Cancer is the world’s second leading cause of death and claimed 9.6 million lives in 2018 . Cancer can affect many of the body’s organs and systems, but the most common sites are the lungs, breasts, prostate, and colon/rectum . The disease is characterized by uncontrolled cell division, irregular apoptosis, and metastasis. There are many possible causes; external factors include ingested chemicals and internal factors include inherited mutations.
Cancer causes alterations in lipid metabolism that link it closely to the endocannabinoid system. Incidentally, the phytocannabinoid cannabidiol (CBD) has exhibited antineoplastic tendencies [3-13].
In animal studies, CBD has been shown to inhibit breast cancer cell growth by inducing apoptosis . McCallister et al. (2007) found that CBD decreases the genetic expression of Id-1 in breast cancer cells; Id-1 is a significant regulator of metastatic activity, and down-regulation appears to reduce tumor aggressiveness .
Shrivastava et al. (2011) reported that CBD creates endoplasmic reticulum stress, inhibiting AKT and mTOR signaling; decreasing phosphorylated mTOR, 4EBP1, and cyclin D1; inhibiting the association of autophagy regulators beclin-1 and Bcl-2; triggering mitochondrial changes; and activating apoptosis in cancer cells . Guindon and Hohmann (2011) describe the mechanisms of CBD’s actions against cancer in even more complex terms (see figure 1) . CBD also inhibits tumor angiogenesis (restricting vessel growth and transport) through effects on tumor and endothelial cells .
Figure 1: Mechanisms of CBD on Cancer Apoptosis. Source: Guindon and Hohmann (2011).
Other types of cancer have also responded to CBD. Researchers in a 2019 study injected 5 mg/kg CBD twice per week in mice with melanoma tumors; the tumors reduced in size and survival rates increased compare to controls . When inserted into animal subjects, human glioma cells saw mitigated proliferation due to CBD-induced apostosis .
CBD has also demonstrated an ability to reduce proliferation of colorectal carcinoma cells in addition to reducing polyps and protecting DNA from oxidative stress . CBD may protect against lung cancer cell invasion through ICAM-1 up-regulation and subsequent increases in tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) . The antineoplastic properties of CBD extend to human prostate cancer cells inserted into animal subjects .
Palliative care is currently the main application of cannabinoids in cancer treatment . Extracts with CBD have helped patients with advanced cancer manage pain when strong opioids fail . A lack of human-based clinical trials currently limits the use of CBD for its anti-cancer properties. Time will tell if future research and clinical trials bring CBD into the light as an ancillary chemo-protective therapy.