Wed Aug 21, 2002
By Adam Marcus
WEDNESDAY, Aug. 21 (HealthScoutNews) -- A man-made molecule may change the debate over medical marijuana.
The compound, called ajulemic acid (AjA), is a synthetic chemical that's structurally similar to tetrahydrocannabinol (THC), the active ingredient in pot. However, it doesn't seem to interact with brain cells in the same way as the plant form, and it generates no "high," unlike marijuana or even occasionally Marinol, a molecular mimic of THC that's prescribed for the nausea associated with AIDS and cancer treatment.
AjA has shown promise in a variety of conditions, from multiple sclerosis, in which it helps ease muscle spasms and pain, to cancer, in which it seems to have the ability at high doses to quash tumor growth.
Now it appears to also show promise in the treatment of arthritis, according to new research by the University of Massachusetts chemist who helped discover AjA's properties and owns patents on it.
Sumner Burstein's earlier work in rats showed the compound almost completely blocked the joint destruction in the rodent version of rheumatoid arthritis, a crippling disorder for people. It also led to significant, though less powerful, effects on pain and inflammation.
The impetus for developing ajulemic acid fell out of Burstein's discovery years ago that the principle breakdown product of THC in the body had mild anti-inflammatory effects.
In the new work, Burstein and his colleagues tested AjA in both rat cells and blood samples from healthy human volunteers. They found AjA had a dose-dependent effect on two key immune system chemicals called interleukin-1b (IL-1b) and tumor-necrosis factor-alpha (TNF-a).
Intriguingly, Burstein says, the synthetic molecule muzzled IL-1b, which in arthritis is an agent involved in joint destruction. Yet, it was less potent against TNF-a.
The data "really fits perfectly" with the initial rat study, conducted in 1998, says Burstein, who was to present his findings today at the American Chemical Society's annual meeting in Boston.
"We got significant decreases in both, but I would say when you compare the two of them that there's no question that the effect on bone damage was much, much more significant" than the reduction in pain and inflammation, he adds.
Even so, Burstein says, AjA appears to be as potent an agent against arthritis pain and swelling as the most powerful drugs on the market.
What's more, he believes the synthetic chemical will have fewer side effects on the gut, kidneys and other organs than non-steroidal anti-inflammatory compounds such as ibuprofen, aspirin or even the newer cox-2 inhibitors.
The substance is being developed as CT-3 by the Lexington, Mass.-based biotech firm Indevus Pharmaceuticals. German scientists are currently testing CT-3 in a small study of people with chronic pain. Results of that trial should be reported in the coming months.
However, it already has raised some professional skepticism.
Dr. Jody Corey-Bloom, a marijuana expert at the University of California, San Diego (UCSD), says she's not familiar with AjA. But, she adds, "none of the [synthetic THC compounds] to date have been very impressive. Marinol's on the market, and nobody likes it."
Corey-Bloom, part of UCSD's Center for Medicinal Cannabis Research, says her patients complain that taking the synthetic drug doesn't offer them the same relief as inhaled marijuana.