March 1, 2019 | Katherine Adams
Two University of Houston-Clear Lake psychology professors and their student team have been conducting novel research into treating
opioid addiction – not by manipulating or substituting the drug, but rather by manipulating
the body's biochemical reactions that cause dependence and tolerance to the drug.
As drug overdose deaths in the United States continue to increase, the Centers for Disease Control is reporting alarming statistics: Between 1999 and 2017, more than 700,000 people have died from a drug overdose, and 68 percent of the 70,200 drug overdose deaths in 2017 involved an opioid. This class of drugs is extremely efficient at relieving pain, but their use is shadowed by risk of addiction, tolerance and other negative side effects. UH-Clear Lake professors of Psychology and Neuroscience David Malin and Chris Ward, along with a team student researchers, have been working to demonstrate a potential therapeutic approach to treating dependence on narcotics.
Malin said their research explored two of the most serious problems facing drug users: narcotic tolerance and physical dependence. “Our student-faculty research group concerned itself with these issues, and the protagonist of the story is neuropeptide FF, or NPFF,” he said.
Malin explained that a peptide is a chain of amino acids somewhat similar to a small protein. Many peptides are involved in communication among cells. They alter various physiological functions, behavioral tendencies and pain sensitivity.
A former collaborator of the UHCL research team, Dr. H-Y. T. Yang of the National Institutes of Health, noticed that NPFF interfered with some actions of the opiate drug, morphine. The UHCL and NIH teams found that chronic morphine exposure dramatically increased the release of NPFF.
“We then hypothesized that by fighting back against the morphine, it might contribute to narcotic tolerance, or a progressive loss of potency, which then leads to increasing the dosage. Also, by fighting back in the opposite direction to opiates, the increased NPFF levels might contribute to physical dependence and the withdrawal syndrome,” Malin said. “The opiates are very effective painkillers. But when substances such as NPFF are fighting back in the opposite direction and then the pain-killing opiate is removed, you become agonizingly more sensitive to pain.”
Ward added, “With opiates, the desire to avoid withdrawal by taking more drug becomes overwhelming. This helps sustain the drug habit.”
In earlier laboratory research with UHCL students and outside collaborators, Malin was able to reduce morphine tolerance and physical dependence with antibodies to NPFF and drugs that interfered with receptors for NPFF. However, things later became more complicated with the discovery of two types of NPFF receptors. These two often seem to have opposite effects when stimulated.
In a recent journal article, the UHCL group found that a drug that stimulated one type while inhibiting the other, reversed tolerance to a substantial dose of morphine. In another journal article, the group reported that a drug that interfered with one of the two receptor subtypes reversed physical dependence as indicated by prevention of withdrawal syndrome.
It is important to note that these experimental drugs are probably not suitable for clinical medical use. Rather, they show they demonstrate a potential strategy for combating the habit-forming effects of opiate narcotics.
Usual approaches to treating these problems focus on the opiate drug itself or its receptors. Instead, the UHCL research focus on interfering with one of the body’s multiple responses to chronic narcotic exposure, responses that lead more directly to tolerance and physical dependence. The ultimate goals of this entire research area include interventions that allow pain patients to continue to find relief from modest doses of opiate pain-killers without having to keep raising the dose. Another goal is to reduce physical dependence so that users can better be eased off narcotic drugs with much less of a withdrawal syndrome.
Currently, a number of approaches toward these goals are undergoing preliminary testing in a number of laboratories. “The more hypothetical approaches under consideration, the greater our chance of eventually finding new powerful tools to combat this overwhelming human problem,” Malin noted.
For more information about UHCL’s Psychology M.S. with Behavioral Neuroscience Concentration, visit www.uhcl.edu/academics/degrees/psychology-ms-behavioral-neuroscience-concentration.