Ultra-Low-dose Naltrexone Can Prevent Opioid Tolerance And Dependence By Karla Gale NEW YORK (Reuters Health) Jun 06 When administered with narcotic opioids, such as morphine and oxycodone, naltrexone in doses 100,000 to one million times lower than that of the opioid, not only enhances analgesia, but prevents or reverses tolerance and physical dependency, according to a report presented here Thursday at the International Conference on Pain and Chemical Dependency. Implications of this finding, Dr. Stanley Crain told Reuters Health, include the possibility that chronic pain patients may be maintained on low, stable doses of medication. All patients with end-stage cancer could possibly remain lucid while receiving adequate treatment for their pain. And, Dr. Crain theorized, this research may enable the withdrawal of highly addictive high-dose opioid preparations, such as Oxy-Contin, from the market because they simply will no longer be needed. The research is based on the relatively new finding that mammals have two opioid receptor pathways. In addition to the inhibitory pathway that results in analgesia, there is also an excitatory pathway that, when stimulated, weakens analgesia, mediates side effects, and contributes to the development of tolerance and addiction. Dr. Crain and Dr. Ke-Fei Shen, both from the Albert Einstein School of Medicine of Yeshiva University in New York, previously reported that the naltrexone/opiate combination allowed low doses of morphine to exert an analgesic effect (see Reuters Health report, January 12, 2001). Administration of naltrexone in picomolar or nanomolar amounts at the same time as opioid administration selectively blocks the excitatory opioid pathway, Dr. Crain explained. He and Dr. Shen conducted hot-water-immersion tail-flick antinociception assays with mice. Mice treated with analgesic doses of opioids twice a day developed "a marked degree of tolerance in a few days," Dr. Crain said. However, when naltrexone was added at each treatment, the mice showed "a nice, strong steady response, day by day." After 5 days of opiate treatment, the animals exhibited signs of withdrawal when the opiate was discontinued. However, Dr. Crain said, when they were co-treated with naltrexone, no withdrawal symptoms developed. "Furthermore," he added, "after having animals go through morphine treatment for 5 days so that they become tolerant and dependent, we can reverse the tolerance within a day if we add for the first time the low dose of naltrexone along with the same dose of morphine." "In preliminary clinical trials, we have not seen any significant signs of euphoria when morphine or oxycodone were given along with low doses of naltrexone, even though analgesia was enhanced," Dr. Crain pointed out. The company Pain Therapeutics, Inc. in San Francisco (NASDAQ:PTIE) has patented combination products of morphine sulfate or oxycodone and low-dose naltrexone, Dr. Crain added. According to the company's Web site, it has completed more than 12 clinical trials, involving over 1000 patients, that replicated these findings. The US Food and Drug Administration has not yet reviewed the findings. Reuters Health Information 2002. © 2002 Reuters Ltd Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.