Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: a study protocol for a pilot and definitive randomised double-blind placebo-controlled trial (CannabisCINV).

BMJ Journals

“Chemotherapy-induced nausea and vomiting (CINV) remains an important issue for patients receiving chemotherapy despite guideline-consistent antiemetic therapy. Trials using delta-9-tetrahydrocannabinol-rich (THC) products demonstrate limited antiemetic effect, significant adverse events and flawed study design. Trials using cannabidiol-rich (CBD) products demonstrate improved efficacy and psychological adverse event profile. No definitive trials have been conducted to support the use of cannabinoids for this indication, nor has the potential economic impact of incorporating such regimens into the Australian healthcare system been established. CannabisCINV aims to assess the efficacy, safety and cost-effectiveness of adding TN-TC11M, an oral THC/CBD extract to guideline-consistent antiemetics in the secondary prevention of CINV.

METHODS AND ANALYSIS:

The current multicentre, 1:1 randomised cross-over, placebo-controlled pilot study will recruit 80 adult patients with any malignancy, experiencing CINV during moderate to highly emetogenic chemotherapy despite guideline-consistent antiemetics. Patients receive oral TN-TC11M (THC 2.5mg/CBD 2.5 mg) capsules or placebo capsules three times a day on day -1 to day 5 of cycle A of chemotherapy, followed by the alternative drug regimen during cycle B of chemotherapy and the preferred drug regimen during cycle C. The primary endpoint is the proportion of subjects attaining a complete response to CINV. Secondary and tertiary endpoints include regimen tolerability, impact on quality of life and health system resource use. The primary assessment tool is patient diaries, which are filled from day -1 to day 5. A subsequent randomised placebo-controlled parallel phase III trial will recruit a further 250 patients.

ETHICS AND DISSEMINATION:

The protocol was approved by ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences.”

https://www.ncbi.nlm.nih.gov/pubmed/30209152

https://bmjopen.bmj.com/content/8/9/e020745

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Cannabis in palliative care: current challenges and practical recommendations.

 “Pain and symptom control challenges are common in palliative care, and the search for other therapeutic strategies is ongoing.

Unfortunately, patients and their caregivers are receiving little information or support from healthcare providers regarding the increasingly popular cannabinoid-based medicines (CBM).

Clinicians, meanwhile, feel understandably perplexed by the discrepancy between the available evidence and the rapid interest in which patients and their families have demonstrated for CBM.

There is an urgent need to address the many challenges that are delaying the appropriate integration of CBM into clinical practice, notwithstanding the obvious need for a solid general knowledge of pharmacology, mechanism of action and available clinical evidence supporting its use.

The authors will address these challenges and provide practical recommendations regarding patient assessment for the use of CBM. The authors will also make suggestions regarding patient expectations in order to define clear objectives, review the necessary precautions prior to initiating treatment, aid in selecting the appropriate strain and route of administration as well as establishing proper titration and monitoring protocols. The authors will also discuss the lesser known but potentially therapeutic psychoactive effects of cannabis.

As this class of therapeutic agents are likely to play a major role in palliative medicine in the near future, clinicians would benefit from familiarizing themselves with CBM and we can expect that patients and their caregivers will appreciate receiving support in their search for safe and effective therapeutic alternatives.”

https://www.ncbi.nlm.nih.gov/pubmed/30180728

http://apm.amegroups.com/article/view/20097

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Cannabinoids in cancer treatment: Therapeutic potential and legislation.

Bosnian Journal of Basic Medical Sciences

“The plant Cannabis sativa L. has been used as an herbal remedy for centuries and is the most important source of phytocannabinoids.

The endocannabinoid system (ECS) consists of receptors, endogenous ligands (endocannabinoids) and metabolizing enzymes, and plays an important role in different physiological and pathological processes.

Phytocannabinoids and synthetic cannabinoids can interact with the components of ECS or other cellular pathways and thus affect the development/progression of diseases, including cancer.

In cancer patients, cannabinoids have primarily been used as a part of palliative care to alleviate pain, relieve nausea and stimulate appetite.

In addition, numerous cell culture and animal studies showed antitumor effects of cannabinoids in various cancer types.

Here we reviewed the literature on anticancer effects of plant-derived and synthetic cannabinoids, to better understand their mechanisms of action and role in cancer treatment. We also reviewed the current legislative updates on the use of cannabinoids for medical and therapeutic purposes, primarily in the EU countries.

In vitro and in vivo cancer models show that cannabinoids can effectively modulate tumor growth, however, the antitumor effects appear to be largely dependent on cancer type and drug dose/concentration.

Understanding how cannabinoids are able to regulate essential cellular processes involved in tumorigenesis, such as progression through the cell cycle, cell proliferation and cell death, as well as the interactions between cannabinoids and the immune system, are crucial for improving existing and developing new therapeutic approaches for cancer patients.

The national legislation of the EU Member States defines the legal boundaries of permissible use of cannabinoids for medical and therapeutic purposes, however, these legislative guidelines may not be aligned with the current scientific knowledge.”

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Anti-tumoural actions of cannabinoids.

British Journal of Pharmacology banner

“The endocannabinoid system has emerged as a considerable target for the treatment of diverse diseases.

In addition to the well-established palliative effects of cannabinoids in cancer therapy, phytocannabinoids, synthetic cannabinoid compounds as well as inhibitors of endocannabinoid degradation have attracted attention as possible systemic anticancer drugs.

As a matter of fact, accumulating data from preclinical studies suggest cannabinoids elicit effects on different levels of cancer progression, comprising inhibition of proliferation, neovascularisation, invasion and chemoresistance, induction of apoptosis and autophagy as well as enhancement of tumour immune surveillance.

Although the clinical use of cannabinoid receptor ligands is limited by their psychoactivity, nonpsychoactive compounds, such as cannabidiol, have gained attention due to preclinically established anticancer properties and a favourable risk-to-benefit profile.

Thus, cannabinoids may complement the currently used collection of chemotherapeutics, as a broadly diversified option for cancer treatment, while counteracting some of their severe side effects.” https://www.ncbi.nlm.nih.gov/pubmed/30019449

“During the last few decades, a large body of evidence has accumulated to suggest endocannabinoids, phytocannabinoids and synthetic cannabinoids exert an inhibitory effect on cancer growth via blockade of cell proliferation and induction of apoptosis. Some studies support the hypothesis that cannabinoids may enhance immune responses against the progressive growth and spread of tumours.”  https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.14426#bph14426-fig-0001
“Previous research has shown that cannabinoids can help lessen side effects of anti-cancer therapies. Now a new British Journal of Pharmacology review has examined their potential for the direct treatment of cancer. Studies have shown that cannabinoids may stop cancer cells from dividing and invading normal tissue, and they may block the blood supply to tumors. Some studies also indicate that cannabinoids may enhance the body’s immune response against the growth and spread of tumors.” https://www.eurasiareview.com/19072018-cannabinoids-may-have-a-vast-array-of-anti-cancer-effects/
“Cannabinoids may have a vast array of anti-cancer effects” https://www.sciencedaily.com/releases/2018/07/180718082143.htm

“Cannabinoids may have a vast array of anti-cancer effects”  https://www.eurekalert.org/pub_releases/2018-07/w-cmh071718.php

Marijuana may help fight cancer” https://nypost.com/2018/07/18/marijuana-may-help-fight-cancer/

“Cannabis stops cancer spreading and boosts immune system, say scientists. Studies show cannabinoids can stop cancer cells from dividing and spreading, and blocks blood supply to tumours” https://www.plymouthherald.co.uk/news/health/cannabis-can-cure-cancer-proof-1803485
“Cannabis stops cancer spreading and boosts immune system, say scientists. Cannabis can act as a treatment for cancer and boost the immune system, claims a new study.” https://www.devonlive.com/news/health/cannabis-can-cure-cancer-proof-1803485
“Cannabis stops cancer spreading and boosts immune system, say scientists. Cannabis can act as a treatment for cancer and boost the immune system, claims a new study.” https://www.cornwalllive.com/news/uk-world-news/cannabis-can-cure-cancer-proof-1803485
Cannabis ‘can act as a treatment for cancer’. Cannabis can enhance the immune system and act as a treatment for cancer, claims a new study. Scientists at Rostock University Medical Centre in Germany claimed the benefits following a review of more than 100 studies.” https://www.thelondoneconomic.com/news/cannabis-can-act-as-a-treatment-for-cancer/19/07/
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Evidence for the use of “medical marijuana” in psychiatric and neurologic disorders.

College of Psychiatric and Neurologic Pharmacists

“Cannabis is listed as a Schedule I substance under the Controlled Substances Act of 1970, meaning the US federal government defines it as an illegal drug that has high potential for abuse and no established medical use; however, half of the states in the nation have enacted “medical marijuana” (MM) laws. Clinicians must be aware of the evidence for and against the use of MM in their patients who may consider using this substance.

RESULTS:

Publications were identified that included patients with dementia, multiple sclerosis, Parkinson disease, Huntington disease, schizophrenia, social anxiety disorder, depression, tobacco use disorder, and neuropathic pain.

DISCUSSION:

There is great variety concerning which medical conditions are approved for treatment with MM for either palliative or therapeutic benefit, depending on the state law. It is important to keep an evidence-based approach in mind, even with substances considered to be illegal under US federal law. Clinicians must weigh risks and benefits of the use of MM in their patients and should ensure that patients have tried other treatment modalities with higher levels of evidence for use when available and appropriate.”

https://www.ncbi.nlm.nih.gov/pubmed/29955495

““Medical marijuana” encompasses everything from whole-plant cannabis to synthetic cannabinoids available for commercial use approved by regulatory agencies. In determining whether MM is of clinical utility to our patients, it is important to keep in mind chemical constituents, dose, delivery, and indication. Selection of the patient appropriate for MM must be carefully considered because clinical guidelines and treatment options with stronger levels of evidence should be exhausted first in most cases. There seems to be strongest evidence for the use of MM in patients with MS and in patients with neuropathic pain; moderate evidence exists to support further research in social anxiety disorder, schizophrenia, PD, and tobacco use disorder; evidence is limited for use in patients with dementia, Huntington disease, depression, and anorexia.”

http://mhc.cpnp.org/doi/10.9740/mhc.2017.01.029?code=cpnp-site

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Cannabis: A Prehistoric Remedy for the Deficits of Existing and Emerging Anticancer Therapies

“Cannabis has been used medicinally for centuries and numerous species of this genus are undoubtedly amongst the primeval plant remedies known to humans.

Cannabis sativa in particular is the most reported species, due to its substantial therapeutic implications that are owed to the presence of chemically and pharmacologically diverse cannabinoids.

These compounds have long been used for the palliative treatment of cancer.

Recent advancements in receptor pharmacology research have led to the identification of cannabinoids as effective antitumor agents.

This property is accredited for their ability to induce apoptosis, suppress proliferative cell signalling pathways and promote cell growth inhibition.

Evolving lines of evidence suggest that cannabinoid analogues, as well as their receptor agonists, may offer a novel strategy to treat various forms of cancer.

This review summarizes the historical perspective of C. sativa, its potential mechanism of action, and pharmacokinetic and pharmacodynamic aspects of cannabinoids, with special emphasis on their anticancer potentials.”

http://www.xiahepublishing.com/ArticleFullText.aspx?sid=2&jid=3&id=10.14218%2FJERP.2017.00012

Cannabis products.

“Cannabis products. First row, left to right: Indian, Lebanese, Turkish and Pakistani hashish. Second row, left to right: Swiss hashish, Zairean marijuana, Swiss marijuana, Moroccan hash oil.”

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Medicinal Cannabinoids in Palliative Care.

 British Journal of Clinical Pharmacology banner

“The treatment of symptoms in people with palliative diagnoses begins with meticulous clinical assessment with treatment choice (s) selected based on an understanding of the symptom aetiology and the evidence which underpins its treatment.

Increasingly the merits of palliative care have been established earlier in the disease trajectory where treatment outcomes may include increased survival and maintenance of function.

There is strong public support for the availability of medicinal cannabis, particularly for people with palliative diagnoses.

There are several areas where there is potential for symptom benefits through modulation of the endocannabinoid system, though clinical data to date has been inconclusive in key symptoms such as pain and nausea, and data from other settings such as chemotherapy-induced nausea and vomiting not readily extrapolated.

Ideally exploration of medicinal cannabinoids should occur within a clinical trial to accelerate the evidence base to inform practice. In people with refractory symptoms the consideration of unregistered products or off label prescribing should be guided by the potential influences of pharmacokinetic, pharmacodynamic and drug-drug interactions, supported by an informed discussion with the patient, and regular review of net clinical benefit.”

https://www.ncbi.nlm.nih.gov/pubmed/29923616

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.13671

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Targeting cannabinoid receptors in gastrointestinal cancers for therapeutic uses: current status and future perspectives

Publication Cover

“A number of studies have consistently shown that cannabinoids are able to prevent or reduce carcinogenesis in different animal models of colon cancer.

Cannabinoids, via CB1 and possibly CB2 receptors, suppress proliferation and migration and stimulate apoptosis in colorectal cancer cells.

Convincing scientific evidence suggests that cannabinoids, in addition to their well-known use in palliative care in oncology (e.g. improvement of appetite, attenuation of nausea associated to antitumoral medicines, alleviation of moderate neuropathic pain) can reduce, via antiproliferative and proapoptotic as well as by inhibiting angiogenesis, invasion and metastasis or by attenuating inflammation, the growth of cancer cells and hinder the development of experimental colon carcinogenesis in vivo.”

https://www.tandfonline.com/doi/full/10.1080/17474124.2017.1367663?src=recsys

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Endocannabinoid system and anticancer properties of cannabinoids

Folia Biologica et Oecologica

“Cannabinoids impact human body by binding to cannabinoids receptors (CB1 and CB2).

The two main phytocannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

THC interacts with CB1 receptors occurring in central nervous system and is responsible for psychoactive properties of marijuana. CBD has low affinity to CB1 receptor, has no psychoactive characteristics and its medical applications can be wider.

CB receptors are part of a complex machinery involved in regulation of many physiological processes – endocannabinoid system.

Cannabinoids have found some applications in palliative medicine, but there are many reports concerning their anticancer affects.

Agonists of CB1 receptors stimulate accumulation of ceramides in cancer cells, stress of endoplasmic reticulum (ER stress) and, in turn, apoptosis. Effects of cannabinoids showing low affinity to CB receptors is mediated probably by induction of reactive oxygen species production.

Knowledge of antitumor activity of cannabinoids is still based only on preclinical studies and there is a necessity to conduct more experiments to assess the real potential of these compounds.”

https://content.sciendo.com/view/journals/fobio/12/1/article-p11.xml

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

 Publication Cover

“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

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