Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder

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Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder

Milivojevic et al., 2022 | Biomolecules | Rct

Citation

Milivojevic Verica, Charron Lily, ... Sinha Rajita. Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder. Biomolecules. 2022-Oct-29;12(11). doi:10.3390/biom12111593

Abstract

Chronic cocaine use leads to adaptations in stress biology and in neuroactive steroid system. These adaptations are associated with high cocaine craving and increased relapse risk. This study tested whether potentiation of the neuroactive steroid system with the precursor pregnenolone (PREG) affects stress- and cue-induced cocaine craving, anxiety and autonomic response in individuals with cocaine use disorder (CUD). Thirty treatment-seeking individuals (21 Male, 9 Female) with CUD were randomized to placebo (PBO) or supraphysiologic PREG doses of 300 mg or 500 mg per day for 8 weeks. After 2 weeks of treatment, participants were exposed to 5-min personalized guided imagery provocation of stress, cocaine, or neutral/relaxing cues in a 3-day experiment, one condition per day on separate days, in a random, counterbalanced order. Repeated assessment of cocaine craving, anxiety, heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) were assessed on each day. PREG significantly increased pregnenolone levels compared to PBO. Both PREG doses decreased stress- and cocaine cue-induced craving and reduced both stress- and cue-induced anxiety only in the 500 mg/day group. The 500 mg/day PREG group also displayed decreased stress-induced HR, SBP and DBP. Findings indicate that pregnenolone decreases stress- and cocaine cue-provoked craving and anxiety and reduces stress-induced autonomic arousal in individuals with CUD.

Key Findings

Findings indicate that pregnenolone decreases stress- and cocaine cue-provoked craving and anxiety and reduces stress-induced autonomic arousal in individuals with CUD.

Outcomes Measured

  • anxiety
  • blood pressure
  • systolic blood pressure
  • diastolic blood pressure

Population

Field Value
Population cocaine use disorder
Sample Size See abstract
Age Range See abstract
Condition anxiety

MeSH Terms

  • Humans
  • Male
  • Female
  • Craving
  • Pregnenolone
  • Neurosteroids
  • Stress, Psychological
  • Anxiety
  • Arousal
  • Cocaine

Evidence Classification

  • Level: Rct
  • Publication Types: Randomized Controlled Trial, Journal Article, Research Support, N.I.H., Extramural
  • Vertical: pregnenolone

Provenance

Source extracted via PubMed E-utilities API on 2026-04-12