Ibudilast attenuates alcohol cue–elicited frontostriatal functional connectivity in alcohol use disorder

Burnette, Elizabeth; Ray, Lara A.; Irwin, Michael R.; Grodin, Erica N.

doi:10.1111/acer.14696

Cited by 20 publications

(12 citation statements)

References 53 publications

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“…Pharmacological manipulation may slightly change sensory processing and normalize attention distribution in AUD patients, followed by the transient off‐medication period, probably due to the delayed onset of drug action and maintenance (Chen & Skolnick, 2007 ). Our findings are in line with evidence from imaging studies indicating that detoxification treatment can influence neural activation and functional connectivity in patients with AUD (Burnette et al, 2021 ; Lukas et al, 2013 ; Vollstadt‐Klein et al, 2019 ). Previous functional MRI studies have indicated improved supramarginal gyrus activity in AUD patients in the emotional faces task after receiving nalmefene (Vollstadt‐Klein et al, 2019 ).…”

Section: Discussionsupporting

confidence: 91%

“…Accumulating evidence has shown that detoxification treatment, even on an acute time scale, contributes to the normalization of brain function and structure in patients with AUD (Burnette et al, 2021 ; George et al, 2008 ; Lukas et al, 2013 ; Son et al, 2015 ; Vollstadt‐Klein et al, 2019 ; Wang et al, 2018 ). To explore the potential effects of medication on the MID‐related brain response, it is better to directly compare treated patients with treatment‐naïve individuals or perform pretreatment and posttreatment comparisons or treatment‐placebo comparisons.…”

Section: Discussionmentioning

confidence: 99%

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A meta‐analysis of the neural substrates of monetary reward anticipation and outcome in alcohol use disorder

Zeng

You

Yang

et al. 2023

Human Brain Mapping

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The capacity to anticipate and detect rewarding outcomes is fundamental for the development of adaptive decision‐making and goal‐oriented behavior. Delineating the neural correlates of different stages of reward processing is imperative for understanding the neurobiological mechanism underlying alcohol use disorder (AUD). To examine the neural correlates of monetary anticipation and outcome in AUD patients, we performed two separate voxel‐wise meta‐analyses of functional neuroimaging studies, including 12 studies investigating reward anticipation and 7 studies investigating reward outcome using the monetary incentive delay task. During the anticipation stage, AUD patients displayed decreased activation in response to monetary cues in mesocortical‐limbic circuits and sensory areas, including the ventral striatum (VS), insula, hippocampus, inferior occipital gyrus, supramarginal gyrus, lingual gyrus and fusiform gyrus. During the outcome stage, AUD patients exhibited reduced activation in the dorsal striatum, VS and insula, and increased activation in the orbital frontal cortex and medial temporal area. Our findings suggest that different activation patterns are associated with nondrug rewards during different reward processing stages, potentially reflecting a changed sensitivity to monetary reward in AUD.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

A meta‐analysis of the neural substrates of monetary reward anticipation and outcome in alcohol use disorder

Zeng

You

Yang

et al. 2023

Human Brain Mapping

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“…Furthermore, animal studies suggest that the PDE system is associated with downregulation of drug-seeking behaviours across opioids, alcohol and psychostimulants 35 . Notably, The PDE4B antagonist, ibudilast, has been shown to reduce heavy drinking among patients with AUD 36,37 and also shown to reduce inflammation in methamphetamine use disorder 38 , and was significant in our drug repurposing analysis. The top 20 correlations are annotated; all results can be found in the Supplementary Results.…”

Section: Discussionmentioning

confidence: 95%

Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders

et al. 2023

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Genetic liability to substance use disorders can be parsed into loci that confer general or substance-specific addiction risk. We report a multivariate genome-wide association meta-analysis that disaggregates general and substance-specific loci from published summary statistics of problematic alcohol use, problematic tobacco use, cannabis use disorder and opioid use disorder in a sample of 1,025,550 individuals of European descent and 92,630 individuals of African descent. Nineteen independent singlenucleotide polymorphisms were genome-wide significant (P < 5 × 10 -8 ) for the general addiction risk factor (addiction-rf), which showed high polygenicity. Across ancestries, PDE4B was significant (among other genes), suggesting dopamine regulation as a cross-substance vulnerability. An addiction-rf polygenic risk score was associated with substance use disorders, psychopathologies, somatic conditions and environments associated with the onset of addictions. Substance-specific loci (9 for alcohol, 32 for tobacco, 5 for cannabis and 1 for opioids) included metabolic and receptor genes. These findings provide insight into genetic risk loci for substance use disorders that could be leveraged as treatment targets.The lives lost, impacts on individuals and families, and socioeconomic costs attributable to substance use reflect a growing public health crisis 1 . For example, in the United States, 13.5% of deaths among young adults 2 are attributable to alcohol, smoking is the leading risk factor for mortality in males 3 , and the odds of dying by opioid overdose are greater than those of dying in a motor vehicle crash 4 . Despite the large impact of substance use and substance use disorders 5 , there is limited knowledge of the molecular genetic underpinnings of addiction broadly.

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“…Additionally, ibudilast improved mood during exposure to alcohol and stress cues, and reduced the mood-altering and stimulant effects of alcohol among participants with more severe depressive symptoms [ 192 ]. Another recent 2-week RCT enrolling 52 participants found that ibudilast also significantly decreased the odds of heavy drinking during the trial by 45% compared to placebo and attenuated neural response to alcohol cues in the ventral striatum [ 193 , 194 ].…”

Section: Pharmacological Treatments For Audmentioning

confidence: 99%

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder

Burnette

Nieto

Grodin

et al. 2022

Drugs

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101

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Alcohol use disorder (AUD) is a highly prevalent but severely under-treated disorder, with only three widely-approved pharmacotherapies. Given that AUD is a very heterogeneous disorder, it is unlikely that one single medication will be effective for all individuals with an AUD. As such, there is a need to develop new, more effective, and diverse pharmacological treatment options for AUD with the hopes of increasing utilization and improving care. In this qualitative literature review, we discuss the efficacy, mechanism of action, and tolerability of approved, repurposed, and novel pharmacotherapies for the treatment of AUD with a clinical perspective. Pharmacotherapies discussed include: disulfiram, acamprosate, naltrexone, nalmefene, topiramate, gabapentin, varenicline, baclofen, sodium oxybate, aripiprazole, ondansetron, mifepristone, ibudilast, suvorexant, prazosin, doxazosin, N-acetylcysteine, GET73, ASP8062, ABT-436, PF-5190457, and cannabidiol. Overall, many repurposed and novel agents discussed in this review demonstrate clinical effectiveness and promise for the future of AUD treatment. Importantly, these medications also offer potential improvements towards the advancement of precision medicine and personalized treatment for the heterogeneous AUD population. However, there remains a great need to improve access to treatment, increase the menu of approved pharmacological treatments, and de-stigmatize and increase treatment-seeking for AUD.

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Ibudilast attenuates alcohol cue–elicited frontostriatal functional connectivity in alcohol use disorder

Cited by 20 publications

References 53 publications

A meta‐analysis of the neural substrates of monetary reward anticipation and outcome in alcohol use disorder

A meta‐analysis of the neural substrates of monetary reward anticipation and outcome in alcohol use disorder

Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder

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