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Preclinical studies show the potential of CBD for cancer treatment, but the clinical evidence is still non-existing. It is established that CB1 and CB2 receptors have an important role in tumor growth, and scientists hope to find more clinical evidence on the efficiency of CBD for cancer treatment. In the meantime, cancer patients are placing high hopes in CBD as a new cure-all medicine, which is far from being scientifically confirmed.
A study published in May 2021 found that out of 164 campaigns on GoFundMe.com fundraising to purchase CBD between June 2017 and May 2019, 96 were set for purchasing CBD for the treatment of cancer.
According to the World Health Organisation (WHO), cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. The most common new cases of cancer in 2020 were breast (2.26 million cases); lung (2.21 million cases); colon and rectum (1.93 million cases); prostate (1.41 million cases); skin (non-melanoma) (1.20 million cases); and stomach (1.09 million cases). The most common causes of cancer death in 2020 were lung (1.80 million deaths), colon and rectum (935 000 deaths), liver (830 000 deaths), stomach (769 000 deaths), and breast (685 000 deaths).
Clinical trials for the efficiency of CBD in the treatment of different types of cancer through all three phases require considerable financial resources and have not been conducted in sufficient numbers. Therefore, there is not enough scientific evidence for the claims that CBD can be the life-saving treatment for the leading cause of death in the world. However, there is some preclinical evidence in support of further research on this subject.
A 2018 study in experimental mice colon cancer conducted at the University of Shiraz is one of the latest studies that found CBD can potentially be considered as an anti-colon cancer medicine. The study found that the cancer growth was slower in mice treated with CBD, with a more notable effect in the 5-mg/kg CBD-treated group than in the one treated with 1-mg/kg dose. A significant difference in tumor size comparing the 5-mg/kg CBD-treated group with cancer and vehicle control groups was found in the fifth to seventh week of the experiment. Also, a significant difference was observed between 1-mg/kg CBD-treated group with cancer and vehicle control groups in the sixth to the seventh week. CBD exerts an inhibitory effect on angiogenesis, tumor growth, and metastasis through reducing VEGF gene expression, decreasing cytokines, and increasing antioxidant enzyme activities, the study found.
In 2008, a study from the Vanderbilt University Medical Center found that the loss or inhibition of CB1 receptors accelerated intestinal tumor growth while the activation of CB1 receptors attenuated intestinal tumor growth by inducing cell death. The endogenous cannabinoid system may represent a potential therapeutic target for the prevention or treatment of colorectal cancer, the scientists concluded.
There is other preclinical evidence that CB1 and CB2 receptors have an important role in tumor growth, depending on the cancer type. A 2020 review on the potential of CBD as an anti-cancer drug shows that, for example, CB1 is upregulated in hepatocellular carcinoma and Hodgkin lymphoma. CB2 is overexpressed in HER2+ breast cancers and gliomas, and the overexpression of both CB1 and CB2 correlates with poor prognosis in stage IV colorectal carcinoma.
In vitro study on prostate cancer cell lines conducted in 2014 at the University of British Columbia concluded that CBD and other non-habit-forming cannabinoids could be used as novel therapeutic agents for the treatment of prostate cancer. Cannabis treatment not only suppresses the spheroid formation ability of prostate cancer cells but also downregulates pro-inflammatory cytokine IL-6 and chemokine IL-8, decreases secreted protein and mRNA expression of prostate-specific antigen and VEGF levels, found the scientists. The overall findings of this study supported the notion that CBD may possess anti-inflammatory, anti-CSC effects, and down-regulates both cannabinoid receptors CB1 and CB2, leading to their anticancer and chemosensitizing effect against prostate cancer.
At the moment, the University of Kentucky is conducting a phase 1 clinical study on the safety of Epidiolex in patients with prostate cancer. The focus of the study is the highest doses the patients with biochemically recurrent prostate cancer after localized therapy with either surgery or radiation.
CBD’s effects on breast cancer have been studied since 2006, with various breast cancer cell lines used to demonstrate a dose-dependent response to CBD. A 2018 study found that, by modulating exosomes and microvesicles (EMV), CBD can be used to sensitize cancer cells to chemotherapy. In that study, 1 to 5 µM of CBD induced significant cell death in MDA-MB-231 cancer cells after 24 hours. Scientists have found that CBD exerts its anti-proliferative effects on breast cancer cells through a variety of mechanisms, including apoptosis, autophagy, and cell cycle arrest. Also, CBD has been shown to inhibit migration, invasion, and metastasis in aggressive breast cancer. In CBD-treated mice. tumor size has been shown to decrease along with the number of lung metastatic foci, volume, and vascularization. One of the most puzzling effects noticed in mice studies was the impact of the regularity of CBD dosage on the effects. For example, when CBD was administered three times a week, and not daily, the number of metastases was reduced and mice survived longer, but the primary tumor was not reduced. CBD has been consistently shown to be efficacious in many breast cancer cells and mouse models with its anti-proliferative and pro-apoptotic effects, but the exact mechanisms of these effects still need to be examined.
The clinical trials of CBD effects on breast cancer presently underway in the US will be studying the effect of CBD in treating joint pain, anxiety in patients scheduled for CT scan, and the effects of CBD on severity and duration of chemotherapy-induced neuropathy.
A report on clinical responses of cancer patients using CBD in the UK, published in Anticancer Research in 2018, found clinical responses to CBD treatment in 92% of patients. Out of 39 patients with breast cancer included in this four-year-long study, seven resulted tumor-free, 21 with stable disease, and eight with extended median survival. Of the total of 119 patients with different types of advanced cancer, 28 were given CBD as the only treatment. In this study, CBD was administered on three days on and three days off basis, with an average dose of 10 mg twice daily. For increased tumor mass, the dose was increased up to 30 mg daily. In many cases where the stable disease was present, the dose was reduced to 5 mg a day.
The anti-invasive action of CBD on lung cancer was found in a 2010 study, with up to 63% reduction in the invasion of A549 cells, used as a model for human lung cancer. However, there was no significant cell death recorded. CBD also significantly reduced tumor size and lung metastatic nodules in a study of the A549 xenograft tumor model and was found to significantly inhibit A549 lung metastasis in CBD-treated mice. In a 2013 study, CBD was found to be decreasing two lung cancer cell lines, a lung adenocarcinoma cell line and a large cell lung carcinoma cell line. Based on in-vitro and in-vivo studies, the scientists concluded that CBD can attenuate the invasion of lung cancers working through CB1, CB2, and TRPV1 receptors.
There are no published results on a clinical trial using CBD to treat lung cancer in humans, but there is a case report of an 81-year-old male UK patient who attempted to self-treat his lung adenocarcinoma using 2% CBD oil. The patient declined chemotherapy since he didn’t want it to affect his quality of life. After self-treating with CBD oil, a CT scan showed that the tumor and mediastinal lymph nodes began to regress. This patient started taking CBD oil 2% (200 mg CBD in 10 mL) from the beginning until the end of September 2017. He took two drops (0.06 mL, 1.32 mg CBD) twice daily for a week and then nine drops (0.3 mL, 6 mg CBD) twice daily. Following the November 2017 CT scan, the patient started taking nine drops twice daily but had to stop a week later because he did not like the taste and it caused him slight nausea. One year later, another CT scan showed a stable condition of the disease.
Preclinical trials have found that endocannabinoids can either inhibit or promote the growth of colorectal cancer cells. This underlines the importance of further preclinical and clinical research on the effects of CBD for cancer treatment. It is found that CBD can produce a synergy and enhance the effects of standard therapy, and patients with colorectal cancer are also included in the clinical trial on the effects of CBD on the severity and duration of chemotherapy-induced neuropathy.
A 2014 study found that Cannabis sativa extract with high content of CBD showed greater affinity than pure CBD for both CB1 and CB2 receptors. The results of this study may have some clinical relevance for the future use of Cannabis-based medicines in colorectal cancer patients.
There is extensive preclinical research indicating CBD has the potential for the treatment of glioblastoma. The Spanish Group for Neuro-oncology (GEINO) proposed developing a phase Ib clinical trial where CBD is used with THC in a 1:1 ratio along with temozolomide and radiotherapy in patients with newly-diagnosed glioblastoma. Also, the preliminary results of an existing clinical trial show promising results in this type of cancer. A 2019 case series of nine patients with a brain tumor who received CBD in a daily dose of 400 mg show a longer survival time than it would be expected with this progressive disease. While median survival is 14 to 16 months, eight out of nine patients who used CBD survived until the submission of the article, with a median survival time of 22.3 months. Two patients had no signs of disease progression for three or more years.
CBD has demonstrated anti-proliferative and pro-apoptotic effects on various cancer types in cultured cancer cell lines and mouse tumor models. Apart from the cancer types mentioned above, there is preclinical evidence CBD could have potential in treating melanoma, leukemia, lymphoma, gastric cancer, ovarian and pancreatic cancer. There are indications that CBD could be an efficient anti-cancer agent either alone or in conjunction with other cannabinoids, chemotherapies, and radiation therapy. Systematic clinical trials are the next step in examining the potential of CBD for cancer treatment.