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Variations in alcohol craving and negative mood during a clinical trial of ibudilast for alcohol use disorder
Lindsay R Meredith1, Erica N Grodin1,2,3, Craig K Enders1
1Department of Psychology, University of California, Los Angeles, California, USA.
Background:
Immune medications, including ibudilast, have shown early potential in mitigating alcohol intake in preclinical models and small-scale trials for alcohol use disorder (AUD). To elucidate clinical utility and clinical mechanisms of these novel treatments, research should carefully assess medication-related changes in AUD symptomatology, including craving and negative mood, over time.
Methods:
This is a secondary analysis of a 12-week randomized clinical trial of ibudilast for AUD. Participants were 102 individuals (40% female, average age 44 years) seeking treatment for AUD and randomized to ibudilast (50 mg twice-daily) or matched placebo. Clinical symptom measures of alcohol craving, depression, and anxiety were collected monthly. Growth models compared rates of change in clinical symptomatology between treatment groups and tested whether changes were moderated by sex. A subsample (n = 25) completed a functional magnetic resonance imaging scan with an alcohol cue-reactivity task at week four to assess a brain-based craving marker.
Results:
At pretreatment, participants reported moderate craving symptoms and nonclinically elevated negative mood symptoms, on average. Participants taking ibudilast showed significantly steeper reductions in craving during the trial, as compared with placebo (1.32 vs. 0.52 points lower per month; p = 0.035). At treatment endpoint, female participants taking ibudilast reported lower craving than female participants taking placebo (p < 0.001). Greater cue-elicited brain activation in bilateral insula, bilateral orbitofrontal cortex, and right precuneus (p's < 0.02) was detected among the placebo subsample, compared to ibudilast. Rates of change for depression and anxiety did not differ between medication conditions, nor were they moderated by sex. Depression symptoms decreased during the trial, while anxiety symptoms remained relatively stable.
Conclusions:
Consistent with prior research, ibudilast reduced neurobiological and self-report markers of craving, with female participants showing a stronger treatment response by trial endpoint. Despite shared neuroimmune correlates between negative mood and addiction, ibudilast did not alleviate negative mood symptoms beyond placebo effects.
Insights
Ibudilast significantly reduced alcohol craving in individuals with alcohol use disorder (AUD), particularly in women. This immune medication showed potential for treating AUD symptoms by impacting brain-based craving markers.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Immune medications like ibudilast show promise for reducing alcohol intake in alcohol use disorder (AUD).
- Further research is needed to understand the clinical utility and mechanisms of these treatments for AUD symptomatology, including craving and mood.
Purpose of the Study:
- To analyze the effects of ibudilast on alcohol craving, depression, and anxiety symptoms in individuals with AUD.
- To investigate potential sex differences in treatment response and examine brain-based craving markers using functional magnetic resonance imaging (fMRI).
Main Methods:
- Secondary analysis of a 12-week randomized clinical trial involving 102 participants with AUD, randomized to ibudilast or placebo.
- Monthly assessments of alcohol craving, depression, and anxiety, with growth models comparing change rates between groups.
- fMRI with an alcohol cue-reactivity task in a subsample to assess brain-based craving markers.
Main Results:
- Ibudilast significantly reduced craving more than placebo (1.32 vs. 0.52 points lower per month).
- Female participants receiving ibudilast reported significantly lower craving at treatment endpoint compared to placebo.
- Ibudilast treatment was associated with reduced cue-elicited brain activation in key areas like the insula and orbitofrontal cortex compared to placebo.
- No significant differences in depression or anxiety symptom changes were observed between ibudilast and placebo groups.
Conclusions:
- Ibudilast effectively reduces both self-reported and neurobiological markers of craving in AUD.
- Female participants demonstrated a stronger treatment response to ibudilast regarding craving.
- Ibudilast did not show significant effects on negative mood symptoms (depression, anxiety) beyond placebo, despite shared neuroimmune pathways with addiction.
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