Originally published 3/14/2018
Research since the March 2018 posting of the blog below supports the anti-tumor effect of non-psychoactive CBD (cannabidiol), one of 100+ identified plant-derived cannabinoid compounds. For example, Kis et al. note that lab studies have shown a chemopreventive effect of cannabidiol in prostate cancer (PCa) as well as stimulating PCa cancer cell death pathways and boosting genomic antitumor activity.[i] Furthermore, CBD is a “potent inhibitor” of the release of exosomes from PCa cells; exosomes are very tiny particles containing molecular messages that can change the behavior of healthy cells that receive them, and are thus a biogenetic pathway for the spread of PCa. A cell study by Kosgodade et al. revealed that CBD’s ability to regulate the release of PCa exosomes is one of its mechanisms for anti-cancer activity, though such dose-dependent activity appears more powerful in some types of cells others.[ii]
Thus, there is clear evidence that CBD has properties that inhibit PCa cell growth and division, encouraging cancer cell death, and block cancer cells from transforming normal cells into PCa. However, all research thus far has been conducted either in lab animals or using lab-cultured PCa cell lines. The only human clinical trials of CBD are with advanced PCa patients for management of pain and chemotherapy side effects. Thus, the potential use of CBD as a PCa prevention or a treatment for localized PCa is promising but remains hypothetical.
Cannabis (marijuana, pot, weed, grass etc.) is a widely used recreational and medicinal drug. In fact, cannabis use dates far back in ancient times, probably for the same two purposes. Today, state laws in the U.S. are rapidly becoming more permissive less than a century after it was made illegal in 1937.
According to Ramos & Bianco (1912), “The plant contains many chemical compounds that have different pharmacological properties, varying in quantity and quality depending on the strain, culture, and storage conditions. In 1964, Mechoulam and colleagues found that delta-9-tetrahydrocannabinol (THC) was the major psychoactive ingredient of cannabis.”[iii] These compounds, including THC, are called cannabinoids, and 66 separate cannabinoids have been identified.
Cannabinoids produce their physical and psychological effects by interacting with specific receptors on cell surfaces that have an affinity for these compounds. There are two types of receptors:
- Cannabinoid receptor type 1 (CB1) are mostly found in the brain, and also in the male and female reproductive systems. To a lesser extent, they exist in central and peripheral pain pathways (nerves) which may explain why pain relief is a benefit of cannabinoids, particularly THC.
- Cannabinoid receptor type 2 (CB2) are primarily found in the immune system, and may be associated with anti-inflammatory and other therapeutic effects of cannabis.
Cannabis and prostate cancer
There has been both enthusiasm and caution about cannabis use and cancer. By mid-2015, 23 states had legalized medical marijuana, one of the primary uses being to ease the side effects of chemotherapy and radiation in cancer treatment. As described above, CB1 receptors play a key role in cancer pain relief.
Now, as scientific research into the two types of cannabinoid receptors has progressed, understanding how cannabinoids interact with prostate cancer cells opens the possibility of using these compounds to restrict the activity, including the growth and spread, of prostate cancer itself.
How cannabis affects prostate cancer cells
Research shows that prostate cancer cells have higher levels of expression of both CB1 and CB2 receptors than normal cells. To put it another way, the cancer cells have a greater affinity for cannabinoids than normal cells. Laboratory studies[iv] have demonstrated that when the cells are treated with a specific cannabinoids, three consequences occur:
- In general, the cells became less viable and more prone to apoptosis (programmed cell death), and
- Androgen receptor activity on the cancer cell surfaces decreased (prostate cancer appears to be “fueled” by androgens, or male hormones)
- Two cannabinoids, THC and CBD, discourage the formation of tumor blood vessels (angiogenesis) needed by prostate cancer tumors to nourish themselves.[v]
A very extensive study was conducted by De Petrocellis et al. (2012)[vi] using both prostate cancer cells in lab containers and prostate cancer tumor cells implanted in mice. Non-THC cannabinoids were thus tested for their biochemical effects on individual cells as well as actual tumor behavior in live animals. The overall results were encouraging, with the authors suggesting that “non-THC cannabinoids, and CBD in particular, retard proliferation and cause apoptosis of PCC [prostate cancer cells] via a combination of cannabinoid receptor-independent, cellular and molecular mechanisms.”
The current state of cannabinoids and prostate cancer
With such promising research evidence that cannabinoids are destructive to prostate cancer cells, what is happening with actual prostate cancer patients? Not much, according to a prostate.net blog:
There are many stories of people who have used cannabis oil to shrink prostate cancer tumors, and many of the people had success combining the oil with traditional therapies to fight their cancer. The problem with getting hard data and studies is that United States laws make it challenging for clinical studies on the marijuana plant to take place. Plus, there seems to be a lack of funding for the research. The studies that have taken place tend to focus on symptoms (such as pain relief and nausea) rather than the efficacy of the cannabis oil to shrink cancer tumors.
Yet the research teams who have published their results with laboratory experiments, both in lab containers and animal studies, are clearly calling for clinical trials with patients. They point out that non-THC cannabinoids demonstrate properties that keep the cells from proliferating, spreading, building their own blood supply, and taking up androgens (male hormones). In addition, the De Petrocellis study found that under certain conditions, cannabinoids had a synergistic effect with chemotherapy (docetaxel) or hormone therapy (bicalutamide). Such features conjure visions of creative directions in prostate cancer treatment.
Ramos & Bianco explicitly describe a constructive scenario for prostate cancer patients with painful metastasis to the bone. As they state, cannabinoids “harbor analgesic properties that aid bone cancer pain, reduce opioid consumption, side effects, and dependence, as well as exhibiting anti-androgenic effects on experimental prostate cancer cells.”
Perhaps today’s trend of relaxing cannabis restrictions will open the path to human clinical trials, and the real value of cannabinoids in the treatment of prostate cancer will be revealed.
[i] Kis B, Ifrim FC, Buda V, Avram S et al. Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer. 2019 Nov 25;20(23):5905
[ii] Kosgodage US, Mould R, Henley AB, AV et al. Cannabidiol (CBD) Is a Novel Inhibitor for Exosome and Microvesicle (EMV) Release in Cancer. Front Pharmacol. 2018 Aug 13;9:889.
[iii] Ramos J, Bianco F. The role of cannabinoids in prostate cancer: basic science perspective and potential clinical applications. Indian J Urol. 2012 Jan-Mar;28(1):9-14.
[iv] Sarfaraz S, Afaq F, Adhami VM, Malik A, Mukhtar H. Cannabinoid receptor agonist-induced apoptosis of human prostate cancer cells LNCaP proceeds through sustained activation of ERK1/2 leading to G1 cell cycle arrest.J Biol Chem. 2006 Dec 22;281(51):39480-91.
[vi] De Petrocellis L, Ligresti A, Schiano Moriello A, Iapelli M et al. Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms.Br J Pharmacol. 2013 Jan;168(1):79-102.