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By Linda Homewood

GAINESVILLE, Fla. - St. John's wort, an herb thought to be a safe, natural remedy for mild depression, may interfere with a powerful cancer-fighting drug's ability to prevent relapse in leukemia patients, a University of Florida pharmacy researcher will report March 27 at the annual meeting of the American Society for Clinical Pharmacology and Therapeutics.

Researchers who studied healthy volunteers to determine whether the herbal preparation interacts with the prescription drug imatinib mesylate, known by the trade name Gleevec, found that taking the two together caused the amount of Gleevec in the blood to drop nearly 30 percent.

Because it targets only cancerous cells, Gleevec has been called a "magic bullet" drug that fights aggressive cancers such as chronic myelogenous leukemia, researchers say. Leukemia patients who go into remission must continue to take daily oral doses of the medicine to prevent a recurrence.

"A 30 percent decrease in the level of Gleevec is significant to cancer patients," said Reginald F. Frye, Ph.D., associate director for the UF Center of Pharmacogenomics. "It is the same as lowering the dose - which is enough to allow for a relapse in the cancer growth."

Frye began the study while he was still working at the University of Pittsburgh Schools of Pharmacy and Medicine, prior to arriving at UF's College of Pharmacy in 2003.

"The emergence of studies such as this shows the need for health-care professionals to have current scientific information on the safety and efficacy of natural supplements," said Veronika Butterweck, Ph.D., the DeSantis professor of natural products at the UF College of Pharmacy.

Patients should be aware that any product they take, whether herbal, nonprescription or prescription, has the potential to alter how their body handles other drugs they are taking, said study collaborator Merrill J. Egorin, M.D., co-director of the Molecular Therapeutics and Drug Discovery Program at the University of Pittsburgh Cancer Institute.

"The interactions of herbal preparations and even certain foods can be an important factor in how well a patient may absorb or metabolize certain drugs, and those differences can have important clinical consequences," Egorin said.

Clinical trials performed on St. John's wort in the United States show that while it doesn't appear useful for major depression, it may help treat mild depression, Frye said.

The first indication that St. John's wort interacts with other medications came after physicians noted drugs designed to prevent organ rejection weren't as effective in transplant patients who were taking the herbal supplement, he added. A few years ago, the U.S. Food and Drug Administration issued a public health advisory after federal research showed St. John's wort interferes with medicines used to treat patients with HIV. Those findings raised concerns that the herb also might interact with drugs taken by patients with heart disease, depression or seizures.

The National Nutritional Foods Association reported in 2000 that more than 242 million Americans used some form of dietary supplement, vitamins, minerals, herbal remedies or specialty products. Although St. John's wort is available over the counter at most national drug stores, little is known about how it may interact with prescription medications. Herbal products aren't evaluated or regulated by the FDA, and don't normally go through the interaction studies required of marketed prescription drugs.

For the current UF study, researchers focused on 12 healthy, nonsmoking volunteers, six men and six women, who took one 400-milligram dose of imatinib mesylate. Researchers then took a series of blood samples over a 72-hour period to see how much of the drug had been metabolized. For two weeks after the blood tests, study participants took 300 milligrams of St. John's wort three times each day. On the 15th day, they again were given one dose of imatinib mesylate, and the blood tests were repeated to measure drug levels.

Frye noted a marked decrease of imatinib mesylate in the subjects' bloodstreams after they took the St. John's wort regimen, indicating the herbal product caused the body to metabolize the medicine at a faster rate, weakening its effectiveness.

"Often, patients don't think of herbal supplements as being a drug, and when their doctor asks what other medications they are taking, they may not report taking herbal products like St. John's wort," Frye said.

The National Center for Natural Products Research at the University of Mississippi School of Pharmacy conducts research on the chemical make-up of the St. John's wort plant. Although only one type of the plant is used in dietary supplements, which rank among the top 10 herbal preparations in national sales, there are actually 370 known species, said Ikhlas Khan, Ph.D., the center's assistant director.

"By examining the chemical profiles of all the species, we hope to better understand the efficacy of this plant," Khan said. "A long-range goal at our center is to provide the science that may help industry and government to establish criteria for product quality and safety."

UF researchers explore why patients' pain recall may be more than total

By Lindy McCollum-Brounley GAINESVILLE, Fla. - In a perfect world, a visit to the dentist's office would be stress-free and painless. But if you're like 25 million other Americans, the mere thought of reclining in a dentist's chair probably fills your heart with dread. You may have been there before and it didn't feel good. Or, at least, you think it didn't. Now, a report published by University of Florida College of Dentistry researchers in this month's Journal of Pain demonstrates much of that negative recall may be mostly in your head. It turns out that an individual's memory of pain intensity months later may have more to do with how emotionally stressed the person was during the experience than with how painful the experience actually may have been. "Clearly, many dental and medical procedures are aversive and anxiety-provoking, fear-provoking and uncomfortable in general," said Jeffrey J. Gedney,Psy.D., a pain behavior research fellow in the college's division of public health services and research. "What we found was that emotional factors became a better predictor over time of what people would recall than was their level of pain during their experience." The study was designed to measure just how much stress - such as the normal anxiety one may feel when receiving medical treatment - influences how painful people remember their experience being. Researchers found that subjects who were stressed during their painful experience recalled more pain after several months than they reported at the time of the painful event, and women remembered more pain than men. Study subjects, 52 men and 48 women, were asked to complete two 15-minute experimental sessions, one stressful and one stress-free. In the stress-inducing session, they were asked to give extemporaneous speeches about difficult social issues to a live audience and before a video camera. During the non-stressful session, participants were allowed to read neutral magazines about gardening or travel. Stress levels of people in both sessions were measured by before and after questionnaires, sampling for stress hormones in saliva and monitoring heart rate. Subjects were found to have both emotional and physical stress responses to session activities during only the stress session. After both sessions, participants were asked to complete a two-minute pain task in which they rated the severity of their pain from an "ice-cream headache" caused by holding a bag of crushed ice against their foreheads. Subjects then completed another series of questionnaires designed to rate their emotional states immediately after the pain task. To determine how much and what subjects remembered of their pain over time, researchers conducted telephone interviews of 68 people who agreed to participate in a six-month follow-up survey. "We found that nearly everyone recalled more pain at six months than they reported at the time of the experience," said Henrietta L. Logan, Ph.D., director of the college's division of public health services and research and Gedney's co-investigator. "Women tended to recall more pain, and moreover, people in the stress condition recalled more than people from the non-stress condition." Patients recalled nearly 10 percent more pain from the stress session than from the non-stress session. Additionally, the emotional state of the subject during the follow-up interview also seemed to influence the level of pain they recalled, Logan said. "So, what we propose is that emotions, indeed, do have an influence on how people process and recall, at least in this case, painful experience," Gedney said, although he was careful to clarify that more research is needed to understand the gender differences in pain recall. "The findings of this report indicate that health-care providers have added reasons to be careful to recognize and treat not just the clinical symptoms of disease, but the emotional reactions of patients during treatment," said Robert Baron, Ph.D., a professor of psychology at the University of Iowa. "Failure to do so will often heighten the patients' negative recollection of treatment stress, which in turn will be likely to discourage them from seeking follow-up or continued treatment." Logan said health-care providers and their staff have a responsibility to recognize and address this phenomenon in patients. "If the goal of the caregiver is to make the patient's experience as positive as possible, and to reduce anxiety by establishing a pleasant setting and paying particular attention to the personal comfort of the individual, it's bound to make a difference not only in the patient's willingness to come back but also in their long-term recall of the amount of pain they experienced," Logan said.