scholarly journals Alcohol Tolerance in Human Laboratory Studies for Development of Medications to treat Alcohol Use Disorder

2020 ◽  
Vol 55 (2) ◽  
pp. 129-135
Author(s):  
Carolina L Haass-Koffler ◽  
Roberta Perciballi
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Motor Impairment ◽  
Alcohol Tolerance ◽  
Subjective Response ◽  
Laboratory Studies ◽  
Phenotypic Profile ◽  
Additional Information ◽  
Research Opportunity ◽  
Human Laboratory

Abstract Aims Human laboratory studies have contributed extensively in the research and development of novel medications to treat alcohol use disorder (AUD). Alcohol tolerance may represent one additional variable that can be utilized to expand the understanding of the AUD wide phenotypic profile and provide support to the medication development process. Tolerance is characterized as an individual’s subjective response to alcohol and has been recognized as a predictor of AUD progression. Tolerance can be evaluated both by self-reported response (e.g. assessments) and objective measurements (e.g. motor impairment); as such, it represents an exploitable variable in the field of alcohol research. Methods This Narrative Review focuses on the use of alcohol tolerance, specifically within alcohol laboratory studies, for medication development. It seeks to identify a research gap and a research opportunity in clinical studies to evaluate biobehavioral responses captured in order to develop medications to treat AUD. Results Alcohol tolerance may provide additional information on the safety and tolerability of medications to treat AUD, in particular, when novel medications are co-administered with alcohol within the AUD population. Conclusions As such, alcohol tolerance represents an additional outcome that may be included in randomized clinical trial (RCT) protocols designed for developing AUD pharmacotherapies.

scholarly journals Translational dynamics of alcohol tolerance of preclinical models and human laboratory studies.

2020 ◽  
Vol 28 (4) ◽  
pp. 417-425
Author(s):  
Carolina L. Haass-Koffler ◽  
Nazzareno Cannella ◽  
Roberto Ciccocioppo
Keyword(s):  
Alcohol Tolerance ◽  
Laboratory Studies ◽  
Preclinical Models ◽  
Human Laboratory

scholarly journals Translational opportunities in animal and human models to study alcohol use disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Steven J. Nieto ◽  
Erica N. Grodin ◽  
Claudia G. Aguirre ◽  
Alicia Izquierdo ◽  
Lara A. Ray
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Animal Species ◽  
Experimental Models ◽  
Future Directions ◽  
Reverse Translation ◽  
Approaches To Study ◽  
Preclinical And Clinical Studies ◽  
Laboratory Models ◽  
Human Laboratory

AbstractAnimal and human laboratory paradigms offer invaluable approaches to study the complex etiologies and mechanisms of alcohol use disorder (AUD). We contend that human laboratory models provide a “bridge” between preclinical and clinical studies of AUD by allowing for well-controlled experimental manipulations in humans with AUD. As such, examining the consilience between experimental models in animals and humans in the laboratory provides unique opportunities to refine the translational utility of such models. The overall goal of the present review is to provide a systematic description and contrast of commonly used animal paradigms for the study of AUD, as well as their human laboratory analogs if applicable. While there is a wide breadth of animal species in AUD research, the paradigms discussed in this review rely predominately on rodent research. The overarching goal of this effort is to provide critical analysis of these animal models and to link them to human laboratory models of AUD. By systematically contrasting preclinical and controlled human laboratory models, we seek to identify opportunities to enhance their translational value through forward and reverse translation. We provide future directions to reconcile differences between animal and human work and to improve translational research for AUD.

scholarly journals A novel human laboratory model for screening medications for alcohol use disorder

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Diana Ho ◽  
Brandon Towns ◽  
Erica N. Grodin ◽  
Lara A. Ray
Keyword(s):  
Clinical Trials ◽  
Alcohol Use ◽  
Early Phase ◽  
Alcohol Use Disorder ◽  
Internal Validity ◽  
Laboratory Model ◽  
Phase 2 ◽  
Motivation To Change ◽  
Quit Attempt ◽  
Human Laboratory

Abstract Background Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the USA. Pharmacotherapy is a promising treatment method for AUD; however, the few FDA-approved medications are only modestly effective. Medications development for AUD is a high priority research area, but the cumbersome drug development process hinders many potential compounds from reaching approval. One area with major opportunities for improvement is the process of screening novel compounds for initial efficacy, also known as early phase 2 trials. Early phase 2 trials incorporate human laboratory paradigms to assess relevant clinical constructs, such as craving and subjective responses to alcohol. However, these controlled paradigms often lack the ecological validity of clinical trials. Therefore, early phase 2 trials can be more efficient and clinically meaningful if they combine the internal validity of experimental laboratory testing with the external validity of clinical trials. To that end, the current study aims to develop and validate a novel early efficacy paradigm, informed by smoking cessation literature, to screen novel medications for AUD. As an established AUD medication, naltrexone will serve as an active control to test both the practice quit attempt model and the efficacy of a promising AUD pharmacotherapy, varenicline. Methods Individuals with current AUD reporting intrinsic motivation to change their drinking will complete a week-long “practice quit attempt” while on study medication. Participants are randomized and blinded to either naltrexone, varenicline, or placebo. During the practice quit attempt, participants will complete daily visits over the phone and fill out online questionnaires regarding their drinking, alcohol craving, and mood. Additionally, participants will undergo two alcohol cue-reactivity sessions. Discussion The successful completion of this study will advance medications development by proposing and validating a novel early efficacy model for screening AUD pharmacotherapies, which in turn can serve as an efficient strategy for making go/no-go decisions as to whether to proceed with clinical trials. Trial registration ClinicalTrials.gov NCT04249882. Registered on 31 January 2020.

scholarly journals Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study

2021 ◽  
Author(s):  
Mehdi Farokhnia ◽  
Kelly M Abshire ◽  
Aaron Hammer ◽  
Sara L Deschaine ◽  
Anitha Saravanakumar ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Heavy Drinking ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Alcohol Administration ◽  
Neuroendocrine Response ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Human Laboratory

Abstract Background Accumulating evidence has established a role for the orexigenic hormone ghrelin in alcohol-seeking behaviors. Accordingly, the ghrelin system may represent a potential pharmacotherapeutic target for alcohol use disorder. Ghrelin modulates several neuroendocrine pathways, such as appetitive, metabolic, and stress-related hormones, which are particularly relevant in the context of alcohol use. The goal of the present study was to provide a comprehensive assessment of neuroendocrine response to exogenous ghrelin administration, combined with alcohol, in heavy-drinking individuals. Methods This was a randomized, crossover, double-blind, placebo-controlled human laboratory study, which included 2 experimental alcohol administration paradigms: i.v. alcohol self-administration and i.v. alcohol clamp. Each paradigm consisted of 2 counterbalanced sessions of i.v. ghrelin or placebo administration. Repeated blood samples were collected during each session, and peripheral concentrations of the following hormones were measured: leptin, glucagon-like peptide-1, pancreatic polypeptide, gastric inhibitory peptide, insulin, insulin-like growth factor-1, cortisol, prolactin, and aldosterone. Results Despite some statistical differences, findings were consistent across the 2 alcohol administration paradigms: i.v. ghrelin, compared to placebo, increased blood concentrations of glucagon-like peptide-1, pancreatic polypeptide, cortisol, and prolactin, both acutely and during the whole session. Lower levels of leptin and higher levels of aldosterone were also found during the ghrelin vs placebo session. Conclusion These findings, gathered from a clinically relevant sample of heavy-drinking individuals with alcohol use disorder, provide a deeper insight into the complex interplay between ghrelin and appetitive, metabolic, and stress-related neuroendocrine pathways in the context of alcohol use.

scholarly journals Additive roles of tobacco and cannabis co-use in relation to delay discounting in a sample of heavy drinkers

2021 ◽  
Author(s):  
Steven J. Nieto ◽  
Alexandra Venegas ◽  
Elizabeth M. Burnette ◽  
James MacKillop ◽  
Lara A. Ray
Keyword(s):  
Delay Discounting ◽  
Alcohol Use Disorder ◽  
Heavy Drinking ◽  
Cannabis Use ◽  
Additive Effect ◽  
Laboratory Studies ◽  
The Past ◽  
Baseline Visit ◽  
Heavy Drinkers ◽  
Human Laboratory

Abstract Rationale Alcohol use disorder (AUD) is associated with steeper delay discounting rates; however, it is unknown whether substance co-use, particularly cannabis use, has an additive effect on discounting rates among heavy drinkers. Furthermore, it is unclear whether substance co-use and delay discounting are independently associated with AUD severity. Objectives The purpose of this study was to determine whether alcohol, tobacco, and cannabis co-use impacts delay discounting rates. We also sought to determine whether substance co-use and delay discounting were associated with AUD symptom counts. Methods The study sample was culled from several human laboratory studies and consisted of 483 heavy drinking individuals who completed a baseline visit (prior to experimental procedures). Participants were divided into groups based on self-reported alcohol, tobacco, and cannabis use during the past 30 days: alcohol only (n = 184), alcohol + cigarettes (n = 89), alcohol + cannabis (n = 82), and tri-use (n = 128). We examined discounting rates across the 4 groups and used multiple linear regression to test whether co-use and delay discounting were associated with AUD symptoms. Results After adjusting for covariates, individuals in the alcohol + cannabis group and the tri-use group had steeper discounting rates relative to the alcohol-only group. In addition, tri-use and delay discounting rates were independently correlated with a greater number of AUD symptoms. Conclusions Delay discounting rates were significantly greater among subgroups reporting cannabis use providing partial support for an additive effect, while also highlighting the importance of co-use substance type. Both tri-use and delay discounting were associated with greater AUD severity, which may provide relevant intervention targets.

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