Presented at 2019 Experimental Biology meeting (6—9 April 2019; FL, USA), researchers have shown that a drug developed as an antidepressant has substantially reversed acute signs of opioid withdrawal in rats in just three days.
Current medicines used to treat and relieve withdrawal symptoms in people recovering from opioid addiction can be problematic as they can cause side effects and maintain the brain changes that led to addiction in the first place. This is especially in the case of buprenorphine and methadone, the most common drugs used, as they themselves are opioids and are addictive.
This experimental drug, rapastinel, could be useful in managing the withdrawal during the critical first days after someone has entered treatment and is trying to abstain from opioid use.
"We have found that rapastinel has potential as a new treatment for opioid dependence, as it is effective in reducing withdrawal signs and has not been shown to produce any negative side effects," explained Julia Ferrante, an undergraduate at Villanova University (PA, USA) who conducted the research with Cynthia M. Kuhn, Professor of Pharmacology and Cancer Biology at Duke University (NC, USA). "By reducing withdrawal symptoms, the patient feels less discomfort during treatment, and we hypothesize this would lead to a decreased risk of relapse."
Ketamine has also been suggested as a non-opioid treatment for opioid withdrawal. Rapastinel, developed as an antidepressant, binds to the same receptor as ketamine but at a different site. This is important, because although ketamine could be used as an alternative, it also has the potential for abuse and can cause hallucinations, amongst other negative side effects.
At this different binding site, rapastinel has a milder effect. In clinical trials (which showed it to be ineffective against depression) it seems to be well tolerated, with no serious side effects.
In this latest study, Ferrante and Kuhn tracked signs of withdrawal in model rats with opioid dependence given either rapastinel, ketamine or a saline solution. By the third day, the rats given rapastinel showed significantly fewer signs of withdrawal than those given ketamine or saline – both of which showed roughly equal amounts of withdrawal.
Moving forward, researchers hope to continue to study the effects of rapastinel on a molecular level and determine if the drug can reduce the likelihood of relapse. Ferrante believes that if approved, patients would be treated with rapastinel intravenously, however treatment times to ensure complete recovery are still uncertain.
"Our research suggests that new alternatives to standard treatments for opioid dependence have potential to be safer and more effective," Ferrante commented. "Rapastinel research for opioid dependency is currently only being done in rodents, but if the drug continues to have successful trials, it may enter clinical trials for use in humans."