Cannabidiol (CBD) in Cancer Care

Abstract

Cannabidiol (CBD) is a medically active but non-psychotropic constituent of Cannabis spp. It is a modulator of the intrinsic endocannbinoid system, which has significant regulatory and homeostatic functions in several important systems in the human body. Of particular interest is the impact CBD may have on the immune system, inflammation, anxiety, pain, and neuronal injury. Emerging evidence suggests these properties of CBD may be a valuable adjunct to the standard of care in oncology. It may reduce harm from chemotherapy and radiation therapy with no reduction in therapeutic efficacy. It may moderate graft-versus-host disease after stem cell transplants and moderate the formation of cancer stem cells involved in cancer progression, spread, treatment resistance, and relapses. CBD may even directly suppress cancer cells via mitochondrial-dependent apoptosis and autophagy mechanisms.

Hemp-derived medicinal CBD

Hemp is a type of cannabis used for many centuries for fiber, fuel, oil, and seed. Canvas and other fabric, rope, and birdseed are examples of industrial products from this plant. Hemp is not marijuana. The content of the psychotropic (mind-bending) cannabinoid THC, that gets people high, is little to none in hemp strains of cannabis. Hemp derivatives carry none of the illicit drug stigma attached to marijuana. Some have argued CBD can convert into psychotropic THC, but this is not proving to be clinically relevant in humans (Golombek et al 2020).

Due to low content of the narcotic cannabinoid THC, hemp seed products (eg, hemp seed oil), without the cannabinoid-rich resin from the flowering tops, are explicitly excluded by the definition of cannabis in the UN 1961 single convention on narcotic drugs, are generally regarded as safe, and are legal to market in many countries (United Nations 2021).

Cannabidiol, or CBD, is the most useful cannabinoid in hemp. CBD acts through our endocannabinoid system, built into almost every organ and function in the human body. We make chemicals similar to the cannabinoids from these plants. We are all using our own built-in human endocannabioids to adjust our critical systems including metabolism, digestion, blood pressure, appetite, body temperature, bone density, synthesis of fats, fertility, moods, anxiety, arousal, pain signaling, immune function, and the inflammatory response. The plant versions of cannabinoids turn out to just be external sources of natural biochemicals that adjust this internal human endocannabinoid system. CBD in cannabis inhibits the enzymatic clearance of our natural human endocannabinoid anandamide (AEA), allowing levels to rise. CBD stimulates the release of our other natural endocannabinoid two-acylglycerol, aka two-arachidonyl glycerol (2 AG), also increasing its abundance in tissues (Britch et al 2021).

CBD binds to the two types of cannabinoid receptors found in the brain and nervous system, the gut, on immune cells, and elsewhere, called CB1-R and CB2-R. Since it acts on receptors in the brain, and increases feel-good substances, it is important to note that it does not have any narcotic or stupefying effect. In fact, CBD may blunt some of the intoxicating effects of THC. So, while CBD does act on the brain and nervous system and is therefore psychoactive, it is not psychotropic (Crippa et al 2018).

CBD has a low affinity for the CB1 and CB2 receptors per se, but it blocks the fatty-acid binding protein that transports our innate endocannabinoids to be hydrolyzed, which prolongs the activation of the CB1 receptor. It also modulates other receptors such as the 5-hydroxytryptamine (5-HT1A) serotonin receptor and the peroxisome proliferator-activated receptor γ (PPAR-γ). Some of its pharmacological effects are also caused by it binding to other cell surface G-protein receptors (GPRs). For example, the anticonvulsant, anti-spasmodic, anxiolytic, anti-emetic, anti-depressant, analgesic and neuro-protective effects of CBD are thought to be conferred by several GPRs on nerve cells (Kiskova et al 2019).

CBD protects brain cells called astrocytes from injury and speeds recovery of nerves from trauma. It is a significant antioxidant, neuro-protective, and anti-inflammatory in various models of brain insults and injuries. In addition, CBD has been shown to reduce pain, spasticity, and seizures, to reduce peripheral and central nervous system inflammation, and to modulate blood circulation and metabolism. It is anxiolytic (treats anxiety) and reduces psychosis. Importantly, CBD is also cytotoxic to cancer cells, meaning it directly kills them (Kozela et al 2017).

Can CBD help cancer patients better tolerate therapy?

Cancer is a frightening disease, and the therapies that can cure it can also be scary. Surgery, chemotherapy, receptor targeted drugs, and radiation all have consequences that can induce anxiety, and in some cases, sleeplessness. CBD has become quite widely accepted as useful for anxiety and insomnia. However, it must be understood that human research trials have so far been limited in number and scope, and so health claims are still classed as “unproven”. That being said, there is a great deal of “pre-clinical evidence” based on studies in cells in petri dishes (in vitro) and in rodents (in vivo) pointing to the potential of CBD, and other cannabinoids, to be of benefit in many aspects of cancer care. While clinical experience is not research evidence, patient uptake of CBD has arisen from a “grassroots” (no pun intended) sharing of experience, and clinicians are seeing many patients who find consistent and significant reasons to use CBD for common ailments. CBD is showing a very favorable benefit versus risk of harm ratio. There is a clear need to get on with proper clinical trials to move from anecdote to evidence.

The first widespread acceptance of cannabinoids in oncology was for chemotherapy-induced nausea and vomiting (Schussel et al 2018). Cannabinoids have been accepted in palliative care for emesis and pain (Sledzinski et al 2018). There is some “reasonable amount of evidence” for cannabis use in nausea and vomiting, loss of appetite, and pain as a supplement to first-line treatments, and data suggestive of possible use to treat chemotherapy-induced peripheral neuropathy, gastrointestinal distress, and sleep disorders. Scant yet more controversial, evidence exists in regard to cannabis for cancer and cancer treatment-related cognitive impairment, anxiety, depression, and fatigue (Kleckner et al 2019).

CBD was found to reduce neuropathic pain from Taxane chemotherapy via the 5-hydroxytryptamine (5-HT1A) serotonin receptor with no cognitive impairment or conditioned rewarding effects (Ward et al 2014). It was neuroactive but not psychotropic. It is clear, however, that for severe pain THC combined with CBD is ideal (Abrams et al 2011, Martin-Sanchez et al 2009). An animal study suggests that CBD is protective against Paclitaxel-induced neurotoxicity mediated in part by the 5-HT1A receptor system, and is able to suppress inflammatory and neuropathic pain (Xiong et al 2012).

Two synthetic THC drugs are FDA approved for use in cancer: nabilone (chemo nausea and vomiting, and sleep) and dronabinol (CINV, cachexia in AIDS). Sativex (nabiximols), a combination of THC and CBD as an oral spray, was approved in Canada and the European Union for neuropathic (nerve) pain in multiple sclerosis (MS) and intractable cancer pain. Clinical studies have shown that Sativex has beneficial effects on spasticity, mobility, bladder function, and pain in MS patients. While researchers report it is well tolerated, patients tend to stop using it due to high cost and mouth irritation with long term use. Many patients want some of these benefits, but for a variety of reasons cannot or will not use THC, the narcotic cannabinoid. Fortunately, CBD acts on nausea and vomiting (N/V, emesis) in a biphasic manner, being quite effective in moderate doses, though it is capable of exacerbating N/V in high doses. The anti-nausea effect of CBD is mediated in part by the 5-HT1A receptor system (Likar and Nahler 2017).

CBD as Epidiolex (GW Pharmaceuticals) was recently approved by the U.S. Food and Drug Administration (FDA) to treat rare forms of epilepsy.

Cannabinoids may improve radiation and chemotherapies in pancreatic and lung cancer (Yasmin-Karim et al 2018). CBD enhances radiation impact on glioblastoma cells (Ivanov et al 2017) and reduces expression of immune-suppressive PD-L1 gene/protein/cell surface expression (Ivanov et al 2019), suggesting it might also synergize with the new classes of immune checkpoint inhibiting drugs.

CBD sensitizes cancer cells to chemotherapy drugs by inhibiting exosome and microvesicle release from cancer cells, trapping more drug in the cancer cells (Kosgodage et al 2018). Extracellular vesicles (EVs) are key mediators for cellular communication through the transfer of proteins and genetic material. Cancers, such as the aggressive brain cancer glioblastoma multiforme (GBM), use EV release for drug-efflux (bailing out drugs out to spare cancer cells from lethal levels), pro-oncogenic (cancer growth stimulation) signaling, invasion, and immune-suppression. EV-inhibitors have been shown to increase sensitivity of cancer cells to chemotherapy. Cannabidiol is such an EV-modulator in GBM cells exposed to the chemotherapy drug temozolomide (TMZ). Compared to controls, CBD-treated cells released EVs containing lower levels of pro-oncogenic miR21 and increased levels of anti-oncogenic miR126; these effects were greater than with TMZ alone. In addition, prohibitin (PHB), a multifunctional protein with mitochondrial protective properties and chemo-resistant functions, was reduced in GBM cells by CBD. CBD may, via modulation of EVs and PHB, act as an adjunct to enhance TMZ treatment efficacy in GBM (Kosgodage et al 2019).

CBD interacts favorably with chemotherapy drugs in part due to its anti-inflammatory and anti-oxidant properties. CBD reduces cardio-myopathy from Doxorubicin (Hao et al 2015), the key issue which limits the lifetime exposure to this class of drugs that is tolerable to the heart. CBD overcomes resistance to Oxaliplatin in colorectal cancer cells via autophagy induced by the overproduction of ROS through mitochondrial dysfunction (Jeong et al 2019A).

Transient receptor potential vanilloid type-2 (TRPV2) is an ion channel that is triggered by agonists like cannabidiol (CBD). Via TRPV2 receptors, CBD increases cancer cell (e.g., leukemia) uptake of chemo drugs such as temozolomide, doxorubicin, and carmustine (Pellati et al 2018). CBD improved chemotherapeutic drugs cytotoxic effects on uterine (endometrial) cancer cells, also linked to TRPV2 over-expression. (Marinelli et al 2020). Activating TRPV2 channels with CBD increased hepatocellular (liver) cancer cell uptake of doxorubicin (Neumann-Raizel et al 2019). TRVP2 is a useful target in triple-negative breast cancer (TNBC), an aggressive cancer with few therapy options other than chemotherapy. TRPV2 activation by CBD significantly increased doxorubicin chemo drug uptake and increased apoptosis (programmed cell death) in TNBC cells(Elbaz et al 2016). This chemo-enhancing effect was more recently confirmed with CBD and doxorubicin in an in vivo mouse model of triple-negative breast cancer (Laezza et al 2020).

Bone marrow or peripheral stem cell transplantation is a life-saving therapy for cancers such as leukemia and some lymphomas. The patient gets rid of the old, damaged marrow that made their immune cells, and a new immune system is installed. The new immune cells can kill remaining cancer cells, but they can also damage the host’s healthy cells and tissues. Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol has potent anti-inflammatory and immune-suppressive properties. In a phase II study of patients with acute leukemia or myelodysplastic syndrome, none of the patients developed acute GVHD while consuming CBD. Lower grade reactions were significantly reduced, well beyond the standard of care procedures for GVHD (Yeshurun et al 2015).

Can CBD actually kill cancer cells on its own?

Cancer patients can get comfort and care from ingesting CBD, and it appears it can enhance the “standard of care” medical and radiation oncology therapeutics. However, those therapies do not save all cancer patients from harm or even eventual death from the disease. There is developing evidence that CBD may actually shrink tumors and extend life.

There are literally hundreds of mutations in cancer cells, a plethora of growth stimulating factors, and metabolic issues that drive the uncontrolled growth of cells that is cancer. Based on the preliminary evidence in various models, it appears that cannabinoids target key signaling pathways involved in all the hallmarks of cancer (Pyszniak et al 2016). There are many other drivers of cancer growth and spread we apparently can target with CBD. Studies demonstrate anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD. It has reduced initiation, progression, and metastasis in several different types of cancer.

The most important single focus of cancer research right now is the issue of cancer stem cells (CSCs). Stem cells are involved in wound healing, tissue repair, and are used as a medical therapy for many conditions. However, stem cells can be corrupted to produce cancer cells, and cancer cells can adapt and develop stem cell properties or “stemness”. These corrupted cells are the only ones inside a tumor that can invade into adjacent tissues or spaces, including into lymph vessels and blood vessels. They are mobile! Cancerized stem cells or CSCs are the only cells able to freely spread into distant organs or metastasize. They can colonize and set a up a new tumor – they are “tumorigenic”. This is typically when cancer is called stage 4 and incurable. They are the only cells in a tumor that can reproduce infinitely – they are “immortal” (Nassar and Blanpain 2016). So, to be clear, CSCs are responsible for the most malignant aspects of the disease, and turn a dangerous situation into a life-threatening one.

Cancer cells acquire a malignant “stemness” through a process called the epithelial–mesenchymal transition (EMT). During the EMT, epithelial markers (including E-cadherin) are down-regulated and mesenchymal markers are upregulated. CBD downregulating expression of receptor CB1 in breast cancer cells, blocking migration and progression of the IL-1-induced signaling pathway IL-1/IL-1RI/-catenin, the primary driver of EMT. Cannabidiol localized E-cadherin and catenin at the adherens junctions. It also prevented catenin nuclear translocation. This reduced cell viability, tumor progression, and spread (Garcia-Morales et al 2020). CBD combined with THC inhibits EMT in non-small cell lung cancer (NSCLC) cells (Milian et al 2020). CBD kills prostate cancer cells in vitro, and significantly reduced melanoma tumor growth and increased survival time and quality of life in vivo (De Petrocellis et al 2013).

One of the most dangerous brain cancers, glioblastoma multiforme (GBM), has a high resistance to our most aggressive therapies and very high rates of reoccurrence. This is partly related to the presence of glioma stem-like cells (GSCs). GSCs express cannabinoid receptors, CB1 and CB2, as well as other components of the endocannabinoid system. Cannabinoid agonists altered the expression of genes involved in stem cell proliferation and differentiation (Laezza et al 2020).

CBD also modulates marrow derived stem cells (MDSCs), innate myeloid cells that possess the ability to control immune responses. These tend to show up when tumors become very large, crowded, low in oxygen, heavily fementative, and are vigorously pumping acid out into their surrounding microenvironment (milieu). Contrary to popular belief that cancer cells are acidic, they are actually slightly alkaline compared to non-cancerous cells of the same type. Fermentative metabolism creates masses of acidic lactate which is pushed by proton efflux pumps out into the extracellular milieu/microenvironment. This is why alkalizing therapies do not do more than palliate the patient, with little to no impact on the cancer growth (Hao et al 2018). When the inflammation around and in the tumors exceeds the capacity of the local immune controls, the big marrow stem cells are brought in to try to put out the fire, but cancer is “the wound that will not heal”. Controlling inflammation at time of surgery and thereafter is key to managing stem cells, invasion, metastasis, and thus to prevent crossing the threshold from curable to incurable.

Stem cells can be brought under control by inducing cell differentiation – forcing them to specialize, and settle down into a normal function. Anti-inflammatory and antioxidant, CBD via TRV2 receptors influences differentiation of glioma stem cells (Pellati et al 2018). In tumors derived from glioma stem cells (GSCs), CBD inhibited disease progression. CBD-dependent production of ROS was accompanied by reduction in glutathione (GSH) and GSH-related enzymes (McAllister et al 2015). Cancer cells acquire, generate, and store (sequester) unusual levels of GSH to protect themselves from stresses of crowding, acid waste, low oxygen, and more. Many oncology therapies work at least in part by depleting tumor glutathione. CBD-dependent production of ROS was accompanied by reduction in glutathione (GSH) and GSH-related enzymes (McAllister et al 2015). The activities of glutathione reductase and glutathione peroxidase were significantly decreased in those treated with CBD, inducing apoptosis (Cerretani et al 2020).

There are three ways cells die. Necrosis is an abrupt and messy process caused by severe circumstances such as burns. Autophagy is a cell self-digesting, often just recycling parts, but in some cases recycling the whole cell. This is a commonly used target in treating brain cancers. Apoptosis or programmed cell death is a more orderly process, used in healthy tissues to remove old or dead cells, recycle them, and to trigger a replacement to be made. Normal cells can only double a limited number of times before this apoptosis program removes them.

Apoptosis is fundamentally how chemotherapy drugs and radiation, two foundations of oncology, actually kill cancer cells. Cancer cells have a way of shutting off this kill switch, so they can continue to double and grow without limit.

Any therapy that forces a cancer cell to restore this safety system will result in cancer cells recognizing it is time to go, and to go quietly.

CBD induces endoplasmic reticulum and mitochondrial membrane stress by inhibiting the AKT/mammalian target of rapamycin (mTOR) signaling, inducing apoptosis in breast cancer cells. CBD led to an interaction between PPAR, mTOR, and cyclin D1 to the advantage of apoptosis induction in breast cancer. Similar induction of apoptosis is also seen in lung, prostate, brain, and colorectal cancer cells (Kis et al 2019).

Mitochondria are key to apoptosis. These are the little metabolic organelles inside cells where fuel is burned with oxygen for energy or fermented (no oxygen) to make cell materials. As cancers progress, cells end up with fewer functioning mitochondria, and the loss of and damage to mitochondria has a direct and linear relationship to the rate of growth and spread. CB1 receptors are present on the mitochondrial membrane, where activation can directly control cellular respiration, energy production, and generation of reactive oxygen species (Benard et al 2012). CBD modulates voltage-dependent anion channel on mitochondria to induce cancer cell death (Rimmerman et al 2013).

CBD reduced invasiveness and metastasis in cells of aggressive breast cancer through its interaction with Id-1, an inhibitor of basic helix-loop-helix transcription factors. Id-1 is a key regulator of the metastatic potential of breast and additional cancers (McAllister et al 2011). CBD inhibits human breast cancer cell proliferation and invasion through differential modulation of the extracellular signal-regulated kinase (ERK) and reactive oxygen species (ROS) pathways, and that both pathways lead to down-regulation of Id-1 expression and up-regulation of the pro-differentiation factor Id-2 (McAllister et al 2011).

CBD treatment perturbs the function of the mitochondria as suggested by loss of mitochondrial membrane potential and release of cytochrome c. The cumulative cellular stress achieves activation of multiple intrinsic and extrinsic caspases, the enzymes that dissolve cells undergoing apoptosis. Importantly, CBD treatment inhibited tumor progression and induced apoptosis in vivo. The ability of CBD to inhibit cancer cell viability/proliferation has been reversed in the presence of antagonists for CB2, TRPV1, TRPM8, COX-2, and PPRγ. CBD produced a concentration-dependent increase in calcium leading to alterations in mitochondrial membrane potential, production of ROS, and ultimately cytotoxicity (Massi et al 2013). CBD induces apoptosis in cancer cells via increased mitochondrial release of Smac, which turns off XIAP, an inhibitor of caspases (Jeong et al 2019A, Zhang et al 2019).

Mitochondrial RNA (miRNA) dysregulation in cancer cells is overcome by CBD, inducing apoptosis in neuroblastoma cells (Alharris et al 2019).

Mitochondria are central to cancer survival and progression, in particular due to their central role in calcium signal control, which is altered in cancer. Critically, CBD has been shown to modulate mitochondrial function, and thus, calcium signaling. (Kosgodage et al 2019). Calcium signaling remodelling in cancers has consequential impact on key events such as proliferation, invasion, and sensitivity to cell death. Specific calcium signaling pathways have also now been identified as playing important roles in the establishment and maintenance of multidrug resistance and the tumor microenvironment (Monteith et al 2017). Mitochondria-associated membranes (MAMs) are critical hubs in signal transduction involved in cancer onset and progression. Perturbation of calcium homeostasis at the MAMs in cancer cells is correlated with impaired cell proliferation and death (Danese et al 2017). CBD potently increases mitochondrial calcium allowing stable transition pores through which the apoptosis caspases can pass. Altered calcium status in mitochondria is a hallmark of cancer and a key to cancer cell resistance to apoptosis. CBD directly targets mitochondria and alters their capacity to handle calcium ions (Ca2+). At lethal concentrations, CBD causes mitochondrial calcium ion overload, stable mitochondrial transition pore formation, and cell death in acute lymphoblastic leukemia of T lineage (T-ALL), but not resting healthy T cells. This effect may be helpful during chemotherapy for leukemia. CBD also induces autophagy (Olivas-Aguirre et al 2019). Based on the same apoptosis and autophagy mechanisms, CBD inhibits breast cancer, gliomas, lung cancer, and leukemia (Massi et al 2013). CBD is an agonist (stimulant) modulating TRPV2 channel passage of essential ions such as Na+ and Ca++, impacting glioblastoma cell proliferation (Ryan et al 2009). This also kills malignant brain oligodendrocytes (Mato et al 2010). CBD-mediated calcium regulation via mitochondria can restore apoptosis (Pumroy et al 2019).

Recall that autophagy is cell death by self-digestion. CBD led to endoplasmic reticulum stress, inhibition of the AKT/mTOR pathway, and up-regulation of autophagy-mediated cell death in breast, pancreatic, and melanoma cell lines. CBD induced autophagic cell death in part through the initial induction of the ROS sensor AMP-activated protein kinase (AMPK) (McAllister et al 2015). CBD induces autophagy in colorectal cancer cells, again, by the overproduction of ROS through induced mitochondrial dysfunction (Jeong et al 2019B).

Recent studies have shown that CBD reduces cancer cell viability in many cancer types such as neuroblastoma, glioblastoma, melanoma, leukemia, colorectal, breast, lung, and prostate cancer. Many in vitro and in vivo experiments have demonstrated that cannabinoids have potential to inhibit angiogenesis (blood vessel growth into tumors) and metastasis. CBD is connected to downregulation of an expression of Id-1, an inhibitor of basic helix–loop–helix transcription factors, which has been shown to be a key regulator of the metastatic potential of breast cancer. It has also been demonstrated that CBD can lead to a decrease in lung tumor cell invasion and metastasis via the mechanism relied on for the upregulation of the intercellular adhesion molecule 1 (ICAM-1). Cannabidiol has anti-cancer activity, acting as potent antagonists of TRPM8 receptors (McAllister et al 2015).

CBD inhibits EGF/EGFR in aggressive forms of breast cancer, including TNBC. CBD significantly inhibits epidermal growth factor (EGF)-induced proliferation and chemotaxis (mobility to invade or metastasize) of breast cancer cells in vitro. Further studies revealed that CBD inhibits EGF induced activation of EGFR, ERK, AKT, and NF-kB signaling pathways as well as MMP2 and MMP9 secretion. CBD inhibits tumor growth and metastasis in in vivo mouse model systems. Analysis of molecular mechanisms revealed that CBD significantly inhibits the recruitment of tumor-associated macrophages in primary tumor stroma and secondary lung metastases (Elbaz et al 2015). Macrophages are large immune cells which can make up to 50% of the volume of some breast tumors. They are associated with tumor growth and spread, including by engulfing but not digesting cancer cells, forming fusion hybrid cells, which carry tumorigenic malignant cells to distant places. Immune cells can transfer or apply their special power to move through tissues to the cancer cells.

CBD is a novel immune modulator via CB1 and CB2 receptors and transient receptor potential vanilloid 1. CBD inhibits critical activators of the Janus kinase/signal transducer and activator of transcription signaling pathway, as well as the nucleotide-binding oligomerization domain-like receptor signaling pathway. This decreases pro-inflammatory cytokine production. Furthermore, CBD protects against cellular damage incurred during immune responses by modulating adenosine signaling. These immune-suppressive effects of CBD mark it as a potentially effective immune modulatory therapeutic (Peyravian et al 2020).

CBD acts on the immune system through transient receptor potential V1 (TRPV1), also known as the vanilloid receptor. CBD’s effects on neuroinflammation and colitis have been shown to be mediated by peroxisome proliferator-activated receptor gamma (PPAR-c). CBD has a biphasic action on the immune system, including activation of immune regulatory cells. T cell-produced IFN-c is a critical target of CBD suppression. CBD’s ability to suppress transcription factors such as NFAT, AP-1, and NF-kB likely accounts for its widespread suppression of many immune cytokines. CBD is anti-inflammatory via inhibition of fatty acid amide hydrolase (FAAH), as well as via some cytokines and chemokines such as IL-4, IL-5, IL-13, and eotaxin (Nichols and Kaplan 2020).

It is very difficult to do long term studies proving any single agent prevents cancer. However, in colorectal adenocarcinoma, there is a link to the formation of aberrant crypt foci (ACF) and progression of polyps to cancer. CBD reduced ACF formation and reduced CRC tumor volume in experimental models (Orrego-Gonzales et al 2020).

Summary

Cannabidiol is a medicine of great value in a variety of medical conditions, including sleep, anxiety, nerve pain, inflammation, nausea, and epilepsy. It is becoming an accepted palliative for these conditions in cancer patients.

There is pre-clinical evidence showing great potential for the use of CBD as a support for the standard oncology therapeutics – surgery, radiation, chemotherapy, and immunotherapy drugs. It may reduce harms and increase the beneficial outcomes beyond the current “standard of care”. It is emerging as potent tool in controlling graft-versus host disease post-stem cell transplant, and prevention as well as treatment of neuropathy from chemotherapeutic drugs.

There are many mechanistic arguments that can be made that CBD has actions that may kill cancer cells via cytotoxicity, apoptosis, autophagy, and immune regulation.

CBD appears to act very favorably to suppress the corrupted cancer stem cells which resist therapy, invade, metastasize, and can reproduce infinitely. CBD may even act as a cancer preventative.

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