Cannabis is an age old therapeutic that has been used to treat several illnesses. Two of its active components (cannabioids) are CBD and THC that have several applications in modern medicine, and multiple clinical trials are going on to find out the use of CBD for cancer treatment. Although CBD was legalized in US in 2018, THC still remains a federally controlled substance and its production and sale are regulated by the marijuana laws of states.

Clinical Trials Suggesting That CBD Can Be Effective In Cancer Treatment

Here are some promising studies conducted to find the effectiveness of CBD in cancer treatment.

• A 2019 review that analyzed several in vitro and in vivo studies, which focused on the effectiveness of CBD in checking the development of pancreatic cancer, found that cannabinoids can slow down the growth of tumors, reduce the invasive capacity of tumors and cause the death of tumor cells. The authors also noted that precise information about ideal dosage, exact mode of action etc is lacking, and hence further studies have to be conducted before making solid conclusions.
• A long term study conducted by California Men’s Health found that cannabis use may be related to the risk of bladder cancer but the study couldn’t establish the exact relationship.
• A 2019 study suggested that CBD can make glioblastoma cells prone to radiation used in cancer treatment, all the while protecting healthy cells.
• A two-year study conducted in rats and mice suggested that cannabinoids may exert a protective effect by preventing the development of certain tumors. In the study, groups of mice and rats were given varying doses of THC. Decrease in the Heptocellular carcinoma (HCC) and hepatic adenoma tumors were noted in the mice, with the effects varying according to the doses. The incidence of benign tumors in organs like uterus, pituitary, pancreas etc was found to have decreased in the rats.
• In another study that involved the use of delta-9 THC, delta-8 THC and CBD in in-vitro and in-vivo clinical trials, the inhibited growth of Lewis lung adenocarcinoma cells was noticed.
• A 2014 in vivo study conducted in experimental models of colon cancer suggested that cannabidiol may check the spread of colorectal cancer cells.

Although the anti-cancer effects of cannabinoids and their working mechanism is not understood completely, it is inferred that they produce anti-tumor effects through mechanisms like cell growth inhibition, inducing the death of cancer cells, inhibition of metastasis and angiogenesis invasion. Cannabinoids have the ability to kill tumor cells but they do not cause any adverse effects on the cells that didn’t undergo transformation.

Programmed cell death in multicellular organisms is called apoptosis. In a study involving glioma cell culture, cannabinoids induced apoptosis in the cells and caused regression of glioma tumors in the tested animals (mice and rats). Some clinical trials have also suggested that cannabinoids stimulated an endoplasmic reticulum stress pathway that was involved in the promotion of apoptosis and activation of autophagy (cell mechanism to remove dysfunctional components) so as to trigger the death of cancer cells.

CB1 and CB2 are the major endocannabinoid receptors that are influenced by cannabinoids CBD and THC. Multiple clinical investigations have reported that the rectors might be potential targets in non-small cell lung carcinoma.

An in vitro study conducted to study the influence of CBD in facilitating programmed cell death along the cell lines in breast cancer tissues found that CBD cancer treatment is possible as it induces programmed cell death, with the action independent of vanilloid, CB1 or CB2 receptors. Cannabidiol checked the growth of both estrogen receptor-negative and estrogen receptor-positive breast cancer cells, all the while hardly affecting the non-tumorigenic breast cells.

Effect Of Cannabinoids In Handling The Side Effects Of Cancer Treatment

Common treatments used to cure cancer include radiation therapy, chemotherapy etc. Treatments like chemotherapy have several side effects including nausea, vomiting, loss of appetite, weight loss etc. CBD and THC can be used individually or in combination to handle the side effects of cancer treatment.

Some clinical trials on mice have suggested that the cannabinoid, anandamide has the ability to enhance the appetite in lab mice. CB1 receptors of the endocannabinoid system may be involved in the reward aspects associated with eating.

Endocannabinoid system of the body regulates the appetite, and the influence of cannabinoids on the system provides insight to the potential of cannabinoids in improving the appetite of the cancer patients. Nausea and vomiting are common side effects associated with cancer therapy and the symptoms has a negative impact on the appetite of the patient, further affecting their overall health as the body doesn’t get enough energy to heal itself.

Antiemetic Effects

Emesis refers to vomiting and nausea refers to the gastrointestinal discomfort that makes one want to vomit. Antiemetic drugs are used to treat vomiting and nausea that are often associated with use of chemotherapy and medication like opioids. Research has suggested that the control of the emetic circuitry is handled by the endocannabinoids in the body, with the antiemetic action facilitated by the interaction of 5-hydroxytryptamine 3(5-HT3) receptor.

Several clinical findings suggest that cannabinoids like CBD and THC are better antiemetics than antiemetics like prochlorperazine, haloperidol, chlorpromazine, metchlopramide etc. It was until recently that the proper mechanism through which cannabinoids offered relief to chemotherapy induced nausea and vomiting (CINV) was found, although the potential of cannabinoid in handling CINV was recognized before several decades.

As of now, there are no FDA approved cannabidiol products except epidolex used to treat two types of epilepsy disorders. However, there are two marijuana-derived drugs, used to treat nausea and vomiting symptoms characteristic of chemotherapy side effects. They are:

• Dronabidiol-THC based drug available in capsule form
• Nabilone- Synthetic cannabinoid working in ways similar to that of THC

Pain Relief

Pain perception is handled by the endocannabinoid system and its receptors spread across different parts of the body are responsible for handling pain symptoms that arise as part of multiple disorders. Cancer and its treatment might cause pain symptoms due to  multiple factors like nerve injury, pressure exerted on internal organs, inflammation etc.

By exerting indirect influence on CB2 receptors, cannabidiol can help relieve the pain caused by inflammation.THC too offers pain relief but it influences the CB1 receptors unlike CBD. THC offers great help in reducing pain caused by nerve damage.

Details of analgesic properties of CBD have been increasingly analyzed based on the spinal, supraspinal and peripheral modes of action, where the cannabinoids acts on the ascending as well as well as descending pathways. CB1 receptors of the endocannabinoid system are majorly found in the central nervous system even though the receptors are found in the peripheral nervous system too. On the other hand, CBD2 receptors are predominantly found in the peripheral nervous system with their numbers in the central nervous system so low. In depth information about the role of several receptors and endocannabinoids in modulating pain can be obtained by developing receptor-specific antagonists.

Some studies have shed insights to the pain relief effects produced by cannabinoids through an anti-inflammatory mechanism. Cannabinoids act on mast cell receptors to distort the release of inflammatory agents in the body like serotonin and histamine.

CBD And THC For Cancer Prevention

After reviewing numerous studies conducted to determine the link between cannabis and cancer, it was found that the clinical trials yielded mixed results. An older study conducted in the US involving 64,845 men concluded that the use of cannabis was in no way connected to tobacco-related cancers.

The authors of a 2015 study found out that a promising relationship exists between cannabis and bladder cancer. After adjusting the test conditions appropriately, the study found out that risk of cannabis users developing bladder cancer was 45 percent low.

Although THC is an actively studied compound in cancer research, the studies about the possibility of smoked marijuana causing cancer remains inconclusive. However ingestible CBD and THC methods do not lead to the entry of carcinogens in to the body.

Cancer Pain Relief Medications

Nabiximol (Sativex) is an approved pain relief medication used in Canada. The medication contains CBD and THC in the ratio 1:1 and is effective in treating the pain symptoms associated with advanced stages of cancer. Sativex is administered as an oral spray and contains extracts derived from two varieties of cannabis plant. The therapeutic mixture contains psychoactive delta-9 tetrahydocannabinol and non-psychoactive cannabidiol in equal amounts. In addition to these active cannabinoids, the mixture contains flavinoids, minor cannabinoids and terpenes.

Cannabis Use Pattern Among Cancer Patients

Seattle Cancer Care Alliance conducted a 6 week survey of cancer patients to identify cannabis use patterns. The survey was conducted between 2015 and 2016. There were 2737 participants in the survey out of which 936 people completed the questionnaire. Among the 936 people, 24 percent considered themselves active cannabis users. Some preferred inhaling CBD, while some chose CBD and THC edibles. A significant percentage preferred dual use. The users reported that the major reasons why they used cannabis included:

• Treatment of physical symptoms
• Treatment of neuropsychiatric symptoms
• Recreational Use

Pain, loss of appetite, nausea etc are some of the common physical symptoms experienced by cancer patients. A major percentage of patients stated that they preferred getting the information about cannabis from their cancer team while a small percentage of patients reported that they preferred getting information from their physician.

Although cannabinoids have been traditionally effective in treating the symptoms associated with cancer and its treatment, no conclusive evidence about the potential of using cannabinoids as cancer cure has been found till date. Hence it is wrong to endorse cannabis products as cancer cure medication.  However the use of CBD and THC is quite popular as a complementary treatment of cancer.