Abstract

Alcohol-associated memories and craving play a crucial role in the development and maintenance of alcohol use disorder (AUD). As treatment options are limited in AUD, novel treatment strategies focus on the manipulation of alcohol-associated memories. The stress hormone cortisol affects various memory processes, and first clinical studies have shown that it inhibits the retrieval of disorder-specific memories and enhances extinction memory. This study aimed to investigate the effects of a single oral administration of cortisol on craving in patients with AUD during repeated in vivo exposure to alcohol pictures and the preferred alcoholic drink. In a double-blind, block-randomized, placebo-controlled cross-over design, 46 patients with AUD were treated with two sessions of in vivo exposure to alcohol. Cortisol (20 mg) or placebo was orally administered 1 h before each test day. Craving, stress, and cortisol were repeatedly measured during exposure sessions. Results show, that cortisol administration had distinct effects on craving depending on the severity of AUD and test day. While cortisol administration significantly enhanced craving during exposure on the first test day in patients with less severe AUD, it reduced craving in patients with more severe AUD. Independent of the cortisol administration, repeated in vivo exposure reduced craving from test day 1 to test day 2. In conclusion, adding cortisol to in vivo exposure might be a promising approach for reducing the strength of alcohol-associated memories and might promote the consolidation of extinction memory in patients with severe AUD. However, the differential effect of cortisol on craving depending on AUD severity cannot be conclusively explained and highlights the need for future studies elucidating the underlying mechanism.

Highlights

  • Alcohol use disorder (AUD) is a severe chronic illness with a multifactorial etiology[1], characterized by high rates of relapse even after intensive residential treatment[2]

  • This study aimed to investigate the effects of a single oral administration of cortisol on craving in patients with alcohol use disorder (AUD) during repeated in vivo exposure to alcohol

  • Cortisol administration had distinct effects on craving depending on the severity of AUD and test day

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Summary

Introduction

Alcohol use disorder (AUD) is a severe chronic illness with a multifactorial etiology[1], characterized by high rates of relapse even after intensive residential treatment[2]. Like other forms of learning, extinction acquisition is followed by a consolidation phase of the extinction memory where a cue is not associated with alcohol use anymore[6,9]. Even though there is some evidence from clinical studies that cue extinction approaches, such as exposure techniques in cognitive behavioral therapy, can reduce some of the conditioned physiological effects induced by drug cues and reduces subjective levels of craving[10,11], many of the patients do not respond to treatment, or achieve only partial remission of symptoms[12]. Drugs with the potential to enhance extinction like glucocorticoids (cortisol in humans)[13,14,15,16] might be promising candidates to enhance exposure therapy and reduce alcohol-taking behavior

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