Dosage and THC:CBD Ratio Considerations for Cancer Treatment
For decades, THC-abundant types of cannabis have been used to reduce signs and symptoms induced by cancer, such as pain, and mitigate the numerous adverse effects of orthodox cancer treatments, such as chemotherapy-induced nausea and vomiting. However, beyond that palliative care, there is a mounting body of evidence that suggests that using specific cannabis-based therapeutics containing plant constituents such as THC, CBD, THCA, or Cannflavin B, for instance, may be used soon as a means for the treatment of cancer itself.
Encouraging results of pre-clinical trial data in the treatment context of 28 different types of cancers have been reported by CannaKeys.com (i.e., Bladder Cancer, Bone Cancer, Brain Cancer, Breast Cancer, Cancer of Soft and Connective Tissues, Cervical Cancer, Colon Cancer, Endometrial/Uterine Cancer, Stomach Cancer, Kaposi’s Sarcoma, Kidney Cancer, Leukemia, Liver and Intrahepatic Bile Duct Cancer, Lung Cancer, Lymphoma, Metastatic Cancer, Oral Cancer, Pancreatic Cancer, Prostate Cancer, Thyroid Cancer, Head and Neck Squamous Cell Carcinoma, Melanoma, Myeloma, Skin Cancer (Non-Melanoma), Neuroblastoma, Ovarian Cancer, Cancer of the Thymus). And, while the resulting findings of the currently available scientific literature for the majority of cancers listed were primarily encouraging, for a few types of cancer, the results indicate mixed/inconclusive or even potential adverse effects (e.g., Testicular Cancer), suggesting that not all cancers may respond equally well to cannabis-based therapeutics. What makes up for the difference is subject to intensive scientific investigations involving, in part:
- Dose-dependent effects of specific cannabinoids such as THC and CBD.
- Ratio-dependent effects between specific cannabinoids, i.e., THC and CBD.
- Endocannabinoid deficiency (as proposed by Ethan Russo, M.D.) or an out-of-balance endocannabinoid tone (potentially due to the chronic lack of diet-based building blocks that make up or influence virtually all components of the ECS, such as sufficient amounts of omega-3 and less omega-6 fatty acids, for example).
- The understanding is that both THC and CBD downregulate immune responsivity and thereby potentially reducing the body’s immune capacity for apoptosis (destruction of cancer cells)
- Contrasting the latter with other proven THC and CBD-based mechanisms for supporting and inducing apoptosis (e.g., via activation of CB1/CB2).
- And, specific pathways that certain cancers may use for proliferation (i.e. GPR55) and the activity of THC (agonist) and CBD (antagonist) at this receptor site.
To a layperson, all of this may be overwhelming. Still, from a practical perspective, the current state of the science of cannabis in the cancer treatment context is pushing the door of hope for an effective treatment a bit more open than what could have been otherwise expected. And, while the lay of the scientific landscape is complex, complexity also means that the more we know about the details of applying for cannabis-based medicines, the more we can induce the precise effects we want, the more we can generate the predictability of the impact, and the more we can stay on this side of the fine line between a therapeutic and an adverse effect. So let’s take a closer look.
By now, it has been very well established that a significant number of cannabis constituents (e.g., THC, CBD) produce their complex effects relevant to the underlying pathologies of cancer using different pharmacodynamics (i.e., what the drug does to the body) and pharmacokinetics (what the body does to the drug in terms of absorption, distribution, and elimination). In other words, THC and CBD alone and in combination may produce different effects on certain types of cancer cells. As such, THC:CBD ratios (as defined by the cannabis chemotypes I, II, and III) may work better on some cancers while not affecting or potentially worsening others. And, to make sure all readers are on the same page, the following is a quick review of cannabis chemotypes.
There are three primary considerations (but not the only variables) to realizing specific therapeutic effects for any cannabis plant. One, the amount of the primary psychoactive cannabis constituent tetrahydrocannabinol (THC for short); two, the amount of the non-psychoactive cannabis constituent cannabidiol (CBD); and third, the ratio of THC to CBD. These three considerations or numbers discern the three basic chemotypes of cannabis. The Roman numerals I, II, and III distinguish them. Chemotype I contains more THC than CBD. Chemotype II contains relatively equal amounts (practically speaking, between 4:1 to 1:4 THC:CBD), and chemotype III contains significantly more CBD than THC. (For more information on cannabis chemotypes, click here).
It may be helpful to use a practical example of treating cancer with cannabis, such as a Rick Simpson Oil (RSO). RSO is named after Rick Simpson, who, in the early nineties, described how he cured himself of melanoma with a concentrated extract of cannabis, aka RSO (however, keep in mind that Simpson has not provided evidence such as a medical diagnosis from a medical provider). Since then, he has shared the recipe for making the concentrate on the internet and social media. As a result, many cancer patients (purported in the thousands) and their caregivers have opted for the use of RSO (many exclusively), a cannabis chemotype I, which is a THC-abundant extract of cannabis at very high dosages reaching 1gm (1,000mg per day). After a three-week escalating dose initiation, patients who chose the RSO protocol consume up to 1,000mg of RSO daily for three months (including the intro phase). And while proponents of RSO primarily focus on the many anecdotal success stories, the emerging clinical picture is more complex. For instance, Kristin Wohlschlagel, an Oncology and Hospice Nurse Navigator, gathered information (observations and interviews) from over 1,000 cancer patients who used various types and forms of full-spectrum (i.e., whole plant) cannabis. While 6 out of 10 patients on high-dose THC regimens reported therapeutic benefits, 4 out of 10 cancer patients using large doses of THC (i.e., >50-100mg x day) said their tumor growth accelerated within 6-8 weeks. Furthermore, the acceleration slowed within one month of reducing THC dosing to 25 mg or less x day. In direct contrast, Wohlschlagel found that oral doses of no more than 25 mg of THC x day, 75 to 100 mg of CBD, or moderate inhaled doses of cannabis, appeared to produce primarily beneficial effects on cancer patients. While Wohlschlagel’s self-published study provided a welcome, novel, and much-needed perspective, future studies will undoubtedly fill in the many unknowns with more specific information such as inclusion criteria, detailed dosing data, types of cancers populations, and retesting the same participants after 6-8 weeks with and without reducing doses.
Here we wanted to highlight one hypothesis that may explain, at least in part, the discrepancy between the effects of high-dose chemotype I concentrate (abundant in THC) on various types of cancer. More specifically, and in the context of three different types of cancer (i.e., triple-negative breast2, ovarian3, and colon cancers4), research has shown that in the case of these types of cancer, the proliferation of cancer growth or metastasis is at least partially dependent on the activation (agonism) of the cellular receptor site GPR55. THC is a known agonist at GPR55, while CBD is an antagonist at the same receptor (i.e., producing the opposite effect). And while currently available research does not answer the question of THC’s complex pharmacodynamic mechanisms (initiated by CB1 or CB2 modulation, for example) balance the potentially harmful effects induced by THC’s activation of GPR55, logic would indicate that until the clinical gap of missing data is filled, other chemotypes with different ratios of CBD and THC (and resulting lower doses of THC) might be considered in future studies and treatment regimens. In particular, for the treatment of these three types of cancers, the use of a cannabis chemotype II (i.e., with relatively equal amounts of 1:4 or 4:1 of THC:CBD) or even a cannabis chemotype III (i.e., containing predominantly CBD with a small amount of THC) may be a safer option due CBD’s ability to tame the effects of THC. The latter is supported by a CannaKeys-informed review of the use of cannabinoid-based therapeutics in the treatment context of metastatic cancer, which suggest that out of 19 trials that directly examined the effects of modulating the endocannabinoid system (ESC) a majority of therapeutic effects were initiated by cannabis chemotype III (3 trials)5, II (2 trials)6, and only one chemotype I trial7 respectively.
The current take-away is that while some types of cancers are vulnerable to the therapeutic mechanisms of higher dose THC, some patients’ cancer growth is not affected or may even accelerate. More research will undoubtedly shine light on the underlying mechanisms such as the opposing effects of THC and CBD via the modulation of GPR55 and its possible impact on certain cancer cells. However, what we already know now is that not all cannabis is the same. When we visit a pharmacy and look at shelves full of pills everybody knows that different pills or drugs are carefully designed to treat different conditions. Everyone knows that taking an inappropriate drug or dose can lead to harm. In contrast, when we go to a cannabis dispensary and see shelves full of cannabis flowers and cannabis-containing products, too many of us still think it’s all the same “cannabis.”
In conclusion: The more we know about the different effects generated by each of the three chemotypes of cannabis, the more we can create the treatment regimen that allows us to maintain or return to our optimal health and well-being.
Disclaimer: Information here is provided for informational purposes only and is not meant to substitute for the advice provided by your own physician or other medical professional. You should not use the information contained herein for diagnosing a health problem or disease. If using a product, you should read carefully all product packaging. If you have or suspect that you have a medical problem, promptly contact your health care provider.
Information is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over-the-counter medication is also available. Consult your physician, nutritionally oriented health care practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications.
Endnotes:
- Kristin Wohlschlagel, RN. (Aug. 2018). Cancer and Cannabis: Initial Observations of an Oncology and Hospice Nurse: Potential benefits and risks of managing Cancer Symptoms and Treatment Side Effects with Medicinal Cannabis. Presented at Cannabis Science Conference. Portland, Oregon.
- Andradas C, Blasco-Benito S, Castillo-Lluva S, Dillenburg-Pilla P, Diez-Alarcia R, Juanes-García A, García-Taboada E, Hernando-Llorente R, Soriano J, Hamann S, Wenners A, Alkatout I, Klapper W, Rocken C, Bauer M, Arnold N, Quintanilla M, Megías D, Vicente-Manzanares M, Urigüen L, Gutkind JS, Guzmán M, Pérez-Gómez E, Sánchez C. (2016 Jul 26) Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer. Oncotarget. 7(30):47565-47575.
- Hofmann NA, Yang J, Trauger SA, Nakayama H, Huang L, Strunk D, Moses MA, Klagsbrun M, Bischoff J, Graier WF. (2015 Aug) The GPR 55 agonist, L-α-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis. Br J Pharmacol. 172(16):4107-18.
- J Kargl, L Andersen, C Hasenöhrl, D Feuersinger, A Stančić, A Fauland, C Magnes, A El-Heliebi, S Lax, 5 S Uranitsch, J Haybaeck, A Heinemann, and R Schicho. (2016 Jan) GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis. Br J Pharmacol. 173(1): 142–154.
- Murase R, Kawamura R, Singer E, et al. (2014) Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer. Br J Pharmacol. 171(19):4464-4477. Brown KJ, Laun AS, Song ZH. (2017 Nov 4) Cannabidiol, a novel inverse agonist for GPR12. Biochem Biophys Res Commun. 493(1):451-454. Allison M. Barrie, Ariane C. Gushue, and Ramez N. Eskander. (August 2019) Dramatic response to Laetrile and cannabidiol (CBD) oil in a patient with metastatic low grade serous ovarian carcinoma. Gynecologic Oncology Reports. Volume 29, Pages 10-12.
- Armstrong JL, Hill DS, McKee CS, Hernandez-Tiedra S, Lorente M, Lopez-Valero I, Eleni Anagnostou M, Babatunde F, Corazzari M, Redfern CPF, Velasco G, Lovat PE. (2015 Jun) Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. J Invest Dermatol. 135(6):1629-1637. Tegeder I. (2016) Endocannabinoids as Guardians of Metastasis. Int J Mol Sci. 17(2):230.
- Zutt M, Hänssle H, Emmert S, Neumann C, Kretschmer L. (2006 May) Dronabinol zur supportiven Therapie metastasierter maligner Melanome mit Lebermetastasen [Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases]. Hautarzt. 57(5):423-7. German.
