New hope for addicts

January 28, 2013 by Barbara Lago

It doesn't take a rocket scientist to quickly grasp what a University of Mississippi professor's research could mean to the millions of people addicted to hardcore narcotics such as heroin, cocaine, methamphetamine and morphine.

School of Pharmacy faculty member Christopher R. McCurdy has made it his mission to find and develop compounds to unlock the shackles that bind people to .

"A lot of people who become addicted to methamphetamine, cocaine or even heroin truly want to quit," McCurdy said. "They begin with recreational use and don't think they will become addicted, but (they) soon get to the point where they almost must take the drug to survive, because withdrawal is so intense."

Making withdrawal more endurable – and therefore, cessation more likely – is the goal of several projects in McCurdy's medicinal chemistry laboratory. Among them is a National Institutes of Health Centers of Biomedical Research Excellence-funded study of kratom, a botanical mixture derived from Mitragyna speciosa, a treelike plant native to . (COBRE grants are awarded by the NIH's National Institute of General Medical Sciences through its Institutional Development Award, or IDeA, program, which builds research capabilities in states that historically have had low levels of NIH funding.)

"In Southeast Asia, kratom has long been used for coughs, diarrhea, muscle aches and pain," McCurdy said. "It is also used as a replacement for opium when opium isn't available and has been used to wean people off (that narcotic)."

McCurdy and his colleagues made a tea from Mitragyna leaves, freeze-dried it and tested it in mice habituated to morphine. Results indicate the tea has some undesirable side effects but that modifications eliminate them and show great promise.

Taking the work a step further, the group isolated the plant's most abundant alkaloid, mitragynine, and tested the pure compound. Results indicate this compound's activity is superior to methadone in the mouse withdrawal assay and that carefully created chemical variations may provide an alternative to methadone in treating addictions to opiates.

"Mitragynine completely blocked all withdrawal symptoms and could provide a remarkable step-down-like treatment for people addicted to hardcore narcotics such as morphine, oxycodone or heroin," McCurdy said. "The compound has been known for years, but we're working to come up with an improved synthetic analog or a better formulation of the tea for testing in humans."

Collaborating on the study is Dr. Edward W. Boyer, professor of emergency medicine and director of medical toxicology at the University of Massachusetts School of Medicine.

"Dr. Boyer is an opium treatment specialist and, through an anonymous chat room, asked kratom users how much they used, how often they used and whether they had any withdrawal symptoms," McCurdy said. "That information helped us determine dosages and frequencies for our animal studies."

Despite the U.S. Drug Enforcement Administration listing kratom as a "drug of concern" because of its abuse potential and stating there is no legitimate medical use for it in this country, several million Americans purchase kratom on the Internet to self-manage chronic pain and/or opioid withdrawal, and some are ending up in emergency rooms. After one who had been using kratom four times a day for more than three years arrived in the ER with seizures, Boyer sent a sample of the material to McCurdy and his colleagues for analysis. They found no contaminants, which helped determine the seizures resulted from co-administration of modafinil 20 minutes earlier (Addiction, 2008, 103, 1048-1050).

Their analysis of material taken by a patient arriving at the University of Colorado ER revealed it was laced with hydrocodone and morphine, and analysis of material taken by a mother giving birth to an opiate-addicted baby at a University of Louisville hospital revealed the material was also laced with hydrocodone.

McCurdy and Bonnie Avery, an Ole Miss associate professor of pharmaceutics who has been instrumental in the analytical and pharmacokinetic analysis of kratom, have become recognized as experts on this plant material. "We can authenticate it and determine when it's adulterated," McCurdy said.

The Mississippi laboratory staff's ability to help answer clinicians' questions is of enormous benefit, Boyer said.

"We have been able to distinguish the effects of kratom from those of other drugs whose presence was unanticipated," he said. "This has allowed us to document that some toxicity of kratom is actually from other pharmaceutical agents that had been added."

Just as promising as the work on kratom is another study funded by the National Institute on Drug Abuse, which indicates several small molecules block the behavioral and toxic effects of cocaine and methamphetamine in animal models by coupling with sigma receptors in the brain. These highly selective compounds have been studied by a group of international collaborators, including McCurdy, Jacques H. Poupaert, a professor at the Université Catholique de Louvain in Belgium, Rae R. Matsumoto, associate dean of research and graduate programs at West Virginia's School of Pharmacy, and Frederick T. Chin, head of cyclotron radiochemistry in the Stanford University Medical Center's molecular imaging program.

"No one has been able to block self-administration of cocaine in rats with compounds in this class, but one of our compounds did, and we are excited about publishing these results soon," McCurdy said.

Jonathan L. Katz, chief of the Psychobiology Section of NIDA's Intramural Research Program in Baltimore and his colleague, Takato Hiranita, tested the compound in cocaine-addicted rats.

"When given the drug, the rats stopped taking cocaine," Katz said. "But what makes this drug so interesting is that the drug had no effect in the other activities of the rats. This kind of selectivity is what makes drugs suitable as medicines."

Today, nothing is available to either treat cocaine and methamphetamine addiction or block the seizures and other complications associated with overdoses of drugs with monikers such as crack, crystal and ecstasy.

"This product could potentially be the first of its kind to hit the market," McCurdy said. "There's still a long way to go, but our research team is motivated to complete the preclinical studies necessary to allow us to start doing human studies."

Fred Taylor, an IDeA program official at the NIH's NIGMS, said that the university's COBRE grant "has enabled the University of Mississippi to successfully train and mentor developing investigators, build state-of-the-art research infrastructure and conduct exemplary research activities. In pursuing these goals of the IDeA program, the center is making an impact on biomedical research and health in Mississippi, the region and the nation."

Explore further: Two-drug combination has potential to fight cocaine addiction: study

Related Stories

Two-drug combination has potential to fight cocaine addiction: study

August 8, 2012
A fine-tuned combination of two existing pharmaceutical drugs has shown promise as a potential new therapy for people addicted to cocaine—a therapy that would reduce their craving for the drug and blunt their symptoms ...

Scientists create vaccine against heroin high

July 20, 2011
Researchers at The Scripps Research Institute have developed a highly successful vaccine against a heroin high and have proven its therapeutic potential in animal models.

Collaborative preclinical efficacy studies suggest a new target for drug addiction treatment

March 14, 2012
In preclinical studies, researchers at SRI International and Astraea Therapeutics have recently evaluated the role of a new drug receptor target that shows promise for the treatment of drug addiction.

Study provides clues for designing new anti-addiction medications

March 22, 2012
Scientists are now one step closer to developing anti-addiction medications, thanks to new research that provides a better understanding of the properties of the only member of the opioid receptor family whose activation ...

Resistance to cocaine addiction may be passed down from father to son, study shows

December 16, 2012
Research from the Perelman School of Medicine at the University of Pennsylvania and Massachusetts General Hospital (MGH) reveals that sons of male rats exposed to cocaine are resistant to the rewarding effects of the drug, ...

Recommended for you

Concern with potential rise in super-potent cannabis concentrates

July 21, 2017
University of Queensland researchers are concerned the recent legalisation of medicinal cannabis in Australia may give rise to super-potent cannabis concentrates with associated harmful effects.

Findings link aldosterone with alcohol use disorder

July 18, 2017
A new study led by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, demonstrates that aldosterone, a hormone produced in the adrenal glands, may contribute ...

Depression among young teens linked to cannabis use at 18

July 17, 2017
A study looking at the cumulative effects of depression in youth, found that young people with chronic or severe forms of depression were at elevated risk for developing a problem with cannabis in later adolescence.

Why does prenatal alcohol exposure increase the likelihood of addiction?

July 7, 2017
One of the many negative consequences when fetuses are exposed to alcohol in the womb is an increased risk for drug addiction later in life. Neuroscientists in the University at Buffalo Research Institute on Addictions are ...

Researchers say U.S. policies on drugs and addiction could use a dose of neuroscience

June 23, 2017
Tens of thousands of Americans die from drug overdoses every year – around 50,000 in 2015 – and the number has been steadily climbing for at least the last decade and a half, according to the National Institute on Drug ...

Study provides further support for genetic factors underlying addictions

June 13, 2017
Impairment of a particular gene raises increases susceptibility to opioid addiction liability as well as vulnerability to binge eating according to a new study.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

kratomlaws
not rated yet Jan 30, 2013
The first correct article I have seen about kratom! Thank you so much for being honest and not teaming up with big pharma! Kratom saved my life! You just made my whole day! I spend 20 hours a day trying to share the good tidings of kratom. While fighting for legality also helping people get free from pain pills that kill 6 people every minute in the US. I work so hard to do everything I am involved in and it is discouraging while the media pumps lies out in care of big pharma who will go bankrupt. While junkies, rapists and thieves turn into productive citizens big pharma becomes bankrupt and that is a problem to them. Thank you so much for an honest report of what saved my life! Kratom is in the same family as the coffee tree. Kratom is all natural and totally harmless. Nobody has ever died from kratom. In the worst case if somebody tried to abuse it they would become nauseous and throw up. There are no known side effects except you sex life comes back. Pain pills even kill that.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.