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An inpatient human laboratory study assessing the safety and tolerability, pharmacokinetics, and biobehavioral effect of GET 73 when co-administered with alcohol in individuals with alcohol use disorder

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Abstract

Rationale

Previous work suggests that GET 73, a novel compound with putative activity on the metabotropic glutamate receptor subtype 5 (mGluR5), may represent a novel pharmacological treatment for alcohol use disorder (AUD).

Objective

In this study, we investigated the safety, tolerability, pharmacokinetics, and biobehavioral effects of GET 73, when co-administered with alcohol, in individuals with alcohol dependence (AD).

Methods

This was an inpatient, cross-over, randomized, double-blind, placebo-controlled, human laboratory study with non-treatment-seeking, alcohol-dependent individuals. The study used a within-subject design, with two counterbalanced stages, during which participants received GET 73 and then placebo, or vice versa. During each stage, participants underwent an alcohol interaction session and, on a separate day, an alcohol cue reactivity, followed by an alcohol self-administration session.

Results

Safety outcomes of GET 73 were excellent with no serious adverse events, nor adverse events of severe grade. The co-administration of alcohol and GET 73 did not affect the pharmacokinetics of GET 73 or alcohol. GET 73, compared to placebo, did not affect the alcohol-related stimulation effects, but increased the subjective sedative effects of alcohol. GET 73 did not affect alcohol cue–induced craving, or alcohol self-administration in the laboratory.

Conclusions

The study confirms the safety and tolerability of GET 73 when co-administered with alcohol. Although, under this experimental condition, we did not detect an effect on alcohol craving and consumption in the laboratory, additional studies should be conducted administering GET 73 for an extended period in an outpatient setting.

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Acknowledgements

The authors thank Dr. Samantha Portis for providing helpful comments during the resubmission of this manuscript.

Funding

This study was funded by CT Laboratories, San Remo, Italy. Roberto Cacciaglia and Antonella Loche are employees of CT Laboratories and travel funds and honoraria from D&A Pharma and Lundbeck. Dr. Haass-Koffler is supported by the National Institute on Alcohol Abuse and Alcoholism (K01 AA023867; R01 AA026589; R01 AA027760; R21 AA027614) and by the National Institute of General Medical Sciences (NIGMS), Center of Biomedical Research Excellence (COBRE, P20 GM130414). Dr. Leggio is supported by the National Institute on Drug Abuse Intramural Research Program and the National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research (ZIA-DA000635 and ZIA AA000218, Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section).

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Authors and Affiliations

  1. Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, 121 South Main Street, Providence, RI, 02903, USA

    Carolina L. Haass-Koffler & Robert M. Swift

  2. Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA

    Carolina L. Haass-Koffler, Roberta Perciballi, Molly Magill & Lorenzo Leggio

  3. Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, NIDA IRP and NIAAA DICBR, Baltimore and Bethesda, MD, USA

    Carolina L. Haass-Koffler & Lorenzo Leggio

  4. Laboratorio CT, San Remo, Italy

    Antonella Loche & Roberto Cacciaglia

  5. Medication Development Program, National Institute On Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, USA

    Lorenzo Leggio

  6. Division of Addiction Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lorenzo Leggio

  7. Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA

    Lorenzo Leggio

  8. Providence Veterans Affairs Medical Center, Providence, RI, USA

    Robert M. Swift

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  1. Carolina L. Haass-Koffler
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  2. Roberta Perciballi
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  4. Antonella Loche
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  5. Roberto Cacciaglia
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  6. Lorenzo Leggio
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  7. Robert M. Swift
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Correspondence to Carolina L. Haass-Koffler.

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Haass-Koffler, C.L., Perciballi, R., Magill, M. et al. An inpatient human laboratory study assessing the safety and tolerability, pharmacokinetics, and biobehavioral effect of GET 73 when co-administered with alcohol in individuals with alcohol use disorder. Psychopharmacology 239, 35–46 (2022). https://doi.org/10.1007/s00213-021-06008-1

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