Cannabis in Cancer Care

Abstract

Cannabis has been used in medicine for thousands of years prior to achieving its current illicit substance status. Cannabinoids, the active components of Cannabis sativa, mimic the effects of the endogenous cannabinoids (endocannabinoids), activating specific cannabinoid receptors, particularly CB1 found predominantly in the central nervous system and CB2 found predominantly in cells involved with immune function. Delta-9-tetrahydrocannabinol, the main bioactive cannabinoid in the plant, has been available as a prescription medication approved for treatment of cancer chemotherapy-induced nausea and vomiting and anorexia associated with the AIDS wasting syndrome. Cannabinoids may be of benefit in the treatment of cancer-related pain, possibly synergistic with opioid analgesics. Cannabinoids have been shown to be of benefit in the treatment of HIV-related peripheral neuropathy, suggesting that they may be worthy of study in patients with other neuropathic symptoms. Cannabinoids have a favorable drug safety profile, but their medical use is predominantly limited by their psychoactive effects and their limited bioavailability.
Authnors: DI Abrams, M Guzman
Clinical Pharmacology and Therapeutics (2015) 97:575

Clinical Trials, Studies and Publications (click to access):

Cannabis in Cancer Care

Use of cannabinoids in cancer care – palliative care

Commentary by Dr. SK Aggarwal on Cannabinoid Integrative Medicine (CIM) in oncologic palliative care.

Summary:

“Integrating CIM into oncologic palliative care promises to improve overall health-related quality of life, to provide further relief from distressing symptoms and spiritual suffering, and to bring hope to patients and families facing terminal illness.”

Author: SK Aggarwal

Current Oncology (2016) 23:S33-S36

Clinical Trials, Studies and Publications (click to access):

Use of cannabinoids in cancer care: palliative care.

Integrating Cannabis Into Clinical Cancer Care

Abstract

Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use.

For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combating anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia.

Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects.

Authors: DJ Abrams

Current Oncology (2016) 23:S8-S14

Clinical Trials, Studies and Publications (click to access):

Integrating cannabis into clinical cancer care.

 

The influence of mast cell mediators on migration of SW756 cervical carcinoma cells

Abstract

The role of mast cell mediators on cervical cancer cell migration was assessed using an in vitro assay of scratch wound healing onto monolayers of HPV18-positive cervical carcinoma cells (SW756). Migration of SW756 cells was accelerated by co-culture with the mast cell line LAD2. This effect was inhibited by the H1R antagonist pyrilamine and the cannabinoid agonists 2-arachidonylglycerol (2AG) and Win 55,212-2. Therefore, the specific effects of histamine and cannabinoids on SW756 migration and LAD2 activation were analyzed. Histamine added to the in vitro assay of scratch wound healing either increased or inhibited SW756 migration rate by acting either on H1R or H4R, respectively. Cannabinoids acted on CB1 receptors to inhibit SW756 migration. Supernatants from SW756 cells stimulated LAD2 cell degranulation, which in turn was inhibited by cannabinoids acting via CB2 receptors. RT-PCR showed that SW756 expressed mRNA for CB1, CB2, H1R, H2R, and H4R. On the other hand, LAD2 expressed mRNA for all four HRs and CB2. The results suggest that mast cells could be contributing to cervical cancer cell invasion and spreading by the release of histamine and cannabinoids. Therefore, therapeutic modulation of specific mast cell mediators may be beneficial for cervical cancer treatment.

Clinical Trials, Studies and Publications:

The influence of mast cell mediators on migration of SW756 cervical carcinoma cells

Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1

Abstract

Although cannabinoids exhibit a broad variety of anticarcinogenic effects, their potential use in cancer therapy is limited by their psychoactive effects. Here we evaluated the impact of cannabidiol, a plant-derived non-psychoactive cannabinoid, on cancer cell invasion. Using Matrigel invasion assays we found a cannabidiol-driven impaired invasion of human cervical cancer (HeLa, C33A) and human lung cancer cells (A549) that was reversed by antagonists to both CB(1) and CB(2) receptors as well as to transient receptor potential vanilloid 1 (TRPV1). The decrease of invasion by cannabidiol appeared concomitantly with upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Knockdown of cannabidiol-induced TIMP-1 expression by siRNA led to a reversal of the cannabidiol-elicited decrease in tumor cell invasiveness, implying a causal link between the TIMP-1-upregulating and anti-invasive action of cannabidiol. P38 and p42/44 mitogen-activated protein kinases were identified as upstream targets conferring TIMP-1 induction and subsequent decreased invasiveness. Additionally, in vivo studies in thymic-aplastic nude mice revealed a significant inhibition of A549 lung metastasis in cannabidiol-treated animals as compared to vehicle-treated controls. Altogether, these findings provide a novel mechanism underlying the anti-invasive action of cannabidiol and imply its use as a therapeutic option for the treatment of highly invasive cancers.

Clinical Trials, Studies and Publications:

Cannabidiol inhibits cancer cell invasion via upregulation of tissue inhibitor of matrix metalloproteinases-1

Medical Use of Marijuana by Patients Undergoing Cancer Chemotherapy or afflicted with AIDS

“Cancer chemotherapy can often prolong the patient’s life by several years. In some instances, a complete “cure” can be obtained. Unfortunately, these drugs also have severe side-effects, most notably nausea and vomiting. Patients sometimes find these effects so distressing they abandon chemotherapy entirely.

People with AIDS (Acquired Immune Disease) also experience these problems. Powerful anti-viral drugs such as AZT and the new protease inhibitors can induce severe nausea, vomiting, and other gastrointestinal effects. Similarly, AIDS “wasting syndrome” can literally starve an individual to death.

Investigations with cannabis have revealed its ability to reduce (or eliminate) the nausea and vomiting associated with chemotherapy while also providing an appetite stimulus. The benefits are thus twofold: 1) the patient is able to retain food and maintain body strength, and 2) he or she can tolerate the life-prolonging chemotherapy treatments.

At least eight published studies have confirmed the ability of cannabis and its psychoactive ingredient delta-9-THC to reduce nausea and vomiting. The first appeared in 1975 in The New England Journal of Medicine. It concluded, “THC is an effective anti-emetic for patients receiving cancer chemotherapy.”

The Food and Drug Administration (FDA), in February, 1980 listed 33 studies of cannabis and nausea and vomiting. Most of these experiments involve efforts to determine the proper dosage of THC and several are comparative studies with other standard anti-emetics.

In New Mexico, a state sponsored study has shown the cannabis cigarette to be 30% more effective than THC in relieving nausea and vomiting. Another study, sponsored by the National Cancer Institute (NCI), discovered that inhaled cannabis resulted in a 71% efficacy rate, as opposed to 44% with oral delta-9-THC. These controlled studies have been fortified by “anecdotal” accounts from individuals who have abandoned legal access to THC because they prefer marijuana obtained illegally. These patients report that smoking marijuana seems to bring an almost instantaneous relief.

This is not a new finding. As early as May 1978, researches at a symposium sponsored by the National Cancer Institute (NCI) concluded, “All in all, the cigarette may be the best means of administering the drug.”

In September 1988 the chief administrative law judge of the Drug Enforcement Administration ruled that marijuana has medical value in the treatment of side-effects caused by cancer chemotherapy. His decision was over-ruled by the administrator of the DEA and marijuana remains illegal for medical purposes.”

Cancer Bibliography

Books

Cannabis in Medical Practice: A Legal, Historical and Pharmacological Overview of the Therapeutic Use of Marijuana, Mary Lynn Mathre, Ed., McFarland Press (1998).

Marijuana Medical Papers, Tod Mikuriya, M.D. (ed.) Medi-Comp Press, (1972).

Cannabinoids as Therapeutic Agents, Raphael Mechoulam (ed.) CRC Press, (1986).

Cancer Treatment & Marijuana Therapy, Robert C. Randall (ed.), Galen Press, (1990).

Marihuana, The Forbidden Medicine, Lester Grinspoon, M.D. and James B. Bakalar, Yale University Press, (1993).

Marijuana and AIDS: Pot, Politics & PWAs in America, Robert C. Randall, Galen Press, (1991).

Journal Articles

Cancer Treatment Reports, 566, 589-592 (1982).

“Cannabinoids for Nausea,” Lancet, January 31, 1981.

Carey, M.P., Burish, T.G., & Brenner, D.E., “Delta-9-THC in Cancer Chemotherapy: Research Problems and Issues,” Annals of Internal Medicine, 99, 106-114 (1983).

Chang, A.E. et al. “Delta-9-Tetrahydrocannabinol as an Antiemetic in Cancer Patients Receiving High-dose Methotrexate,” Annals of Internal Medicine, 91, 819-824 (1979).

Frytek, S. & Moertel, C.G. “Management of Nausea and Vomiting in Cancer Patients,” Journal of the American Medical Association, 245:4, 393-396 (1981).

Harris, L., “Analgesic and Antitumor Potential of the Cannabinoids,” The Therapeutic Potential of Marijuana, Cohen & Stillman (eds.), 299-305 (1976).

Harris, L., Munson, A. & Carchman, R “Anti-tumor Properties of Cannabinoids,” The Pharmacology of Marihuana, Braude & Szara (eds.), 749-762 (1976).

Neidhart, J., Gagen, M., Wilson, H. & Young, D. “Comparative Trial of the Antiemetic Effects of THC and Haloperidol,” Journal of Clinical Pharmacology, 21, 385-425 (1981).

 

Medical Marijuana and Cancer

Overview of CancerCancer therapy word cloud

Cancer occurs as the result of the growth of abnormal cells in your body. They say that everyone is born with some cancer cells, but in some individuals, the cells multiply and grow rapidly. When this happens they overtake the healthy cells and develop into masses or tumors that can cause illness and death. Some forms of cancer can be cured with chemotherapy, radiation or removal of the cancerous area if caught early.

There are various types of cancer. While we tend to describe them by the part of the body they effect, such as lung cancer, stomach cancer, brain tumor, etc., they are generally described in the following medical terms:

• Carcinoma – Accounting for 80% to 90% of all cancers, carcinoma is found in the tissues that line our glands, organs or body structures. Carcinoma often affects bodily organs or glands that involve secretions such as breasts.
• Sarcoma – Sarcoma is a malignant tumor stemming from connecting tissues. It’s most commonly found as a bone tumor, typically in young adults.
• Lymphoma – Lymphoma is a cancer originating from the lymph nodes or glands or in specific organs like the breasts or the brain.
• Leukemia – Leukemia, a cancer of the bone marrow, is also known as blood cancer. There are several types of leukemia, such as chronic lymphocytic leukemia, acute myelogenous leukemia, acute lymphocytic leukemia and chronic myelogenous leukemia.
• Myeloma – Myeloma develops in the plasma cells of the bone marrow. The cells may start in a bone and develop into a single tumor.

Symptoms of Cancer

While cancer often seems to come out of nowhere, knowing what symptoms may be problematic and indicative of cancer can help the patient seek early treatment. Although some types of cancer do not have symptoms, here are some symptoms that may be experienced by cancer patients.

• Anemia
• Bruising
• Persistent weakness and/or fatigue
• Pain in bones and joints
• Swollen lymph nodes
• Chest pains
• Breathing difficulties
• Coughs that don’t seem to go away
• Loss of weight
• Loss of appetite

Use of Medical Marijuana/Cannabis as an Alternative Treatment for Cancer

The human body produces endocannabinoids, which play an important role in keeping our bodies healthy. One way they do this is by generating and regenerating our immune systems, which is what prevents us from getting sick. Cannabis contains various cannabinoids; cannabidiol (CBD) is just one of more than 85 cannabinoids that can be found in cannabis. When used with cancer patients, CBD acts as a sedative, while also increasing alertness, unlike common prescription drugs.

Additionally, studies have indicated that CBD reduces the growth in breast cancers and also reduces the cancer’s invasiveness. Cannabis, in general, is known to actually shrink cancerous tumors. In addition to being used as a treatment for cancer, medical marijuana is often used to help some of the symptoms of cancer, such as nausea and pain. One of the major side effects of chemotherapy is vomiting and nausea. Cancer patients on medical marijuana don’t generally experience these side effects.

Benefits of Using Medical Marijuana As Alternatives to Prescription Drugs

We often hear of cancer patients who refuse treatment because they want to feel as normal as possible during their last days rather than feeling drugged, tired, in pain and nauseous. While it may be the cancer causing the pain, it’s generally the prescription drugs that are causing the other discomfort. Prescription drugs used in cancer patients often make the patient drowsy, tired and nauseous. Additionally, the patient is at high risk of becoming addicted to these drugs. Cancer patients can get relief through medical marijuana without experiencing all the unpleasant side effects of prescription drugs.

The endocannabinoid anandamide has been reported to affect breast cancer growth at multiple levels

Abstract:

Breast cancer is one of the most frequently diagnosed malignancies and a leading cause of cancer death in women. Great advances in the treatment of primary tumors have led to a significant increment in the overall survival rates, however recurrence and metastatic disease, the underlying cause of death, are still a medical challenge. Breast cancer is highly dependent on neovascularization to progress. In the last years several anti-angiogenic drugs have been developed and administered to patients in combination with chemotherapeutic drugs. Collected preclinical evidence has proposed the endocannabinoid system as a potential target in cancer. The endocannabinoid anandamide has been reported to affect breast cancer growth at multiple levels, by inhibiting proliferation, migration and invasiveness in vitro and in vivo and by directly inhibiting angiogenesis.

Clinical Trials, Studies and Publications:

Anandamide inhibits breast tumor-induced angiogenesis

Therapies using cannabinoid receptor ligands will have efficiency in reducing tumor burden in malignant lymphoma

Clinical Trials, Studies and Publications:

Expression of cannabinoid receptors type 1 and type 2 in non-Hodgkin lymphoma: growth inhibition by receptor activation

Cannabinoid receptor-mediated apoptosis induced by R(+)-methanandamide and Win55,212-2 is associated with ceramide accumulation and p38 activation in mantle cell lymphoma

Cannabinoid receptor ligands mediate growth inhibition and cell death in mantle cell lymphoma

 

 

Cannabinoids encouraged cancer cell death, while decreasing growth, proliferation and metastasis of melanoma cells

Clinical Trials, Studies and Publications:

Cannabinoid receptors as novel targets for the treatment of melanoma

Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors

The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities