Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

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“Many in vitro and in vivo studies have reported on the antitumorigenic effects of plant-derived cannabinoids (CBDs) and their synthetic analogs, including effects in inducing apoptosis and inhibiting tumor cell growth and metastasis.

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.

The advantage of combining CBDs with other therapies is that this may allow simultaneous targeting of tumor progression at different levels, while minimizing toxicities for these therapies relative to toxicities from higher doses when used as monotherapies.”

“Cannabis Science Announces the Second Frontiers Peer-Reviewed Publication of its Research Results on the Use of Cannabinoids in the Treatment of Cancers”  https://globenewswire.com/news-release/2018/05/01/1493854/0/en/Cannabis-Science-Announces-the-Second-Frontiers-Peer-Reviewed-Publication-of-its-Research-Results-on-the-Use-of-Cannabinoids-in-the-Treatment-of-Cancers.html

Cannabis in End-of-Life Care: Examining Attitudes and Practices of Palliative Care Providers.

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“Medical cannabis research has become quite extensive, with indications ranging from glaucoma to chemotherapy-induced nausea.

Despite increased interest in cannabis‘ potential medical uses, research barriers, cannabis legislation, stigma, and lack of dissemination of data contribute to low adoption for some medical populations.

Of interest, cannabis use appears low in palliative care settings, with few guidelines available to palliative care providers. The present study sought to examine the attitudes, beliefs, and practices of palliative care providers regarding the use of cannabis for terminally ill patients.

Results demonstrated that palliative care providers endorse cannabis for a wide range of palliative care symptoms, end-of-life care generally, and as an adjuvant medication.

Nevertheless, the gap between these beliefs and actual recommendation or prescription appears vast. Many who support the use of cannabis in palliative care do not recommend it as a treatment. These data suggest recommendations for healthcare providers and palliative care organizations.”

https://www.ncbi.nlm.nih.gov/pubmed/29714640

https://www.tandfonline.com/doi/abs/10.1080/02791072.2018.1462543?journalCode=ujpd20

Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal.

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“Cannabidiol (CBD), a non-intoxicating cannabinoid, may be a promising novel smoking cessation treatment due to its anxiolytic properties, minimal side-effects and research showing it may modify drug cue salience.

We used an experimental medicine approach with dependent cigarette smokers to investigate if (1) overnight nicotine abstinence, compared with satiety, will produce greater attentional bias (AB), higher pleasantness ratings of cigarette-related stimuli and increased craving and withdrawal; (2) CBD in comparison to placebo, would attenuate AB, pleasantness of cigarette-related stimuli, craving and withdrawal and not produce any side-effects.

FINDINGS:

When participants received placebo, tobacco abstinence increased AB (p=.001, d =.789) compared with satiety. However, CBD reversed this effect, such that automatic AB was directed away from cigarette cues (p=.007, d= .704) and no longer differed from satiety (p=.82). Compared with placebo, CBD also reduced explicit pleasantness of cigarette images (p=.011; d=.514). Craving (Bayes Factor: 7.07) and withdrawal (Bayes Factor: 6.48) were unaffected by CBD, but greater in abstinence compared with satiety. Systolic blood pressure decreased under CBD during abstinence.

CONCLUSIONS:

A single 800mg oral dose of cannabidiol (CBD) reduced the salience and pleasantness of cigarette cues, compared with placebo, after overnight cigarette abstinence in dependent smokers. CBD did not influence tobacco craving or withdrawal or any subjectively rated side-effects.”

https://www.ncbi.nlm.nih.gov/pubmed/29714034

https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14243

“Cannabidiol reduces attentional bias to cigarette cues in nicotine addicts, study finds” http://www.psypost.org/2018/06/cannabidiol-reduces-attentional-bias-cigarette-cues-nicotine-addicts-study-finds-51351

β-Caryophyllene (BCP) ameliorates MPP+ induced cytotoxicity.

Biomedicine & Pharmacotherapy

“Parkinson’s disease (PD) is one of the most common neurodegenerative diseases resulting from the continuous death of dopaminergic neurons in substantia nigra. MPP+ (1-methyl-4-phenylpyridinium) has been reported to be a major neurotoxin causing neurotoxic insults on dopaminergic neurons in humans.

β-Caryophyllene (BCP), an important cannabinoid derived from the essential oils of different species, has displayed pharmacological properties in different kinds of tissues and cells. However, neuroprotective effects of BCP in PD haven’t been reported before.

Our results indicate that treatment with MPP+ in SH-SY5Y cells led to a significant decrease in cell viability, which was restored by BCP. Additionally, BCP suppressed MPP+-induced release of lactic dehydrogenase (LDH) and the generation of reactive oxygen species (ROS). In contrast, BCP treatment restored the reduction in mitochondrial membrane potential (MMP) induced by MPP+. BCP treatment increased intracellular GSH and GPx activity.

Also, we found that the antioxidant effects of BCP against MPP+- induced neurotoxicity are dependent on cannabinoid receptor type 2 (CB2R). Moreover, our results indicated that BCP prevented MPP+-induced apoptosis of SH-SY5Y through inhibiting the up-regulation of cleaved Caspase-3, Bax, and restoring the expression of Bcl-2. Besides, BCP markedly suppressed HO-1 activation and c-Jun N-terminal Kinase (JNK) phosphorylation.

We conclude that BCP might act as a promising therapeutic agent against MPP+ toxicity in neuronal cells.”

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

The role of cannabinoid signaling in acute and chronic kidney diseases.

 Image result for Kidney Int. “The endogenous cannabinoids anandamide and 2-arachidonoylglycerol bind to the cannabinoid receptors of type 1 and 2. These receptors are also the binding sites for exogenous, both natural and synthetic, cannabinoids that are used for recreation purposes.

Until recently, cannabinoids and cannabinoid receptors have attracted little interest among nephrologists; however, a full endocannabinoid system (ECS) is present in the kidney and it has recently emerged as an important player in the pathogenesis of diabetic nephropathy, drug nephrotoxicity, and progressive chronic kidney disease.

This newly established role of the ECS in the kidney might have therapeutic relevance, as pharmacological modulation of the ECS has renoprotective effects in experimental animals, raising hope for future potential applications in humans.

In addition, over the last years, there has been a number of reported cases of acute kidney injury (AKI) associated with the use of synthetic cannabinoids that appear to have higher potency and rate of toxicity than natural Cannabis. This poorly recognized cause of renal injury should be considered in the differential diagnosis of AKI, particularly in young people.

In this review we provide an overview of preclinical evidence indicating a role of the ECS in renal disease and discuss potential future therapeutic applications.”

https://www.ncbi.nlm.nih.gov/pubmed/29706358