The brain signal is there — but it doesn’t translate to fewer drinks
STUDY: Klausen MK et al, JCI Insight 2022;7(19):e159863, PMID: 36047535
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Industry (Novavi, Lundbeck); multiple Danish research foundations
Background
GLP-1 receptor agonists reduce alcohol consumption in rodents and primates, possibly by dampening the brain’s reward response to alcohol cues. This trial tested whether that effect translates to humans.
The Study
One hundred twenty-seven treatment-seeking adults with DSM-5 Alcohol Use Disorder received weekly subcutaneous injections of exenatide 2 mg or placebo for 26 weeks, added to standard cognitive-behavioral therapy. The primary outcome was reduction in heavy drinking days. A subgroup underwent fMRI and dopamine transporter (DAT) SPECT imaging at baseline and week 26.
Exenatide did not reduce heavy drinking days compared with placebo (–19.6% vs. –26.8%, p = 0.37) — both groups improved substantially, likely driven by the robust CBT all patients received. In an exploratory post hoc analysis, obese patients (BMI > 30, n = 30) showed a meaningful reduction in heavy drinking days with exenatide versus placebo (23.6 percentage points, p = 0.034). The brain imaging findings were striking: exenatide reduced alcohol cue reactivity in the ventral striatum and septal area on fMRI, and lowered dopamine transporter availability in the striatum, caudate, and putamen on SPECT — suggesting real central engagement. Gastrointestinal side effects were common (nausea 37% vs. 15%, vomiting 23% vs. 8%), and injection site nodules occurred in 42% of the exenatide group.
Practice Implications
- Many treatments show promise for addictions in early trials, but ultimately fail in clinical populations. So far, GLP-1 agonists do not have a track record to support the media hype.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
What’s Your Take? Share in Comments
- Is your experience with GLP-1 agonists different?
