Marijuana, Inflammation, and CT-3 (DMH-11C): Cannabis Leads to New Class of Antiinflammatory Drugs
Rheumatoid arthritis researchers are testing CT-3, a synthetic derivative of a metabolite of marijuana, as a potentially new kind of experimental antiinflammatory drug--without the gastric and other side effects of today's non-steroidal antiinflammatories, and without the psychoactive effect or "high" of marijuana. The natural metabolite has the same antiinflammatory effect, but is less powerful. Although CT-3 is far from human testing, it is interesting for several reasons:
Inflammation is not a single process, but many different ones. It may be important in the pathogenesis of HIV disease, and certainly can exacerbating some of its consequences. Much is still unknown, but a new class of antiinflammatory drugs will open new approaches for research and treatment.
An antiinflammatory effect separate from the psychoactive effect may be responsible for most of the relief which many patients find from medicinal marijuana. If the only benefit of the drug were in masking pain or other discomfort, then it would be hard to design scientific research except to confirm that the effect is real--and it is difficult to prove a subjective effect, especially with a substance like marijuana where it is probably impossible to use a placebo effectively. But if the drug is also an antiinflammatory, then all kinds of research opportunities open up, and the subjectivity problem can usually be avoided.
Obtaining the medical without the psychoactive effects of cannabis will be important to patients, since the "high" when it is not wanted is a major drawback, and can be debilitating.
A recent paper1 on CT-3 (also called DMH-11C, chemical name dimethylheptyl-THC-11 oic acid) was published in the January 1998 Arthritis and Rheumatism. The findings were also presented in November 1997 at the 61st National Scientific Meeting of the American College of Rheumatology.
THC (tetrahydrocannabinol) is the major active ingredient of marijuana; THC is also available legally in the U.S. as the prescription drug Marinol®. When the body metabolizes THC, it produces a number of related chemicals. It was previously known that at least one of these metabolites has antiinflammatory and pain-relieving effects. CT-3 was produced synthetically by modifying this metabolite so that it is more powerful and can be given in smaller doses.
The paper also acknowledged much earlier work, citing a Chinese text from around 2000 BC. "It was claimed that cannabis 'undoes rheumatism,' suggesting possible antiinflammatory effects."1
Animal tests found CT-3 effective against both chronic and acute inflammation; it also prevented destruction of joint tissue from chronic inflammation. These results suggest possible usefulness against chronic inflammatory conditions such as rheumatoid arthritis.
The drug is currently in very early pre-clinical animal testing. The long safety record of marijuana--no one has ever died of an overdose--and the fact that a metabolite with the desired antiinflammatory effect is produced in the body when marijuana is used, strongly suggest that safe and effective antiinflammatory drugs in this class are possible.
CT-3 should not be confused with a different synthetic marijuana-like drug, WIN 55212, recently reported to reduce pain in animal tests, by neurologists at the University of California San Francisco. Several other university research teams are also studying painkilling effects of cannabinoids. These studies suggest other potential uses of marijuana or its derivatives--for example, they might reduce the doses of opiates needed to control pain. But this mechanism is different from that of the antiinflammatory effect of CT-3.
CT-3 is being developed by Atlantic Pharmaceuticals in Raleigh, North Carolina. The research was done at the University of Massachusetts Medical Center in Worcester, Massachusetts.
References
1. Zurier RB, Rossetti RG, Lane JH, Goldberg JM, Hunter SA, and Burstein SH. Dimethylheptyl-THC-11 Oic Acid: A Nonpsychoactive Antiinflammatory Agent with a Cannabinoid Template Structure. Arthritis and Rheumatism. January 1998; volume 41, number 1, pages 163-170.
