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Does the Neuroimmune Modulator Ibudilast Alter Food Craving? Results in a Sample With Alcohol Use Disorder.

ABSTRACT: OBJECTIVE:Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor. A randomized, placebo-control, crossover human laboratory trial advanced IBUD development for alcohol use disorder and found that IBUD reduced tonic levels of alcohol craving. Given the importance of considering medication effects on other appetitive behavior, the present study tested the effect of IBUD (50?mg bid) on food craving. METHOD:The present study was a secondary data analysis of the trial of IBUD in non-treatment seekers with alcohol use disorder (N?=?19). High-fat/high-sugar food craving was measured daily. Moreover, because substantial literatures show that small alcohol doses and psychological stress increase eating of high-fat/high-sugar food, craving for high-fat/high-sugar food was measured after alcohol infusion and stress reactivity. RESULTS:Results indicated that IBUD did not alter tonic high-fat/high-sugar food craving. Alcohol infusion did not generally increase high-fat/high-sugar food craving but psychological stress did. Likewise, IBUD did not affect high-fat/high-sugar food craving after alcohol infusion but IBUD did increase high-fat/high-sugar food craving after psychological stress. Follow-up analyses revealed that, among individuals with lower depressive symptomatology, IBUD compared to placebo heightened the effect of psychological stress on high-fat/high-sugar food craving. CONCLUSIONS:These results advance the development of IBUD for addiction indications by demonstrating that IBUD compared to placebo does not suppress other appetitive responses, namely craving for high-fat/high-sugar food among individuals with alcohol use disorder.

SUBMITTER: Cummings JR

PROVIDER: S-EPMC6167170 | biostudies-literature | 2018 Sep/Oct

REPOSITORIES: biostudies-literature

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Does the Neuroimmune Modulator Ibudilast Alter Food Craving? Results in a Sample With Alcohol Use Disorder.

Cummings Jenna R JR Tomiyama A Janet AJ Ray Lara A LA

Journal of addiction medicine 20180901 5

<h4>Objective</h4>Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor. A randomized, placebo-control, crossover human laboratory trial advanced IBUD development for alcohol use disorder and found that IBUD reduced tonic levels of alcohol craving. Given the importance of considering medication effects on other appetitive behavior, the present study tested the effect of IBUD (50 mg bid) on food craving.<h4>Method</h4>The ...[more]

PMID: 29794557

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Project description:Current directions in medication development for alcohol use disorder (AUD) emphasize the need to identify novel molecular targets and efficiently screen new compounds aimed at those targets. Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterase-4 and -10 and macrophage migration inhibitory factor and was recently found to reduce alcohol intake in rats by ?50%. To advance medication development for AUD, the present study consists of a randomized, crossover, double-blind, placebo-controlled laboratory study of IBUD in nontreatment-seeking individuals with current (ie, past month) mild-to-severe AUD. This study tested the safety, tolerability, and initial human laboratory efficacy of IBUD (50?mg b.i.d.) on primary measures of subjective response to alcohol as well as secondary measures of cue- and stress-induced changes in craving and mood. Participants (N=24) completed two separate 7-day intensive outpatient protocols that included daily visits for medication administration and testing. Upon reaching a stable target dose of IBUD (or matched placebo), participants completed a stress-exposure session (day 5; PM), an alcohol cue-exposure session (day 6; AM), and an i.v. alcohol administration session (day 6; PM). Participants stayed overnight after the alcohol administration, and discharge occurred on day 7 of the protocol. Medication conditions were separated by a washout period that was ?7 days. IBUD was well tolerated; however, there were no medication effects on primary measures of subjective response to alcohol. IBUD was associated with mood improvements on the secondary measures of stress exposure and alcohol cue exposure, as well as reductions in tonic levels of craving. Exploratory analyses revealed that among individuals with higher depressive symptomatology, IBUD attenuated the stimulant and mood-altering effects of alcohol as compared with placebo. Together, these findings extend preclinical demonstrations of the potential utility of IBUD for the treatment of AUD and suggest that depressive symptomatology should be considered as a potential moderator of efficacy for pharmacotherapies with neuroimmune effects, such as IBUD.

Project description:BackgroundAlcohol use disorder (AUD) is a chronic and relapsing condition for which current pharmacological treatments are only modestly effective. The development of efficacious medications for AUD remains a high research priority with recent emphasis on identifying novel molecular targets for AUD treatment and to efficiently screen new compounds aimed at those targets. Ibudilast, a phosphodiesterase inhibitor, has been advanced as a novel addiction pharmacotherapy that targets neurotrophin signaling and neuroimmune function.MethodsThis study will conduct a 12-week, double-blind, placebo controlled randomized clinical trial of ibudilast (50 mg BID) for AUD treatment. We will randomize 132 treatment-seeking men and women with current AUD. We will collect a number of alcohol consumption outcomes. Primary among these is percent heavy drinking days (PHDD); secondary drinking outcomes include drinks per day, drinks per drinking day, percent days abstinent, percent subjects with no heavy drinking days, and percent subjects abstinent, as well as measures of alcohol craving and negative mood. Additionally, participants will have the option to opt-in to a neuroimaging session in which we examine the effects of ibudilast on neural activation to psychosocial stress and alcohol cues. Finally, we will also collect plasma levels of proinflammatory markers, as well as subjective and biological (salivary cortisol) markers of stress response.DiscussionThis study will further develop ibudilast, a safe and promising novel compound with strong preclinical and clinical safety data for AUD, and will probe biological mechanisms underlying the effects of Ibudilast on stress, neuroinflammation, and alcohol cue-reactivity and craving. If ibudilast proves superior to placebo in this study, it will set the stage for a confirmatory multi-site trial leading to FDA approval of a novel AUD treatment.Trial registrationClinicalTrials.gov NCT03594435 "Ibudilast for the Treatment of Alcohol Use Disorder". Registered on 20 July 2018.

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Does the Neuroimmune Modulator Ibudilast Alter Food Craving? Results in a Sample With Alcohol Use Disorder.

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Does the Neuroimmune Modulator Ibudilast Alter Food Craving? Results in a Sample With Alcohol Use Disorder.

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