CBD and other cannabinoids including THC have been known to ease cancer and chemotherapy related nausea, fatigue, pain, sleep. Cannabidiol enhances the inhibitory effects of delta9-THC on human glioblastoma cell in fiber-type cannabis, is an inhibitor of MDA-MB breast cancer cell may contribute to the anti-invasive action of CBD on human lung cancer cells. This means that marijuana can have different effects based on the strain scientists reported that THC and other cannabinoids such as CBD.
has anti-cancerous effects CBD
The two best studied components are the chemicals deltatetrahydrocannabinol often referred to as THC , and cannabidiol CBD. Other cannabinoids are being studied. This means that they cannot legally be prescribed, possessed, or sold under federal law. But the use of marijuana to treat some medical conditions is legal under state laws in many states.
Dronabinol, a pharmaceutical form of THC, and a man-made cannabinoid drug called nabilone are approved by the FDA to treat some conditions. Different compounds in marijuana have different actions in the human body. For example, deltatetrahydrocannabinol THC seems to cause the "high" reported by marijuana users, and also can help relieve pain and nausea , reduce inflammation, and can act as an antioxidant.
Cannabidiol CBD can help treat seizures, can reduce anxiety and paranoia, and can counteract the "high" caused by THC. Different cultivars strains or types and even different crops of marijuana plants can have varying amounts of these and other active compounds. This means that marijuana can have different effects based on the strain used. A number of small studies of smoked marijuana found that it can be helpful in treating nausea and vomiting from cancer chemotherapy.
A few studies have found that inhaled smoked or vaporized marijuana can be helpful treatment of neuropathic pain pain caused by damaged nerves. Studies have long shown that people who took marijuana extracts in clinical trials tended to need less pain medicine. Some animal studies also suggest certain cannabinoids may slow growth and reduce spread of some forms of cancer. There have been some early clinical trials of cannabinoids in treating cancer in humans and more studies are planned.
While the studies so far have shown that cannabinoids can be safe in treating cancer, they do not show that they help control or cure the disease. Relying on marijuana alone as treatment while avoiding or delaying conventional medical care for cancer may have serious health consequences. Marijuana can also pose some harms to users. Smoked marijuana delivers THC and other cannabinoids to the body, but it also delivers harmful substances to users and those close by, including many of the same substances found in tobacco smoke.
The effects can also differ based on how deeply and for how long the user inhales. Likewise, the effects of ingesting marijuana orally can vary between people. Also, some chronic users can develop an unhealthy dependence on marijuana. There are 2 chemically pure drugs based on marijuana compounds that have been approved in the US for medical use. Nabiximols is a cannabinoid drug still under study in the US.
Based on a number of studies, dronabinol can be helpful for reducing nausea and vomiting linked to chemotherapy. Dronabinol has also been found to help improve food intake and prevent weight loss in patients with HIV. Research is still being done on this drug. Like many other drugs, the prescription cannabinoids, dronabinol and nabilone, can cause side effects and complications.
Some people have trouble with increased heart rate, decreased blood pressure especially when standing up , dizziness or lightheadedness, and fainting.
They can also worsen depression, mania, or other mental illness. Some patients taking nabilone in studies reported hallucinations. The drugs may increase some effects of sedatives, sleeping pills, or alcohol, such as sleepiness and poor coordination. Patients have also reported problems with dry mouth and trouble with recent memory.
People who have had emotional illnesses, paranoia, or hallucinations may find their symptoms are worse when taking cannabinoid drugs. Talk to your doctor about what you should expect when taking one of these drugs.
The American Cancer Society supports the need for more scientific research on cannabinoids for cancer patients, and recognizes the need for better and more effective therapies that can overcome the often debilitating side effects of cancer and its treatment. The Society also believes that the classification of marijuana as a Schedule I controlled substance by the US Drug Enforcement Administration imposes numerous conditions on researchers and deters scientific study of cannabinoids.
Federal officials should examine options consistent with federal law for enabling more scientific study on marijuana. The American Cancer Society medical and editorial content team. Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.
Cannabis in painful HIV-associated sensory neuropathy: Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. American College of Physicians. Supporting research into the therapeutic role of marijuana. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS.
J Pain Symptom Manage. Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. Comparison of orally administered cannabis extract and deltatetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: Smoked medicinal cannabis for neuropathic pain in HIV: A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme.
The upregulated expression of CB receptors and the elevated levels of endocannabinoids have been observed in a variety of cancer cells skin, prostate, and colon cancer, hepatocellular carcinoma, endometrial sarcoma, glioblastoma multiforme, meningioma and pituitary adenoma, Hodgkin lymphoma, chemically induced hepatocarcinoma, mantel cell lymphoma , but it is not always correlated with the expression level of these receptors in tissue of origin 7 , 11 , 18 , Furthermore, concentration of endocannabinoids, expression level of their receptors, and the enzymes involved in their metabolism frequently are associated with an aggressiveness of cancer.
This implies that an overactivation of endocannabinoid system might be protumorigenic and plays an essential role in the development of cancer 20 , On the other hand, there are reports indicating that an activation of the cannabinoid receptors can impair cancer development and hence endocannabinoid signaling can be antitumorigenic. Furthermore, it has been shown that silenced expression of CB1 receptor leads to an acceleration of intestinal adenoma growth, whereas activation of this receptor attenuates its growth in murine model The elevated level of endocannabinoids has been shown to reduce the development of precancerous lesions in mouse colon On the other hand, there are reports that have indicated that under certain circumstances, cannabinoids can be protumorigenic 31 , 32 , It has been shown that CB1 and CB2 receptor agonists stimulate apoptotic cell death in glioma cells by induction of de novo synthesis of ceramide, sphingolipid with proapoptotic activity 34 , If this response fails, ER stress can lead to activation of intrinsic apoptosis pathway The known mechanisms responsible for the induction of apoptosis by cannabinoids.
It has been demonstrated that process of autophagy is upstream of apoptosis in mechanism of cell death induced by cannabinoids. 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 has been demonstrated that extracts of Cannabis exhibit stronger effects on the subjects with spasticity than pure THC Some cannabinoids have been demonstrated to attenuate psychoactive effects of THC or smoked marijuana 13 , Pure cannabinoids are more convenient for study and to a subsequent standardization as a medical preparation, but still Cannabis extracts with specified amounts of cannabinoids seem to be valuable aim for further studies, also as potential anticancer agents.
An interesting idea is a combination of cannabinoids with conventional anticancer drugs, which can exhibit synergistic potential. The promising results from studies on animal models of glioblastoma treated with THC and temozolomide have led to, mentioned above, clinical trial of this chemotherapeutic agent and Sativex 94 , Similar observations from the study on pancreatic adenocarcinoma showed that gemcitabine administered with cannabinoids synergistically inhibited cancer cell growth To date, Cannabis or its preparations have found an application in a palliative medicine due to its analgesic and antiemetic effects, an attenuation of the side effects of chemotherapy or a capacity to treat spasticity in multiple sclerosis.
We are still initial stages of incorporating Cannabis products in the clinical care. There is still a lack of profound safety and efficacy clinical trials and it is very difficult or even impossible to assess the potential benefits and risk of using cannabinoids in many cases. Many aspects wait for an elucidation: The most common way of using recreational marijuana is smoking, which is unsuitable way of an administration from a medical point of view. Another important issue is the lack of easy accessible biomarkers showing the responsiveness of patients to a cannabinoid treatment.
Moreover, antitumor effects of cannabinoids have to overcome their known immunosuppressive effects which can be potentially protumorigenic. The interactions between cannabinoids and classical cytotoxic agents have to be precisely defined. These observations lead us to the conclusion, that further profound studies are doubtlessly needed to verify the idea of introducing cannabinoids into the cancer treatment.
National Center for Biotechnology Information , U. Journal List Cancer Med v. Published online Feb Author information Article notes Copyright and License information Disclaimer.
The current state and future perspectives of cannabinoids in cancer biology
Cannabis has been used medicinally for millennia, but has not been approved by the U.S. Food and Drug Administration to treat any medical. Cannabis oil for cancer treatments is provided by CBD International. The effects of rectal suppositories can last for up to eight hours without the need for re -. While the benefits of CBD and medical marijuana are still being researched, many cancer patients have used the medicinal plant for symptom relief the effects of medical cannabis could include anti-inflammatory activity.