Delta-9-tetrahydrocannbinol (THC), the major active component of the cannabis plant, and a synthetic cannabinoid induced a remarkable regression of a usually fatal type of brain tumour when tested on laboratory rats, Spanish researchers said on 28 February in the journal Nature Medicine.

Malignant gliomas, a quick-killing cancer for which there is currently no effective treatment, were induced in 45 rats. A third were treated with THC, and another third with the cannabinoid agonist WIN-55,212-2, while the remainder were left untreated. Within 18 days the untreated rats died. But the two cannabinoids had a dramatic effect, destroying the tumours in a third of the treated rats over a period of seven days, and prolonging the life of another third by up to six weeks.

12 days after cell injection THC or WIN-55,212-2 were continually injected directly at the site of tumour inoculation over a period of 7 days. THC administration was ineffective in 3 animals and increased the survival of 9 rats up to 19-35 days. The tumour was completely eradicated in 3 of the treated animals. Likewise the synthetic cannabinoid was ineffective in 6 rats, increased the survival of 4 rats up to 19-43 days; and completely eradicated the tumour in 5 animals.

The team led by Dr Manuel Guzman from the Complutense university in Madrid said: "These results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas." He said that the current experiment tested THC at very low doses and at a late stage, when untreated rats were already starting to die. He predicts that THC should work better if given earlier. But cancer treatments that work in animals may be too toxic or not effective in humans.

Cannabinoids are thought to kill tumour cells by inducing programmed cell death, or apoptosis, via an intracellular signalling mechanism. Experiments carried out with two subclones of glioma cells in culture demonstrated that cannabinoids signal apoptosis by a pathway involving cannabinoid receptors, sustained accumulation of the lipid ceramide and Raf-1/ERK (extracellular signal-regulated kinase) activation, inducing a cascade of reactions that leads to cell death.

In a commentary for Nature Medicine, Dr. Daniele Piomelli, from the University of California at Irvine, said the findings could have important implications. This would be the first convincing study to show that a marijuana-based drug treatment may combat cancer. If the drug works as well in humans, Piomelli says, "then this will be a paper of great importance." But it would take a lot of testing, both in animals and in people, to prove it is effective. The smoking of marihuana would not be effective.

(Sources: Galve-Roperph I, Sanchez C, Cortesz ML, Gomez del Pulgar T, Izquierdo M, Guzman M: Antitumoral action of cannabinoids: involvement of sustained ceramide accumulation and ERK activation. Nature Medicine 6, 313-319 (2000); Piomelli D: Nature Medicine 6, 255-256, (2000))