Can You Pass the Acid Test? Critical Review and Novel Therapeutic Perspectives of Δ9-Tetrahydrocannabinolic Acid A.

Mary Ann Liebert, Inc. publishers

“Δ9-tetrahydrocannabinolic acid A (THCA-A) is the acidic precursor of Δ9-tetrahydrocannabinol (THC), the main psychoactive compound found in Cannabis sativa. THCA-A is biosynthesized and accumulated in glandular trichomes present on flowers and leaves, where it serves protective functions and can represent up to 90% of the total THC contained in the plant. THCA-A slowly decarboxylates to form THC during storage and fermentation and can further degrade to cannabinol. Decarboxylation also occurs rapidly during baking of edibles, smoking, or vaporizing, the most common ways in which the general population consumes Cannabis. Contrary to THC, THCA-A does not elicit psychoactive effects in humans and, perhaps for this reason, its pharmacological value is often neglected. In fact, many studies use the term “THCA” to refer indistinctly to several acid derivatives of THC. Despite this perception, many in vitro studies seem to indicate that THCA-A interacts with a number of molecular targets and displays a robust pharmacological profile that includes potential anti-inflammatory, immunomodulatory, neuroprotective, and antineoplastic properties. Moreover, the few in vivo studies performed with THCA-A indicate that this compound exerts pharmacological actions in rodents, likely by engaging type-1 cannabinoid (CB1) receptors. Although these findings may seem counterintuitive due to the lack of cannabinoid-related psychoactivity, a careful perusal of the available literature yields a plausible explanation to this conundrum and points toward novel therapeutic perspectives for raw, unheated Cannabis preparations in humans.”

https://www.ncbi.nlm.nih.gov/pubmed/28861488

http://online.liebertpub.com/doi/10.1089/can.2016.0008

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A Review of the Therapeutic Antitumor Potential of Cannabinoids.

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“The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment.

RESULTS:

Cannabis sativa is a plant rich in more than 100 types of cannabinoids. Besides exogenous plant cannabinoids, mammalian endocannabinoids and synthetic cannabinoid analogues have been identified. Cannabinoid receptors type 1 (CB1) and type 2 (CB2) have been isolated and characterized from mammalian cells. Through cannabinoid receptor and non-receptor signaling pathways, cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. The dual antiproliferative and proapoptotic effects of cannabinoids and associated signaling pathways have been investigated on a large panel of cancer cell lines. Cannabinoids also display potent anticancer activity against tumor xenografts, including tumors that express high resistance to standard chemotherapeutics. Few studies have investigated the possible synergistic effects of cannabinoids with standard oncology therapies, and are based on the preclinically confirmed concept of “cannabinoid sensitizers.” Also, clinical trials aimed to confirm the antineoplastic activity of cannabinoids have only been evaluated on a small number of subjects, with no consensus conclusions regarding their effectiveness.

CONCLUSIONS:

A large number of cannabinoid compounds have been discovered, developed, and used to study the effects of cannabinoids on cancers in model systems. However, few clinical trials have been conducted on the use of cannabinoids in the treatment of cancers in humans. Further studies require extensive monitoring of the effects of cannabinoids alone or in combination with standard anticancer strategies. With such knowledge, cannabinoids could become a therapy of choice in contemporary oncology.”

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Medical Cannabis in the Palliation of Malignant Wounds—A Case Report

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“Anecdotal accounts of the use of topical extracts from the cannabis plant being used on open wounds date back to antiquity. In modern times, cannabinoid therapies have demonstrated efficacy as analgesic agents in both pharmaceutical and botanical formats. Medical cannabis (MC), also known as medical marijuana,…

The endogenous cannabinoid system, consisting of cannabinoid receptors and their endogenous ligands, is ubiquitous throughout the human bodyAvailable research shows that cancer cells express higher levels of the cannabinoid receptors, CB1 and CB2, relative to their noncancer counterparts, while also demonstrating an overall state of upregulationHuman in vitro studies, using nonmelanoma skin lines, have demonstrated direct induction of tumor cell apoptosis and inhibition of tumor-related angiogenesis, both by way of activation of cannabinoid receptors.

The analgesic outcomes observed in this case are supported by the results of a recent systematic review and meta-analysis of cannabinoids for medical useUnlike intact skin, which is polar and hydrophilic, wounds lack epithelial coverage and are nonpolar and lipophilic. Therefore, lipophilic compounds such as the THC and CBD cannabinoids may be readily absorbed through cutaneous wounds.

Before the use of topical MC oil, the patient’s wound was growing rapidly. Yet, after a few weeks, a modest regression of his malignant wound was observed while the patient used topical MC. This secondary outcome suggests that topical MC may promote antineoplastic activity as per the findings of Casanova et al.

In summary, this is the first case report to demonstrate the potential for MC to provide effective pain and symptom management in the setting of malignant wounds. The rapid onset of analgesia after topical placement suggests that the effects were mediated through absorption of the THC and CBD cannabinoids that subsequently interacted with peripheral nociceptors, immune cells, and cancer cells. The postapplication analgesia may be because of the gastrointestinal absorption of ingested residual MC oil. This case suggests that MC delivered in vaporized and topical oil formats warrants further investigation in human malignancy, including randomized controlled trials capable of establishing long-term efficacy, optimal dosage, schedules of administration, mixture composition, and safety.”

http://www.jpsmjournal.com/article/S0885-3924(16)30328-1/fulltext

“Can Cannabis Oil Help Heal Wounds?”                              http://www.livescience.com/57500-can-medical-cannabis-help-heal-wounds.html

“Oral cancer patient, 44, claims cannabis oil helped to shrink a hole in his cheek that was caused by the disease” http://www.dailymail.co.uk/health/article-4124752/Oral-cancer-patient-44-claims-cannabis-oil-helped-shrink-hole-cheek-caused-disease.html

“Miracle plant: Can medical marijuana heal wounds?” http://www.nydailynews.com/life-style/medical-marijuana-heal-wounds-article-1.3384572

“Cannabis Oil Shows Potential To Heal Cancer Wounds Fast”  http://www.healthaim.com/cannabis-oil-shows-potential-heal-cancer-wounds-fast/71395

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May cannabinoids prevent the development of chemotherapy-induced diarrhea and intestinal mucositis? Experimental study in the rat.

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“The antineoplastic drug 5-fluoruracil (5-FU) is a pirimidine analog, which frequently induces potentially fatal diarrhea and mucositis.

Cannabinoids reduce gastrointestinal motility and secretion and might prevent 5-FU-induced gut adverse effects.

Here, we asked whether cannabinoids may prevent diarrhea and mucositis induced by 5-FU in the rat.

CONCLUSIONS AND INFERENCES:

5-FU-induced diarrhea, but not mucositis, was partly prevented by WIN at a low dose.

Cannabinoids might be useful to prevent chemotherapy-induced diarrhea.”

https://www.ncbi.nlm.nih.gov/pubmed/27686064

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Comparing the effects of endogenous and synthetic cannabinoid receptor agonists on survival of gastric cancer cells.

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“Anti-neoplastic activity induced by cannabinoids has been extensively documented for a number of cancer cell types; however, this topic has been explored in gastric cancer cells only in a limited number of approaches.

SIGNIFICANCE:

Through a comparative approach, our results support and confirm the therapeutic potential that cannabinoid receptor agonists exert in gastric cancer cells and open possibilities to use cannabinoids as part of a new gastric cancer therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27640887

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Hydroxytyrosol Inhibits Cannabinoid CB1 Receptor Gene Expression in 3T3-L1 Preadipocyte Cell Line.

“The 3T3-L1 preadipocyte cell line is a well characterized cell model for studying the adipocyte status and the molecular mechanisms involved in differentiation of these cells. 3T3-L1 preadipocytes have the ability to synthesize and degrade endocannabinoid anandamide (AEA) and their differentiation into adipocytes increases the expression of cannabinoid (CB1) and PPAR-γ receptors.

Clinically, the blocking stimulation of the endocannabinoid pathway has been one of the first approaches proposed to counteract the obesity and obesity-associated diseases (such as diabetes, metabolic syndrome and cancer).

In this connection, here we studied in cultured 3T3-L1 pre-adipocytes the effects of n-3-PUFA, α-Linolenic acid (OM-3), n-6-PUFA, Linoleic acid (OM-6) and hydroxytyrosol (HT) on the expression of CB1 receptor gene and the adipogenesis-related genes PPAR-γ, Fatty Acid Synthase (FAS) and Lipoprotein Lipase (LPL).

HT was able to inhibit 3T3-L1 cell differentiation by down-regulating cell proliferation and CB1 receptor gene expression. HT exhibited anti-adipogenic effects, whereas OM-3 and OM-6 exerted an inhibitory action on cell proliferation associated with an induction of the preadipocytes differentiation and CB1 receptor gene expression.

Moreover, the expression of FAS and LPL genes resulted increased after treatment with both HT and OM-3 and OM-6.

The present study points out that the intake of molecules such as HT, contained in extra virgin olive oil, may be considered also in view of antiobesity and antineoplastic properties by acting directly on the adipose tissue and modulating CB1 receptor gene transcription.”

http://www.ncbi.nlm.nih.gov/pubmed/26189725

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delta 9-Tetrahydrocannabinol for refractory vomiting induced by cancer chemotherapy.

“Fifty-three patients receiving antineoplastic chemotherapy who had experienced severe nausea and vomiting refractory to standard antiemetic agents were treated with delta 9-tetrahydrocannabinol (THC).

These patients were given THC 8 to 12 hours before, during, and for 24 hours after chemotherapy.

Ten patients (19%) had no further nausea and vomiting; 28 (53%) had at least a 50% reduction of nausea and vomiting compared to previous courses with the same agents.

We suggest that, since THC is a useful antimetic agent in patients having refractory chemotherapy-induced vomiting, existing restrictions prohibiting its therapeutic use should promptly be eased.”

http://www.ncbi.nlm.nih.gov/pubmed/6244418

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The Inhibitory Effects of Cannabidiol on Systemic Malignant Tumors

“Cannabidiol may attenuate tumor growth in a number of other systemic malignancies.

Decreased tumor growth in pulmonary malignancies is seen after administration of cannabidiol.

Tumor metastasis also is markedly attenuated.

Similar attenuation of tumor growth is seen in breast malignancies.

The above examples clearly illustrate the significant antineoplastic effects of cannabidiol. Hopefully, the next few years will see increased studies to fully and further evaluate these antineoplastic effects.”

http://www.jpsmjournal.com/article/S0885-3924(13)00115-2/fulltext#article-outline

http://www.thctotalhealthcare.com/category/cancer/

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Cannabidiol (CBD) Shown To Kill Breast Cancer Cells -Cafemom

“Cannabidiol (CBD) has been on the receiving end of a lot of attention from the scientific community for several decades now.

However, it is only now that we are really starting to begin to get a grasp on how wonderful this cannabinoid truly is.

study from 2011 states that cannabidiol is considered an antineoplastic agent on the basis of its in vitro and in vivo activity against tumor cells. However, the exact molecular mechanism through which CBD works in this capacity is yet to be understood. The study, titled “Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy,” focuses on how CBD can kill breast cancer cells. Breast cancer is the second leading cause of cancer-related death in women in the United States.

What the scientists found was that CBD influences apoptosis by interacting with a key protein, called beclin-1, found within the cancerous cell. Beclin-1 is also known to play a key role in autophagy, or cellular self-degradation of non-vital components, which may lead to programmed cell death. This causes a distortion of the electrical signals between the outer mitochondrial membrane and the rest of the cell, disrupting the transfer to the cell interior of certain molecules that are necessary for metabolism. What this means is that the cell cannot transfer energy, and the cell starves to death, and in doing so activates the self-destruction process of apoptosis.

The study concludes by stating, “In summary, we showed that CBD, a plant-derived cannabinoid, preferentially kills breast cancer cells by inducing ER stress, inhibiting mTOR signaling, enhancing ROS generation, and mediating a complex balance between autophagy and mitochondria-mediated apoptosis in MDA-MB-231 breast cancer cells. These findings support the continued exploration of CBD as an alternative agent for breast cancer treatment.””

http://www.cafemom.com/group/99198/forums/read/19190923/Cannabidiol_CBD_Shown_To_Kill_Breast_Cancer_Cells

“Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy… In summary, we showed that CBD, a plant-derived cannabinoid, preferentially kills breast cancer cells…” http://mct.aacrjournals.org/content/10/7/1161.full

http://www.thctotalhealthcare.com/category/breast-cancer/

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Antineoplastic Effect of WIN 55,212-2, a Cannabinoid Agonist, in a Murine Xenograft Model of Gastric Cancer.

“We have previously reported the antineoplastic effects of a cannabinoid agonist in gastric cancer cells. Our aim was to evaluate this in a murine xenograft model…

Conclusion: WIN 55,212-2 has antineoplastic effect on the gastric cancers in in vivo model.”

http://www.ncbi.nlm.nih.gov/pubmed/24335109

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