an antiemetic and for cancer-related pain, recent findings have revealed antiproliferative and anti-metastatic PCa: Prostate Cancer; CB: Cannabinoid receptor; effects to 9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the main this research will highlight potential side effects of cannabinoids. Keywords: Cancer, Cannabidiol, Cannabinoids, Cannabis, CBD, . Similar results have been obtained in prostate carcinoma cells (Table S1) .. Cannabinoid pharmacology in cancer research: A new hope for cancer. Cannabidiol (CBD) has been recently covered in the media, and you may have A study from the European Journal of Pain showed, using an animal model, for wild, indefensible claims, such that CBD is a cure-all for cancer, which it is not. .. How to handle a relapse after treatment for prostate cancer.
Cannabidiol and Research on Recent (CBD) Prostate Cancer
This study digs in deeper to examine possible mechanisms by which this occurs involving the COX-2 gene. Results showed that CBDA inhibits migration of highly invasive human breast cancer cells. This was apparently done through a mechanism involving inhibition of a protein kinase. It was established that activation of certain signaling pathway led to inhibition of the mobility of various cancer cells, including aggressive tumor cells.
This study investigated the exact molecular mechanism through which CBD combats tumor cell growth and migration. They were able to show that cannabidiol induced death of breast cancer cells without involving activation of cannabinoid receptors.
Further investigation showed that CBD produces a chain of reactions within cancer cells to ultimately activate apoptosis normal cell death in breast cancer cells. An intricate interplay was shown between cell death apoptosis and the normal process for the destruction of the cells autophagy in CBD-treated breast cancer cells.
A conclusion was that continued investigation into the potential use of CBD as an antineoplastic anti-cancer agent was warranted. This team had previously shown that cannabidiol downregulates Id-1 gene expression in breast cancer cells which inhibited tumor invasion and metastasis.
They now look at how this happens and the pathways used. Using various assays, they were able to demonstrate those pathways, which inhibited human breast cancer cell proliferation and invasion through modulation of the extracellular signal-regulated pathways. Both of those pathways led to down-regulation of Id-1 expression. The study was also able to demonstrate that CBD up-regulates Id All of this showed that treatment with CBD significantly reduces primary tumor mass as well as the size and number of lung metastatic foci in two models of metastasis.
The basis for this study was; since THC exhibited anti-tumor activity, do other cannabinoids also possess such anti-tumor qualities?
Results indicated that pure CBD was the most potent of the cannabinoids in inhibiting tumor cell growth. With regards to potency ranking, cannabigerol and cannabichromene followed in the rank behind cannabidiol. Both cannabidiol and the cannabidiol-rich extract inhibited the growth of human breast carcinoma xenograft tumors in mice. Also, growth of tumors were inhibited in thyroid epithelial cells and lung metastases using rat and mice subjects with cancerous implants.
Experiments indicated that the CBD effect was due to its ability to induce apoptosis through activation of the CB 2 and vanilloid receptors. This breast cancer focused study focused on metastatic breast cancer cells and whether CBD would down-regulate Id-1 shown as a key regulator of breast cancer metastasis. It was demonstrated that cannabidiol CBD did indeed down-regulate the Id-1 gene expression and showed that CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the reduction of tumor aggressiveness.
As a basis for this study, growing evidence suggested CBD, a non-psychotropic compound, has anti-tumor capabilities, including effectiveness against glioblastomas. Therefore, this study looked at CBD alone and CBD in combination with chemotherapy agents and their effectiveness in fighting human and mice glioblastoma cell lines.
Along with this angle of testing, they also looked at whether CBD had any potential toxic effects within the nervous system, using mice cells in culture. Results demonstrated that CBD induced a reduction in proliferation and viability of cancer cells in proportion to dose. When both CBD and chemotherapy drugs were used, they showed synergistic anti-proliferating and cell-killing responses in various concentrations. In a press release from GW Pharmaceuticals, they announced that clinical trials had provided some positive results when using a THC: CBD proprietary blend in combination with dose-intensive temozolomide a chemotherapy drug.
The trial showed that patients with documented recurrent glioblastomas treated with THC: CBD had an 83 percent one year survival rate compared with 53 percent for patients using the placebo. Average survival for the THC: CBD group was greater than days compared with days in the placebo group. Keep in mind, they were treating a very aggressive form a brain cancer with very low prognosis for survival.
These promising results are of particular interest as the pharmacology of the THC: CBD product appears to be distinct from existing oncology medications and may offer a unique and possibly synergistic option for future glioma treatment. Research was conducted of all major medical study publishers up through the end of for the anti-tumoral effects of cannabinoids on gliomas.
CBD was not singled out in this review. Only 35 articles matched the criteria. All studies discovered were experimental except for one involving a clinical trial. In all of the experimental studies, cannabinoids were shown to have antitumoral activity and properties both in vitro and in vivo in lab dish and in animal subjects. Thereby, normal cells used as controls were not affected. These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.
This study targeted glioblastoma, the most common form of adult brain tumors, and the regulator Id-1 protein inhibitor. It had been shown that Id-1 played a critical role in controlling the invasiveness of glioblastoma cells and their ability to migrate throughout the brain. They were able to show that cannabidiol CBD downregulates the Id-1 gene expression and therefore decreases the invasiveness of glioblastoma cells and their ability to self renew.
CBD was found to inhibit glioma cell line UMG and T98G proliferation and invasiveness in culture dish and decreased proteins involved in tumor growth and angiogenesis. Results showed that cannabidiol positively affects many antitumor actions and pathways — effective in fighting tumors. This study supported exploitation of CBD as an anti-cancer drug in managing gliomas.
Given the previous demonstrations of cannabinoids to inhibit tumor growth, this study looked at THC and CBD loaded microparticles as a delivery system in attacking tumor growth, specifically glioma. This method of microencapsulation was shown to facilitate a sustained release of the two cannabinoids for several days. Treatment with the cannabinoid loaded microparticles was shown to enhance apoptosis and decreased cell proliferation and angiogenesis in the glioma tumors.
Microparticles administered every 5 days was equivalent to daily administration of straight solution. This study addressed the aggressive behavior and invasiveness of glioblastoma and the resistance to all forms of chemotherapy. They were able to demonstrate that CBD activated TRPV2 increased chemo drug uptake and potentiated toxic activity in human glioma cells. In combination, they produced induction of a reactive oxygen species and apoptosis.
An inhibition of autophagy prevents apoptosis induced by cannabinoids, while an inhibition of apoptosis prevents only cell death but not the autophagy 39 , 41 , 42 , It has been shown that cannabinoids induce process of autophagy in cancer cell lines such as glioma, melanoma, hepatic, and pancreatic cancer 39 , 41 , 42 , Moreover, some additional mechanisms have been demonstrated to contribute to the process of an induction of cell death by cannabinoids in certain cell lines.
Similar results have been obtained in prostate carcinoma cells Table S1 Cannabinoids devoid of psychoactive properties also exhibit anticancer potential. They do not affect CB receptors directly and their exact mechanism of action is still not fully elucidated.
Another interesting explanation is that CBD can prevent the degradation of anandamide AEA and subsequently leads to increased endocannabinoid concentration by acting as an inhibitor of fatty acid amide hydrolase FAAH 52 , This notion raises the possibility that the observed actions of CBD can be, in fact, partially the result of an elevated level of AEA.
These observations are in line with the described earlier relations between endocannabinoids and cancer development. Most of the research implicates that the action of CBD and other cannabinoids devoid of psychoactive properties is not linked to a direct activation of the CB receptors. However, there are reports suggesting that CBD can induce apoptosis in cancer cells partially via direct or indirect activation of CB2 receptor Recent studies have shown that CBD reduces cancer cell viability in many cancer types such as neuroblastoma, glioblastoma, melanoma, leukemia, colorectal, breast, lung, or prostate cancer Table S1 41 , 50 , 51 , 54 , 56 , 57 , 58 , The mechanism of the immunomodulatory effects of cannabinoids is still not fully elucidated.
Research has been focused mainly on the CB2 receptor, mostly due to its expression primarily in cells of the immune system. CB1 receptors have been noticed in the T lymphocytes and it is proposed that their activation may be connected with the cytokine biasing induced by cannabinoids The highest level of CB2 expression has been observed in B cells, followed by NK cells, monocytes, polymorphonuclear neutrophils, and T cells It has been shown that the expression level of CB2 correlates with the cell activation state and with the presence of immune modulators The immune system is postulated to be involved in the control of growth and development of many types of cancer.
One of the key regulators of the antitumor immune response is cytokines profile. It is postulated that a Th1 response is crucial for an effective immune response against many tumors Phytocannabinoids with high affinity for CB2 receptors, such as THC, exhibit modulatory effects on both cellular and humoral immunity.
Nonpsychotropic cannabinoids with low affinity for CB receptors have also been proven to exhibit immunomodulatory action.
Most of the studies indicate that cannabinoids exhibit immunosuppressive action The most extensively examined immunomodulatory effects of cannabinoids in context of cancer are regarding the changes in the activity of T cells. It has also been proposed that cannabinoids can affect T cells by the induction of apoptosis 73 , Another possibility is that cannabinoids effects on immune cells are at least partially induced indirectly via other suppressive mechanisms such as release of cortisone The effects on the Th17 cells subsets have not been fully described to date.
Interestingly, CB receptors seem to take part in the modulation of those phenomena Indeed, there are reports indicating the suppression of anticancer immune response by THC. It has been demonstrated that THC suppresses host immune reactivity against cancer in murine lung cancer model Lewis lung carcinoma, 3LL and line 1 alveolar cell carcinoma L1C2 , leading to the increase in the tumor growth CB2 receptors antagonists also blocked the effects of THC administration.
Similar results were obtained in the study of mouse mammary carcinoma. It has been demonstrated that THC exposure leads to the significant increase in the 4T1 carcinoma growth and metastasis due to the inhibition of the specific antitumor immune response Observed effects were mediated by CB2 receptors It is possible that tumors originating from tissues of low CB receptors expression would be significantly less sensitive to cannabinoids anticancer action and, eventually, due to THC immunosuppressive properties, such tumors may find a favorable environment for growth and development.
It is also possible that anticancer properties of cannabinoids may be compensated by their immunosuppressive action, finally leading to promotion of the tumor growth. Chronic inflammation has been associated with the development of neoplasia; therefore, reducing inflammation may, to some extent, contribute to the prevention of carcinogenesis.
Viability of noncancerous cells seems to remain unchanged or sometimes even elevated by cannabinoids 34 , 35 , 36 , 39 , On the other hand, cannabinoids can trigger apoptotic cell death in some types of nontransformed cells, especially those of high proliferative properties such as endothelial cells The cellular response to cannabinoids relies on different mechanisms in cancerous and noncancerous cells.
It has been demonstrated in vitro that cannabinoids can exhibit a stimulatory activity in nanomolar concentration and an inhibitory activity in micromolar concentration biphasic response , which significantly exceeds concentrations usually detected in blood of marijuana smokers Concentration of THC used in described experiment corresponded to its serum concentration obtained by smoking or oral administration of THC Besides the above described proapoptotic effect in cancer cells, cannabinoids exhibit some other important and potentially valuable properties.
It has been demonstrated that they can inhibit angiogenesis by blocking an activation of the vascular endothelial growth factor VEGF pathway. Cannabinoids have also been shown to reduce spontaneous and induced metastases in animal models and to inhibit an invasiveness of cancer cells in vitro breast, lung, cervical cancer, and glioma 86 , 87 , 88 , 89 , These effects are partially connected with a modulation of the activity of extracellular proteases and their inhibitors 86 , The pharmacological inhibition of ceramide biosynthesis and the expression of p8 protein lead to the prevention of the mentioned effects The studies conducted to date indicate that antiangiogenic and antimetastatic characteristics of CB receptor agonists, similar to their antiproliferative effects, rely on the stimulation of ceramide biosynthesis and a modulation of pathways involving p8 protein.
Cannabinoids that are not agonists of CB receptors CBD , have also been shown to exhibit such properties. Increased levels of FAAH substrates e. Data collected to date regarding anticancer effects of cannabinoids are almost completely limited to preclinical studies conducted on cell lines and animal models. The first experiment that was conducted on human subjects was a pilot clinical study on nine terminal patients with recurrent glioblastoma who were resistant to the standard therapy Patients received THC intratumorally.
This way of administration was safe and patients did not exhibit any overt psychoactive effects. In some patients the tumor growth rate decreased. Changes observed upon THC administration in two patients can be connected with anticancer effect of THC according to previous preclinical studies decreased cell proliferation, occurrence of apoptosis Despite these interesting observations, it is not possible to draw significant conclusions from the study on a group of nine.
This shows a need for further clinical trials, which could help to assess the dosage and the potential interaction of cannabinoids with other substances. These studies are currently ongoing or have ended recently, but the results have not been published to date. Cannabis plants produce a substantial amount of cannabinoids and other secondary metabolites. It is the second most prevalent of the active ingredients of cannabis marijuana.
While CBD is an essential component of medical marijuana, it is derived directly from the hemp plant, which is a cousin of the marijuana plant. To date, there is no evidence of public health related problems associated with the use of pure CBD.
CBD is readily obtainable in most parts of the United States, though its exact legal status is in flux. Currently, many people obtain CBD online without a medical cannabis license.
The legality of CBD is expected to change, as there is currently bipartisan consensus in Congress to make the hemp crop legal which would, for all intents and purposes, make CBD difficult to prohibit. In numerous studies, CBD was able to reduce the number of seizures, and in some cases it was able to stop them altogether.
Videos of the effects of CBD on these children and their seizures are readily available on the Internet for viewing, and they are quite striking. CBD is commonly used to address anxiety, and for patients who suffer through the misery of insomnia, studies suggest that CBD may help with both falling asleep and staying asleep.
CBD may offer an option for treating different types of chronic pain. A study from the European Journal of Pain showed, using an animal model, CBD applied on the skin could help lower pain and inflammation due to arthritis. Another study demonstrated the mechanism by which CBD inhibits inflammatory and neuropathic pain, two of the most difficult types of chronic pain to treat.
More study in humans is needed in this area to substantiate the claims of CBD proponents about pain control. Side effects of CBD include nausea, fatigue and irritability. CBD can increase the level in your blood of the blood thinner coumadin, and it can raise levels of certain other medications in your blood by the exact same mechanism that grapefruit juice does. A significant safety concern with CBD is that it is primarily marketed and sold as a supplement, not a medication.
Currently, the FDA does not regulate the safety and purity of dietary supplements. So you cannot know for sure that the product you buy has active ingredients at the dose listed on the label. In addition, the product may contain other unknown elements.
Some CBD manufacturers have come under government scrutiny for wild, indefensible claims, such that CBD is a cure-all for cancer, which it is not.
We need more research but CBD may be prove to be an option for managing anxiety, insomnia, and chronic pain. Should one take as gospel the equivalencies between CBD and Grapefruit juice? Omeprazole is pretty safe, by and large; I think the biggest concern with CBD would be with medications where an altered, irregular dosage could be dangerous, such as blood thinners….
I suffered two concussions within a space of 7 weeks: That was about 18 months ago and I still suffer from post-concussion syndrome, which is barely tolerable.
Hyper-sensitivity to light and sound, exhaustion, some dizziness, some cognitive impairment. I hesitate to try anything that might further impair my cognitive function but I am willing to give cannabis a try now that it is legal in Canada. There is some evidence that cannabis is neuroprotective, and can help protect against Traumatic Brain Injury: It looks like if one has THC in their system prior to the trauma, some of the damage might be mitigated. Am I wrong on this?
I just started cbd oil and want to learn everything I can about it. I need some clarification here. However, I do want to know,what you base these claims on? Thank you for your questions. Marijuana and hemp are two extremely different strains of the same cannabis sativa plant that have been bred over thousands of years to have entirely different purposes. Hemp is not the male version of the marijuana plant.
Combining CBD with Chemotherapy Posts Promising Results in Pancreatic Cancer Model
Cannabinoids offer new directions for prostate cancer treatment. Now, as scientific research into the two types of cannabinoid receptors has with the authors suggesting that “non-THC cannabinoids, and CBD in particular. Cannabis has been used medicinally for millennia, but has not been approved by the U.S. Food and Drug Administration to treat any medical. CBD research - In Vitro Anticancer Activity of Plant-Derived Cannabidiol on could be used as novel therapeutic agents for the treatment of prostate cancer. of Cannabis sativa Linnaeus, have received renewed interest in recent years due .