There is a lot of talk about cannabis and its potential for treating cancer. Yes, there have been several small-scale studies. There have not, however, been any clinical trials with humans. And while the results from research on animals are promising, there is a long way to go before cannabis is available as a cancer treatment.
Cannabis use for medicinal purposes dates back at least 3,000 years. It was introduced into Western medicine in 1839 by W.B. O’Shaughnessy, a surgeon who learned of its medicinal properties while working in India for the British East India Company. Its use was promoted for reported analgesic, sedative, anti-inflammatory, antispasmodic, and anticonvulsant effects.
In 1951, Congress passed the Boggs Act, which for the first time included Cannabis with narcotic drugs. In 1970, with the passage of the Controlled Substances Act, marijuana was classified by Congress as a Schedule I drug. Drugs in Schedule I are distinguished as having no currently accepted medicinal use in the United States. Other Schedule I substances include heroin, LSD, mescaline, and methaqualone.
Despite its designation as having no medicinal use, Cannabis was distributed by the U.S. government to patients on a case-by-case basis under the Compassionate Use Investigational New Drug program established in 1978. The distribution of Cannabis through this program was closed to new patients in 1992.
Although federal law prohibits the use of Cannabis, many states and territories have legalized Cannabis use for medical purposes. Additional states have legalized only one ingredient in Cannabis, such as cannabidiol (CBD). Some medical marijuana laws are broader than others, and there is state-to-state variation in the types of medical conditions for which treatment is allowed.
One study in mice and rats suggested that cannabinoids may have a protective effect against the development of certain types of tumors. During this 2-year study, groups of mice and rats were given various doses of THC by gavage. A dose-related decrease in the incidence of benign liver tumors and liver cancer was observed in the mice. Decreased rates of benign tumors in other organs (mammary gland, uterus, pituitary, testis, and pancreas) were also noted in the rats. In another study, delta-9-THC, delta-8-THC, and cannabinol were found to inhibit the growth of Lewis lung adenocarcinoma cells in vitro and in vivo. Also, other tumors are sensitive to cannabinoid-induced growth inhibition. (1)
(Note: In vitro means the testing is performed in a test tube, culture dish, or elsewhere outside a living organism. In vivo means the process takes place in a living organism, i.e., an animal or human trial.)
Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis invasion and metastasis. (2)
The effects of delta-9-THC and a synthetic agonist of the CB2 receptor were investigated in HCC. Both agents reduced the viability of HCC cells in vitro and demonstrated antitumor effects in HCC subcutaneous xenografts in nude mice. The investigations documented that the anti-HCC effects are mediated by way of the CB2 receptor. Similar to findings in glioma cells, the cannabinoids were shown to trigger cell death through stimulation of an endoplasmic reticulum stress pathway that activates autophagy and promotes apoptosis. Other investigations have confirmed that CB1 and CB2 receptors may be potential targets in non-small cell lung carcinoma and breast cancer. (3, 4)
An in vitro study of the effect of CBD on programmed cell death in breast cancer cell lines found that CBD induced programmed cell death, independent of the CB1, CB2, or vanilloid receptors. CBD inhibited the survival of both estrogen receptor-positive and estrogen receptor-negative breast cancer cell lines, inducing apoptosis in a concentration-dependent manner while having little effect on nontumorigenic mammary cells. Other studies have also shown the antitumor effect of cannabinoids (i.e., CBD and THC) in preclinical models of breast cancer. (5, 6)
CBD has also been demonstrated to exert a chemopreventive effect in a mouse model of colon cancer. In this experimental system, azoxymethane increased premalignant and malignant lesions in the mouse colon. Animals treated with azoxymethane and CBD concurrently were protected from developing premalignant and malignant lesions. In in vitro experiments involving colorectal cancer cell lines, the investigators found that CBD protected DNA from oxidative damage, increased endocannabinoid levels, and reduced cell proliferation. In a subsequent study, the investigators found that the antiproliferative effect of CBD was counteracted by selective CB1 but not CB2 receptor antagonists, suggesting an involvement of CB1 receptors. (7)
Another investigation into the antitumor effects of CBD examined the role of intercellular adhesion molecule-1 (ICAM-1). ICAM-1 expression in tumor cells has been reported to be negatively correlated with cancer metastasis. In lung cancer cell lines, CBD upregulated ICAM-1, leading to decreased cancer cell invasiveness. (8)
CBD, together with THC, may enhance the antitumor activity of classic chemotherapeutic drugs such as temozolomide in some mouse models of cancer. A meta-analysis of 34 in vitro and in vivo studies of cannabinoids in glioma reported that all but one study confirmed that cannabinoids selectively kill tumor cells. (9)
Citations
(1) PubMed. NTP Toxicology and Carcinogenesis Studies of 1-Trans-Delta(9)-Tetrahydrocannabinol (CAS No. 1972-08-3) in F344 Rats and B6C3F1 Mice (Gavage Studies). https://www.ncbi.nlm.nih.gov/pubmed/12594529?dopt=Abstract
(2) PubMed. Cannabinoids: potential anticancer agents. https://www.ncbi.nlm.nih.gov/pubmed/14570037?dopt=Abstract
(3) PubMed. Cannabinoid receptors, CB1 and CB2, as novel targets for inhibition of non-small cell lung cancer growth and metastasis. https://www.ncbi.nlm.nih.gov/pubmed/21097714?dopt=Abstract
(4) PubMed. Crosstalk between chemokine receptor CXCR4 and cannabinoid receptor CB2 in modulating breast cancer growth and invasion. https://www.ncbi.nlm.nih.gov/pubmed/21915267?dopt=Abstract
(5) PubMed. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. https://www.ncbi.nlm.nih.gov/pubmed/20649976?dopt=Abstract
(6) PubMed. Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. https://www.ncbi.nlm.nih.gov/pubmed/20859676?dopt=Abstract
(7) PubMed. Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer. https://www.ncbi.nlm.nih.gov/pubmed/22231745?dopt=Abstract
(8) PubMed. Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1. https://www.ncbi.nlm.nih.gov/pubmed/22198381?dopt=Abstract
(9) PubMed. Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas. https://www.ncbi.nlm.nih.gov/pubmed/24142199?dopt=Abstract