Effects of the neuroactive steroid precursor pregnenolone on stress- and alcohol cue-provoked pain responses in individuals with alcohol use disorder.
Source: PubMed, NCBI / U.S. National Library of Medicine
Chronic alcohol use reduces GABAergic activity and neuroactive steroid levels, contributing to stress response dysregulation and heightened pain sensitivity in individuals with alcohol use disorder (AUD). Neuroactive steroid precursor pregnenolone (PREG) reduces stress- and cue-related craving and anxiety responses in individuals with AUD, but its effects on pain responses in AUD have not been assessed. Sixty treatment-seeking men and women with AUD in an 8-week randomized trial receiving placebo (PBO;= 21), 300 mg PREG/day (= 21), or 500 mg PREG/day (= 18) completed a 3-day script-guided imagery provocation in Week 2. Following exposure to stress (S), alcohol cue (C), and neutral (N) conditions (administered across three separate laboratory days in a counterbalanced order), participants provided self-reports of pain, craving, and anxiety before, immediately after, and at various time points following the provocation. Analyses utilized a mixed factorial design with medication as a between-subjects factor and imagery condition and time point as within-subjects factors. The 300-mg PREG group did not exhibit significant increases in stress- or cue-induced pain compared with neutral condition (S:N:= .705; C:N:= .705), whereas increases in stress-induced pain in PBO (S > N:= .009; C:N:= .152) and stress- and cue-induced pain in the 500-mg PREG group (S > N:< .001; C > N:= .002) were observed. Pain was associated with alcohol craving (< .001) and anxiety (< .001). A PREG treatment
Abstract
Chronic alcohol use reduces GABAergic activity and neuroactive steroid levels, contributing to stress response dysregulation and heightened pain sensitivity in individuals with alcohol use disorder (AUD). Neuroactive steroid precursor pregnenolone (PREG) reduces stress- and cue-related craving and anxiety responses in individuals with AUD, but its effects on pain responses in AUD have not been assessed. Sixty treatment-seeking men and women with AUD in an 8-week randomized trial receiving placebo (PBO;= 21), 300 mg PREG/day (= 21), or 500 mg PREG/day (= 18) completed a 3-day script-guided imagery provocation in Week 2. Following exposure to stress (S), alcohol cue (C), and neutral (N) conditions (administered across three separate laboratory days in a counterbalanced order), participants provided self-reports of pain, craving, and anxiety before, immediately after, and at various time points following the provocation. Analyses utilized a mixed factorial design with medication as a between-subjects factor and imagery condition and time point as within-subjects factors. The 300-mg PREG group did not exhibit significant increases in stress- or cue-induced pain compared with neutral condition (S:N:= .705; C:N:= .705), whereas increases in stress-induced pain in PBO (S > N:= .009; C:N:= .152) and stress- and cue-induced pain in the 500-mg PREG group (S > N:< .001; C > N:= .002) were observed. Pain was associated with alcohol craving (< .001) and anxiety (< .001). A PREG treatment effect showed positive associations between pain and alcohol craving in the PREG groups (300 mg:< .001; 500 mg:< .001) but not PBO (= .962) and positive associations between pain and anxiety in the 300-mg PREG group (300 mg:< .001) but not the PBO or 500-mg PREG groups (PBO:= .325; 500 mg:= .213). PREG dose specifically reduced stress-provoked pain responses and affected concurrent pain and craving and anxiety associations, warranting further examination of PREG effects on pain and alcohol use outcomes in AUD. (PsycInfo Database Record (c) 2026 APA, all rights reserved).