Tailored from The Cannabis Cancer Connection: How to use cannabis and hemp to kill cancer cells by Joe D. Goldstrich, MD, with Angela Bacca (Flower Valley Press, 2023).
There’s a rising physique of anecdotal and scientific proof that the “main cannabinoids” tetrahydrocannabinol (THC) and cannabidiol (CBD), sure “minor cannabinoids” (some with out a identify), and different hashish compounds have antineoplastic motion towards most cancers cells.
The overwhelming majority of the present analysis is on how particular cannabinoids kill most cancers, however a rising physique of labor is revealing how the entourage of compounds present in whole-plant hashish kills most cancers.
Though a lot of the research introduced right here demonstrated the antineoplastic results of particular person or remoted cannabinoids, most of this analysis factors to what lay healers and sufferers who make and use their very own hashish oil already know: the entire hashish plant, together with hemp varieties, each a part of them, comprise antineoplastic compounds that collectively kill most cancers.
How THC Kills Most cancers
Till comparatively just lately, nearly all medical research about hashish have been particularly on THC, as is a lot of the preclinical analysis displaying the antineoplastic exercise of hashish. With a number of exceptions, tumor cells all through the physique have cannabinoid receptors on their floor, and THC can bind to those receptors and induce apoptosis or programmed cell dying. Put merely, when THC binds to the most cancers cell, it forces the cancer cell to commit suicide.
Along with inducing apoptosis when binding to a most cancers cell, THC may assist relieve ache. THC binds to 2 varieties of cannabinoid receptors, CB1 and CB2. CB1 receptors are discovered within the mind and all the foremost organs within the physique. Ache impulses are lowered when THC binds to CB1 receptors in nerves carrying painful impulses again to the mind.
The second receptor to which THC binds is CB2. CB2 receptors are discovered within the digestive and immune system, and particularly on many tumors, particularly malignancies associated to the immune system like leukemias and lymphomas. Many tumors contain each CB1 and CB2 receptors.
Curiously, many tumors with a excessive degree of malignancy and an inclination to metastasize have excessive ranges of cannabinoid receptors, making them significantly susceptible to cannabinoid-induced apoptosis. Both CB1, CB2, or each have to be current within the tumor cells for THC to induce apoptosis within the tumor.1-3
THC and CBD additionally restrict tumor development by blocking the manufacturing of vascular endothelial development issue, which stimulates the expansion of recent blood vessels wanted for most cancers to develop. With out elevated blood circulation, the tumor doesn’t have sufficient diet to maintain its improvement.4,5
How CBD Kills Most cancers
CBD displays apoptotic, anti-proliferative, and anti-invasive exercise.6,7 Though CBD doesn’t bind on to the CB1 or CB2 receptors, it additionally has a robust antineoplastic impact. CBD’s presence weakens THC’s binding to the CB1 receptor and will mitigate undesirable psychoactivity brought on by THC.
CBD produces its anticancer impact in a number of methods. Maybe most intriguing is the downregulation of the ID-1 gene. ID-1 is a traditional gene extremely expressed in newborns and younger kids. It stimulates the expansion and improvement of cells, tissues, and organs wanted in early improvement. There may be no use for this in maturity, and ID-1 exercise in regular cells turns into minimal or nonexistent as people get older. Nevertheless, most cancers cells can reactivate this dormant gene and use it to advertise their development. ID-1 not solely encourages the expansion of most cancers cells, it additionally will increase their survival. ID-1 additionally facilitates most cancers’s potential to metastasize whereas defending it from chemotherapeutic brokers.8-12
CBD has been proven to assist flip off ID-1 by downregulating its tumor expression. Like THC, CBD limits tumor development by blocking the manufacturing of vascular endothelial development issue. CBD has additionally been proven to inhibit most cancers cell migration and metastases by stopping most cancers cells from adhering to different tissues.
Combining THC, CBD & CBG
Regardless of the highly effective antineoplastic exercise of all these cannabinoids individually, little or no analysis has been accomplished to indicate their mixed results on most cancers. Nevertheless, preliminary research have proven that combining THC and CBD may be efficient towards melanoma pores and skin most cancers cells and a number of myeloma cell traces.13,14
Extra promising, nevertheless, is a research performed by St. George’s College of London, which demonstrated that CBD was nearly twice as highly effective as THC in its potential to kill leukemia cells in a selected cell line. When THC and CBD have been mixed, the impact was twice as sturdy as CBD alone.
These researchers additionally experimented with a second sort of leukemia cell and located that the magnitude of the cell dying with THC and CBD mixed was lower than with the primary cell sort, however nonetheless confirmed these cannabinoids have been more powerful together than alone.
Additionally they examined combos of CBD and THC with cannabigerol (CBG). As soon as once more, the combos have been persistently extra highly effective than particular person cannabinoids alone. CBD plus CBG proved to be an particularly potent mixture on one of many cell traces. CBD plus CBG additionally improved outcomes when paired with one sort of chemotherapy. When used with one other chemotherapy, CBD with CBG was counterproductive.
Lastly, they demonstrated that when THC and CBD are mixed with chemotherapy, the timing of the administration of those brokers makes an important distinction within the dying of most cancers cells. There was extra most cancers cell dying when the cannabinoids have been administered after the chemotherapy than earlier than it.
Each CBD and THC can have an effect on the metabolic breakdown of many chemotherapeutic medication. Drug interactions can enhance toxicity from chemotherapy by boosting blood drug ranges of chemotherapeutic brokers. I counsel my sufferers to cease utilizing hashish for 36 to 48 hours previous to chemotherapy and to start out once more 36 to 48 hours after their session. (See chapter: Utilizing Hashish Oil with Conventional Most cancers Therapies).
THC & CBD (Sativex®) with Temozolomide: A Phase 2 Study
Earlier than a drug may be submitted for FDA approval, it should bear three testing phases. Section 2 is the primary research degree performed on sufferers with the illness for which the drug is meant and determines whether or not it’s protected and efficient.
United Kingdom-based GW Prescription drugs has produced the world’s first accredited cannabis-based medicines for the UK, US, and European markets, Sativex® and Epidiolex®. Epidiolex is a high-CBD tincture, and Sativex® has a roughly 1:1 ratio of THC and CBD. As a part of the approval course of for all markets, they’ve performed essential Section 2 research on varied situations, together with most cancers.
GW Prescription drugs’ analysis on glioblastoma multiforme (GBM) is vital and promising. They performed a double-blind, placebo-controlled part 2 scientific trial utilizing Sativex® along side temozolomide to deal with recurrent glioblastoma multiforme (GBM). GBM is a extremely aggressive mind tumor with a really poor prognosis. There isn’t any persistently profitable pharmaceutical drug remedy out there to deal with it, and whereas temozolomide is among the finest prescribed drugs at present used, efficacy by itself is sorely missing.
Twenty-one sufferers with recurrent GBM acquired a most of 12 sprays of Sativex® every day, plus temozolomide. In comparison with the placebo group solely receiving temozolomide, 83% of the sufferers handled with Sativex® lived for at the very least one yr, whereas solely 53% of the sufferers within the placebo group lived that lengthy. The median survival for the group taking the Sativex® and temozolomide mixture was larger than 550 days in contrast with 369 days for the placebo group.
Twelve sprays of Sativex® every day (the utmost dose administered on this research) equals 32.4 mg of THC and 30 mg of CBD. Though this can be a far cry from the “gram a day” many sufferers use on their very own and far decrease than the doses normally really useful in most cancers therapy, particularly for extremely malignant tumors like GBM, these remarkably low doses are encouraging. This research additionally speaks to the potential benefits of combining cannabinoids with chemotherapy to realize outcomes neither would possibly obtain on their very own.
[Note: In May 2021, GW Pharmaceuticals was acquired by Jazz Pharmaceuticals.]
How CBG Kills Most cancers
CBG has demonstrated antineoplastic exercise and inhibits the expansion of colorectal most cancers cells primarily by inducing apoptosis. It additionally increases reactive oxygen species (ROS), a mechanism THC and CBD use to kill most cancers cells. Destroying most cancers cells through the ROS mechanism signifies that CBG, like THC and CBD, oxidizes the most cancers cells. Taking antioxidant dietary supplements whereas utilizing hashish as an antineoplastic agent could also be counterproductive. (See chapter: Dietary Dietary supplements & Antioxidants).
Israeli scientist Dedi Meiri has additionally demonstrated the antineoplastic exercise of CBG towards all kinds of cancers. In experiments with 12 most cancers cell traces, Meiri confirmed that CBG demonstrated important cancer-killing exercise towards six of them.
Different preclinical analysis has proven that when CBG is mixed with different cannabinoids, antineoplastic exercise is enhanced in each glioblastoma and breast most cancers cells.15,16
The Earliest Analysis Reveals CBN Kills Most cancers
Cannabinol (CBN) was one of many cannabinoids found initially to be antineoplastic in experiments performed as early as 1975. There have solely been a number of publications demonstrating the antineoplastic results of CBN since then. A newer study has proven {that a} mixture of THC, CBD, CBG, and CBN have probably the most highly effective antineoplastic exercise towards estrogen-positive breast most cancers cells.
A Promising Have a look at CBC
A latest preprint (not but peer-reviewed) publication from Israel confirmed that probably the most potent antineoplastic cannabinoid mixture for killing ovarian most cancers cells was THC, CBG, and cannabichromene (CBC). This analysis was expedited and printed as a preprint as a result of ovarian most cancers is so aggressive and deadly that they wished to get the data within the public area as quickly as attainable.
One other 2021 analysis publication from Israel confirmed that when CBC was paired with both CBD or THC, it “led to cell cycle arrest and cell apoptosis” towards bladder urothelial carcinoma (UC), the most typical urinary system most cancers. Combining CBC with THC or CBD additionally inhibited cell migration (metastasis).
Whereas these research are promising, it’s a problem to include important quantities of CBC into full-spectrum hashish protocols as a result of CBC is current in such low portions in each hemp and hashish cultivars. Till CBC is bred greater within the plant by way of pure strategies, extremely concentrated CBC merchandise are probably a results of artificial processes, resembling these used to provide Δ8-THC. I don’t advocate these artificial merchandise to most cancers sufferers due to their potential toxicity. (See chapter: Cannabinoids, Terpenes & Flavonoids).
Different Promising Cannabinoids
Analysis performed by Dedi Meiri has proven that many different so-called “minor“ cannabinoids, some but even to be named, have antineoplastic exercise. The 2 most researched cannabinoids present in very low concentrations in some cultivars that reveal antineoplastic exercise are tetrahydrocannabivarin (THCV) and cannabidivarin (CBDV). One other cannabinoid recognized by Meiri, at present recognized solely by a quantity 331-18B, has additionally proven important antineoplastic exercise. As a result of the concentrations of those cannabinoids fluctuate so broadly between cultivars, utilizing a number of types of THC-rich hashish to organize therapeutic oil will enhance the chance of incorporating these desired cannabinoids.
The Acid (Uncooked) Cannabinoids
Acid cannabinoids are present in massive portions in “uncooked” (unheated) plant materials. When heated, THCA, CBDA, CBGA, and different acid cannabinoids are transformed into THC, CBD, and CBG, respectively.
In a 2016 research, tetrahydrocanabinolic acid (THCA) was proven to be efficient in inhibiting the expansion of two totally different human breast most cancers cell traces; triple-negative breast most cancers and HER2-positive breast most cancers, which is taken into account to be probably the most treatment-resistant of all breast cancers. Nevertheless, investigators have been unable to find out precisely how THCA achieved anti-neoplasia.
Research from Meiri’s lab has proven that for some prostate most cancers cells, THCA is probably the most antineoplastic cannabinoid.
Two Japanese research exploring the actions of cannabidiolic acid (CBDA) towards one cell line of breast most cancers confirmed that CBDA was in a position to restrict the flexibility of those cells emigrate, which means it might restrict the flexibility of most cancers cells to metastasize. The researchers estimated that this identical mechanism would apply to roughly 40% of invasive breast cancers in people. They uncovered a attainable mechanism of motion within the second printed analysis paper.17,18
Preclinical research have proven that extracts of hashish with excessive content material of each CBDA and cannabigerolic acid (CBGA) inhibit aldose reductase, an enzyme concerned in irritation and most cancers development.19,20
CBGA and THCA every act independently as antineoplastic brokers when used towards precancerous adenomatous polyps and colon most cancers cells. When used in combination, the antineoplastic impact is even stronger.
A Patent for Mixed CBGA & CBDA to Kill Most cancers
GW Prescription drugs was awarded a patent in 2018 by the US Patent and Trademark Workplace for the usage of CBGA and CBDA to kill most cancers. This motion signifies they probably have impartial and proprietary analysis establishing some efficacy. You will need to word that they point out cannabinoids are more practical when utilized in mixture as an alternative of getting used alone. The patent reads:
“The current invention pertains to an energetic pharmaceutical ingredient (API) which contains or consists primarily of cannabidiol (CBD) and one different cannabinoid chosen from cannabigerol (CBG), cannabigerolic-acid (CBGA), cannabidiolic-acid (CBDA), and tetrahydrocannabivarin (THCV) to be used as a medicament, and extra significantly, to be used within the therapy of most cancers. These combos have proven themselves to be synergistic in treating a number of of: breast most cancers; liver most cancers; lung most cancers; pancreatic most cancers; melanoma; ovarian most cancers; gastric most cancers; renal most cancers or bladder most cancers. Two significantly favored API combos are: cannabidiol (CBD) and cannabigerol (CBG); and cannabidiolic (CBDA) and tetrahydrocannabivarin (THCV).”
Terpenes
Greater than 200 terpenes have been recognized within the hashish plant, and a few have demonstrated antineoplastic exercise. In a superb review of hashish pharmacology, Ethan Russo, MD et al. described antineoplastic exercise for the next terpenes discovered within the hashish plant: limonene, ɑ-terpineol, linalool, camphene, humulene (ɑ-caryophyllene), β-elemene, guaiol, and eudesmol.
Nevertheless, one experiment failed to indicate advantages when humulene and linalool have been added to pure THC.
Flavonoids
Thus far, just one flavonoid discovered solely within the hashish plant has been proven to kill most cancers cells.
In 2019, researchers from the Brigham and Girls’s Hospital, Dana-Farber Most cancers Institute, Harvard Medical Faculty, and the College of Massachusetts found {that a} by-product of Cannflavin B, FBL-03G, “demonstrates important remedy potential within the therapy of pancreatic most cancers, together with radio-sensitizing and most cancers metastasis therapy potential.”
A number of different flavonoids present in hashish (and different crops) have additionally demonstrated antineoplastic exercise.21,22 (See chapter: Cannabinoids, Terpenes & Flavonoids).
Joe D. Goldstrich, MD, FACC, is a retired heart specialist who has studied and explored unconventional medical approaches to wellness all through his six-decade profession. Angela Bacca has authored a whole bunch of articles and edited and/or co-authored over a dozen books in addition to edited varied on-line and print cannabis-centric publications. The Cannabis Cancer Connection is printed as an book and paperback.
Footnotes
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171598/
- https://tinyurl.com/pb8uxfes
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352507/
- https://tinyurl.com/5cnm4uee
- https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.2012.02050.x
- https://www.sciencedirect.com/science/article/abs/pii/S0301468109602358
- https://www.mdpi.com/1422-0067/20/23/5905/htm
- https://www.ncbi.nlm.nih.gov/gene/3397#prime
- https://biosignaling.biomedcentral.com/articles/10.1186/s12964-016-0161-y
- https://tinyurl.com/bdznbdu3
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410650/
- https://www.jidonline.org/article/S0022-202X(15)37287-0/fulltext
- https://www.jidonline.org/article/S0022-202X(15)37287-0/fulltext
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363603/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587381/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914500/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009504/
- https://hyperlink.springer.com/article/10.1007/s11418-016-1030-0
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142792/
- https://tinyurl.com/2r83bpun
- https://pubmed.ncbi.nlm.nih.gov/16097445/
- https://pubs.acs.org/doi/pdf/10.1021/acsomega.1c00318
