Opioid drug abuse is a significant public health problem in the United States, and while treatments exist, there is a high rate of relapse and failure to keep to the program. A new study suggests that the prescription weight-loss drug lorcaserin has potential as a new treatment for opioid use disorder. Tests on rats reveal that it not only reduces self-administration of oxycodone but also that it can weaken reaction to drug-taking cues, which are often associated with relapse.

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The researchers note that many current treatments for opioid use disorder are often associated with high relapse rates and too many people stopping treatments early.

The study - led by Kathryn A. Cunningham, a professor of pharmacology and director of the Center for Addiction Research in the University of Texas Medical Branch at Galveston - is published in the journal ACS Chemical Neuroscience.

According to the Department of Health and Human Services, the U.S. is in the "midst of an unprecedented opioid epidemic."

Opioids are substances that attach to opioid receptors in parts of the brain that control pain and emotion. Examples include heroin, morphine, and certain prescription pain relievers such as oxycodone, codeine, and fentanyl.

As well as reducing pain, opioids produce states of euphoria and relaxation, which is the main reason that opioid pain relievers tend to be misused.

On an average day in the U.S., more than 650,000 prescriptions for opioid pain relievers are dispensed, and 3,900 people start using them for nonmedical reasons.

Estimates from the Centers for Disease Control and Prevention (CDC) suggest that more than 3 out of 5 deaths from drug overdose involve an opioid. In 2014, overdose deaths involving opioids totalled more than 28,000.

Treatments need to address 'cue reactivity'

While treatments for opioid use disorder exist, they are not ideal because they are often associated with high relapse rates and too many people stopping treatments early, note the authors of the new study.

One of the problems with many of the current treatments is that while they reduce the feeling of euphoria that results from taking opioids such as oxycodone, they do not address "cue reactivity" - the powerful effect that a familiar drug-taking environment can exert on anticipation of the drug experience.

Cue reactivity is often the reason that people on opioid misuse treatment relapse when they encounter the people, places, situations, and equipment that they associate with their opioid use. It results from the repeated pairing of these stimuli with the experience of the drug use.

In their new research, which takes the form of a preclinical study, the team shows that the prescription weight-loss drug lorcaserin reduced not only the use but also the craving for oxycodone in rats.

Lorcaserin is prescribed for weight loss; it affects the sensation of fulness by altering the brain's serotonin system. Through another pathway involving serotonin 2C receptors, serotonin also regulates the brain circuit that influences cue reactivity and drug reward.

Lorcaserin reduced opioid use and cue reactivity

In previous work, Prof. Cunningham and colleagues showed that lorcaserin reduces the frequency with which rats will complete a task to earn a dose of cocaine. However, this does not explain how lorcaserin might affect the feeling of reward invoked by opioid drugs working through the serotonin 2C receptors.

So, for the new study, the researchers allowed rats to give themselves oxycodone when they were exposed to a particular pattern of lights and sounds - thus creating a specific drug-taking environment.

After a period during which the rats got used to self-administering oxycodone in the drug-taking environment, the team withdrew the oxycodone. They exposed the rats to their familiar drug-taking environment and gave some of them lorcaserin and the rest a placebo.

They then allowed the rats to self-administer oxycodone again. The rats that had been given lorcaserin not only gave themselves less oxycodone, but they also reacted less strongly to the cues of the drug-taking environment.

To confirm that this effect was due to lorcaserin, the researchers gave a group of rats lorcaserin plus a drug that blocks its effect by denying access to serotonin 2C receptors. These rats then "tried very hard" to self-administer the oxycodone.

The researchers say that the study shows that lorcaserin appears not only to reduce oxycodone self-administration, but also cue reactivity associated with relapse.

"The effectiveness of lorcaserin in reducing oxycodone seeking and craving highlights the therapeutic potential for lorcaserin in the treatment of opioid use disorder."

Prof. Kathryn A. Cunningham

The team is now planning to carry out further studies on drugs such as lorcaserin in order to better understand how they might help to tackle the opioid epidemic.

Learn why opioid prescriptions continue after overdose.