Is it possible to use cannabis for the treatment of cancer?
Cannabis and THC are used to treat the side effects of cancer chemotherapy, of appetite loss in cancer cachexia and in cancer pain. Moreover, there are several recent cell and animal studies which demonstrate that cannabinoids may also be useful in the treatment of some forms of cancer. Howver, it is still unclear how and whether these observations can be used for the treatment of cancer patients. Some effects of THC on the immune system may even have a negative impact. On 24 October 2001 the Spanish Health Minister announced the first study in humans who suffer from a glioma, an aggressive brain tumor, with THC (dronabinol).
(Galve-Roperph and colleagues):
Here, we show that administration of delta-9-tetrahydrocannabinol and a synthetic cannabinoid agonist into the tumor induced a considerable regression of malignant gliomas in rats and in mice. Cannabinoid treatment did not produce any substantial neurotoxic effect in the conditions used. Experiments with two glioma cell lines in culture showed that cannabinoids signal apoptosis (programmed cell death) by a pathway involving cannabinoid receptors. These results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas.
Modified according to: Galve-Roperph I, et al. Antitumoral action of cannabinoids: involvement of sustained ceramide accumulation and ERK activation. Nature Medicine 2000;6(3):313-319.
(De Petrocellis and colleagues):
Anandamide binds to the CB1 cannabinoid receptor. Here we report that this endogenous cannabinoid potently and selectively inhibits the proliferation of human breast cancer cells in vitro (in a cell culture). The proliferation of several other tumoral cell lines was not affected by anandamide. The anti-proliferative effect of anandamide was not due to toxicity or to programmed cell death but was accompanied by a reduction of cells in the S phase of the cell cycle.
Modified according to: De Petrocellis L, et al. The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proc Natl Acad Sci U S A 1998;95(14):8375-8380.
(Zhu and colleagues):
In this study, we show that delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, suppresses host immune reactivity against lung cancer. In two different lung cancer models in mice, intermittent administration of THC led to accelerated growth of tumor implants. Our findings suggest that THC promotes tumor growth by inhibiting antitumor immunity by a CB2 receptor-mediated pathway.
Modified according to: Zhu LX, et al. Delta-9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. J Immunol 2000;165(1):373-380.
(Recht and colleagues):
One of the mteabolites of THC is 11-COOH-THC, and ajulemic acid (AJA) is a synthetic analog of 11-COOH-THC. In preclinical studies, AJA has been found to be a potent anti-inflammatory agent without psychoactive properties. Based on recent reports suggesting antitumor effects of cannabinoids, we assessed the potential of AJA as a tumor inhibiting agent. In cell cultures AJA proved to be approximately one-half as potent as THC in inhibiting tumor growth against a variety of tumor cell lines. However, its effects lasted longer. (...) We conclude that AJA produces significant antitumor activity and effects its actions primarily via CB2 receptors.
Modified according to: Recht LD, et al. Antitumor effects of ajulemic acid (CT3), a synthetic non-psychoactive cannabinoid. Biochem Pharmacol 2001;62(6):755-763.
(Casanova and colleagues):
Here we show that both CB1 and CB2 receptors are present in the skin and hair follicles. The synthetic cannabinoid WIN55,212-2 induced a time-dependent decrease in viability of several mouse skin cancer cell lines, while non-cancer cell lines were unaffected. The cannabinoid induced death of skin cancer cells occurred by a mechanism of apoptosis (programmed cell death), and was prevented by antagonists of the CB1 and the CB2 receptor, pointing to the involvement of cannabinoid receptors.
Modified according to: Casanova ML, et al. CB1 and CB2 receptors are expressed in the skin and their activation inhibits the growth of skin cancer cells. In: 2001 Symposium on the Cannabinoids. Burlington, Vermont: International Cannabinoid Research Society, 2001, p. 151.