Extended-release naltrexone (XR-NTX) attenuates brain responses to alcohol cues in alcohol-dependent volunteers: A bold FMRI study

Abstract

Oral naltrexone reduces heavy drinking, but is less consistent as an abstinence promoter, whereas once-monthly extended-release naltrexone (XR-NTX) also maintains abstinence. The present study sought to determine if alcohol cue reactivity is attenuated by XR-NTX. Twenty-eight detoxified alcohol-dependent adult male and female volunteers received a single i.m. injection of either XR-NTX or placebo under double-blind conditions. An fMRI/cue reactivity procedure was conducted immediately before and two weeks after injection. At baseline, alcohol-related visual and olfactory cues elicited significant increases in orbital and cingulate gyri, inferior frontal and middle frontal gyri. Subsequently, brain activation was significantly altered in XR-NTX-treated individuals. These affected brain regions are associated with the integration of emotion, cognition, reward, punishment, and learning/memory, suggesting that XR-NTX attenuates the salience of alcohol-related cues. Such an effect on brain function may interrupt the processes associated with "slips" and relapse, which may account for XR-NTX's ability to maintain abstinence.

The Effects of Pharmacological Opioid Blockade on Neural Measures of Drug Cue-Reactivity in Humans

“…Of the two studies that have directly compared naltrexone to placebo effects on wholebrain BOLD measures of drug cue-reactivity in alcohol-and nicotine-dependent samples, both reported naltrexoneinduced changes in the precentral and postcentral gyri (Lukas et al, 2013;Ray et al, 2015b), suggestive of the reliability of the naltrexone findings in cue-reactivity paradigms across substances of abuse. Importantly, these observed naltrexone-induced effects were independent of global changes to CBF, which had not been ascertained in previous studies, ruling out the possibility that our BOLD effects were confounded by medication-induced changes in CBF.…”

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

“…In human alcoholics, the opioid antagonist naltrexone decreases alcohol drinking, craving and relapse [e.g., Brown and Holtzman, 1981;Hall et al, 2001;Liu and Weiss, 2002;Kuzmin et al, 2003;Pastor et al, 2011;Lukas et al,2013] [see reviews by Heinz, 1997;Le Merrer et al, 2009]. In MOP-r knockout mice, there is a decrease in alcohol drinking or selfadministration [Roberts et al, 2000;Hall et al, 2001;Ben Hamida et al, 2018] (Table 2), further indicating that the β-endorphin/MOP-r plays a functional role in the modulation of alcohol drinking.…”

Neuroimaging the Effectiveness of Substance Use Disorder Treatments

“…The alcohol-dependent patients in the other study were exposed to both visual and olfactory cues. The XRNTX decreased activation in cue related regions known to be involved in cognition, reward processing, and memory, altering the responsiveness to drug cues (Lukas et al 2013). XRNTX has been shown to have similar results as oral naltrexone as far as treatment potential, but with the added advantage of facilitating treatment compliance.…”

“…These results provide evidence supporting the effectiveness of an acute combination treatment for reducing alcohol-related cravings in alcohol use disorders (AUD Studies have also been done with an extended-release naltrexone (XRNTX) injection, which improves compliance over that of oral medication. Drug cue reactivity was evaluated before and between 10 and 14 days after a single XRNTX injection, in both heroin and alcohol dependent patients (Langleben et al 2014;Lukas et al 2013). Both of the study populations reported decreases in drug craving.…”