression of matrix metalloproteinase (MMP) 2/MMP-9, as a metastasis biomarker, can fortify the metastatic potential of leukemia. Furthermore, investigations have confirmed the inhibitory effect of cannabinoid and endocannabinoid on the proliferation of cancer cells in vitro and in vivo. Methods: In the present study, the inhibitory effect of WIN 55212-2 (a CB1/CB2 receptor agonist) and AM251 (a selective CB1 receptor antagonist) on K562 cells, as a chronic myelogenous leukemia (CML) model, was evaluated using MTT and invasion assay. Expressions of MMP-2 and MMP-9 were then assessed by Western blot analysis. Results: The data obtained from MTT assay showed that WIN 55212-2 could attenuate cell proliferation; however, AM251 was less effective in this regard. Our results showed that WIN 55212-2 considerably reduced cancer cell invasiveness, while AM251 exhibited a converse effect. Moreover, CB1 activation resulted in decreased expression of MMP-2 and MMP-9. Conclusion: Our findings clarifies that CB1 receptors are responsible for anti-invasive effects in the K562 cell line. 5. Front Mol Neurosci. Cannabinoids in Glioblastoma Therapy: New Applications for Old Drugs. Dumitru CA(1), Sandalcioglu IE(1), Karsak M(2). Author information: (1)Department of Neurosurgery, KRH Klinikum Nordstadt, Nordstadt Hospital Hannover, Hannover, Germany. (2)Neuronal and Cellular Signal Transduction, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany. Glioblastoma (GBM) is the most malignant brain tumor and one of the deadliest types of solid cancer overall. Despite aggressive therapeutic approaches consisting of maximum safe surgical resection and radio-chemotherapy, more than 95% of GBM patients die within 5 years after diagnosis. Thus, there is still an urgent need to develop novel therapeutic strategies against this disease. Accumulating evidence indicates that cannabinoids have potent anti-tumor functions and might be used successfully in the treatment of GBM. This review article summarizes the latest findings on the molecular effects of cannabinoids on GBM, both in vitro and in (pre-) clinical studies in animal models and patients. The therapeutic effect of cannabinoids is based on reduction of tumor growth via inhibition of tumor proliferation and angiogenesis but also via induction of tumor cell death. Additionally, cannabinoids were shown to inhibit the invasiveness and the stem cell-like properties of GBM tumors. Recent phase II clinical trials indicated positive results regarding the survival of GBM patients upon cannabinoid treatment. Taken together these findings underline the importance of elucidating the full pharmacological effectiveness and the molecular mechanisms of the cannabinoid system in GBM pathophysiology.