IACM-Bulletin of March 5, 2000

Science — THC destroys brain cancer in animal research

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); UPI of 28 February 2000; AP of 29 February 2000; Reuters of 29 February 2000; PA News of 29 February 2000, personal communication by Manual Guzman)

Science — Cannabinoids reduce tremor in animal model of multiple sclerosis

In the journal Nature scientists said on 1 March they had for the first time scientifically demonstrated the link between cannabis and the suppression of multiple sclerosis (MS) symptoms. The study with mice suffering from chronic allergic encephalomyelitis (CREAE) -- an animal model for MS -- found that cannabinoids ameliorated CREAE symptoms.

The mouse MS study "is the first to show definitive objective evidence that synthetic compounds, which stimulate the receptor that cannabis (marijuana) binds to, can alleviate spasticity and tremor in an MS-like condition. This gives a rationale of why patients may perceive benefit from taking cannabis and supports the establishment of a clinical trial to assess the benefit of medical cannabis in MS," Lorna Layward, head of research of the Multiple Sclerosis Society of Great Britain and Northern Ireland, said.

In the study, led by David Baker of University College in London, the researchers injected THC, other cannabinoid receptor agonists and antagonists into mice with CREAE. Layward said it was now up to drug companies to develop compounds that mimicked cannabis but avoided the side-effects experienced by cannabis smokers. The scientists cautioned the research is in the preliminary stages; whether similar results can be obtained in large-scale human studies is unknown.

(Sources: UPI of 2 March 2000, Reuters of 2 March 2000; PA News of 2 March 2000)

Science — Smoking marijuana my increase risk of heart attack

Smoking marijuana significantly increases the risk of a heart attack for middle-aged and elderly users during the first hour after using the drug, researchers reported on 2 March. They said they were not sure whether the marijuana itself or other components of smoke such as carbon monoxide were responsible for it.

The study by Dr. Murray Mittleman, a professor at Harvard Medical School and director of cardiovascular epidemiology at Beth Israel-Deaconess Medical Centre, and colleagues were being presented at an American Heart Association (AHA) conference in San Diego. The heart attack risk was 4.8 times higher during the first hour following marijuana use than it was during times of non-use. In the second hour, the relative risk dropped to 1.7.

"These effects may pose significant risk, especially in people with unrecognised coronary disease," Mittleman said. Mittleman's research team collected information from 3,882 people who had heart attacks. Of that group, 124 were identified as current marijuana users, including 37 who said they smoked the drug within 24 hours before their heart attack and nine who reported smoking pot within an hour of their first symptoms.

The increased risk is nowhere near what is seen with other drugs -- like the 25-fold spike in heart attack risk from cocaine -- and may not even be as dangerous as taking a jog might be for a sedentary person. But, Mittleman, says, "The risk is there. It's real." Other studies have shown that younger marijuana smokers are not at a greater risk for heart attacks.

(Sources: Reuters of 2 March 2000, UPI of 2 March 2000, AP of 2 March 2000)

News in brief

USA

A panel of the state Medical Quality Assurance Commission of Washington will consider whether to make anyone suffering certain debilitating symptoms eligible to legally use marijuana for medical purposes. Dr. Rob Killian is petitioning the board to add a list of symptoms rather than specific diseases. The list suggested by Killian includes: gastrointestinal symptoms such as nausea, vomiting, anorexia, appetite loss and cramping; neurological symptoms such as seizures, muscle spasms and spasticity; mood disorders, including insomnia and post-traumatic stress disorder. A final decision is expected on 2 June. (Source: Seattle Times of 2 March 2000)