Dataset Information

The effect of neuroimmune modulation on subjective response to alcohol in the natural environment.

ABSTRACT:

Background

Despite the promising implications for novel immune therapeutics, few clinical trials have tested these therapies to date. An understanding of how immune pharmacotherapies influence complex alcohol use disorder (AUD) profiles, including subjective response to alcohol, is very limited. Initial findings show that ibudilast, a neuroimmune modulator, reduces rates of heavy drinking and measures of alcohol craving.

Methods

This study is a secondary analysis of a 2-week clinical trial of ibudilast that enrolled a nontreatment-seeking sample with AUD. Eligible participants (N = 52) were randomized to receive ibudilast or matched placebo and completed daily diary assessments (DDAs) during the 2-week period. Each morning, participants reported on their mood and craving levels both before and during the previous day's drinking episode, as well as stimulation and sedation levels during the previous day's drinking episode. Multilevel models were used to compare the effects of ibudilast and placebo on subjective alcohol response. Exploratory analyses tested whether ibudilast moderated the relationship between daily stimulation/sedation and alcohol intake and whether withdrawal-related dysphoria moderated ibudilast's effects on subjective response.

Results

Ibudilast did not significantly alter mean levels of stimulation or sedation (p's > 0.05). It did, however, moderate the effect of daily stimulation on drinking (p = 0.045). Ibudilast attenuated alcohol-induced increases in craving compared with placebo (p = 0.047), but not other subjective response measures. Ibudilast significantly tempered daily alcohol-induced changes in urge to drink and positive mood only among individuals without withdrawal-related dysphoria.

Conclusions

Ibudilast's effects on subjective alcohol responses appear to be nuanced and perhaps most salient for individuals drinking for positive reinforcement as distinguished from those who drink to feel normal. Consistent with previous findings, reductions in alcohol craving may represent a primary mechanism of ibudilast's effects on drinking. The ecologically valid nature of DDAs provide a clinically useful window into how individuals experience alcohol's effects while taking ibudilast.

SUBMITTER: Meredith LR

PROVIDER: S-EPMC10460619 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

The effect of neuroimmune modulation on subjective response to alcohol in the natural environment.

Meredith Lindsay R LR Grodin Erica N EN Montoya Amanda K AK Miranda Robert R Squeglia Lindsay M LM Towns Brandon B Evans Christopher C Ray Lara A LA

Alcoholism, clinical and experimental research 20220411 5

<h4>Background</h4>Despite the promising implications for novel immune therapeutics, few clinical trials have tested these therapies to date. An understanding of how immune pharmacotherapies influence complex alcohol use disorder (AUD) profiles, including subjective response to alcohol, is very limited. Initial findings show that ibudilast, a neuroimmune modulator, reduces rates of heavy drinking and measures of alcohol craving.<h4>Methods</h4>This study is a secondary analysis of a 2-week clini ...[more]

PMID: 35362101

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Project description:BackgroundFor decades, laboratory alcohol challenges have been the "gold standard" for measuring individual differences in alcohol's subjective effects. However, these approaches are expensive and labor-intensive, making them impractical for large-scale use. This study examined the reliability and validity of a new high-resolution EMA (HR-EMA) ambulatory approach to assessing alcohol use and subjective responses in drinkers' natural environments.MethodsParticipants were 83 young adult heavy social drinkers (58% male; mean ± SD age = 25.4 ± 2.6 years) who completed up to two smartphone-based, 3-h HR-EMA assessments of alcohol use and related subjective responses in their typical drinking environments. Reported alcohol consumption during the HR-EMA periods was used to calculate estimated blood alcohol concentration (eBAC). Subjective effects were measured using the Brief Biphasic Alcohol Effects Scale (B-BAES) and Drug Effects Questionnaire (DEQ). All participants also completed identical measures during a separate, 4 to 5-h laboratory session in which they received a 0.8 g/kg alcohol challenge.ResultsMost natural environment drinking episodes (87%) met or exceeded the threshold for binge drinking (final mean eBAC = 0.12 g/dl). Associations between reported alcohol use and subjective responses on the B-BAES and DEQ were strongest earlier in the drinking events, with fair reliability of reported subjective effects across two HR-EMA episodes (intraclass correlation [ICC] range = 0.46-0.49). There was fair-to-good correspondence between HR-EMA- and laboratory-derived subjective responses (ICC range = 0.49-0.74), even after accounting for differences in alcohol consumption and drinking context. Reported stimulating and rewarding alcohol effects were higher in the ambulatory than laboratory setting, and vice versa for sedating effects.ConclusionsThis study supports the reliability and validity of smartphone-based HR-EMA to measure alcohol use and subjective responses in heavy drinkers' natural environments. These findings lend support to the use of ambulatory HR-EMA as a measure of alcohol subjective responses in risky drinkers when a laboratory protocol is not practical, feasible, or safe.

Project description:BackgroundA functional polymorphism within the μ-opioid receptor (OPRM1) gene, rs1799971 (A118G), previously has been associated with measures of alcohol use and sensitivity to its effects, but findings have been inconclusive. A recent study suggested that a second nearby variant within OPRM1, rs3778150, is robustly associated with heroin dependence and fully explained a smaller observed association with rs1799971. Given evidence that the rs3778150-C allele is associated with decreased OPRM1 expression levels in the human brain, the current study sought to test the hypothesis that rs3778150 represents a causal variant within OPRM1 that increases risk for a variety of alcohol use phenotypes.MethodsParticipants with genotype and phenotype data from a larger experimental study (N = 152) were assessed on measures of subjective response to alcohol and alcohol use. Measures included (i) the Self-Rating of the Effects of Alcohol and the Alcohol Sensitivity Questionnaire, (ii) the Biphasic Alcohol Effects Scale (BAES) and ratings of subjective intoxication, and (iii) average number of drinks per week in the past month.ResultsCompared to rs3778150-T homozygous individuals, carriers of the rs3778150-C allele exhibited significantly lower retrospective self-report levels of alcohol sensitivity. Carriers of the rs3778150-C allele also exhibited lower levels of BAES alcohol-related stimulation during an alcohol challenge and reported higher levels of drinking in the last 30 days. With the exception of lower levels of BAES alcohol-related sedation, the rs1799971 variant did not show consistent significant association with any of the alcohol phenotypes in the presence of rs3778150.ConclusionsResults suggest that rs3778150 may be causally related to alcohol use phenotypes, and could potentially account for previously observed associations of rs1799971 with substance use phenotypes. Future studies may investigate potential causal relations among genetic variants in OPRM1, subjective response to alcohol, and drinking phenotypes to further delineate the effects of rs3778150.

Dataset Information

The effect of neuroimmune modulation on subjective response to alcohol in the natural environment.

Background

Methods

Results

Conclusions

Publications

The effect of neuroimmune modulation on subjective response to alcohol in the natural environment.

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