Incubation of neural alcohol cue reactivity after withdrawal and its blockade by naltrexone

Abstract

During the first weeks of abstinence, alcohol craving in patients may increase or “incubate.” We hypothesize that Naltrexone (NTX) blocks this incubation effect. Here, we compared NTX effects on neural alcohol cue reactivity (CR) over the first weeks of abstinence and on long‐term clinical outcomes to standard treatment. Male alcohol‐dependent patients (n = 55) and healthy controls (n = 35) were enrolled. Participants underwent baseline psychometric testing and functional magnetic resonance imaging (fMRI) assessment of mesolimbic alcohol CR. Patients participated in a standard treatment program with the option of adjuvant NTX. They received another scan after 2 weeks of treatment. We found higher CR in several brain regions in patients versus healthy controls. CR significantly increased over 2 weeks in the standard treatment group (n = 13) but not in the NTX group (n = 22). NTX significantly attenuated CR in the left putamen and reduced relapse risk to heavy drinking within 3 months of treatment. Additionally, increased CR in the left putamen and its course over time predicted both NTX response and relapse risk. Carrier status for the functional OPRM1 variant rs1799971:A > G was considered but had no effect on NTX efficacy. In conclusion, NTX was most effective in patients with high CR in the left putamen. While the results from our naturalistic study await further confirmation from prospective randomized trials, they support a potential role of neural CR as a biomarker in the development of precision medicine approaches with NTX.

Interaction between behavioral inhibition and neural alcohol cue-reactivity in ADHD and alcohol use disorder

“…Regarding alcohol-associated cues, previous studies described increased cue related activity in the insula, striatum, the amygdala and frontal regions such as the ACC, medial PFC or OFC (Bach et al, 2020;Goldstein & Volkow, 2002;Heinz, Beck, Grusser, Grace, & Wrase, 2009;Vollstädt-Klein et al, 2012;Vollstädt-Klein et al, 2010). Our results suggest that salience attribution and cue-reactivity in response to alcohol cues is Further examination is needed to determine whether depleted cognitive resources might underlie this increased cue reactivity, as the current study did not reveal a significant negative correlation between prefrontal activity and ADHD severity.…”

“…The association between increased cue reactivity within the striatum and later relapse risk was further examined using pharmacotherapy in individuals with AUD. Naltrexone, a opioid antagonist, was most effective in individuals with high cue reactivity within the DS and further reduced the relapse risk during the first three months of abstinence (Bach et al, 2020). It has also been observed that individuals, who drink primarily for the rewarding effects of alcohol, benefitted the most from a treatment with Naltrexone (Witkiewitz, Roos, Mann, & Kranzler, 2019).…”

Developing neuroscience-based treatments for alcohol addiction: A matter of choice?

“…The overall effect size of naltrexone is modest 7 , but this represents an average of a heterogeneous response, that varies strongly as a function of individual patient characteristics. Among these characteristics, predictors of clinical response include a family history of alcohol problems, early onset of problem drinking, being male, experiencing strong alcohol reward-related memories or cravings, and complying with treatment 17,18 . The role of compliance can be viewed in light of extensive empirical data in support of the notion that opioid transmission plays a key role for the “liking” of natural rewards 19 .…”

A common molecular mechanism for cognitive deficits and craving in alcoholism

“…Such a trial would benefit from an enrichment strategy based on the here described FDG-PET biomarker. Second, we suggest performing a cue-elicited craving study in alcohol-dependent patient in the MRI scanner in order to demonstrate normalized functional connectivity in brain areas known to be involved in neuronal cue reactivity following a single application of an mGluR2 PAM (66)(67)(68). In the case that both proposed human experimental studies yield positive results, an RCT for testing the antirelapse properties of a given mGluR2 PAM is indicated.…”