Anticancer mechanisms of cannabinoids.

“In addition to the well-known palliative effects of cannabinoids on some cancer-associated symptoms, a large body of evidence shows that these molecules can decrease tumour growth in animal models of cancer.

They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival. In addition, cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals.

In this review, we discuss the current understanding of cannabinoids as antitumour agents, focusing on recent discoveries about their molecular mechanisms of action, including resistance mechanisms and opportunities for their use in combination therapy.

Those observations have already contributed to the foundation for the development of the first clinical studies that will analyze the safety and potential clinical benefit of cannabinoids as anticancer agents.”

http://www.ncbi.nlm.nih.gov/pubmed/27022311

Integrating cannabis into clinical cancer care.

“Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use.

However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use.

For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression.

Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite.

Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy.

A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia.

Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis.

Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating.

Human studies should be conducted to address critical questions related to the foregoing effects.”

http://www.ncbi.nlm.nih.gov/pubmed/27022315

Use of cannabinoids in cancer care: palliative care

Page Header

“Cannabinoid Integrative Medicine In Oncologic Palliative Care.

The opportunities to improve and expand palliative care are many. In this supplement, Current Oncology is presenting a discussion on cannabinoid therapeutics. I believe that, as a therapeutic class, cannabinoids have an important role to play in oncologic palliative care—a role that I predict will only grow with time, as knowledge and acceptance of these agents becomes mainstream once more, as in the 19th and early 20th century in North America and Europe.”

http://www.current-oncology.com/index.php/oncology/article/view/2962/2087

In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma.

“Neuroblastoma (nbl) is one of the most common solid cancers in children. Prognosis in advanced nbl is still poor despite aggressive multimodality therapy. Furthermore, survivors experience severe long-term multi-organ sequelae. Hence, the identification of new therapeutic strategies is of utmost importance.

Cannabinoids and their derivatives have been used for years in folk medicine and later in the field of palliative care. Recently, they were found to show pharmacologic activity in cancer, including cytostatic, apoptotic, and antiangiogenic effects.

We investigated, in vitro and in vivo, the anti-nbl effect of the most active compounds in Cannabis, Δ(9)-tetrahydrocannabinol (thc) and cannabidiol (cbd)…

Both compounds have antitumourigenic activity in vitro and impeded the growth of tumour xenografts in vivo. Of the two cannabinoids tested, cbd was the more active. Treatment with cbd reduced the viability and invasiveness of treated tumour cells in vitro and induced apoptosis. Moreover, cbd elicited an increase in activated caspase 3 in treated cells and tumour xenografts.

 

Our results demonstrate the antitumourigenic action of cbd on nbl cells. Because cbd is a nonpsychoactive cannabinoid that appears to be devoid of side effects, our results support its exploitation as an effective anticancer drug in the management of nbl.”

http://www.ncbi.nlm.nih.gov/pubmed/27022310

“Neuroblastomas are cancers that start in early nerve cells (called neuroblasts) of the sympathetic nervous system, so they can be found anywhere along this system.”  http://www.cancer.org/cancer/neuroblastoma/detailedguide/neuroblastoma-what-is-neuroblastoma

Techniques and technologies for the bioanalysis of Sativex®, metabolites and related compounds.

“Sativex® is an oromucosal spray indicated for the treatment of moderate-to-severe spasticity in multiple sclerosis and is also an effective analgesic for advanced cancer patients.

Sativex contains Δ9-tetrahydrocannabinol (THC) and cannabidiol in an approximately 1:1 ratio.

The increasing prevalence of medicinal cannabis products highlights the importance of reliable bioanalysis and re-evaluation of the interpretation of positive test results for THC, as legal implications may arise in workplace, roadside and sports drug testing situations. This article summarizes published research on the bioanalysis of THC and cannabidiol, with particular focus on Sativex.”

http://www.ncbi.nlm.nih.gov/pubmed/27005853

Medical marijuana use in head and neck squamous cell carcinoma patients treated with radiotherapy.

Supportive Care in Cancer

“The purpose of the study was to better understand why patients with history of head and neck cancer (HNC) treated with radiotherapy are using medical marijuana (MM).

RESULTS:

There was a 100 % response rate. Median time from treatment was 45 months (21-136 months). Most patients smoked marijuana (12 patients), while others reported ingestion (4 patients), vaporizing (3 patients), and use of homemade concentrated oil (1 patient). Six patients reported prior recreational marijuana use before diagnosis. MM provided benefit in altered sense, weight maintenance, depression, pain, appetite, dysphagia, xerostomia, muscle spasm, and sticky saliva.

CONCLUSIONS:

HNC patients report MM use to help with long-term side effects of radiotherapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27005465

https://link.springer.com/article/10.1007%2Fs00520-016-3180-8

Medical Marijuana Use in Oncology: A Review.

“Medicinal marijuana use is currently legal in 23 states and the District of Columbia. As more states approve marijuana use for medical indications, physicians will be asked by their patients for more information regarding the risks and benefits of use. This article reviews the history, adverse effects, and proposed mechanisms of action of marijuana and summarizes the available literature regarding symptom relief and therapeutic value in patients with cancer.

OBSERVATIONS:

Marijuana in oncology may have potential for use as an antiemetic, for refractory cancer pain, and as an antitumor agent. However, much of the data are based on animal data, small trials, or are outdated.

CONCLUSIONS AND RELEVANCE:

More research is needed in all areas related to the therapeutic use of marijuana in oncology.”

http://www.ncbi.nlm.nih.gov/pubmed/26986677

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

Cannabinoids: Medical implications.

“Herbal cannabis has been used for thousands of years for medical purposes.

With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored.

While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy.

While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards.

Where medical cannabis is legal, patients typically see a physician who “certifies” that a benefit may result.

Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis.

Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.

Key messages The medical disorders with the current best evidence that supports a benefit for cannabinoid use are the following: multiple sclerosis patient-reported symptoms of spasticity (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis central pain or painful spasms (nabiximols, nabilone, dronabinol, and oral cannabis extract), multiple sclerosis bladder frequency (nabiximols), and chronic cancer pain/neuropathic pain (nabiximols and smoked THC).

Participating physicians should be knowledgeable about cannabinoids, closely look at the risk/benefit ratio, and consider certain important criteria in selecting a patient, such as: age, severity, and nature of the medical disorder, prior or current serious psychiatric or substance use disorder, failure of standard medical therapy as well as failure of an approved cannabinoid, serious underlying cardiac/pulmonary disease, agreement to follow-up visits, and acceptance of the detailed explanation of potential adverse risks.

The normal human endocannabinoid system is important in the understanding of such issues as normal physiology, cannabis use disorder, and the development of medications that may act as agonists or antagonists to CB1 and CB2.

By understanding the endocannabinoid system, it may be possible to enhance the beneficial effects of cannabinoid-related medication, while reducing the harmful effects.”

http://www.ncbi.nlm.nih.gov/pubmed/26912385

Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents.

“Treatment of cancer is a significant challenge in clinical medicine, and its research is a top priority in chemical biology and drug discovery. Consequently, there is an urgent need for identifying innovative chemotypes capable of modulating unexploited drug targets.

The transient receptor potential (TRPs) channels persist scarcely explored as targets, despite intervening in a plethora of pathophysiological events in numerous diseases, including cancer.

Both agonists and antagonists have proven capable of evoking phenotype changes leading to either cell death or reduced cell migration.

Among these, natural products entail biologically pre-validated and privileged architectures for TRP recognition.

Furthermore, several natural products have significantly contributed to our current knowledge on TRP biology. In this Tutorial Review we focus on selected natural products, e.g. capsaicinoids, cannabinoids and terpenes, by highlighting challenges and opportunities in their use as starting points for designing natural product-inspired TRP channel modulators.

Importantly, the de-orphanization of natural products as TRP channel ligands may leverage their exploration as viable strategy for developing anticancer therapies.

Finally, we foresee that TRP channels may be explored for the selective pharmacodelivery of cytotoxic payloads to diseased tissues, providing an innovative platform in chemical biology and molecular medicine.”

http://www.ncbi.nlm.nih.gov/pubmed/26890476

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

Endocannabinoids as Guardians of Metastasis.

“Endocannabinoids including anandamide and 2-arachidonoylglycerol are involved in cancer pathophysiology in several ways, including tumor growth and progression, peritumoral inflammation, nausea and cancer pain.

Recently we showed that the endocannabinoid profiles are deranged during cancer to an extent that this manifests in alterations of plasma endocannabinoids in cancer patients, which was mimicked by similar changes in rodent models of local and metastatic cancer.

The present topical review summarizes the complexity of endocannabinoid signaling in the context of tumor growth and metastasis.”

http://www.ncbi.nlm.nih.gov/pubmed/26875980