Nalmefene is a µ- and δ-opioid receptor antagonist, κ-opioid receptor partial agonist that was approved in 2013 in the UK and several European countries for treating alcohol use disorder. In an important double blind, placebo controlled study, Dr. Barbara Mason reported Nalmefene was safe and effective in preventing relapse to heavy alcohol drinking. She described her findings at the first RiverMend Health Scientific Advisory Board meeting.

It Works Like Naltrexone, But with Differences

Nalmefene is considered an opioid antagonist like naltrexone but may have advantages over oral naltrexone in the treatment of alcohol dependence. Nalmifene is a universal opioid antagonist which may allow treatment without injections with reduced side effects and longer duration of antagonist action after oral dosing. Like naltrexone, nalmefene is a pure opioid antagonist with no agonist activity and no abuse potential that may also give a more sustained mu opioid antagonist effect than naltrexone. But, nalmefene also binds to other opioid receptors which are generally thought to have roles in alcohol reinforcement, drinking, and relapse.

Non-µ receptors (Δ and κ) are thought to reinforce alcohol consumption, and nalmefene binds more competitively with µ, Δ, and κ receptors than naltrexone.

New Study Sheds Some Light

Numerous human studies using functional magnetic resonance imaging (FMRI) have demonstrated activation of the mesolimbic dopamine system during reward, learning, the use of psychoactive substances and anticipation of reward. However, the formation of blood-oxygen-level dependent (BOLD) responses in the mesolimbic dopamine system during activation in humans is not well understood. Using a randomized, double-blind, placebo-controlled, crossover design, Quelch DR, Mick I, et al.) uses FMRI, to determine whether a single dose of nalmefene would have a measurable effect on striatal BOLD signaling during anticipation of reward. The authors report that nalmefene “blunted” the BOLD response in the striatum during anticipation of monetary reward and alcohol intake. The authors offer their findings as support for nalmefene’s mechanism of action, e.g., its effect on opioid receptor modulation in the mesolimbic dopamine system.

Why Does This Matter?

Naltrexone has been successful in reducing drinking and as a medically-assisted therapy for alcohol dependence. Double blind, placebo controlled direct comparison of Naltrexone vs Nalmefene might allow for both comparable efficacy, adherence and cost-benefit analysis. The overall goal would be to improve access, reduce side effects and cost to such treatments that can be given orally. Alcohol Use Disorder remains the number one reason people seek treatment in the US, and is causally related to the growing health burden in the US, even after adjusting for its beneficial effects. An estimated 88,000 people (approximately 62,000 men and 26,000 women) die from alcohol-related causes each year, making alcohol the fourth leading preventable cause of death in the United States. Surely prevention remains a priority, but the need for more effective treatment modalities will save lives.