Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stanford scientists identify drug to treat opioid addiction

19.02.2009
Scientists at Stanford University School of Medicine have discovered that a commonly available non-addictive drug can prevent symptoms of withdrawal from opioids with little likelihood of serious side effects. The drug, ondansetron, which is already approved to treat nausea and vomiting, appears to avoid some of the problems that accompany existing treatments for addiction to these powerful painkillers, the scientists said.

Opioids encompass a diverse array of prescription and illegal drugs, including codeine, morphine and heroin. In 2007, about 12.5 million Americans aged 12 and older used prescription pain medications for non-medical purposes, according to the National Survey on Drug Use and Health, administered by the federal government's Substance Abuse and Mental Health Services Administration.

"Opioid abuse is rising at a faster rate than any other type of illicit drug use, yet only about a quarter of those dependent on opioids seek treatment," said Larry F. Chu, MD, assistant professor of anesthesia at the School of Medicine and lead author of the study that will be published online Feb. 17 in the Journal of Pharmacogenetics and Genomics. "One barrier to treatment is that when you abruptly stop taking the drugs, there is a constellation of symptoms associated with withdrawal." Chu described opioid withdrawal as a "bad flu," characterized by agitation, insomnia, diarrhea, nausea and vomiting.

Current methods of treatment are not completely effective, according to Chu. One drug used for withdrawal, clonidine, requires close medical supervision as it can cause severe side effects, while two others, methadone and buprenorphine, don't provide a satisfactory solution because they act through the same mechanism as the abused drugs. "It's like replacing one drug with another," said co-investigator Gary Peltz, MD, PhD, professor of anesthesia.

"What we need is a magic bullet," said Chu. "Something that treats the symptoms of withdrawal, does not lead to addiction and can be taken at home."

The researchers' investigation led them to the drug ondansetron, after they determined that it would block certain receptors involved in withdrawal symptoms.

The scientists were able to make this connection thanks to their having a good animal model for opioid dependence. Mice given morphine for several days develop the mouse equivalent of addiction. Researchers then stop providing morphine to trigger withdrawal symptoms. Strikingly, these mice, when placed into a plastic cylinder, will start to jump into the air. One can measure how dependent these mice are by counting how many times they jump. Like humans, dependent mice also become very sensitive to pain when they stop receiving morphine.

But the responses vary among the laboratory animals. There are "different flavors of mice," explained Peltz. "Some strains of mice are more likely to become dependent on opioids." By comparing the withdrawal symptoms and genomes of these different strains, it's possible to figure out which genes play a major role in addiction.

To accomplish this feat, Peltz and his colleagues used a powerful computational "haplotype-based" genetic mapping method that he had recently developed, which can sample a large portion of the genome within just a few hours. This method pinpoints genes responsible for the variation in withdrawal symptoms across these strains of mice.

The analysis revealed an unambiguous result: One particular gene determined the severity of withdrawal. That gene codes for the 5-HT3 receptor, a protein that responds to the brain-signaling chemical serotonin.

To confirm these results, the researchers injected the dependent mice with ondansetron, a drug that specifically blocks 5-HT3 receptors. The drug significantly reduced the jumping behavior of mice as well as pain sensitivity — two signs of addiction.

The scientists were able to jump from "from mouse to man" by sheer luck: It turns out that ondansetron is already on the market for the treatment of pain and nausea. As a result, they were able to immediately use this drug, approved by the Food and Drug Administration, in eight healthy, non-opioid-dependent humans. In one session, they received only a single large dose of morphine, and in another session that was separated by at least week, they took ondansetron in combination with morphine. They were then given questionnaires to assess their withdrawal symptoms.

Similar to mice, humans treated with ondansetron before or while receiving morphine showed a significant reduction in withdrawal signs compared with when they received morphine but not ondansetron. "A major accomplishment of this study was to take lab findings and translate them to humans," said principal investigator J. David Clark, MD, PhD, professor of anesthesia at Stanford University School of Medicine and the Palo Alto Veterans Affairs Health Care System.

Chu plans on conducting a clinical study to confirm the effectiveness of another ondansetron-like drug in treating opioid withdrawal symptoms in a larger group of healthy humans. And the research team will continue to test the effectiveness of ondansetron in treating opioid addiction.

The scientists warned that ondansetron will not by itself resolve the problems that arise with continued use of these painkillers. Addiction is a long-term, complex process, involving both physical and psychological factors that lead to compulsive drug use. "This is not a cure for addiction," said Clark. "It's naïve to think that any one receptor is a panacea for treatment. Treating the withdrawal component is only one way of alleviating the suffering. With luck and determination, we can identify additional targets and put together a comprehensive treatment program."

Collaborators on this study included De-Yong Liang, PhD, the study's co-lead author, previously a research associate in the Department of Anesthesia and currently a research associate at the Palo Alto Institute for Research and Education; Xiangqi Li, MD, a life science research assistant in the department; Nicole D'Arcy, a medical student: Peyman Sahbaie, MD, a research associate at the institute; and Guochun Liao, PhD, of the pharmaceutical company Hoffman-La Roche. This work was supported by grants to Clark from the National Institutes of Health and the National Institute on Drug Abuse, and grants to Chu from the NIH and the National Institute of General Medical Sciences.

The researchers are working with the Stanford University Office of Technology Licensing to seek a patent for the use of ondansetron and related medicines in the treatment of drug addiction.

Rosanne Spector | EurekAlert!
Further information:
http://www.stanford.edu
http://mednews.stanford.edu

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>