Research
Pregnenolone
25 peer-reviewed studies curated from PubMed and Semantic Scholar.
Studies
Sorted by quality and recency
Pregnenolone effects on parasympathetic response to stress and alcohol cue provocation in treatment-seeking individuals with alcohol use disorder.
RCT of 55 treatment-seeking individuals with alcohol use disorder, randomized to placebo or pregnenolone at 300mg or 500mg daily for 8 weeks. The study assessed heart rate variability (HRV) during stress and alcohol cue provocations. Pregnenolone groups showed normalization of autonomic response, suggesting therapeutic potential for enhancing autonomic function in AUD.
Pregnenolone reduces provoked craving and cocaine use in men and women with cocaine use disorder: A pilot trial.
Pilot RCT of 55 individuals with cocaine use disorder assessing pregnenolone supplementation at 300mg and 500mg doses over 8 weeks. Pregnenolone increased plasma levels and reduced stress and cocaine cue-induced craving compared to placebo. The 300mg group used less cocaine than the 500mg and placebo groups.
Reduced urine pregnenolone concentration after clinical response in patients with depression: An open-label short-term prospective study.
Open-label trial assessing the effects of antidepressant treatment on urine concentrations of pregnenolone (PREG) and allopregnanolone (ALLO) in patients with depression. Significant reduction in urine PREG concentration was observed in responders after 28 days of treatment with either venlafaxine or mirtazapine.
Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial.
Randomized, double-blind, placebo-controlled clinical trial of pregnenolone in 94 Iraq- and Afghanistan-era US military veterans with chronic low back pain. Participants receiving pregnenolone reported significant reductions in pain intensity and pain interference scores compared to placebo. Pregnenolone was well tolerated and may be a safe and effective treatment for chronic low back pain.
Does Pregnenolone Adjunct to Risperidone Ameliorate Irritable Behavior in Adolescents With Autism Spectrum Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial?
RCT evaluating pregnenolone as an adjunct to risperidone in 64 adolescents with autism spectrum disorders. Pregnenolone group showed greater improvement in irritability, stereotypy, and hyperactivity subscales compared to placebo, with no significant difference in adverse effects.
Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder.
RCT of 43 individuals with alcohol use disorder testing pregnenolone's effects on stress, anxiety, and alcohol craving. Pregnenolone decreased stress- and alcohol cue-induced craving, reduced stress-induced anxiety, and normalized HPA axis and autonomic responses.
Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder.
RCT of 30 individuals with cocaine use disorder testing pregnenolone (PREG) at doses of 300 mg or 500 mg per day for 8 weeks. PREG decreased stress- and cocaine cue-induced craving and anxiety, and reduced stress-induced autonomic arousal, with significant effects in the 500 mg/day group.
Pregnenolone as an adjunct to risperidone for treatment of women with schizophrenia: A randomized double-blind placebo-controlled clinical trial.
Randomized double-blind clinical trial of 82 female inpatients with chronic schizophrenia receiving risperidone plus either pregnenolone or placebo for 8 weeks. No significant difference was found in the PANSS total score changes between the two arms, though initial differences in PANSS negative and general psychopathology change scores did not survive correction for multiple testing.
Neurosteroid Levels in Patients With Bipolar Disorder and a History of Cannabis Use Disorders.
The study evaluated baseline neurosteroid levels in bipolar depressed participants with a history of cannabis use disorders (CUDs) before receiving pregnenolone or placebo. Participants with a history of CUD had higher serum pregnanolone, lower allopregnanolone, and altered ratios compared to those without a history of cannabis use.
Does Pregnenolone Enhance Exposure Therapy in Obsessive-Compulsive Disorder? - A Pilot, Interim Report of a Randomized, Placebo-Controlled, Double-Blind Study.
Pilot, interim report of a randomized, placebo-controlled, double-blind study investigating pregnenolone as an adjunct to exposure therapy in OCD patients. Pregnenolone was well-tolerated, but no significant effects compared to placebo were detected in interim analyses.
Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia.
RCT of 120 participants with schizophrenia testing adjunctive pregnenolone versus placebo for 8 weeks. Pregnenolone improved functional capacity but did not improve cognitive symptoms. Neurosteroid changes correlated with functional improvements in female participants.
A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression.
RCT of pregnenolone as an add-on therapy for bipolar depression in 80 adults. Pregnenolone group showed greater depression remission rates compared to placebo, with significant changes in neurosteroid levels. Pregnenolone was well tolerated and may improve depressive symptoms in BPD.
Adjunctive Pregnenolone Ameliorates the Cognitive Deficits in Recent-Onset Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial.
This 8-week, double-blind, randomized, placebo-controlled trial examined the effect of pregnenolone on neurocognitive dysfunctions in patients with recent-onset schizophrenia and schizoaffective disorder. Pregnenolone significantly improved visual and sustained attention, as well as executive functions, compared to placebo.
Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial.
This 8-week, double-blind, randomized, placebo-controlled trial tested the efficacy of pregnenolone as an add-on treatment in 60 patients with recent-onset schizophrenia or schizoaffective disorder. Pregnenolone significantly reduced negative symptoms compared to placebo, particularly in patients not on mood stabilizers, and was well tolerated.
Pregnenolone for cognition and mood in dual diagnosis patients.
RCT of 70 participants with bipolar disorder or recurrent major depressive disorder and history of substance abuse, comparing pregnenolone (100mg/day) to placebo for 8 weeks. Pregnenolone showed trends toward greater improvement in mood, with a significant reduction in HRSD scores, but no effect on cognition.
Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial.
This 8-week, double-blind, randomized, placebo-controlled trial investigated the effects of pregnenolone and dehydroepiandrosterone as adjunctive treatments in 58 patients with chronic schizophrenia or schizoaffective disorder. Low-dose pregnenolone significantly improved positive symptoms, extrapyramidal side effects, attention, and working memory performance compared to placebo.
Microtubule associated protein 2 in bipolar depression: Impact of pregnenolone.
This study examined serum MAP2 levels in people with bipolar depression and controls, assessing the impact of pregnenolone treatment. MAP2 levels were higher in bipolar patients compared to controls and decreased non-significantly with pregnenolone treatment. Changes in MAP2 levels correlated with changes in depressive symptoms in the pregnenolone group.
Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial.
Double-blind, placebo-controlled trial of pregnenolone and L-theanine augmentation in 40 patients with chronic schizophrenia or schizoaffective disorder. The study found significant improvements in negative symptoms and anxiety scores, with moderate effect sizes, compared to placebo. Pregnenolone and L-theanine were well-tolerated.
Active immunisation against pregnenolone reduces testicular steroidogenesis and GnRH synthesis in rabbits.
RCT investigating the effects of active immunisation against pregnenolone on reproductive traits in 16 early pubertal male rabbits. Immunisation led to increased serum antibody titres and decreased testosterone and LH levels, resulting in testicular atrophy, arrested spermatogenesis, and suppressed steroidogenesis.
Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder.
Open-label pilot study assessing pregnenolone in reducing irritability in adults with autism spectrum disorder over 12 weeks. Pregnenolone significantly improved ABC-Irritability scores and was well-tolerated, with no severe side effects reported.
Allopregnanolone elevations following pregnenolone administration are associated with enhanced activation of emotion regulation neurocircuits.
RCT investigating the effects of pregnenolone administration on emotion regulation neurocircuits. Pregnenolone increased allopregnanolone levels, which reduced activity in the amygdala and insula, increased activity in the dorsal medial prefrontal cortex, and enhanced connectivity between the amygdala and dorsal medial prefrontal cortex, associated with reduced self-reported anxiety.
Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia.
Pilot randomized, placebo-controlled, double-blind trial investigating adjunctive pregnenolone for cognitive and negative symptoms in schizophrenia patients on stable doses of second-generation antipsychotics. Pregnenolone was well tolerated and significantly improved SANS scores compared to placebo. Serum pregnenolone increases predicted BACS composite scores, suggesting potential cognitive benefits.
Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum.
The study validated a method using gas chromatography-mass spectrometry to quantify 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of neuroactive steroids in serum. Administration of pregnenolone to rats and progesterone to women showed selective effects on these neuroactive steroids, indicating differential regulation of their biosynthetic pathways.
Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation.
Two preliminary studies assessed the effects of pregnenolone in humans. In Study 1, 17 volunteers received pregnenolone and placebo in a cross-over design, showing no significant effects on mood, memory, sleep quality, or well-being. In Study 2, 11 subjects were tested for the impact of pregnenolone pre-treatment on diazepam-induced sedation, showing significantly less sedation in pregnenolone-pretreated subjects.
Pregnenolone, 17-OH-pregnenolone, and testosterone in plasma of patients with congenital adrenal hyperplasia.
The study found that pregnenolone and 17-OH-pregnenolone levels were higher in patients with poorly controlled congenital adrenal hyperplasia compared to normal subjects. The levels correlated with urinary 17-ketosteroid and pregnanetriol excretion and plasma testosterone. The study suggests product inhibition as a possible explanation for elevated levels in patients with 21-hydroxylase deficiency.