Substance in cannabis 'could boost pancreatic cancer treatments'
A substance found in cannabis plants might boost treatments for patients with pancreatic cancer, research in mice has suggested.
Cannabidiol, or CBD, is not psychoactive, meaning it does not produce feelings of being high in those who take it. It is extracted from hemp plants and is legal in the UK, although a CBD product must be licensed before it can be advertised as having health benefits. At present, there are no licensed CBD-only medicines in the UK, but it is being used in a number of clinical trials, including for treating psychosis.
Now scientists say CBD could boost the effect of drugs used to treat pancreatic cancer – a disease with a bleak prognosis. Only about 5% of those with the condition survive for five years, and around 80% die within a year of diagnosis.
“It is very aggressive, so it is very important to find new therapies for this cancer,” said Dr Riccardo Ferro, first author of the research from Queen Mary University of London.
While the latest study was conducted in mice, the team behind the research say that if the results are replicated in humans, the treatment could result in many patients having their lives extended by a matter of years.
Writing in the journal Oncogene, Ferro and colleagues from the UK, Italy and Australia describe how they carried out experiments both on cells in dishes and on mice that had been genetically modified to develop pancreatic cancer, to show that a gene known as GPR55 is involved in the growth and multiplication of pancreatic cancer cells. This gene gives rise to proteins that sit in cell membranes and detect various substances, including certain cannabis-derived chemicals. The team found about 26% of human pancreatic cancer samples showed raised levels of such receptors, suggesting an accumulation in cancer tissues – at least for some patients.
Among the subsequent experiments, the team took mice that had been genetically modified to develop pancreatic cancer and split them into four groups.
Ten mice were given CBD, eight were given the chemotherapy drug gemcitabine, seven were given both drugs, and nine were given a placebo.
Mice in the placebo group lasted for just under 19 days on average, while those in the CBD group lived for just over 25 days and those in the gemcitabine group for almost 28 days.
When the two drugs were combined, the effect was even more dramatic, extending the average survival to almost 53 days after starting treatment.
The team say the CBD blocks the receptors produced by the GPR55 gene, preventing them from interacting with other substances that promote the growth and multiplication of the cancer cells. What’s more, they found CBD hinders the development of resistance to gemcitabine.
However, others cautioned that as the study involved only a small number of mice, it is unclear whether the effects of CBD would also be seen in humans, and that it is unknown whether CBD might interact with other drugs taken by those with pancreatic cancer.
Dr Catherine Pickworth from Cancer Research UK said it was encouraging that researchers were looking into new ways to tackle pancreatic cancer, but that clinical trials are crucial and until there is evidence that CBD will help humans with the cancer, patients should be cautious.
“We don’t advise patients to use cannabis oil or any alternative therapies to treat cancer,” she said. “Some ‘natural’ remedies can interfere with medical treatment, so it’s really important that patients speak to their doctor before making any decisions.”
The Effect of Cannabis in Pancreatic Cancer
The prevalence of malnutrition is overwhelming in pancreatic cancer patients, >80% experience a weight loss >10% of their habitual weight, which may develop into cancer cachexia. Cachexia may cause decreased quality of life, increased mortality and morbidity e.g. poorer response to antitumor treatment, longer length of stay, higher complications rate and shorter life expectancy. There is currently no effective treatment of cancer cachexia, but clinical research in medical cannabis show promising results. The cannabinoids THC and CBD show the highest pharmacological effect, but cannabis consists of >70 cannabinoids. THC and CBD exert their effect on the endocannabinoid system which modulate physiological systems such as pain, inflammation, appetite and energy balance. Thus, this potential orexigenic effect from THC and CBD may improve the nutritional state in patients with pancreatic cancer. Taking the above scientific rationale and the lack of evidence into account, the relevance of this clinical trial appears high.
This clinical trial is an eight-week crossover design examining the effects of the cannabinoids THC and CBD on energy- and protein intake and lean body mass as a measure of appetite, nausea and quality of life. A characterization of the metabolism is analysed through a metabolomics analysis.
|Condition or disease||Intervention/treatment||Phase|
|Neoplasms Pancreatic Cachexia; Cancer Cannabis Appetite Loss Palliative Medicine Morbidity Mortality||Drug: THC and CBD Mixture||Phase 2|
The aim is to investigate the effect of the cannabinoids THC (tetrahydrocannabinol) and CBD (cannabidiol) on energy- and protein intake and lean body mass in patients with pancreatic cancer. A metabolomics analysis is conducted to determine the simultaneous and quantitative intracellular metabolites when medical cannabis is administered in patients with pancreatic cancer.
The clinical trial is designed as a crossover intervention trial with a four week intervention period and a four week control period. The study subjects are instructed to administer individual titered doses of medical cannabis during the intervention period. Dietary history, height, weight, bio- impedance, VAS scales and quality of life measurements are conducted at baseline, every second week and at the end of the clinical trial. Six study subjects are invited to a semi-structured interview. Blood samples and urine samples are used for the metabolomics analysis thus a research biobank is established.
Study population: 32 study subjects diagnosed with pancreatic cancer in palliative care are included. Inclusions criteria: adult, weight loss > 5% of habitual weight. Able to understand and read Danish. Exclusion criteria: regular use of cannabis, psychiatric disorders e.g. Anorexia Nervosa, alcohol abuse, life expectancy
Descriptive statistics is used to characterize the study population. The statistical analysis is carried out in R-Project and all primary data are analyzed as intention-to-treat. P value 90% of patients with pancreatic cancer in the palliative phase experience reduced energy- and protein intake. The quantity of the reduction is, however, very poorly described and appear to depend on cancer progression.
The trial which is approved by the Research Ethics Committee is expected to commence May 2017 after approval by the Danish Medicines Agency and the Data Protection Agency. The clinical trial finish no later than February the 6th 2018. The specified time limit is due to the trial is also basis for a master’s thesis in Clinical Nutrition at the Department of Nutrition, Exercise and Sports, University of Copenhagen. A PhD based on this master thesis will proceed afterwards. Taking into account the patients’ usual control times and to minimize dropout, patient inclusion takes place ongoing, so that there is a control- and intervention period at the same time. Outcome measurements including anthropometry and dietary interviews are carried out at baseline, every two weeks and at the termination of each period. Quality of life measurements and VAS scales are filled out weekly in both periods. The semi-structured interview is carried out at the end of the clinical trial.
The results are going to be published, this applies to both positive, inconclusive and negative results. The clinical trial is registered in the two trial databases ClinicalTrials.gov and EudraCT (clinicaltrialsregister.eu). Scientific articles based on the findings are submitted to relevant journals such as The American Journal of Clinical Nutrition (2014 Impact Factor: 6.770). The results are furthermore used in a master’s thesis in Clinical Nutrition at the Department of Nutrition, Exercise and Sports, University of Copenhagen by Ninette Renee Jensen and Rikke Lundsgaard Nielsen. The results will be presented at congresses. reported in scientific articles, in the master"s thesis, in the information material, on the department’s website, at the public master ́s thesis defense as well as at future congresses, or wherever desired. When the clinical trial is completed a report is sent to relevant authorities including the Research Ethics Committee and the Danish Medicines Agency within 90 days of completion.
Necessary permits from the Data Protection Agency, the Danish Medicines Agency and the Research Ethics Committee are obtained before the initiation of the clinical trial. The protocol is approved by the Research Ethics Committee. Side effects caused by medical cannabis varies in the literature, thus an individual titration period is implemented. No fatal cases have been reported with the use of medical cannabis in human clinical trials. Potential beneficial effects are expected when the study subjects are being treated with medical cannabis, since a gain in appetite and quality of life is expected through a modulation in the endocannabinoid system. Patients are informed that the drug is discontinued after the intervention period. The two master’s thesis students review patient charts weekly to evaluate potential side effects to the drug. The clinical trial is terminated immediately in case of serious side effects. Relevant information material is handed out to the study subjects.
Upon loss of muscle mass and function as seen in cancer cachexia, the administration of individually titrated doses of medical cannabis could hypothetically slow down the condition further, by affecting any negative protein – and energy balance through the endocannabinoid system. When relieving cancer cachexia and improving steady-state, we expect improved prognosis’s for the included patients
The overall objective of the study is that it must be orientated towards clinical significance, so that it can be implemented in clinical practice, thus benefit patients with cancer. The short-term goal is that the patients in this trial experience positive effects in terms of increased appetite and quality of life. Positive effects may contribute to increased research into this area thus resulting in improved evidence. In the longer term, the aim is that the results from this study may contribute to a treatment protocol on malnutrition recommending the use of medical cannabis based on high scientific evidence, so a larger group of patients with cancer may benefit. The results from the study may be used for recommendations on doses, side effects and likely beneficial effects when administer medical cannabis. The metabolomics analysis can contribute to a improved understanding of the cancer cachexia pathophysiology and management in a more experimental matter.
Marijuana and Pancreatic Cancer: 5 Things to Know
Cancer patients have reported finding pain relief and appetite stimulation from the use of medical marijuana, also known as cannabis. In fact, the Pancreatic Cancer Action Network’s (PanCAN) Patient Services, which provides free, in-depth and personalized resources and information about pancreatic cancer, has received many questions about the use and effects of medical marijuana. For example, how is marijuana derived and how can it be used by cancer patients?
Marijuana is a plant that contains substances called cannabinoids. The cannabinoids found in marijuana plants may help treat the symptoms and side effects caused by cancer and cancer treatments. In addition to the naturally occurring cannabinoids found in marijuana plants, cannabinoid drugs have been developed in laboratories for use in helping to treat side effects and symptoms of cancer and cancer treatments.
The use of marijuana and cannabinoid drugs for medicinal purposes, such as controlling pain and stimulating appetite in cancer patients, have been and continue to be studied in the lab and in clinics. Consequently, conflicting information has been reported in clinical studies using cannabinoids as pain relievers or appetite stimulants for cancer patients.
Some studies have reported that patients regained appetite and sense of taste, while others reported cannabinoids are no more helpful than other prescription appetite stimulant medications. Likewise, some studies about pain relief report promising results, while others have shown cannabinoids are no more helpful than prescription medications for controlling pain.
This map shows U.S. states and territories where marijuana is legal for medical purposes.
(Image courtesy of the National Cancer Institute.)
It is important for patients to speak with their doctor to determine if marijuana would be helpful in their fight against pancreatic cancer. According to Anne-Marie Duliege, MD, PanCAN’s Chief Medical Officer, “Since there has not been sufficient data generated yet to produce consistent clinical results about the benefits of medical marijuana for patients, we encourage patients to discuss problems such as pain and appetite stimulation with their doctor to determine the right medications to help control such issues.”
Patient Services often receives questions about how medical marijuana can be used when fighting pancreatic cancer. Here are five things to know: