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A Critical Review of Alcohol Administration Guidelines in Laboratory Medication Screening Research: Is It Time to Include Treatment Seekers?

ABSTRACT: Human laboratory studies play an important role in alcohol use disorder (AUD) medication development. Medications that are found to be safe and effective during human laboratory screening will then move to more expensive clinical trials in patient populations. Given the gatekeeping role of human laboratory studies in the medication development pipeline, it is critical that these studies accurately forecast how pharmacotherapies will perform under true-to-life clinical conditions. On the other hand, the design of these studies also must adhere to ethical guidelines: certain aspects of clinical reality cannot be incorporated into screening studies because doing so might place the participant at risk for harm or breach other ethical guidelines. Conventions exist that guide the resolution of these conflicting ideals. This article considers the practice of recruiting non-treatment-seeking heavy drinkers to participate in laboratory screening studies. By convention, volunteers are excluded from laboratory screening studies that involve alcohol administration if they are deemed "treatment seeking," meaning that they recently stopped drinking or are motivated to do so. Although this common practice may reduce risk to participants, findings may not accurately predict medication effects on treatment seekers. Indeed, there is empirical evidence that treatment seekers differ from nontreatment seekers in their responses to medications (Neuropsychopharmacology 2017a; 42: 1776; Am J Drug Alcohol Abuse 2017b; 43: 703; J Psychiatr Res 2006; 40: 383). Here, we argue for the importance of recruiting treatment seekers for this research due to their qualitative difference from nontreatment seekers. We argue that these individuals should be the default population in human laboratory medication screening studies. We conclude by discussing 2 case examples of medication experiments led by our research groups that involved administering medications to treatment seekers.

SUBMITTER: Roberts W

PROVIDER: S-EPMC7855436 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Motivational models of alcohol use suggest that individual differences in sensitivity to the acute subjective effects of alcohol play an important role in motivational pathways to alcohol use. However, few studies have examined the link between drinking motives and subjective responses to alcohol. This study investigated the associations of coping and enhancement drinking motives with subjective stimulant and sedative effects during a laboratory alcohol administration session. We also examined whether stimulation and sedation following alcohol administration mediated the relationships between drinking motives and postalcohol ratings of alcohol wanting and liking.Heavy episodic drinkers (n = 147, ages 19 to 25) at 2 sites participated in an intravenous alcohol administration session in which blood alcohol concentration was raised to a target of 80 mg% over 20 minutes. Participants completed measures of stimulation and sedation at baseline and 20 minutes and also rated alcohol liking and wanting at 20 minutes. Drinking motives and alcohol use were assessed during a previous laboratory visit.A path analysis controlling for baseline stimulation and sedation showed that enhancement motives were positively associated with postalcohol stimulation and negatively associated with postalcohol sedation. In contrast, coping motives were positively associated with postalcohol sedation. In turn, postalcohol stimulation, but not sedation, was associated with alcohol wanting and liking. Further, indirect pathways from enhancement motives to postalcohol wanting and liking mediated through postalcohol stimulation were statistically significant. Coping motives, on the other hand, were directly associated with increased postalcohol wanting and liking.The results demonstrate that drinking motives are linked with individual differences in sensitivity to the effects of alcohol, which may serve as a mechanism underlying alcohol reinforcement and the motivation to consume more alcohol during a drinking episode.

Project description:BackgroundAlcohol 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.MethodsIndividuals 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.DiscussionThe 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 registrationClinicalTrials.gov NCT04249882 . Registered on 31 January 2020.

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A Critical Review of Alcohol Administration Guidelines in Laboratory Medication Screening Research: Is It Time to Include Treatment Seekers?

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