Source: Dr. Willaim Makis on Substack
Cannabidiol (CBD) is a naturally occurring compound found in the resinous flower of cannabis, a plant with a rich history as a medicine going back thousands of years. Today the therapeutic properties of CBD are being tested and confirmed by scientists and doctors around the world. A safe, non-addictive substance, CBD is one of more than a hundred “phytocannabinoids,” which are unique to cannabis and endow the plant with its robust therapeutic profile.
Cannabidiol (CBD) is derived from the cannabis plant, and comes with a wealth of health benefits. CBD is one of over 60 compounds found in cannabis that belong to a class of ingredients called cannabinoids and the medical world is realizing that its list of medical benefits is continuing to grow. Those who are new to cannabis find CBD to be a great first step, because unlike psychoactive THC, CBD doesn’t give you the intoxication or “high” effect. It can be vaporized using a pen, but many patients using CBD as medicine are turning to sublingual tinctures, ingestible oils and treats, capsules, and even topical products. CBD Oil is a great remedy for a lot of different ailments.
Which cancers might benefit from CBD or CBD Oil?
Paper Reviewed:
- (2022 Feb, Kylie O’Brien) – Cannabidiol (CBD) in Cancer Management
- (2023 May, Miranda-Massari et al) – CBD as a Physiological Modulator for Cancer
- (2022 May, Heider et al) – Mechanisms of Cannabidiol (CBD) in Cancer Treatment: A Review
- (2023 Nov, Smith et al) – Full spectrum cannabidiol oil reduces breast cancer cell viability and expression of epidermal growth factor receptor
- (2020 Oct, Seltzer et al) – Cannabidiol (CBD) as a Promising Anti-Cancer Drug
- (2019 Oct, Likar et al) – Concomitant Treatment of Malignant Brain Tumours With CBD – A Case Series and Review of the Literature
(2022 Feb, Kylie O’Brien) – Cannabidiol (CBD) in Cancer Management
- The plant Cannabis sativa has been used medicinally for thousands of years in many cultures including Chinese, Japanese, Indian, and Egyptian
- There are over 540 secondary metabolites in the cannabis plant, of which there are over 120 phytocannabinoids
- Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two most well-researched of the phytocannabinoids
- In addition, over 200 terpenes have been isolated from cannabis, along with phenols, steroids, polysaccharides, coumarins, glycosides, flavonoids, alcohols, and other plant nutrients, and these have their own therapeutic actions
- ‘ENTOURAGE EFFECT’ refers to the cooperative effect between the various constituents of the plant, whereby the therapeutic effect of the other constituents may contribute to the overall therapeutic effect of the main phytocannabinoids (i.e., THC, CBD)
- CBD-predominant products typically have very low amounts of THC
- THC (intoxicating effects) vs CBD (no intoxicating effects)
- Both THC and CBD have many therapeutic actions in common, but their mechanisms of action differ
- THC is a partial agonist of the CB1 and CB2 receptors
- CBD has a low affinity to the cannabinoid receptors, and is believed to exert its actions predominantly via activating the ECS (endocannabinoid system) indirectly, as well as interacting with other targets or receptors
- Our Endocannabinoid System – one of the most important neuroregulatory systems we have, responsible for the homeostasis of most systems in the body, including immune system (innate, adaptive), inflammation, pain/analgesia, stress response, emotion/moods, cognitive function, memory, sleep, gastrointestinal, etc
Endocannabinoid System in Cancer
- Cannabinoid receptors are widely expressed on cancer cells as well as normal cells, some are overexpressed, some are underexpressed
- example: overexpression of CB1 and CB2 receptors was found to be correlated with poor prognosis in stage 4 colorectal cancer
- endocannabinoid system is specific to the type of cancer
- animal cancer models show CBD has ability to inhibit progression of glioblastoma, breast, lung, prostate, colon cancer and melanoma.
- CBD affects many tumoral features and molecular pathways, it has many targets
- regulates reactive oxygen species – shown in glioma cells, leukemia, breast cancer cells (but doesn’t harm normal brain cells)
- immune modulation
- tumor microenvironment – reduces secretion of cytokines from cancer cells, suppresses angiogenesis within tumor, also inhibits exosomes – mediators of intracecullar communication released by cancer cells which affect cell migration and differentiation (breast ca, prostate ca, hepatocellular ca)
- endoplasmic reticulum stress – has to do with folding of proteins
- In human glioma – CBD induced cell death, inhibited cell migration and invasion, reduced size of tumors, reduced vascularization, induced tumor regression and increased survival.
- Mouse glioblastoma – inhaled CBD changed tumor microenvironment, cellular and molecular signaling, limited tumor growth and helped immune system recognize the cancer, increased CD8 response
- Breast cancer – CBD works through many mechanisms – apoptosis, autophagy, cell cycle arrest, strongly inhibits tumor growth, downregulates a factor in metastasis
- CBD inhibits GPR55 (G-protein receptor) which promotes uncontrolled proliferation, angiogenesis, cancer cell adhesion, migration and metastasis (breast cancer, colon cancer, pancreatic adenoca)
CBD In Management of Symptoms endured by cancer patients:
- Anxiety – CBD has anxiolytic effects
- Depression – CBD may reduce depressive-like behaviors
- Sleep disorders – 20-75% of cancer patients have sleep disturbances, research on CBD is mixed. 50% of cannabis (not CBD) users use it to treat insomnia
- cancer pain – CBD and THC have similar impact on pain relief (however THC superior to CBD in improving sleep duration)
Combining CBD with “orthodox cancer treatment”
- CBD can synergise with various chemotherapeutic agents to increase their efficacy
- CBD has been found to sensitize cancer cells to cisplatin and significantly increase cisplatin-mediated apoptosis
- CBD enhanced the effects of gemcitabine: mice treated with a combination of CBD and gemcitabine survived almost three times longer than mice treated with gemcitabine alone
- Combination of CBD and THC reduced multiple myeloma (MM) cell migration
- CBD alone and in combination with the proteasome inhibitor bortezomib was found to strongly inhibit growth, arrest cell cycle progression, and induce death of multiple myeloma cells
- CBD and THC combined synergistically with common anti-leukemia drugs, sensitising leukemia cells to the cytotoxic effects of the drugs and allowing the doses of these drugs to be reduced substantially whilst remaining efficacious
Barriers to use in Oncology
- lack of standardization of CBD products
- variable quality of products
- Oncologists don’t know how to use them, what dose to use, etc
(2023 May, Miranda-Massari et al) – CBD as a Physiological Modulator for Cancer
- CBD products classified into 3 groups:
- 1. CBD isolate (purified form of CBD) (no entourage effect)
- 2. full spectrum hemp extract (contains CBD and other naturally occurring terpenes and cannabinoids)
- 3. broad spectrum CBD (similar to full spectrum but lacks THC)
- CBD has anti-cancer effects on mitochondrial function (mitochondrial dysfunction can lead to cancer, CBD improves mitochondrial function)
- CBD and Cancer Gene Expression
- ID-1 is a protein that plays a prominent role in tumor proliferation and progression
- ID-1 is overexpressed in more than 20 types of cancer
- CBD is the only agent shown to be able to downregulate ID-1, inhibiting production of ID-1 protein
- CBD & Growth factors – CBD inhibits epidermal growth factor (EGF) in breast cancer, and inhibits expression of EGFR (EGF receptor) in lung cancer
- CBD upregulates p53 (When p53 detects cellular DNA damage, it terminates the cell cycle and stimulates apoptosis. Loss of p53 function results in uncontrolled cell proliferation and tumor cell resistance to apoptosis)
- CBD & Exosomes – tumor cells release higher volume of exosomes than normal cells (share proteins that contribute to malignancy and growth, interact with immune system to shiled cancer cells from detection)
- CBD reduces number of exosomes with pro-oncogenic proteins, and increases exosomes with anti-oncogenic proteins
- inhibition of exosome release is dose dependent
- at higher oral doses of CBD, CBD can block 50% of exosome release in prostate cancer, breast cancer and hepatocellular cancer (CBD doses of 750 to 1500mg were tolerated with mild adverse effects)
(2022 May, Heider et al) – Mechanisms of Cannabidiol (CBD) in Cancer Treatment: A Review
(2023 Nov, Smith et al) – Full spectrum cannabidiol oil reduces breast cancer cell viability and expression of epidermal growth factor receptor
- A “triple negative” breast cancer cell line was tested against an over-the-counter CBD oil product to determine if it possessed cell cytotoxic properties
- Cancer cells exposed to CBD oil had reduced cell viability, broad changes in gene expression, and reduced expression of a key growth factor receptor compared to control cells
- CBD oil is effective at reducing breast cancer cell viability in vitro
(2020 Oct, Seltzer et al) – Cannabidiol (CBD) as a Promising Anti-Cancer Drug
- At present, FDA has approved only Epidiolex, purified CBD for use in patients with seizures
- more than 40 countries have approved medical marijuana/cannabis programs
- Glioma (Grade 4 glioma = glioblastoma) – CBD extensively studied due to lack of treatment options
- CBD induces cell death, decreases tumor size, inhibits cell migration and invasion, vascularization, growth, increases survival
- breast cancer – dose dependent response to CBD, including triple negative breast cancer cells
- CBD acts on breast ca through variety of mechanisms: apoptosis, autophagy, cell cycle arrest
- CBD has also been shown to inhibit migration, invasion, and metastasis in aggressive breast cancer in vivo and in vitro
- breast cancer cells treated with CBD had increased sensitization to cisplatin
- CBD significantly decreased the release of exosomes and microvesicles (EMV) (at 100–200 nm), which typically aid the spread of tumors and cause chemo-resistance
- CBD has been consistently shown to be efficacious in many breast cancer cells and mouse models when it comes to its anti-proliferative and pro-apoptotic effects
- lung cancer – CBD stimulates apoptosis in lung cancer
- CBD also inhibits invasiveness of lung cancer
- colorectal cancer – CBD stimulates apoptosis in colorectal cancer through ROS production
- CBD can also overcome resistance to chemotherapy
- there are no clinical trials related to CBD in CRC
- leukemia/lymphoma – CBD induces a dose- and time-dependent killing effect on leukemia and lymphoma cell lines
- majority of research on leukemia/lymphomas confirmed apoptosis as the mechanism by which CBD-mediated cell death occurs, either alone or in combination with other treatment modalities
- prostate cancer – CBD can inhibit the expression of the androgen receptor
- CBD induced anti-proliferative effects and apoptosis-mediated cell death
- effects of CBD on a variety of other cancers have also been reported, however to a lesser degree
- cervical cancer – concentration-dependent killing effects that were shown to be mediated by apoptosis and independent of cell cycle arrest
- hepatocellular cancer
- gastric cancer
- melanoma
- pancreatic
- Conclusions:
- CBD has demonstrated robust anti-proliferative and pro-apoptotic effects on a wide variety of cancer types both in cultured cancer cell lines and in mouse tumor models
- CBD not only acts on tumor cells (apoptosis, autophagy) but can also affect the tumor microenvironment
- CBD can also inhibit tumor migration, invasion and angiogenesis.
- CBD has multiple cellular targets and different targets in different tumors
- “There is extensive preclinical research indicating CBD as an efficacious anti-cancer agent either alone or in conjunction with other cannabinoids, chemotherapies, and radiation therapy”
HUMAN STUDIES:
(2019 Oct, Likar et al) – Concomitant Treatment of Malignant Brain Tumours With CBD – A Case Series and Review of the Literature
- 9 Grade 4 Glioblastoma patients treated with pure CBD with daily dose of 400mg. Results are as of October 2019.
- Case 1: 38F, Grade 2 Astrocytoma removed. Post surgery asked only for CBD starting July 2018 (400mg/day). Pain reduced from 4 to 0-1 and disease stable as of Oct.2019
- Case 2: 13M, Grade 2 meningioma removed, started CBD Aug.2018 (400mg/day), disease stable
- Case 3: 40M, Grade 4 glioblastoma treated with chemorad, on CBD from May 2017 (400mg/day), tumor shrinking, no further seizures
- Case 4: 44F, Grade 2 oligodendroglioma, CBD started Feb.2017 (2x300mg/day), stable disease.
- Case 5: 60M Grade 4 glioblastoma operated, started CBD Feb.2019 (200mg/day), stable disease
- Case 6: 61M, Grade 4 glioblastoma removed, started CBD May 2017 (400mg/day), stable disease
- Case 7: 41M, Grade 4 glioblastoma 5cm, started CBD Feb.2018 (400mg/day), stable disease
- Case 8: 49F, Grade 4 glioblastoma removed, started CBD Nov.2018 (400mg/day), stable disease
- Case 9: 35F, Grade 4 glioblastoma partially removed, chemorad, started CBD Mar.2018 (2x100mg/day) – slight regression x 10 months, then progression at month 11 and died 2 months later.
- Conclusion: 8 of 9 patients have stable disease, mean survival time of 22 months (longer than expected), only one progressed (had a lower dose 200mg/day instead of 400-600mg/day)
Dr. Makis’s Take…
CBD and Cancer Treatment is a very complicated topic.
According to a review by Seltzer et al (2020): “There is extensive preclinical research indicating CBD as an efficacious anti-cancer agent either alone or in conjunction with other cannabinoids, chemotherapies, and radiation therapy”
Animal cancer models show CBD has ability to inhibit progression of glioblastoma, breast, lung, prostate, colon cancer and melanoma.
Very few human studies, but there is a case series (2019, Likar et al) of 9 brain cancer patients who responded extremely well to 400 mg of pure CBD per day, with 8 of 9 still alive and mean survival time of 22 months, which is longer than expected.
Here are the cancers that might best benefit from CBD and/or CBD Oil:
- Brain Cancer – this is the best studied cancer with CBD. Given the lack of treatment options, adding CBD here is a no brainer. The 2nd most common COVID-19 mRNA Vaccine Induced Turbo Cancer is glioblastoma and it has an even worse prognosis than normal glioblastomas. But whether mRNA vaxxed or unvaxxed, adding CBD is an almost definite “yes” to any treatment regimen.
- Breast Cancer – 2nd best studied cancer with CBD. There has been a surge of recent research with CBD in breast cancer including the most aggressive type: Triple negative breast cancer. The 3rd most common COVID-19 mRNA Vaccine Induced Turbo Cancer is breast cancer (typically triple negative, but not always). CBD also improves efficacy of chemo in breast cancer. Adding CBD to a treatment regimen for very advanced cases is very reasonable and logical.
- Lung Cancer – there is a 2019 case report of a 81M with advanced lung cancer who was denied chemorad and treated himself with 2% CBD Oil and achieving tumor shrinkage a year later (Sule-Suso et al). It’s not much but it’s something. Lung cancer is in the top 5 mRNA Induced Turbo Cancers and they are very nasty with a poor prognosis. I’ve seen many 30 year olds presenting with Stage 4 Lung Cancer – CBD may be an interesting alternative treatment addition.
- Colon Cancer – there is extensive preclinical research but lack of any reports in humans. There are 8 animal studies and all showed decrease in size of tumor (source). CBD can also overcome resistance to chemo. Colon cancer is in the top 5 mRNA Induced Turbo Cancers – I would consider adding CBD in desperate cases with an understanding that all the evidence is preclinical, but animal models are very promising.
- Prostate Cancer – again, extensive preclinical research but nothing in humans. There are 6 animal studies with CBD and all showed decrease in size of tumor (source). In vitro studies also show decrease in invasiveness of prostate cancer. Would consider adding CBD in advanced or desperate cases.
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