Navigation Links
Scripps Research Institute Scientists Develop Antidote for Cocaine Overdose

LA JOLLA, Calif., April 18, 2012 /PRNewswire-USNewswire/ -- Scientists at The Scripps Research Institute have shown that an injectable solution can protect mice from an otherwise lethal overdose of cocaine. The findings could lead to human clinical trials of a treatment designed to reverse the effects of cocaine in case of emergency. Cocaine is involved in more than 400,000 emergency-room visits and about 5,000 overdose deaths each year in the United States.

The findings, reported recently in the journal Molecular Pharmaceutics, demonstrate the therapeutic potential of a human antibody against cocaine.

"This would be the first specific antidote for cocaine toxicity," said Scripps Research Kim Janda, PhD, senior author of the report. A pioneer in the field of vaccines against drugs of abuse, Janda is the Ely R. Callaway, Jr. Chair in Chemistry, a professor in the Department of Immunology and Microbial Science, and director of The Worm Institute for Research and Medicine, all at Scripps Research. "It's a human antibody so it should be relatively safe, it has a superior affinity for cocaine, and we examined it in a cocaine overdose model that mirrors a real-life scenario," he said.

Candidate Vaccines

Janda and his laboratory colleagues have been developing candidate vaccines against cocaine, heroin, nicotine, and even Rohypnol, the "date-rape" drug. But most of these have been active vaccines—solutions of drug-mimicking molecules that provoke a long-term antibody response against a drug, greatly reducing its ability to reach the brain. These are potentially useful against addiction and relapse, but take weeks to stimulate an effective antibody response and thus are of limited value in drug overdose emergencies, which require a fast-acting antidote. Cocaine is a leading cause of illegal-drug overdoses in developed countries; it can cause hyperthermia, irregular heartbeats, seizures and death.

One possibility for an antidote is a "passive" cocaine vaccine, a ready-made solution of antibodies much like those used to treat snakebite. As Janda and his colleagues have shown in previous research, injected drug-specific antibodies can swiftly remove drug molecules from the bloodstream. This immediately reduces a drug's direct effects on the heart and nearby organs, but it also pulls the drug from the organ where it does the most damage—the brain. If the drug molecules are small enough to cross the blood-brain barrier, the sudden lowering of their bloodstream concentration causes them to diffuse rapidly out of brain tissue.

Cocaine molecules are small enough to diffuse this way, and in 2005 Janda and his lab reported that injections of a mouse-derived anti-cocaine antibody, GNC92H2, could keep mice alive despite cocaine doses that killed unprotected mice. Mouse antibodies are not ideal for use in humans, though; they are "foreign" enough that human immune systems eventually develop a reaction against them.

Promising New Results

In the new study, Janda and Jennifer B. Treweek, PhD, a research associate in Janda's laboratory, used a genetically engineered mouse that can produce fully human antibodies against cocaine molecules. The best of these antibodies, GNCgzk, showed ten times the cocaine-binding affinity of GNC92H2, the molecule in the 2005 study.

In a preliminary test, the scientists showed an injection of GNCgzk antibodies 30 minutes before an injection of a lethal cocaine dose greatly reduced the signs of overdose—such as awkward movements and seizures—and kept all treated mice alive. By contrast, about half of untreated mice and 15 percent of GNC92H2-treated mice died.

In a test that better simulated a real-life emergency situation, mice were first given a cocaine overdose, and three minutes later were infused with GNCgzk. About half of untreated mice were killed by such a dose. While GNC92H2 reduced that rate to about 28 percent, the new GNCgzk antibodies reduced the mortality rate further, to 20 percent.

More strikingly, a stripped-down version of GNCgzk—F(ab')2-gzk, which contains only the antibody's cocaine-binding segments—reduced the mortality to zero, as well as significantly reducing overdose signs such as seizures. It also did so at a much smaller, clinically feasible dose than GNC92H2's. "There was a reversal of the signs of cocaine toxicity within seconds of the injection," said Treweek.

Janda and Treweek are now trying to find ways to produce their F(ab')2-gzk antidote economically and in large quantities. "If we can do that, then there would be no reason not to push it into clinical trials," Janda said.

He notes that such a treatment could be useful not only in reducing the immediate effects of an overdose, but also in preventing near-term relapses. "A lot of people that overdose end up going back to the drug rather quickly," Janda said, "but this antibody would stay in their circulation for a few weeks at least, and during that time the drug wouldn't have an effect on them." Likewise, this antibody could be administered to patients in addiction recovery or detox programs as a prophylactic treatment to supplement other medications, such as antidepressants, and counseling.  An acute relapse during this recovery period would be immediately nullified by the antibody dose that is already in circulation.

The research in the paper "An Antidote for Acute Cocaine Toxicity" was supported by the National Institute on Drug Abuse of the National Institutes of Health and Scripps Research's Skaggs Institute of Chemical Biology. For more information on the paper, see

About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neuroscience, and vaccine development, as well as for its insights into autoimmune, cardiovascular, and infectious disease. Headquartered in La Jolla, California, the institute also includes a campus in Jupiter, Florida, where scientists focus on drug discovery and technology development in addition to basic biomedical science. Scripps Research currently employs about 3,000 scientists, staff, postdoctoral fellows, and graduate students on its two campuses. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, is ranked among the top ten such programs in the nation. For more information, see  



SOURCE The Scripps Research Institute
Copyright©2010 PR Newswire.
All rights reserved

Related medicine technology :

1. New Lupus Drug Results From Scripps Research Technology
2. The Scripps Research Institute Names Michael A. Marletta as President
3. Quest Diagnostics Brings Genetic Testing for Plavix(R) Response to Coronary Stent Patients at Scripps Health
4. Poniard Pharmaceuticals Licenses Kinase Inhibitors From The Scripps Research Institute
5. Research Alert -- Empire Asset Management Co. Initiates Coverage on Pacira Pharmaceuticals Inc. (NASDAQ: PCRX)
6. Stemline Therapeutics Announces Two Presentations of Direct Injection Synthetic Peptide Vaccine for Brain Cancer, Now Being Developed as SL-701, at the Annual Meeting of the American Association of Cancer Research (AACR)
7. Sustained Growth Forecast for Medical Devices and Drug Delivery Markets According to New Market Research Available from Global Information Inc.
8. New 60,000 Square Foot Lease at the Pacific Research Center Signed by Biomed Realty and Depomed
9. Research Finds Overdose Deaths Occur When Changing Opioids
10. Elsevier Launches New Journal: Journal of Applied Research in Memory and Cognition
11. Life Technologies Launches Ion AmpliSeq™ Custom Panels, Unlocking Thousands of Disease-Related Research Samples for Analysis
Post Your Comments:
(Date:12/1/2015)... , Dec. 1, 2015  Lexicon ... today that top-line data from its TELECAST ... etiprate in treating carcinoid syndrome in cancer ... the clinical benefit observed in its pivotal ... as a companion to TELESTAR primarily to ...
(Date:12/1/2015)... 2015 North America ... with analysis and forecast of revenue. --> ... segments the concerned market with analysis and forecast of ... Report "North American Orthobiologics Market by Type (Bone Allograft, ... Stem Cell Therapy, Viscosupplementation), by End-User (Hospitals, Point-of-Care Testing) ...
(Date:12/1/2015)... , December 1, 2015 ... the addition of the  "2016 Shigella ... Innovative Technologies, Competitive Strategies, Emerging Opportunities--US, ... Japan"  report to their offering. ... the addition of the  "2016 Shigella ...
Breaking Medicine Technology:
(Date:12/1/2015)... PITTSBURGH, PA (PRWEB) , ... December 01, 2015 ... ... or imaging facilities, radiographic technicians must mark the film for accurate interpretation by ... keep track of. Fortunately, an inventor from Sacramento, Calif., has found a way ...
(Date:12/1/2015)... , ... December 01, 2015 , ... ... it has been selected as a finalist in this year’s Fierce Innovation Awards: ... Next IT Healthcare was recognized as a finalist in the category of Digital ...
(Date:12/1/2015)... ... December 01, 2015 , ... PYA’s latest white paper, ... addresses a main “pain point” for merging or aligning healthcare provider organizations—when mergers ... is signed. This quick-read guidance suggests that failing to recognize the power ...
(Date:12/1/2015)... ... 01, 2015 , ... Nurotron Biotechnology Co., Ltd., maker of cochlear implant systems, ... , The order will be from the China Disabled Persons’ Federation, a central government ... effective solution for children and adults suffering from severe and profound hearing loss ...
(Date:11/30/2015)... ... November 30, 2015 , ... ... companies, announced today that it has officially launched a sleek, mobile-ready and user-centric ... that his company’s new website clearly outlines the benefits that its SEO services ...
Breaking Medicine News(10 mins):