Because chronic pain sufferers frequently need narcotic drugs to relieve their discomfort, they are at risk of developing psychological and physiological dependence and addiction to the pain medications that are prescribed for them. “Most pain medicines cause some euphoric brain effects that promote addiction,” said Dr. Greg Sullivan of Parkway Medical Center in Birmingham. “The personality changes that characterize opiate dependence and addiction are most easily noticed by family members or close friends as an obsession with or increasing appetite for the pain medication they are taking.” Sullivan added that even without addiction or dependence, severe chronic pain patients suffer significant distraction because of the pain itself and can have similar personality changes. “In those cases, the patient is more focused on the pain and ways to minimize it and less concerned with the emotional effects of a particular pain medication,” he said. “The differentiation between attitude changes caused by chronic pain and those caused by opiate dependence is difficult and almost always requires detailed discussions with family members or loved ones.” Because of the dependency problem, researchers began in the early 1960s to study opiate structure and receptor function to determine what part of the molecule caused pain relief and what part caused addiction. They were on a quest for a potent pain reliever with no addictive features. England’s Reckitt Benckiser (the makers of Lysol) began a 14-year project to look for an over-the-counter pain medicine to mix with aspirin for chronic pain. Using codeine and morphine as starting points, they hired 20 academic medicinal chemists to modify two specific molecular sites that regulated how addictive particular opiates were to humans. These scientists developed and tested 200 different molecular candidates over the next 14 years to find an effective pain reliever with fewer addictive characteristics than standard opiates. “Their modifications yielded what are called N-CPM orvinols, which were still structurally related to opiates but affected different parts of the brain in unique ways. Buprenorphine was judged the best candidate of the more than 200 that were developed, patented and animal tested during this project,” said Sullivan. Buprenorphine’s injectable form (Buprenex) has been marketed in Europe since 1978 and was approved and first marketed in the United States in 1982. It was approved for use in acute pain by the Food and Drug Administration (FDA) and is used by emergency rooms throughout the United States for kidney stone pain because of its high potency and ability to stop the severe pain of renal colic. “The U.S. government became interested in buprenorphine even before its approval for pain,” Sullivan said. “Since 1974, the Federal Prison/Medical Center in Lexington, Ky., has been using the drug for opiate addicted inmates. The results were so positive and dramatic that the National Institutes of Health in the U.S. agreed to partner with Reckitt to help bring this drug to market for opiate addiction as an alternative to methadone.” The newly developed formulations of buprenorphine are called Suboxone® and Subutex® and were first approved by the FDA in October 2002 for the treatment of opiate addiction and dependence. In order for it to be used outside of drug treatment centers, special federal legislation called DATA 2000 was enacted to dismantle some of the restrictions placed on physicians when dealing with drug-addicted patients as required by the Harrison Narcotics Act of 1914. This act and the prohibition of alcohol five years later are thought to be the seeds of the drug black market in the United States, which still flourishes, said Sullivan. To treat any drug-addicted patient with this medication, a physician must be certified and must receive a federal waiver from the U.S. Drug Enforcement Administration. After being certified for a full year, doctors can treat up to 100 drug-addicted patients at a time with the substance. Sullivan is one of 25 physicians in the state of Alabama who has been given a waiver to use buprenorphine for the treatment of addiction to pain medications and street drugs. “When treating chronic pain without addiction, there are no such federal restrictions,” he said. Sullivan pointed out that oral buprenorphine is too strong for any patient who has not taken significant opiates in the past. Patients must have been on the equivalent of 30 mg of Lortab, oxycodone or morphine in the past before attempting to take buprenorphine tablets. “This medication is 30 times stronger than morphine for pain control and is a stimulant. Patients who have never taken opiate pain medicines before will vomit and feel terrible for several hours if it is given orally. Patients who have experience taking opiates daily in the past will have no ill effects and will achieve excellent pain relief without personality changes or sedation,” he said. Chronic pain sufferers who take opiates often build up a tolerance to a drug’s pain relief effects, but they rarely develop tolerance to buprenorphine, Sullivan said. “Buprenorphine causes fewer psychological changes, so when patients stop the opiates and start taking the buprenorphine, they become less self-centered and more emotionally responsive and sensitive to others’ needs.” Substantial personality improvements are apparent in the first 72 hours of stopping standard opiates and beginning buprenorphine, Sullivan said, because buprenorphine does not cause many of the personality changes seen with older opiates. It guards against hyperanalgesia and opiate tolerance, both of which are problems with conventional opiates. “The change is always dramatic but is different in everyone and depends on how much the opiates were affecting their normal baseline personality,” he said. The biggest change seems to be a motivation to get well, Sullivan added. “Buprenorphine has a unique effect because it blocks the kappa opiate receptor. This makes it a powerful antidepressant and stimulant,” he said. “Patients feel energized and motivated to be productive. When you add its pain-relieving effect that is 30 times stronger than morphine, you generally have happy patients and even happier families and employers.” August 2007