N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial

Kirkland, Anna E.; Browning, Brittney D.; Green, ReJoyce; Liu, Helen; Maralit, Anna M.; Ferguson, Pamela L.; Meyerhoff, Dieter J.; Prisciandaro, James J.; Miranda, Robert; Brady, Kathleen T.; Tomko, Rachel L.; Gray, Kevin M.; Squeglia, Lindsay M.

doi:10.1038/s41386-023-01553-z

Cited by 7 publications

(4 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adolescent participants between the ages of 17 and 19 years were recruited into two groups: one comprising individuals who heavily used alcohol ( n = 21; 52.4% female) and the other who did not use any alcohol or other substances ( n = 18; 44.4% female). Some participants in the alcohol‐using group were a part of a larger preliminary, within‐subjects, randomized clinical trial (Kirkland et al., 2023), but only their baseline data is presented here. The control group completed the baseline visit only.…”

Section: Methodsmentioning

confidence: 99%

Adolescent alcohol use is associated with differences in the diversity and composition of the oral microbiome

Browning,

Kirkland,

Green

et al. 2024

Alcohol, Clinical and Experimental Research

Self Cite

View full text Add to dashboard Cite

BackgroundAdolescence is a sensitive stage of oral microbial development that often coincides with the initiation and escalation of alcohol use. Thus, adolescents may be particularly susceptible to alcohol‐induced alterations in the oral microbiome, though minimal research has been done in this area. Understanding the connection between the oral microbiome and alcohol use during adolescence is important to understand fully the biological consequences of alcohol use to mitigate potential adverse outcomes.MethodsSaliva samples were collected from adolescents aged 17–19 who used alcohol heavily (n = 21, 52.4% female) and those who did not use alcohol or any other substances (n = 18, 44.4% female). We utilized 16S rRNA sequencing to examine differences in microbial diversity and composition between the groups.ResultsFor alpha diversity, evenness was significantly lower in the drinking group than the control group as indicated by Pielou's evenness, Shannon, and Simpson indices. There were no statistically significant findings for beta diversity. Differential abundance analyses revealed higher abundances of Rothia and Corynebacterium in the alcohol‐using group using both centered‐log‐ratio and relative abundance normalization. These genera are known for their high capacity to convert alcohol into acetaldehyde, a toxic metabolite reported to play a role in the neurobiological effects of alcohol. An unclassified Clostridia UCG‐014, Streptobacillus, Comamonas, unclassified Lachnospiraceae, and Parvimonas were also identified as significantly different between groups when using only one of the normalization techniques.ConclusionsThis is the first study designed specifically to compare the oral microbiome of adolescents who use alcohol with that of control participants. Our findings reveal distinct alcohol‐related differences in microbial composition and taxon abundance, emphasizing the importance of understanding the impact on the oral microbiome of alcohol use during adolescence. Because the oral microbiome is malleable, this study provides foundational work for future prevention and intervention studies.

show abstract

Section: Methodsmentioning

confidence: 99%

Adolescent alcohol use is associated with differences in the diversity and composition of the oral microbiome

Browning,

Kirkland,

Green

et al. 2024

Alcohol, Clinical and Experimental Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Randomized participants ( N = 32) were 17 to 19 years old and completed courses of both N ‐acetylcysteine and placebo. All inclusion and exclusion criteria are published elsewhere (Kirkland et al., 2023) and included in the Supplementary Materials. Briefly, all participants met criteria for heavy drinking (i.e., consumed at least three standard drinks per occasion at least four times per month in the past 90 days; Lees et al., 2021; Squeglia et al., 2012; Winters, 2011) and were not seeking treatment for their alcohol use.…”

Section: Methodsmentioning

confidence: 99%

“…The objective of this study was to describe and assess the pairwise concordance between three commonly used, non‐biological medication adherence assessment methods within non‐treatment seeking adolescents who use alcohol. Medication adherence measures were collected as part of a preliminary within‐subjects placebo‐controlled study investigating the neurobiological effects of N ‐acetylcysteine (Kirkland et al., 2023). Participants took N ‐acetylcysteine and placebo for 10‐days each, and medication adherence was assessed (20 days total) via (1) pill count, (2) medication videos, and (3) MEMS.…”

Section: Introductionmentioning

confidence: 99%

Pairwise comparisons of three medication adherence outcomes in adolescents who use alcohol

Kirkland,

Tomko,

Green

et al. 2023

Alcohol: Clinical and Experimental Research

Self Cite

View full text Add to dashboard Cite

BackgroundAccurate assessment of medication adherence is important for understanding pharmacotherapy outcomes across all phases of adolescent substance use disorder (SUD) clinical trials. The objective of this study was to describe and assess the concordance between three commonly used, non‐biological medication adherence assessment methods within adolescents who use alcohol to inform selection of medication adherence measures to incorporate in future youth SUD trials.MethodsParticipants (N=32, 17‐19‐years‐old) took N‐acetylcysteine and placebo, in randomized cross‐over design, for 10 days each. Medication adherence was assessed (20 days total) via pill count, medication videos submitted twice daily, and Medication Event Monitoring System (MEMS®). Lin's Concordance Correlation Coefficient (CCC) assessed concordance and Bland‐Altman plots are reported. Linear mixed effects models with main effects of medication, treatment block (first medication, second medication), and sequence were also run.ResultsMedication videos yielded the lowest (64%) and pill count yielded the highest (89%) adherence estimates. CCC values indicated poor correspondence, except between pill count and MEMS. The Bland‐Altman plots showed good agreement between all methods. Linear mixed effects models indicated a difference between the first and second crossover medication, with adherence estimates being lower for the second medication, regardless of whether it was N‐acetylcysteine or placebo.ConclusionsFindings suggest several important and practical points. Incorporating more than one method of adherence assessment may capture estimated floor and ceiling adherence in the absence of a biological marker. This is particularly relevant for remote or hybrid studies where biomarker collection is challenging. Selection of assessment methods will depend on study goals. The continuation of medication adherence research can benefit each phase of clinical trials and inform rigorous pharmacotherapy evaluation.

show abstract

“…Behavioral therapies, such as cognitive-behavioral therapy and motivational therapy, as well as family-based approaches, have all demonstrated varying degrees of efficacy in treating alcohol use disorders among youth [18]. Although pharmaceutical therapies are not commonly used to treat alcohol use disorders among youth in most jurisdictions, research has demonstrated that these approaches can be helpful in some circumstances [18], particularly when combined with psychological and behavioral treatments [19,20]. Given that little is known about how sex-and gender-related factors are assessed and…”

Section: Introductionmentioning

confidence: 99%

A sex- and gender-based analysis of alcohol treatment intervention research involving youth: A methodological systematic review

Lowik,

Mniszak,

Pang

et al. 2024

PLoS Med

View full text Add to dashboard Cite

Background While there is widespread consensus that sex- and gender-related factors are important for how interventions are designed, implemented, and evaluated, it is not currently known how alcohol treatment research accounts for sex characteristics and/or gender identities and modalities. This methodological systematic review documents and assesses how sex characteristics, gender identities, and gender modalities are operationalized in alcohol treatment intervention research involving youth. Methods and findings We searched MEDLINE, Embase, Cochrane Central Registry of Controlled Trials, PsycINFO, CINAHL, LGBT Life, Google Scholar, Web of Science, and grey literature from 2008 to 2023. We included articles that reported genders and/or sexes of participants 30 years of age and under and screened participants using AUDIT, AUDIT-C, or a structured interview using DSM-IV criteria. We limited the inclusion to studies that enrolled participants in alcohol treatment interventions and used a quantitative study design. We provide a narrative overview of the findings. Of 8,019 studies screened for inclusion, 86 articles were included in the review. None of the studies defined, measured, and reported both sex and gender variables accurately. Only 2 studies reported including trans participants. Most of the studies used gender or sex measures as a covariate to control for the effects of sex or gender on the intervention but did not discuss the rationale for or implications of this procedure. Conclusions Our findings identify that the majority of alcohol treatment intervention research with youth conflate sex and gender factors, including terminologically, conceptually, and methodologically. Based on these findings, we recommend future research in this area define and account for a spectrum of gender modalities, identities, and/or sex characteristics throughout the research life cycle, including during study design, data collection, data analysis, and reporting. It is also imperative that sex and gender variables are used expansively to ensure that intersex and trans youth are meaningfully integrated. Trial registration Registration: PROSPERO, registration number: CRD42019119408

show abstract

N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial

Cited by 7 publications

References 88 publications

Adolescent alcohol use is associated with differences in the diversity and composition of the oral microbiome

Adolescent alcohol use is associated with differences in the diversity and composition of the oral microbiome

Pairwise comparisons of three medication adherence outcomes in adolescents who use alcohol

A sex- and gender-based analysis of alcohol treatment intervention research involving youth: A methodological systematic review

Contact Info

Product

Resources

About