Synthetic cannabinoids nano-micelles for the management of triple negative breast cancer.

Posted on October 28, 2018 by David

Journal of Controlled Release

“Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with poor prognosis and inadequate therapeutic outcome. This contribution reports the use of a cannabinoid derivative, WIN55,212-2 (WIN) on the growth of TNBC in a 4T1 syngeneic mouse model.

To reduce the well-known psychoactive side effects of cannabinoids, we prepared a nanomicellar formulation of WIN (SMA-WIN). In vivo biodistribution, in silico ADME predictions, anticancer activity, and psychoactive effect of WIN and SMA-WIN studies suggest that SMA-WIN formulation can reduce to greater extent tumor growth with milder psychoactive side effects when compared to free drug.

Finally, the effects of WIN and SMA-WIN in combination with doxorubicin (Doxo), an established chemotherapeutic agent for the treatment of TNBC, were investigated in vitro and in vivo. SMA-WIN in combination with Doxo showed therapeutic efficacy and was able to reduce the tumor volume of TNBC murine model drastically. Moreover, SMA-WIN, while favoring drug tumor accumulation, minimized the adverse psychoactive effects that have impeded the use of this agent in the clinic.

To our knowledge, this is the first report for the assessment of cannabinoid nanoparticles in vivo for the treatment of TNBC and its enhanced anticancer effect at low doses with Doxo. These findings suggest a new therapeutic strategy in the management of TNBC.”

https://www.ncbi.nlm.nih.gov/pubmed/30367922

https://www.sciencedirect.com/science/article/pii/S0168365918306114?via%3Dihub

What do Cochrane systematic reviews say about the use of cannabinoids in clinical practice?

Posted on October 27, 2018 by David

SciELO - Scientific Electronic Library Online

“The therapeutic effects of cannabinoid compounds have been the center of many investigations.

This study provides a synthesis on all Cochrane systematic reviews (SRs) that assessed the use of cannabinoids as a therapeutic approach.

CONCLUSIONS:

This review identified eight Cochrane systematic reviews that provided evidence of unknown to moderate quality regarding the use of cannabinoids as a therapeutic intervention. Further studies are still imperative for solid conclusions to be reached regarding practical recommendations.”

https://www.ncbi.nlm.nih.gov/pubmed/30365598

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-31802018005016102&lng=en&tlng=en

The Role of Cannabis in the Management of Inflammatory Bowel Disease: A Review of Clinical, Scientific, and Regulatory Information: Commissioned by the Crohn’s and Colitis Foundation.

Posted on October 26, 2018 by David

“There is significant interest among patients and providers in using cannabis (marijuana) and its derivatives to treat a number of chronic illnesses, including inflammatory bowel disease. Despite the Schedule I classification of cannabis by the federal government, state governments have sought ways to make cannabis available for specific medical conditions, and some states have legalized cannabis outright. This white paper summarizes the preclinical data, clinical data, safety data, and the regulatory landscape as they apply to medical cannabis use in inflammatory bowel disease. Animal models of cannabinoid chemistry and physiology give evidence of anti-inflammatory, antidiarrheal, and nociceptive-limiting properties. Human studies have found benefit in controlling symptoms and improving quality of life, but no studies have established true disease modification given the absent improvement in biomarker profiles or endoscopic healing. Finally, this review describes the legal, regulatory, and practical hurdles to studying the risks and benefits of medical cannabis in the United States.”

https://www.ncbi.nlm.nih.gov/pubmed/30358848

https://academic.oup.com/ibdjournal/advance-article-abstract/doi/10.1093/ibd/izy319/5144402?redirectedFrom=fulltext

Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats.

Posted on October 25, 2018 by David

Click to expand “The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆ ⁹-tetrahydrocannabinol (THC) to male and female Long-Evans (LER) and Wistar (WR) rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP). A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfosexpression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to a sub-threshold dose of d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.”

https://www.ncbi.nlm.nih.gov/pubmed/29770212.2

https://f1000research.com/articles/7-342/v2

Up-regulation of heme oxygenase-1 expression and inhibition of disease-associated features by cannabidiol in vascular smooth muscle cells.

Posted on October 25, 2018 by David

Image result for oncotarget

“Aberrant proliferation and migration of vascular smooth muscle cells (VSMC) have been closely linked to the development and progression of cardiovascular and cancer diseases.

The cytoprotective enzyme heme oxygenase-1 (HO-1) has been shown to mediate anti-proliferative and anti-migratory effects in VSMC. This study investigates the effect of cannabidiol (CBD), a non-psychoactive cannabinoid, on HO-1 expression and disease-associated functions of human umbilical artery smooth muscle cells (HUASMC).

HO-1 protein and mRNA were significantly increased by CBD in a time- and concentration-dependent manner. Although the expression of several cannabinoid-activated receptors (CB₁, CB₂, G protein-coupled receptor 55, transient receptor potential vanilloid 1) was verified in HUASMC, CBD was shown to induce HO-1 via none of these targets. Instead, the CBD-mediated increase in HO-1 protein was reversed by the glutathione precursor N-acetylcysteine, indicating the participation of reactive oxygen species (ROS) signaling; this was confirmed by flow cytometry-based ROS detection.

CBD-induced HO-1 expression was accompanied by inhibition of growth factor-mediated proliferation and migration of HUASMC. However, neither inhibition of HO-1 activity nor knockdown of HO-1 protein attenuated CBD-mediated anti-proliferative and anti-migratory effects. Indeed, inhibition or depletion of HO-1 resulted in induction of apoptosis and intensified CBD-mediated effects on proliferation and migration.

Collectively, this work provides the first indication of CBD-mediated enhancement of HO-1 in VSMC and potential protective effects against aberrant VSMC proliferation and migration. On the other hand, our data argue against a role of HO-1 in CBD-mediated inhibition of proliferation and migration while substantiating its anti-apoptotic role in oxidative stress-mediated cell fate.”

https://www.ncbi.nlm.nih.gov/pubmed/30349652

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=26191&path[]=81658

Combined THC and CBD to treat pain in epidermolysis bullosa: a report of three cases.

Posted on October 23, 2018 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 are unable to provide adequate analgesia in a significant proportion of patients. Cannabinoid-based medicines (CBMs) have been increasingly studied for pain conditions of various etiologies and pose as a novel dimension for pain-care in EB. We present three cases of EB who were prescribed pharmaceutical-grade sublingually administered CBMs comprising tetrahydrocannabinol (THC) and cannabidiol (CBD). 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/abs/10.1111/bjd.17341

Light-activatable cannabinoid prodrug for combined and target-specific photodynamic and cannabinoid therapy.

Posted on October 23, 2018 by David

“Cannabinoids are emerging as promising antitumor drugs. However, complete tumor eradication solely by cannabinoid therapy remains challenging. In this study, we developed a far-red light activatable cannabinoid prodrug, which allows for tumor-specific and combinatory cannabinoid and photodynamic therapy. This prodrug consists of a phthalocyanine photosensitizer (PS), reactive oxygen species (ROS)-sensitive linker, and cannabinoid. It targets the type-2 cannabinoid receptor (CB2R) overexpressed in various types of cancers. Upon the 690-nm light irradiation, the PS produces cytotoxic ROS, which simultaneously cleaves the ROS-sensitive linker and subsequently releases the cannabinoid drug. We found that this unique multifunctional prodrug design offered dramatically improved therapeutic efficacy, and therefore provided a new strategy for targeted, controlled, and effective antitumor cannabinoid therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/30334393

https://www.spiedigitallibrary.org/journals/Journal-of-Biomedical-Optics/volume-23/issue-10/108001/Light-activatable-cannabinoid-prodrug-for-combined-and-target-specific-photodynamic/10.1117/1.JBO.23.10.108001.short?SSO=1

Translational potential of allosteric modulators targeting the cannabinoid CB1 receptor.

Posted on October 23, 2018 by David

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“The cannabinoid type-1 (CB₁) receptor, a G-protein-coupled receptor, is an attractive target for drug discovery due to its involvement in many physiological processes. Historically, drug discovery efforts targeting the CB₁ receptor have focused on the development of orthosteric ligands that interact with the active site to which endogenous cannabinoids bind. Research performed over the last several decades has revealed substantial difficulties in translating CB₁ orthosteric ligands into druggable candidates. The difficulty is mainly due to the adverse effects associated with orthosteric CB₁ ligands. Recent discoveries of allosteric CB₁ modulators provide tremendous opportunities to develop CB₁ ligands with novel mechanisms of action; these ligands may potentially improve the pharmacological effects and enhance drug safety in treating the disorders by regulating the functions of the CB₁ receptor. In this paper, we review and summarize the complex pharmacological profiles of each class of CB₁ allosteric modulators, the development of new classes of CB₁ allosteric modulators and the results from in vivo assessments of their therapeutic value.”

https://www.ncbi.nlm.nih.gov/pubmed/30333554

https://www.nature.com/articles/s41401-018-0164-x

Cannabis and epilepsy.

Posted on October 22, 2018 by David

“The one-third of people who do not gain seizure control through current treatment options need a revolution in epilepsy therapeutics.

The general population appears to be showing a fundamental and rapid shift in its opinion regarding cannabis and cannabis-related drugs. It is quite possible that cannabidiol, licensed in the USA for treating rare genetic epilepsies, may open the door for the widespread legalisation of recreational cannabis.

It is important that neurologists understand the difference between artisanal cannabidiol products available legally on the high street and the cannabidiol medications that have strong trial evidence.

In the UK in 2018 there are multiple high-profile reports of the response of children taking cannabis-derived medication, meaning that neurologists are commonly asked questions about these treatments in clinic. We address what an adult neurologist needs to know now, ahead of the likely licensing of Epidiolex in the UK in 2019.”

https://www.ncbi.nlm.nih.gov/pubmed/30337476

https://pn.bmj.com/content/early/2018/10/18/practneurol-2018-002058

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test.

Posted on October 18, 2018 by David

SciELO - Scientific Electronic Library Online

“Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans.

The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method.

Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.”

https://www.europeanneuropsychopharmacology.com/article/S0924-977X(16)31702-3/abstract

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462018005007102&lng=en&tlng=en

www.thctotalhealthcare.com

Tag Archives: cannabinoid

Synthetic cannabinoids nano-micelles for the management of triple negative breast cancer.

What do Cochrane systematic reviews say about the use of cannabinoids in clinical practice?

CONCLUSIONS:

The Role of Cannabis in the Management of Inflammatory Bowel Disease: A Review of Clinical, Scientific, and Regulatory Information: Commissioned by the Crohn’s and Colitis Foundation.

Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats.

Up-regulation of heme oxygenase-1 expression and inhibition of disease-associated features by cannabidiol in vascular smooth muscle cells.

Combined THC and CBD to treat pain in epidermolysis bullosa: a report of three cases.

Light-activatable cannabinoid prodrug for combined and target-specific photodynamic and cannabinoid therapy.

Translational potential of allosteric modulators targeting the cannabinoid CB1 receptor.

Cannabis and epilepsy.

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test.

Our findings confirm the anxiolytic-like properties of CBD and are consonant with results of animal studies describing bell-shaped dose-response curves. Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.”