Using cannabis in prostate cancer patients
In our hospital’s daily practice we notice the popular use of cannabis oil in prostate cancer (PCa) patients. As a nursing specialist for urology, I have even met patients who are so convinced of the curative benefits of cannabis oil in treating prostate cancer that they replace standard treatment with the use of cannabis oil.
These patients include those who have localised prostate cancer where active surveillance is followed, those with biochemical recurrence after treatment, and patients with metastatic PCa. I have always wondered whether cannabis oil could indeed be a cure for prostate cancer. Unfortunately, I do not see in practice the desired beneficial effect and the PSA values continue to rise. To find some answers, I did a search in scientific literature.
Cannabis, a very easy plant to grow, has been used for centuries for its medicinal properties. The oldest known document about cannabis use originates from the Chinese emperor Shen Nung in 2727 B.C. It suggested that cannabis has a neuron-protective effect. The Egyptians used cannabis to treat glaucoma and as an anti-inflammatory agent (inflammation of the eyes, fever). Cannabis was even used in obstetrics (mixed with honey) and the mixture was applied in the vagina to “cool” the uterus. In the Old Testament, there is also an account of God instructing Moses to make a holy anointing olive oil-based “Kaneh Bosm.”
Cannabis contains more than 400 chemical components 80 of which contain cannabinoid components and 200 non-cannabinoids components. For medical purposes, cannabinoid substances such as THC (Delta-9-tertrahydrocannabinol), CBD (cannabidiol) and non-cannabinoid substances such as terpenoids and flavonoids are relevant.
Medicinal cannabis must be distinguished from recreational cannabis which is used to achieve a psychotomimetic state of ‘high’. Cannabis strains used for recreational purposes contain a higher THC and lower CBD ratio than cannabis for medicinal use. Usually two cannabis plants are used: cannabis sativa which has a higher THC concentration and cannabis indica which has a higher CBD concentrate. The flavonoids are known for their antioxidant and anti-inflammatory effects. The terpenoids are resins (oil) with a strong odour.
In the 1990s, the endocannabinoid system (ESC) of the body was discovered by Raphael Mechoulam, an Israeli professor of medical chemistry. The endocannabinoid system, a central regulatory system, is the body’s largest receptor system and is important to maintain the homeostasis of the body.
Human beings produce their own cannabinoids (endocannabinoids) according to need and are not stored in the body. Like endorphins, the human body produces endocannabinoids in response to activities such as physical exercise (the high of runners might be due to endocannabinoids, not endorphins!).
Cannabinoid receptor type 1 (CB1) is mainly found in the brain, and also in the lungs, the reproductive organs, etc. Cannabinoid receptor type 2 (CB2) is usually located in the immune system and in the bones. THC mainly works on CB1 receptors, CBD on CB2 receptors.
In vitro studies with THC have shown that cannabinoids affect migration, angiogenesis and apoptosis (programmed cell death) of cancer cells, but each type of cancer appears to respond differently to the effect of exogenous cannabinoids. Many types of cancer cells have a higher concentration of CB1 and CB2 receptors.
Use of cannabis in cancer
– Pain: Cannabinoids have been used for centuries to lessen pain. Historical texts and old pharmacopoeia noted the use of cannabis for menstrual cramps, pain during childbirth, and headaches. Studies have shown that the cannabinoids have no effect on acute pain and post- operative pain. Two placebo-controlled studies with a cannabis extract showed modest benefits when using cannabinoids in addition to opioids and other adjuvant pain-killers in cancer patients with chronic pain. However, the effect of cannabinoids in chronic neuropathic pain was clearly demonstrated in 29 randomized studies.
– Nausea and vomiting: An initial study in 1975 showed a beneficial effect of THC on nausea induced by chemotherapy. Subsequently, two systematic reviews showed benefits of cannabinoids in nausea and vomiting due to chemotherapy, but most studies were observational or uncontrolled.
– Stimulation of appetite: Cannabinoids seem to have only a modest effect in cancer patients with cachexia. More promising results were seen in studies in the population without cancer.
– Pre-clinical studies (in vitro = cells in laboratory and in vivo = in mouse model) have shown the antiproliferative, anti-metastatic, anti-angiogenic and pro-apoptotic effects of cannabinoids in various malignancies (lung, glioma, thyroid, lymphoma, skin, pancreas, endometrium, breast and prostate). Even if an identified substance in vitro / in vivo appears to have a beneficial effect on a disease, it is important to realise that only one in 5,000-500,000 substances obtain a registration and becomes available to the patient (after 10-16 years of different study phases). Cannabis has never been clinically studied as a treatment for malignancy.
On the Internet, patients can get a lot of information about the curative effect of cannabis oil on prostate cancer but this information extrapolate the results of pre-clinical work to possible effects in people without any factual evidence. I often see patients in the doctor’s office showing me a website where it has been proven that cannabis oil can cure prostate cancer, which is obviously their own interpretation. In my view this can be a misleading message even though the website does not explicitly provide false information. The website [See figure below] shows information which is based on a study published in the British Journal of Cancer. This is correct, but the website “neglects” to mention that this is a publication of an in vitro study. The patient might not even know what an in vitro study is and is not aware that there are no studies on humans yet to prove this.
A challenge for the caregiver can be that the patient is convinced that we as healthcare practitioners work together with the pharmacists, and that we do not wish to carry out clinical trials (unfortunately, I hear that very often). We can hardly persuade patients that this is not true.
It is also important that we inform the patient about the possible interactions of cannabis oil with certain regular medications such as Coumarin (this blood thinner interacts with cannabis oil, leading to an increase of the INR and a greater risk of bleeding!). There are different types of cannabis oil available, such as CBD and THC oils with different concentrations which makes it difficult for patients to make a choice.
• There is no proof of cannabis oil as cure for prostate cancer;
• It is important not to be prejudiced or judgmental against patients who use cannabis oil;
• Listening to the patient’s view can be helpful since the patient often confides to the nurse rather than to their physicians;
• Avoid persuading patients not to use cannabis oil, but try to convince them of the need to follow a regular treatment combined with cannabis oil;
• Consider adverse interactions between cannabis oil and certain medications and inform your patient about these.
In our hospital we notice the popular use of cannabis oil in prostate cancer (PCa) patients, they even replace standard treatment with the use of cannabis oil.
Cannabis and Prostate Cancer
By: Dr. Dan Sperling
- Imaging & mpMRI
- Active Surveillance
- Health & Wellness
- Prostate Cancer Diagnosis
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.”[i] 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[ii] 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.[iii]
A very extensive study was conducted by De Petrocellis et al. (2012)[iv] 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] 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.
[ii] 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.
[iv] 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.
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
Cannabinoids offer new directions for prostate cancer treatment.