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 MAYO 2018

Cannabinoids and cancer

 

Pharmaceuticals (Basel).

Endocannabinoids in Body Weight Control.

Horn H(1), Böhme B(2), Dietrich L(3), Koch M(4).

Author information: 
(1)Institute of Anatomy, Medical Faculty, University of Leipzig, 04103 Leipzig,
Germany. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo." target="_blank">Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.leipzig.de.
(2)Institute of Anatomy, Medical Faculty, University of Leipzig, 04103 Leipzig,
Germany. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo." target="_blank">Beatrice.Schuetzelt@medizin.uni-leipzig.de.
(3)Institute of Anatomy, Medical Faculty, University of Leipzig, 04103 Leipzig,
Germany. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..
(4)Institute of Anatomy, Medical Faculty, University of Leipzig, 04103 Leipzig,
Germany. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo." target="_blank">Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo.leipzig.de.

Maintenance of body weight is fundamental to maintain one's health and to promote
longevity. Nevertheless, it appears that the global obesity epidemic is still
constantly increasing. Endocannabinoids (eCBs) are lipid messengers that are
involved in overall body weight control by interfering with manifold central and 
peripheral regulatory circuits that orchestrate energy homeostasis. Initially,
blocking of eCB signaling by first generation cannabinoid type 1 receptor (CB1)
inverse agonists such as rimonabant revealed body weight-reducing effects in
laboratory animals and men. Unfortunately, rimonabant also induced severe
psychiatric side effects. At this point, it became clear that future cannabinoid 
research has to decipher more precisely the underlying central and peripheral
mechanisms behind eCB-driven control of feeding behavior and whole body energy
metabolism. Here, we will summarize the most recent advances in understanding how
central eCBs interfere with circuits in the brain that control food intake and
energy expenditure. Next, we will focus on how peripheral eCBs affect food
digestion, nutrient transformation and energy expenditure by interfering with
signaling cascades in the gastrointestinal tract, liver, pancreas, fat depots and
endocrine glands. To finally outline the safe future potential of cannabinoids as
medicines, our overall goal is to address the molecular, cellular and
pharmacological logic behind central and peripheral eCB-mediated body weight
control, and to figure out how these precise mechanistic insights are currently
transferred into the development of next generation cannabinoid medicines
displaying clearly improved safety profiles, such as significantly reduced side
effects.

DOI: 10.3390/ph11020055 
PMID: 29849009 


2. Pain.

Cannabis and cannabinoids for the treatment of people with chronic non-cancer
pain conditions: a systematic review and meta-analysis of controlled and
observational studies.

Stockings E(1), Campbell G(1), Hall WD(2)(3), Nielsen S(1), Zagic D(1), Rahman
R(1), Murnion B(4)(5), Farrell M(1), Weier M(1), Degenhardt L(1).

Author information: 
(1)National Drug and Alcohol Research Centre UNSW Sydney Sydney NSW Australia.
(2)Centre for Youth Substance Abuse ResearchUniversity of Queensland Brisbane
Queensland Australia.
(3)National Addiction Centre Kings College London London England.
(4)Discipline of Addiction Medicine, Faculty of Medicine University of Sydney
Sydney NSW Australia.
(5)Drug Health Services, Concord Repatriation General Hospital, Sydney Local
Health District NSW Health Sydney NSW Australia.

This review examines evidence cannabinoids in chronic non-cancer pain (CNCP), and
addresses gaps in the literature by: considering differences in outcomes based on
cannabinoid type and specific CNCP condition; including all study designs; and
following IMMPACT guidelines. MEDLINE, Embase, PsycINFO, CENTRAL and
clinicaltrials.gov were searched in July 2017. Analyses were conducted using
Revman 5.3 and Stata 15.0. A total of 91 publications containing 104 studies were
eligible (n = 9958 participants), including 47 RCTs and 57 observational studies.
Forty-eight studies examined neuropathic pain, seven studies examined
fibromyalgia, one rheumatoid arthritis, and 48 other CNCP (13 MS-related pain, 6 
visceral pain, and 29 samples with mixed or undefined CNCP). Across RCTs, PERs
for 30% reduction in pain were 29.0% (cannabinoids) vs 25.9% (placebo),
significant effect for cannabinoids, number needed to treat to benefit (NNTB): 24
(95%CI 15-61); for 50% reduction in pain, PERs were 18.2% vs. 14.4%; no
significant difference. Pooled change in pain intensity (standardised mean
difference: -0.14, 95%CI -0.20, -0.08) was equivalent to 3mm on a 100mm visual
analogue scale greater than placebo. In RCTs, PERs for all-cause AEs were 81.2%
vs. 66.2%; number needed to treat to harm (NNTH): 6 (95%CI 5-8). There were no
significant impacts upon physical or emotional functioning, and low-quality
evidence of improved sleep and patient global impression of change. Evidence for 
effectiveness of cannabinoids in CNCP is limited. Effects suggest NNTB are high, 
and NNTH low, with limited impact on other domains. It appears unlikely that
cannabinoids are highly effective medicines for CNCP.


3. BMC Cancer.

Involvement of the CB2 cannabinoid receptor in cell growth inhibition and G0/G1
cell cycle arrest via the cannabinoid agonist WIN 55,212-2 in renal cell
carcinoma.

Khan MI(1)(2), Sobocińska AA(3)(4), Brodaczewska KK(3), Zielniok K(5), Gajewska
M(5), Kieda C(3), Czarnecka AM(3), Szczylik C(3)(6).

Author information: 
(1)Molecular Oncology Laboratory, Department of Oncology, Military Institute of
Medicine, ul. Szaserów 128, 04-141, Warsaw, Poland. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..
(2)Department of Otolaryngology - Head & Neck Surgery, Western University,
London, ON, N6A 3K7, Canada. Esta dirección de correo electrónico está siendo protegida contra los robots de spam. Necesita tener JavaScript habilitado para poder verlo..
(3)Molecular Oncology Laboratory, Department of Oncology, Military Institute of
Medicine, ul. Szaserów 128, 04-141, Warsaw, Poland.
(4)Faculty of Biology, Warsaw University, ul. Miecznikowa 1, 02-096, Warsaw,
Poland.
(5)Department of Physiological Sciences, Warsaw University of Life Sciences-SGGW,
Nowoursynowska 159, 02-776, Warsaw, Poland.
(6)Warsaw Medical University, Żwirki i Wigury 61, 02-091, Warsaw, Poland.

BACKGROUND: The anti-tumor properties of cannabinoids have been investigated in
many in vitro and in vivo studies. Many of these anti-tumor effects are mediated 
via cannabinoid receptor types 1 and 2 (CB1 and CB2), comprising the
endocannabinoid system (ECS). In this study, we investigated the ECS based on CB 
1 and CB 2 receptor gene and protein expression in renal cell carcinoma (RCC)
cell lines. In view of their further use for potential treatments, we thus
investigated the roles of CB1 and CB2 receptors in the anti-proliferative action 
and signal transduction triggered by synthetic cannabinoid agonists [such as
JWH-133 and WIN 55,212-2 (WIN-55)] in RCC cell lines.
METHODS: Human RCC cell lines were used for this study. The CB 1 and CB 2 gene
expression levels were analyzed using real-time PCR. Flow cytometric,
immunocytochemical and western blot analyses were performed to confirm CB1 and
CB2 receptor protein expression. The anti-proliferative effects of synthetic
cannabinoids were investigated on cell viability assay. The CB1 and CB2 receptors
were blocked pharmacologically with the antagonists SR141716A and AM-630,
respectively, to investigate the effects of the agonists JWH-133 and WIN-55. Cell
cycle, apoptosis and LDH-based cytotoxicity were analyzed on cannabinoid-treated 
RCC cells.
RESULTS: The CB1 and CB2 genes expression was shown by real-time PCR and flow
cytometric and western blot analysis indicating a higher level of CB2 receptor as
compared to CB1 in RCC cells. Immunocytochemical staining also confirmed the
expression of the CB1 and CB2 proteins. We also found that the synthetic
cannabinoid agonist WIN-55 exerted anti-proliferative and cytotoxic effects by
inhibiting the growth of RCC cell lines, while the CB2 agonist JWH-133 did not.
Pharmacologically blocking the CB1 and CB2 receptors with their respective
antagonists SR141716A and AM-630, followed by the WIN-55 treatment of RCC cells
allowed uncovering the involvement of CB2, which led to an arrest in the G0/G1
phase of the cell cycle and apoptosis.
CONCLUSIONS: This study elucidated the involvement of CB2 in the in vitro
inhibition of RCC cells, and future applications of CB2 agonists in the
prevention and management of RCC are discussed.



4. Pain.

A peripherally restricted cannabinoid 1 receptor agonist as a novel analgesic in 
cancer-induced bone pain.

Zhang H(1), Lund DM(1), Ciccone HA(1), Staatz WD(1), Ibrahim MM(1)(2),
Largent-Milnes TM(1), Seltzman HH(3), Spigelman I(4), Vanderah TW(1).

Author information: 
(1)Department of Pharmacology, College of Medicine, University of Arizona,
Tucson, AZ, USA.
(2)Department of Anesthesiology, College of Medicine, University of Arizona,
Tucson, AZ, USA.
(3)Center for Drug Discovery, Research Triangle Institute, Research Triangle
Park, NC, USA.
(4)Division of Oral Biology & Medicine, School of Dentistry, University of
California, Los Angeles, CA, USA.

Many malignant cancers, including breast cancer, have a propensity to invade
bones, leading to excruciating bone pain. Opioids are the primary analgesics used
to alleviate this cancer-induced bone pain (CIBP) but are associated with
numerous severe side effects, including enhanced bone degradation, which
significantly impairs patients' quality of life. In contrast, agonists activating
only peripheral CB1 receptors (CB1Rs) have been shown to effectively alleviate
multiple chronic pain conditions with limited side effects, yet no studies have
evaluated their role(s) in CIBP. Here, we demonstrate for the first time that a
peripherally selective CB1R agonist can effectively suppress CIBP. Our studies
using a syngeneic murine model of CIBP show that both acute and sustained
administration of a peripherally restricted CB1R agonist,
4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3-yl]ethyl}morpholin
e (PrNMI), significantly alleviated spontaneous pain behaviors in the animals.
This analgesic effect by PrNMI can be reversed by a systemic administration but
not spinal injection of SR141716, a selective CB1R antagonist. Additionally, the 
cancer-induced bone loss in the animals was not exacerbated by a repeated
administration of PrNMI. Furthermore, catalepsy and hypothermia, the common side 
effects induced by cannabinoids, were measured at the supra-therapeutic doses of 
PrNMI tested. PrNMI induced mild sedation, yet no anxiety nor a decrease in limb 
movements were detected. Overall, our studies demonstrate that CIBP can be
effectively managed by using a peripherally restricted CB1R agonist, PrNMI,
without inducing dose-limiting central side effects. Thus, targeting peripheral
CB1Rs could be an alternative therapeutic strategy for the treatment of CIBP.



5. Front Oncol. 2018 Apr 24;8:114. doi: 10.3389/fonc.2018.00114. eCollection 2018.

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids.

Yasmin-Karim S(1)(2)(3), Moreau M(2)(3)(4), Mueller R(1)(2)(5), Sinha N(1)(2),
Dabney R(6), Herman A(6), Ngwa W(1)(2)(3)(4).

Author information: 
(1)Radiation Oncology, Brigham and Women's Hospital, Boston, MA, United States.
(2)Dana-Farber Cancer Institute, Boston, MA, United States.
(3)Harvard Medical School, Boston, MA, United States.
(4)University of Massachusetts Lowell, Lowell, MA, United States.
(5)University Medical Center Mannheim, Heidelberg University, Mannheim, Germany.
(6)Cannabis Science, Inc., Irvine, CA, United States.

Over the years, many in vitro and in vivo studies have shown the antineoplastic
effects of cannabinoids (CBDs), with reports advocating for investigations of
combination therapy approaches that could better leverage these effects in
clinical translation. This study explores the potential of combination approaches
employing CBDs with radiotherapy (RT) or smart biomaterials toward enhancing
therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro
studies, clonogenic assay results showed greater effective tumor cell killing,
when combining CBDs and RT. Meanwhile, in vivo study results revealed major
increase in survival when employing smart biomaterials for sustained delivery of 
CBDs to tumor cells. The significance of these findings, considerations for
further research, and viable roadmap to clinical translation are discussed.