Effects of cortisol administration on craving during in vivo exposure in patients with alcohol use disorder

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.

Mechanisms of memory under stress

“…Indeed, several interventions that build directly on basic research on the stress-memory link have been suggested. For instance, pharmacological treatments targeting corticosteroid or NA signaling were used to either facilitate the consolidation of therapeutic interventions or interfere with the retrieval of dysfunctional memories in phobia or PTSD (for a review see de Quervain et al, 2017), and more lately in addiction (Soravia et al, 2021). Beyond pharmacological treatments, cognitive interventions were recently introduced that aim at either contextualizing or intentionally controlling overly strong memories for highly stressful, traumatic events (Abed et al, 2020;Mary et al, 2020).…”

Is There an Association Between Salivary Cortisol and Dropping Out of Inpatient Substance Addiction Treatments? A Prospective Repeated Measures Study

“…Reduced cravings after cortisol administration has been found in individuals addicted to cocaine 72 and alcohol, 73 as well as in patients who received a low dose of heroin. 74 , 75 Findings for opioid maintenance also points to possible effects for stress-responses, in that the administration of buprenorphine seems to normalize cortisol levels.…”

A novel stress-based intervention reduces cigarette use in non-treatment seeking smokers

“…In fear-related studies, elevated stress hormones during extinction learning (either endogenously or through prior cortisol administration) can further reduce fear responses post-extinction and at follow-up [57][58][59][60][61][62]. In the only study to date examining the role of pre-extinction stress on appetitive memories in a clinical population, administration of cortisol before exposure to alcohol cues decreased within-session cravings in those with a severe alcohol use disorder but increased cravings in those with less severe symptoms [63]. These limited results with a short follow-up (<8 days) are challenging to interpret and compare with the current findings.…”