Not a sentence anymore? CBD for cancer treatment
Cancer. For many years already, this word has sounded like a sentence for patients meaning that their life will never be the same from this moment. Rethinking the life values and permanent struggle for life - these people learn to live anew. Specialists in modern science and medicine all over the globe are looking for treatment for cancer. They search for a treatment that will transform this scary diagnosis from hopeless to curable. Even with the comparably high level of medical technologies nowadays, cancer is still considered as an undefeated disease.
To date, different types of cancer are the leading cause of death worldwide. Billions of dollars are being spent on cancer treatment. In addition to this, cancer is not one disease, but at least 200 - each of which has its symptoms, methods of diagnosis and treatment, that significantly complicates the treatment. The World Health Organization estimates that the number of cancer cases in the next 20 years will increase by 70%. What does this mean for humanity? Nowadays, 14.1 million new cancer cases worldwide are registered annually. More than eight million people die from cancer every year, which is 13% of deaths worldwide. According to British oncologists, the list of the most common types of cancer has not significantly changed over the past 40 years. Among the most common cancer diagnoses for today are:
- lung cancer;
- breast cancer;
- intestine cancer;
- prostate cancer;
- stomach cancer;
- liver cancer;
- cervical cancer;
- oesophagal cancer;
- bladder cancer;
- non-Hodgkin lymphoma.
According to the Globoscan project, which is a database maintained by the International Association for the Registration of Cancer, the four most common types of cancer — lung, breast, intestine, and prostate, account for 42% of all cancer cases worldwide.
Lung cancer is the most common type among men around the world, while breast cancer is most common among women. Specialists estimate the loss of healthy years of life as a result of cancer in 169.3 million years. For 2018, more than 18 million cancer cases, 9.6 million of which were fatal have been registered. It means that every fifth man and every sixth woman gets cancer at some stage of life. The latest World Health Organization report indicates that more than 60% of new cases are reported in Africa, Asia, Central, and South America. 70% of all cancer deaths in the world have been registered in these regions.
However, cancer incidence does not necessarily correlate with overall mortality in specific countries. In some regions, more resources are available to treat cancer patients and improve their chances of survival. For example, Europe and North America have lower cancer mortality than the total number of cases, while Asia and Africa have a higher number of cancer deaths. Among the TOP 5 countries with the highest number of cancers are:
- Denmark (338.1 per 100 thousand people);
- France (324.6 per 100 thousand people);
- Australia (323 per 100 thousand people);
- Belgium (321.1 per 100 thousand people);
- Norway (318.3 per 100 thousand people).
These five countries are followed by the United States, Ireland, Korea, the Netherlands, and New Caledonia. In the Middle East, the worst evidence is in Israel, which ranks 19th in a list of 50 countries. 57% of all cancers are registered in less developed countries. However, cancer is often called a disease of developed countries, as 43% of all cancers are registered in developed countries.
What are the main risk factors for this disease? According to research, one-third of all cases of cancer are associated with four leading risk factors for nutrition and behaviour:
- Nutrition and obesity;
- Alcohol use;
- Inadequate exercise.
Smoking remains the most significant risk factor, causing about 20% of all lung cancer deaths. Alcohol consumption is the most common cause of death in Europe and America, while unhealthy diets and obesity are becoming more common risk factors in low- and middle-income countries. In addition to this, infections are responsible for 18% of global cancer cases, with a much higher percentage in poorer regions.
Oncologists predict a 70% increase in cancer cases worldwide in the next 20 years. Let’s see what we have now and which treatments are expected to reduce this prognosis in the nearest future.
Cancer treatments for today. What choice do we have?Among the most prevalent cancer treatments for today are chemotherapy and radiation therapy. Both of these treatments show good results in case of timely diagnosis and the correct approach. Let’s find out how each of these treatments works and what are their main side effects and health benefits.
Cancer cells grow and divide much faster in comparison with other types of cells in our bodies. Chemotherapy is an aggressive form of chemical drug therapy aimed at destroying these rapidly growing cells. In most cases, chemotherapy is used in combination with other therapies, such as radiation, hormone therapy or surgery. The choice of the most appropriate treatment or combination of treatment programs usually depends on:
- the overall state of your health;
- the type of cancer you have and its stage;
- previous cancer treatments you had;
- your personal treatment preferences;
- the location of the cancer cells.
Chemotherapy is considered as a systematic treatment, which means it affects the entire organism. This treatment program has been proven to effectively attack cancer cells, slowing down their division and destroying them. However, together with noticeable results, chemotherapy can cause serious side effects and severely impact the quality of your life. All of the side effects should be weighed carefully before deciding that this treatment is right for you. As chemotherapy is aimed at killing cells that divide quickly, cells in the following areas of your organism can be affected as well:
- the lining of the intestinal tract;
Because of such influence, the main side effects of chemotherapy include:
- easy bruising and excessive bleeding;
- mouth sores;
- hair loss;
- loss of appetite;
- dry mouth;
- weight loss;
- memory and concentration problems;
- sexual and fertility changes.
As a rule, all of these side effects are managed with medications and life tips by your doctor. Most of the side effects subside when the treatment is over, although there is a particular risk of long-lasting effects that may develop even years after the treatment. The appearance of such long-term effects depends on the type of chemotherapy used.
Even with such an extensive list of side effects, chemotherapy is considered as one of the most effective cancer treatments nowadays. It is primarily used to shrink tumour size, lower the number of cancer cells in the body, reduce current symptoms and the likelihood of cancer spreading. If you have undergone surgery to remove a cancerous tumour, for example, a lumpectomy for breast cancer, your oncologist may prescribe you chemotherapy to ensure that all the lingering cancer cells are killed as well. In addition to this, chemotherapy may be used to prepare a patient for other treatments. As it can help to shrink the tumour, chemotherapy may be used to prepare you for surgery or radiation therapy. In the case of late-stage cancer and palliative way of treatment, chemotherapy may help patients to relieve pain.
Besides cancer treatment, chemotherapy may also be used to prepare people with bone marrow diseases for the treatment of bone marrow stem cells, or patients with immune system disorders. In such cases, doses of the medications are much lower than those used to treat cancer. In addition to this, chemotherapy may also be used to help disorders in which the immune system of our bodies attacks healthy cells, like rheumatoid arthritis or lupus.
How is chemotherapy performed? Usually, the best way to determine the best course of your treatment is discussed by you and your doctor to evaluate all the possible side effects and variables of the chemotherapy. This type of therapy is typically given in pill form or by injection directly into veins. These are two main options of chemotherapy delivering, although it may be delivered in several other ways such as:
- Some types of skin cancers can be treated using chemotherapy creams;
- Depending on tumour location, chemotherapy can be delivered directly to the tumour;
- Chemotherapy can be delivered to a specific part of the patient’s body, such as directly into the chest, central nervous system, abdomen, or into the bladder through the urethra;
- Liquid types of chemotherapy medications can be taken as single shots;
- In many cases, a special port is installed under the computer tomography control in a place where a needle is inserted for each treatment;
- In case you undergo surgery to remove the tumour, slow-dissolving discs that release medications over time can also be implanted.
The effectiveness of chemotherapy treatment is regularly monitored by your doctor and the cancer treatment team. Based on the results of blood tests and imaging techniques, your doctor can adjust the treatment at any time.
Together with chemotherapy, radiation therapy is often prescribed for people with a cancer diagnosis. Radiation therapy is a special kind of cancer treatment that uses high-energy concentrated radiation beams to kill cancer cells. To date, external beam radiation remains the most common type of radiation therapy. This type involves a special machine - linear accelerator that directs high-energy radiation beams at cancer cells. This equipment allows radiation to be targeted at specific sites, avoiding the irradiation of healthy organs and tissues that lies on the beam way. External beam radiation can be used for nearly all types of cancer and, according to National Cancer Institute data, nowadays about half of all people with oncological diseases undergo the course of radiation therapy.
In many cases, radiation therapy is used in conjunction with other therapies, such as chemotherapy or surgery. Among the primary radiation therapy goals are to kill cancer cells and shrink tumours. This kind of treatment injures healthy cells, but due to the cells’ ability to recover from radiation therapy, the damage isn’t permanent. To maximally minimise the radiation effect on the healthy tissues and organs with the technologies of dosimetry planning, the radiation is targeted only to the tumour area. Radiation therapy can be prescribed for different outcomes and during different stages of cancer treatment. It can be used:
- as a primary treatment program;
- to shrink a tumour before the surgery;
- to alleviate symptoms in case of late-stage cancer (palliative treatment program);
- in conjunction with other treatments;
- to kill all the remaining cancer cells after surgery.
Regardless of what type of radiation is used, hair loss and fatigue are the most common side effects of radiation therapy. Hair loss happens only on the part of the body which has been irradiated. In addition to this, radiation also affects skin cells causing such changes as:
Besides this, other side effects can include:
- mouth sores;
- sexual dysfunction;
- trouble swallowing;
- painful urination;
All the side effects may vary greatly depending on the area being treated. According to the National Cancer Institute, most of the side effects disappear within two months after the treatment course completion. However, in rare cases, some of the side effects can appear six months or more after the radiation therapy course has been finished. These late side effects may include:
- joint problems;
- tissue swelling;
- mouth problems;
- secondary cancer.
How is radiation therapy performed? The course of radiation therapy usually consists of several treatment sessions five days a week. The duration of the course is chosen by the doctor and may vary from one to ten weeks. As a rule, the number of treatment fractions depends on the cancer type and size of the primary tumour. Each session lasts from ten to thirty minutes, depending on your particular case. The patient is always given each weekend off from radiation therapy so healthy cells can restore normally.
Unlike chemotherapy, during the radiation therapy session, there is no invasive intrusion into the body. The patient lies on a special treatment table, and the team of specialists positions him in the same way it was performed during the initial radiation simulation. Linear accelerator, which is the machine providing radiation therapy, directs radiation at the appropriate spot by moving around the treatment table at certain angles. The procedure of radiation therapy isn’t painful. Moreover, a patient is able to communicate with the team of doctors and technicians during the treatment if necessary.
The results of the radiation therapy are evaluated based on imaging scans during and after radiation, so doctors can observe how well your organism is responding to treatment. Also, these scans, together with additional tests, can tell the doctor if any changes need to be made to your treatment program.
CBD as a new promising way of the cancer treatment
More and more often, along with chemotherapy and radiation therapy, a new word appears - cannabidiol. Cannabis is considered the most effective and oldest medicine. Starting in 1975, researchers began to examine cannabis as an anticancer agent. Despite legal restrictions almost in all countries worldwide, medical centres continued studying cannabis anticancer properties. One of the many cannabinoids found in the marijuana plant that shows the highest potential is cannabidiol.
Along with tetrahydrocannabinol (THC), cannabidiol (CBD) is the most famous cannabinoid nowadays. Nevertheless, even being the most popular, these cannabinoids are different, and their influence on our organism differs drastically. Unlike THC, cannabidiol doesn’t cause psychoactive effects on our brain, being much more applicable for various uses. Because of this significant difference, the interest in using CBD in different areas of medicine has risen rapidly during the last years. Moreover, the legalisation of CBD use for medicinal purposes in several states and countries has triggered lots of new studies and trials, discovering the unique abilities of this cannabinoid. The interest in cannabidiol as a cancer-fighting agent has significantly increased in recent years, giving a new area of study for scientists and hope for patients with a cancer diagnosis.
According to the preliminary research, CBD seems to target cancer on several different levels. Evidence shows that CBD oil could prevent cancer cell migration, trigger cell death, and reduce cancer invasiveness. In addition to this, CBD may also have angiogenesis properties, which means it can block new blood cell formation, thereby slowing the spread of cancer cells. Altogether, these anticancer properties have caused a real agiotage among cancer research centres all over the world, cancer patients, and the whole CBD oil industry in general.
Among the main CBD benefits that have sparked the interest for this compound as a possible anticancer agent are:
- antitumour effects;
- antiemetic effects;
- appetite stimulation;
- anxiety and sleep.
Let’s consider each of these benefits separately to understand the mechanism of CBD’s work and its influence on cancer cells in the human organism.
Antitumour effects. According to one study on mice and rats, cannabinoids may have a unique protective effect against certain types of tumours. The study lasted two years, and during all of this period, groups of mice and rats were given various THC doses by gavage. As a result, a dose-related decrease in hepatocellular carcinoma and hepatic adenoma tumours was observed. Moreover, a decreased incidences of such benign tumours as adenomas and polyps in uterus, pancreas, testis, and mammary glands were noted in rats during this study. Another study confirmed that the use of CBD, delta-9-THC, and delta-8-THC might help to inhibit the growth of Lewis lung adenocarcinoma cells both in vitro and in vivo. In addition to this, other tumour types have also been shown to be sensitive to CBD-induced growth inhibition.
How does this mechanism work? The antitumour effects of CBD may be caused by various mechanisms, including inhibition of cancer cell growth, induction of cell death, or inhibition of metastasis and tumour angiogenesis invasion. The primary molecular mechanisms of cannabinoids action as antitumour agents are summarised in this review. Based on this analysis and this study, it appears that cannabinoids are focused on killing tumour cells, while at the same time, they do not affect the non transformed counterparts of the cells. Moreover, cannabinoids may even protect them from cell death. The antitumour effects of delta-9-THC and a synthetic agonist of the CB2 receptor were also investigated in hepatocellular carcinoma (HCC) cases. Both of these agents showed the reduced viability of HCC cells in vitro, thereby demonstrating antitumour effects in mice. The study confirmed that the anti-HCC effects are mediated by the CB2 receptor. Thus, the cannabinoids were suggested to trigger cell death by way of stimulation of an endoplasmic reticulum stress pathway that is responsible for autophagy activation and apoptosis promotion. In addition to this, other studies have shown that both CB1 and CB2 receptors may become potential targets in breast cancer and non-small cell lung carcinoma cases.
Cannabidiol has also shown the chemopreventive effect in case of colon cancer in mice. During this study, a special drug, azoxymethane, increased both premalignant and malignant lesions in the mouse colon. Mice that were treated with azoxymethane together with CBD were protected from developing premalignant and malignant lesions. Also, during the in vitro experiments investigating colorectal cancer, the researchers found that CBD was able to protect DNA from oxidative damage, reduce cell proliferation, and increase endocannabinoid levels. Besides these CBD effects, another hypothesis regarding phytocannabinoids and endocannabinoids has been developed. Due to the anti-inflammatory effects of endogenous and plant-derived cannabinoids, another mice study was held. It was shown that the endogenous cannabinoid system signalling is likely to provide intrinsic protection against colonic inflammation. Based on the study results, it was suggested that endocannabinoids might be useful in the risk reduction as well as in the treatment of colorectal cancer.
Antiemetic effects. Nausea and vomiting are one of the most widespread and debilitating side effects of modern cancer treatments. According to several preclinical research, our emetic circuitry is controlled by endocannabinoids. The mechanism of antiemetic effects of cannabinoids is believed to be regulated by their interaction with the 5-hydroxytryptamine 3 (5-HT3) receptor. The role of the CB1 receptor in emesis prevention has also been shown by the ability of CB1 antagonists to reverse the effects of THC and other synthetic cannabinoid CB1 agonists in suppressing vomiting caused by cisplatin.
Appetite stimulation. Many studies have already confirmed that THC, together with other cannabinoids, can cause a stimulatory effect on our appetite and increase food intake. It is also believed that the endogenous cannabinoid system may act as a regulator of feeding behaviour. In addition to this, it was shown that the endogenous cannabinoid anandamide potently enhances appetite in mice. Furthermore, CB1 receptors located in the hypothalamus may be involved in the motivational or reward aspects of eating.
Anxiety and sleep. Our internal ECS is believed to be responsible for the regulation of mood and the extinction of aversive memories. Some animal studies have shown the anxiolytic properties of cannabidiol. These anxiolytic properties were confirmed in mice and rats, but the mechanism of their action is still unknown. The anxiolytic effects of cannabidiol have been shown in several animal models. Also, it was shown that ECS plays a key role in the modulation of the sleep-waking cycle in rats.
Analgesia. The theory of cannabidiol-induced analgesia was confirmed by the study of endocannabinoids, cannabinoid receptors, synthetic agonists and antagonists. The mechanism of the cannabinoids analgesia effects lies in producing analgesia through supraspinal, spinal, and peripheral modes of action, acting on both ascending and descending pain pathways. The CB1 receptor of our endocannabinoid system is found in both the central nervous system (CNS) and in peripheral nerve terminals. As well as opioid receptors, increased levels of the CB1 receptor are found in regions of our brain that are responsible for regulation nociceptive processing. At the same time, CB2 receptors that are located predominantly in peripheral tissue, exist in the CNS at very low levels. Also, cannabinoids may play a key role in pain modulation through their anti-inflammatory mechanism. Cannabinoids are able to decrease the release of such inflammatory agents as serotonin and histamine. They also act on keratinocytes to enhance the release of analgesic opioids. According to one of the studies, the efficacy of synthetic CB1- and CB2-receptor agonists can be comparable with the efficiency of morphine in case of tumour pain.
Also, cannabinoids have shown to be the effective agents to prevent neuropathy caused by chemotherapy in animal models exposed to such drugs as vincristine, paclitaxel, or cisplatin.
CBD for different types of cancers
The evidence shows that cannabidiol could act as an antitumour agent, triggering cell death, reducing cancer invasiveness, and preventing cancer cell migration. In addition to this, it also has the angiogenesis properties that means CBD can block new blood cell formation, slowing the spread of cancer cells. When it comes to the cannabidiol use for treatment, it has been suggested to be effective for different types of cancer. CBD can be used for the treatment of lung cancer, skin cancer, leukaemia, breast cancer, colon cancer, prostate cancer, and other types of malignant tumours.
- Breast cancer. According to the study, published in the “Journal of Pharmacology and Experimental Therapeutics,” CBD can be chosen for breast cancer treatment. The primary antitumour efficiency of cannabinoids is focused on the cannabidiol effects on carcinoma in the human breast. Cannabidiol coordinates communication between apoptosis and autophagy, thereby triggering and enhancing programmed cell death of the breast cancer cells. During the research held by the group of researchers at the Istituto di Chimica Biomolecolare in Italy, it was shown that in comparison with three other cannabinoids, cannabidiol appeared to be the most effective one in the case of breast cancer treatment. It showed better results than other potent anticancer cannabinoids, such as THC. Throughout more than ten years of research, the team of Italian researchers revealed many of the complex mechanisms of CBD work, explaining its effect on the proliferation of breast cancer cells and breast cancer metastasis inhibition.
- Colon cancer. Besides positive effects on fighting breast cancer, CBD also shows promising results in combating colon cancer. Several scientific reviews have shown that cannabidiol can prevent colon cancer by reducing the development of some carcinogenic factors that are usually found in colorectal cancer patients. CBD may also help to reduce abnormal glands in the rectum and colon, reduce tumour formation, and the number of polyps.
- Brain cancer. In a study published in the “Journal Pharmacology and Experimental Therapeutics,” it was investigating whether cannabidiol can inhibit the growth of brain tumour cells in mice. During the study, all mice were given a dose of 0.5mg of CBD, and the growth of implanted human U87 glioma cells was observed. As a result, significant antitumour activity caused by cannabidiol was obtained.
- Lung cancer. A case study held in February 2019 has attracted attention due to the positive results obtained. During this study, a patient with adenocarcinoma in the lung was treated with cannabidiol. Eventually, the tumour in his lung decreased significantly proving the antitumour CBD effects. One of the studies gives indications of how this effect occurs and explains the role of the COX-2 and PPAR-γ receptors in CBD-induced apoptosis (“suicide program” of biological cells) of lung cancer cells.
The vast majority of preliminary research published for today demonstrates the positive benefit of CBD for cancer therapy. Some other research for cannabidiol and prostate cancer, bladder cancer, and other cancer types are still ongoing.
CBD today and tomorrow. What are the future perspectives of cannabinoids?
According to the research published in the journal “Carcinogenesis”, cannabidiol can make glioblastoma more susceptible to chemotherapy. To date, according to statistics, glioblastoma is the most common malignant brain tumour in adults. The mechanism of CBD’s action is aimed at increasing the TRPV2 activity, which in its turn enhances the ability of glioma cells to absorb chemotherapeutic agents. At the same time, no adverse effect on the body’s normal astrocytes was caused. In addition to this, it was shown in several studies that CBD is able to counteract neuropathic pain without adversely affecting nervous system function or the effectiveness of chemotherapy.
Besides enhancing the effectiveness of the chemotherapy, cannabinoids mainly have been allowed for use in palliative treatment. Antiemetic and analgesic properties of these agents allowed them to be used to reduce side effects from other cancer treatments and to improve the patient’s quality of life maximally. Nevertheless, the situation has changed dramatically with the increasing number of preclinical studies demonstrating the anticancer properties of cannabinoids. It was shown that cannabinoids mechanism of action lies in a modulation of the signalling pathways that play a key role in the control of cell proliferation and survival. Many in vitro and in vivo experiments have shown that cannabinoids are able to inhibit proliferation of cancer cells, stimulate autophagy and apoptosis, and also have a potential to inhibit angiogenesis and metastasis.
Today, one of the essential tasks of CBD oil in cancer treatment is to alleviate the side effects of chemotherapy as much as possible. Cannabidiol can be useful in minimisation of such side effects as:
- chronic pain;
The mechanism of the new cannabis-based preparations lies in synergistic interactions between their various components. Among such interactions may be:
- changes in bioavailability or cellular transport;
- activation or deactivation of other metabolites;
- multi‐target effects of synergistic partners.
It has also been shown that cannabis extracts demonstrate more potent effects on the subjects with spasticity in comparison to pure THC. Moreover, some cannabinoids can alleviate the psychoactive effects caused by THC or smoked marijuana. Terpenes, flavonoids, and other metabolites of cannabis can significantly contribute to the modulation of cannabinoids pharmacokinetics. However, for the moment, pure cannabinoids are considered to be the most convenient for study and further standardisation as a medical preparation. As a future perspective, cannabis extracts with specified amounts of cannabinoids also seem to become a valuable aim for new research, including their role as potential anticancer agents.
Among the modern methods of CBD introduction to the cancer treatment is the idea of cannabinoids combination with conventional anticancer medications. It is suggested that such a combination can exhibit synergistic potential. Scientists have already obtained promising results from the studies that included the animal model of glioblastoma treated with temozolomide together with THC. Similar results were achieved from the study on pancreatic adenocarcinoma demonstrated that gemcitabine administered with cannabinoids could synergistically inhibit the growth of cancer cells.
Despite the fact that several cannabinoid-based drugs have already been registered in several countries (such as dronabinol, nabiximols, and nabilone), there isn’t still enough evidence from clinical trials to fully support the use of these medications for treatment. Most of the evidence obtained by now refers to the use of cannabinoid-based drugs for alleviating spasticity and chronic pain condition. There were also proofs regarding the use of the cannabinoids for the treatment of nausea, vomiting, sleep disorders, Tourette syndrome, and weight loss in case of AIDS.
The incorporation of cannabis products is still at the initial stage in clinical care. Today, there is still a lack of clinical trials researching cannabis efficacy and profound safety of its clinical use. It is difficult to fully access all the potential benefits and risks of choosing cannabinoids in case of cancer and other treatments. Also, such crucial moments as the way of administration, dosage, adverse effects, and interaction with other medications should be elucidated. The most common and famous all over the world way of using marijuana - smoking is unsuitable from the medical point of view. Available today cannabinoid-based drugs have a form of capsules or oromucosal sprays. Another vital issue regarding the current situation with cannabis drugs is the lack of accessible biomarkers that can show the patient's’ responsiveness to cannabinoid treatment.
Currently, there are no CBD products with the FDA-approved status for cancer treatment. Thus, aside from Epidiolex for epilepsy, all the products that are available today haven’t been evaluated by the agency and haven’t got the final verdict yet. However, even without enough proofs, people are using these medications for alleviating side effects of debilitating cancer treatment. Because of this, it is highly recommended for patients to talk to their doctor before including CBD or any other cannabidiol-based products into their cancer treatment in order to avoid the adverse reaction with other medications.
Cannabinoids showed very perspective results in animal studies. Their antitumour activity in cell lines and animal models looks promising. However, there is still a lack of data concerning the cannabinoids’ efficacy and safety supported by results from clinical trials. Even taking into account all the potential benefits of CBD oil and cannabinoid-based products, further profound studies and trials are doubtlessly needed to confirm the idea of introducing cannabinoids into the cancer treatment.