CANNABINOID RECEPTOR AGONISTS MAY BE NOVEL CLASS OF ANTI-LYMPHOMA AGENTS

NEW YORK (Reuters Health) Jul 25 - Delta-9-tetrahydrocannibinol (THC),
the major component of marijuana, and other cannabinoids induce
apoptosis in murine tumors of immune origin, according to researchers
at Virginia Commonwealth University in Richmond.

Like other immune cells, cancers of the immune system express a
cannabinoid receptor known as CB2, Dr. Mitzi Nagarkatti explained in
an interview with Reuters Health. Compounds that bind CB2 receptors
selectively induce apoptosis in these cancer cells, she said.
Moreover, "compounds that interact with CB2 will not exhibit
psychotropic effects."

In a series of in vitro experiments, Dr. Nagarkatti and her colleagues
exposed murine lymphoma and mastocytoma cells to four cannabinoid
receptor agonists. THC and two of the others significantly reduced
cell viability and increased apoptosis, they report in the July 15th
issue of Blood.

In vivo experiments confirmed the effect of THC. Ten days after mice
were injected with lymphoma cells, cells collected from animals
treated with the highest dose of THC showed 77.3% apoptosis. Two weeks
of THC treatment cured 25% of lymphoma-bearing mice.

"It is possible that the immunosuppressive effects of THC may have
interfered with the host's antitumor immunity, which may account for a
lower percentage of cures," the researchers comment. They are
currently conducting murine dose-ranging studies.

The research group also demonstrated that three human leukemia and
lymphoma cell lines expressed CB2 and not CB1. Three cannabinoids,
including THC, induced apoptosis in these cell lines in vitro, and THC
showed the same effect when cultured with cells from patients
diagnosed with acute lymphoblastic leukemia.

"Recently, however, we identified a human cell line that was
resistant," Dr. Nagarkatti's team reports. "Further studies are in
progress to address whether this cell line lacks physical or
functional cannabinoid receptors and/or signaling molecules that
trigger apoptosis."

In addition, the research team is currently "screening a large number
of CB2 analogs to identify compounds that are highly efficacious in
killing the cancer cells," Dr. Nagarkatti said. "We are also
investigating whether endogenous cannabinoids can exert antitumor activity."