Cannabinoids and cancer: potential for colorectal cancer therapy.

“Despite extensive research into the biology of CRC (colorectal cancer), and recent advances in surgical techniques and chemotherapy, CRC continues to be a major cause of death throughout the world. Therefore it is important to develop novel chemopreventive/chemotherapeutic agents for CRC.

Cannabinoids are a class of compounds that are currently used in the treatment of chemotherapy-induced nausea and vomiting, and in the stimulation of appetite. However, there is accumulating evidence that they could also be useful for the inhibition of tumour cell growth by modulating key survival signalling pathways.

The chemotherapeutic potential for plant-derived and endogenous cannabinoids in CRC therapy is reviewed.”

http://www.ncbi.nlm.nih.gov/pubmed/16042581

Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists.

“Cannabinoids can mimic the infarct-reducing effect of early ischemic preconditioning, delayed ischemic preconditioning, and ischemic postconditioning against myocardial ischemia/reperfusion. They do this primarily through both CB1 and CB2 receptors.

Cannabinoids are also involved in remote preconditioning of the heart.

The cannabinoid receptor ligands also exhibit an antiapoptotic effect during ischemia/reperfusion of the heart.

The acute cardioprotective effect of cannabinoids is mediated by activation of protein kinase C, extracellular signal-regulated kinase, and p38 kinase.

The delayed cardioprotective effect of cannabinoid anandamide is mediated via stimulation of phosphatidylinositol-3-kinase-Akt signaling pathway and enhancement of heat shock protein 72 expression.

The delayed cardioprotective effect of another cannabinoid, Δ9-tetrahydrocannabinol, is associated with augmentation of nitric oxide (NO) synthase expression, but data on the involvement of NO synthase in the acute cardioprotective effect of cannabinoids are contradictory.

The adenosine triphosphate-sensitive K+ channel is involved in the synthetic cannabinoid HU-210-induced cardiac resistance to ischemia/reperfusion injury.

Cannabinoids inhibit Na+/Ca2+ exchange via peripheral cannabinoid receptor (CB2) activation that may also be related to the antiapoptotic and cardioprotective effects of cannabinoids.

The cannabinoid receptor agonists should be considered as prospective group of compounds for creation of drugs that are able to protect the heart against ischemia-reperfusion injury in the clinical setting.”

http://www.ncbi.nlm.nih.gov/pubmed/26487546

[Psychedelics and quasi-psychedelics in the light of contemporary research: medical cannabis, MDMA, salvinorin A, ibogaine and ayahuasca].

“According to the long-held official view these drugs are entirely harmful and have no medical use. However, a recent surge of clinical and pharmacological studies in the field indicates that many psychedelic-like agents have therapeutic potentials under proper circumstances.

In this paper, from a biomedical and psychological perspective, we provide a brief review of the general effects and promising treatment uses of medical cannabis, 3,4-methylenedioxy-methamphetamine (MDMA), salvinorin A, ibogaine and the dimethyltryptamine-(DMT)-containing ayahuasca.”

http://www.ncbi.nlm.nih.gov/pubmed/26485742

Plant derived substances with anti-cancer activity: from folklore to practice.

“Plants have had an essential role in the folklore of ancient cultures. In addition to the use as food and spices, plants have also been utilized as medicines for over 5000 years.

It is estimated that 70-95% of the population in developing countries continues to use traditional medicines even today. A new trend, that involved the isolation of plant active compounds begun during the early nineteenth century.

This trend led to the discovery of different active compounds that are derived from plants.

In the last decades, more and more new materials derived from plants have been authorized and subscribed as medicines, including those with anti-cancer activity.

Cancer is among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next two decades. Thus, there is a real need for new efficient anti-cancer drugs with reduced side effects, and plants are a promising source for such entities.

Here we focus on some plant-derived substances exhibiting anti-cancer and chemoprevention activity, their mode of action and bioavailability. These include paclitaxel, curcumin, and cannabinoids.

In addition, development and use of their synthetic analogs, and those of strigolactones, are discussed. Also discussed are commercial considerations and future prospects for development of plant derived substances with anti-cancer activity.”

http://www.ncbi.nlm.nih.gov/pubmed/26483815

http://journal.frontiersin.org/article/10.3389/fpls.2015.00799/full

Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

“Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations.

Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation…

These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.”

http://www.ncbi.nlm.nih.gov/pubmed/26483633

Alcohol Versus Cannabinoids: A Review of Their Opposite Neuro-Immunomodulatory Effects and Future Therapeutic Potentials.

“Due to the legalization of marijuana and the increased demand for cannabis and alcohol consumption, research efforts highlighting the biomedical consequences of the use of alcohol and cannabinoids are not only relevant to the substance abuse scientific field, but are also of public health interest.

Moreover, an overview of the recent literature about alcohol and cannabinoids neuro-immunomodulatory effects highlighting their future therapeutic potentials will provide a significant contribution to science and medicine.

Therefore, in the current review, we will first discuss briefly the prevalence of alcohol and marijuana abuse, followed by a discussion on the individual effects of alcohol and cannabinoids on the immune system; then, we will focus on the role of endocannabinoids on the alcohol-induced inflammatory effects.

In addition, the review also incorporates cytokine array data obtained from human monocyte-derived dendritic cells, providing a different perspective on the alcohol and cannabinoid abuse divergent effects on cytokine production.

The final section will highlight the therapeutic potential of cannabinoid receptors and the novel strategies to treat alcohol dependence as determined by in vitro, in vivo and clinical studies.”

http://www.ncbi.nlm.nih.gov/pubmed/26478902

Further Characterization of Hemopressin Peptide Fragments in the Opioid and Cannabinoid Systems.

“Hemopressin, so-called because of its hypotensive effect, belongs to the derivatives of the hemoglobin α-chain. It was isolated from rat brain membrane homogenate by the use of catalytically inactive forms of endopeptidase 24.15 and neurolysin. Hemopressin has antihyperalgesic features that cannot be prevented by the opioid receptor antagonist, naloxone.

Here, we further confirm that hemopressins can modulate CB1 receptors and can have a slight modulatory effect on the opioid system.”

http://www.ncbi.nlm.nih.gov/pubmed/26465932

Training-Associated Emotional Arousal Shapes Endocannabinoid Modulation of Spatial Memory Retrieval in Rats.

“Variations in environmental aversiveness influence emotional memory processes in rats. We have previously shown that cannabinoid effects on memory are dependent on the stress level at the time of training as well as on the aversiveness of the environmental context. Here, we investigated whether the hippocampal endocannabinoid system modulates memory retrieval depending on the training-associated arousal level…

The present findings indicate that the endocannabinoid 2-AG in the hippocampus plays a key role in the selective regulation of spatial memory retrieval of stressful experience, shedding light on the neurobiological mechanisms involved in the impact of stress effects on memory processing.

SIGNIFICANCE STATEMENT:

Endogenous cannabinoids play a central role in the modulation of memory for emotional events. Here we demonstrate that the endocannabinoid 2-arachidonoylglycerol in the hippocampus, a brain region crucially involved in the regulation of memory processes, selectively modulates spatial memory recall of stressful experiences. Thus, our findings provide evidence that the endocannabinoid 2-arachidonoylglycerol is a key player in mediating the impact of stress on memory retrieval.

These findings can pave the way to new potential therapeutic intervention for the treatment of neuropsychiatric disorders, such as post-traumatic stress disorder, where a previous exposure to traumatic events could alter the response to traumatic memory recall leading to mental illness.”

http://www.ncbi.nlm.nih.gov/pubmed/26468197

Human lung-resident macrophages express CB1 and CB2 receptors whose activation inhibits the release of angiogenic and lymphangiogenic factors.

“Macrophages are pivotal effector cells in immune responses and tissue remodeling by producing a wide spectrum of mediators, including angiogenic and lymphangiogenic factors.

Activation of cannabinoid receptor types 1 and 2 has been suggested as a new strategy to modulate angiogenesis in vitro and in vivo.

We investigated whether human lung-resident macrophages express a complete endocannabinoid system by assessing their production of endocannabinoids and expression of cannabinoid receptors…

Activation of cannabinoid receptors on tissue-resident macrophages might be a novel strategy to modulate macrophage-assisted vascular remodeling in cancer and chronic inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/26467187

Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients’ survival.

Tumor Biology

“Cannabinoid receptors (CB1R and CB2R) constitute essential members of the endocannabinoid system (ECS) which participates in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to assess the clinical significance of CB1R and CB2R protein expression in mobile tongue squamous cell carcinoma (SCC). The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue SCC and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy.” http://www.ncbi.nlm.nih.gov/pubmed/26459312

https://link.springer.com/article/10.1007%2Fs13277-015-4182-8