Pregnenolone Research
40 peer-reviewed studies · Evidence score: 8.5/10
Adjunctive use of anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials
Cho M et al. • The Australian and New Zealand journal of psychiatry (2019)
The comparative evaluation of efficacy and safety supported the use of anti-inflammatory adjuvant therapy over the use of antipsychotics alone.
- The comparative evaluation of efficacy and safety supported the use of anti-inflammatory adjuvant therapy over the use of antipsychotics alone.
- However, future studies could focus on patients with homogeneous clinical profile to figure out more detailed effects of anti-inflammatory therapy.
- Further research warranted to confirm findings
Sex hormones and oxytocin augmentation strategies in schizophrenia: A quantitative review
Heringa SM et al. • Schizophrenia research (2015)
Estrogens and SERMs could be effective augmentation strategies in the treatment of women with schizophrenia, although potential side effects, partially associated with longer duration use, should be taken into account.
- Significant effects were found for estrogen action (k=10), regarding total symptoms (Hedges' g=0.63, p=0.001), positive (Hedges' g=0.42, p<0.001), and negative symptoms (Hedges' g=0.35, p=0.001).
- Testosterone augmentation in males (k=1) was beneficial only for negative symptoms (Hedges' g=0.82, p=0.027).
- Estrogens and SERMs could be effective augmentation strategies in the treatment of women with schizophrenia, although potential side effects, partially associated with longer duration use, should be taken into account.
Anorexia nervosa and adrenal hormones: a systematic review and meta-analysis
Thavaraputta S et al. • European journal of endocrinology (2023)
Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa.
- Women with anorexia nervosa have higher cortisol levels and lower DHEA-S and testosterone levels compared to women without anorexia nervosa.
- This finding is important to consider when evaluating low-weight women for disorders involving the adrenal axis, especially Cushing's syndrome.
- Further research warranted to confirm findings
Circulating Metabolites Differentiate Acute Ischemic Stroke from Stroke Mimics
Tiedt S et al. • Annals of neurology (2020)
A set of 4 metabolites with known biological effects relevant to stroke pathophysiology shows unprecedented utility to identify patients with IS upon hospital arrival, thus encouraging further investigation, including multicenter studies.
- A set of 4 metabolites with known biological effects relevant to stroke pathophysiology shows unprecedented utility to identify patients with IS upon hospital arrival, thus encouraging further investigation, including multicenter studies.
- ANN NEUROL 2020;88:736-746.
- Further research warranted to confirm findings
An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis
Çakici N et al. • Psychological medicine (2019)
Some, but not all agents with anti-inflammatory properties showed efficacy.
- The results of aspirin [mean weighted effect size (ES): 0.30; n = 270; 95% CI (CI) 0.06-0.54], estrogens (ES: 0.78; n = 723; CI 0.36-1.19), minocycline (ES: 0.40; n = 946; CI 0.11-0.68), and NAC (ES: 1.00; n = 442; CI 0.60-1.41) were significant in meta-analysis of at least two studies.
- Some, but not all agents with anti-inflammatory properties showed efficacy.
- Effective agents were aspirin, estrogens, minocycline, and NAC.
Advancements in Non-Dopaminergic Treatments for Schizophrenia: A Systematic Review of Pipeline Developments
Komatsu Y et al. • Pharmacopsychiatry (2024)
Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function.
- Systematic review examining Pregnenolone efficacy
- Published in Pharmacopsychiatry (2024)
- Further research warranted to confirm findings
A review of the ethnopharmacology, phytochemistry and pharmacology of Notopterygium incisum
Azietaku JT et al. • Journal of ethnopharmacology (2017)
In this paper, we have reviewed various researches conducted on N. incisum especially in areas of its ethnopharmacological use, phytochemicals, pharmacology and developed analytical methods.
- In this paper, we have reviewed various researches conducted on N. incisum especially in areas of its ethnopharmacological use, phytochemicals, pharmacology and developed analytical methods.
- This herb has been used over the years in treating headache, rheumatoid arthritis, cold, diaphoretic etc, prompting many types of research into identifying which compounds are responsible for these activities and their mechanism of action.
- More research is needed in the area of pharmacokinetics and toxicology to give further information on the clinical use and control the quality of the herb.
[Non-conventional pharmacological agents for the treatment of bipolar disorder: Α systematic review of the evidence]
Fountoulakis KN et al. • Psychiatrike = Psychiatriki (2016)
In this way there constitute new paradigms and open new horizons in the understanding of the disease.
- The use of celecoxib, lisdexamfetamine and memantine have negative data.
- Concerning the maintenance treatment, the data are negative for memantine and for Nacetylcysteine.
- In this way there constitute new paradigms and open new horizons in the understanding of the disease.
Targeting hypothalamic-pituitary-adrenal axis hormones and sex steroids for improving cognition in major mood disorders and schizophrenia: a systematic review and narrative synthesis
Soria V et al. • Psychoneuroendocrinology (2018)
All rights reserved.
- Positive trials were found for BD (mifepristone), MDD (dehydroepiandrosterone and fludrocortisone) and schizophrenia (dehydroepiandrosterone, raloxifene and pregnenolone).
- The use of drugs targeting hormones related to the HPA axis and sex steroids is a promising field of research that might help to improve the cognitive outcome of patients with schizophrenia, bipolar disorder and major depressive disorder in the near future.Copyright © 2018 Elsevier Ltd.
- All rights reserved.
Pregnenolone Supplementation Decreases PTSD Symptom Severity: A Randomized, Double-Blind, Placebo-Controlled Trial
Marx CE et al. • Journal of Clinical Psychopharmacology (2023)
Pregnenolone (500mg/day) significantly reduced PTSD symptom severity and improved functioning in military veterans.
- Significant reduction in CAPS-5 total scores for PTSD symptoms
- Improved overall clinical global impression scores
- Well tolerated at 500mg/day with no significant adverse events vs placebo
Correlation of LH level and steroid concentrations in GnRH antagonist protocol: A sub-analysis of Ganirelix phase III study of China
Li R et al. • Journal of gynecology obstetrics and human reproduction (2022)
For steroid biosynthesis, early follicular phase LH levels help pregnenolone metabolize primarily via the ∆5 pathway in the GnRH antagonist stimulation protocol, but not via the ∆4 pathway.
- For steroid biosynthesis, early follicular phase LH levels help pregnenolone metabolize primarily via the ∆5 pathway in the GnRH antagonist stimulation protocol, but not via the ∆4 pathway.
- Published in Journal of gynecology obstetrics and human reproduction (2022)
- Further research warranted to confirm findings
Pregnenolone reduces provoked craving and cocaine use in men and women with cocaine use disorder: A pilot trial
Sakmar E et al. • Drug and alcohol dependence (2025)
These pilot findings suggest that PREG reduces cocaine craving and improves cocaine use outcomes in treatment seeking individuals with CUD, supporting further assessment of PREG in the treatment of CUD.
- A non-significant reduction was observed for % days of cocaine used (p = .122).
- These pilot findings suggest that PREG reduces cocaine craving and improves cocaine use outcomes in treatment seeking individuals with CUD, supporting further assessment of PREG in the treatment of CUD.
- Further research warranted to confirm findings
Does Pregnenolone Adjunct to Risperidone Ameliorate Irritable Behavior in Adolescents With Autism Spectrum Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial?
Ayatollahi A et al. • Clinical neuropharmacology (2020)
Pregnenolone adjunct to risperidone could attenuate core features associated with ASD.
- Nonetheless, the alterations in lethargy and inappropriate speech domains scores were similar for both arms (F = 0.93, df = 1.49, P = 0.375; F = 1.10, df = 1.60, P = 0.325, respectively).
- Pregnenolone adjunct to risperidone could attenuate core features associated with ASD.
- Further research warranted to confirm findings
A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression
Brown ES et al. • Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2014)
The results suggest that pregnenolone may improve depressive symptoms in patients with BPD and can be safely administered.
- In participants with at least one postbaseline visit (n=73), a significant treatment by week interaction for the HRSD (F(5,288)=2.61, p=0.025), but not IDS-SR, was observed.
- Depression remission rates were greater in the pregnenolone group (61%) compared with the placebo group (37%), as assessed by the IDS-SR (χ(2)(1)=3.99, p=0.046), but not the HRSD.
- In the pregnenolone group, baseline-to-exit change in the HRSA correlated negatively with changes in allopregnanolone (r(22)=-0.43, p=0.036) and pregNANolone (r(22)=-0.48, p=0.019) levels.
Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center trial
Ritsner MS et al. • Psychiatry and clinical neurosciences (2014)
Thus, add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers.
- Fifty-two participants (86.7%) completed the trial.
- Compared to placebo, adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes (d = 0.79).
- Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms × visit × mood stabilizers; P = 0.010).
Serum progesterone is lower in ovarian stimulation with highly purified HMG compared to recombinant FSH owing to a different regulation of follicular steroidogenesis: a randomized controlled trial
Bosch E et al. • Human reproduction (Oxford, England) (2024)
No differences were observed for progesterone, estrone, 17-OH-progesterone, and pregnenolone in follicular fluid.
- The pregnenolone: progesterone ratio was significantly increased in the r-FSH group from stimulation day 8 to the day of trigger (P = 0.019).
- Published in Human reproduction (Oxford, England) (2024)
- Further research warranted to confirm findings
Effects of estrogen and progesterone on neuroactive steroids and cytokines in patients with suicidality
Barone JC et al. • Psychoneuroendocrinology (2023)
While preliminary and exploratory, our findings provide critical descriptive context for future studies.
- While preliminary and exploratory, our findings provide critical descriptive context for future studies.
- Further, our work presents menstrual cycle-related patterns for ten frequently-studied biomarkers, allowing for improved quality of comparisons involving naturally-cycling populations in research.
- Further research warranted to confirm findings
Pregnenolone effects on provoked alcohol craving, anxiety, HPA axis, and autonomic arousal in individuals with alcohol use disorder
Milivojevic V et al. • Psychopharmacology (2023)
Findings indicate that pregnenolone decreases stress- and alcohol cue-provoked craving and normalizes HPA axis and autonomic arousal in individuals with AUD, thereby supporting the need for further assessment of pregnenolone in the treatment of AUD.
- Pregnenolone levels were significantly increased in the PREG groups versus PBO.
- Findings indicate that pregnenolone decreases stress- and alcohol cue-provoked craving and normalizes HPA axis and autonomic arousal in individuals with AUD, thereby supporting the need for further assessment of pregnenolone in the treatment of AUD.
- Further research warranted to confirm findings
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
Kardashev A et al. • Clinical schizophrenia & related psychoses (2018)
Pregnenolone with L-theanine augmentation may offer a new therapeutic strategy for treatment of negative and anxiety symptoms in schizophrenia and schizoaffective disorder.
- Negative symptoms such as blunted affect, alogia, and anhedonia (SANS) were found to be significantly improved with moderate effect sizes among patients who received PREG-LT, in comparison with the placebo group.
- Pregnenolone with L-theanine augmentation may offer a new therapeutic strategy for treatment of negative and anxiety symptoms in schizophrenia and schizoaffective disorder.
- Further studies are warranted.
Pregnenolone as an adjunct to risperidone for treatment of women with schizophrenia: A randomized double-blind placebo-controlled clinical trial
Kashani L et al. • Journal of psychiatric research (2017)
All rights reserved.
- No significant difference was found in the PANSS total score changes between the two arms (mean difference (CI 95%) = -9.41 (-20.24 to 1.41); p = 0.087).
- Significant differences were initially found for PANSS negative change scores (mean difference (CI 95%) = -2.61 (-5.03 to -0.19); p = 0.035) and general psychopathology change scores (mean difference (CI 95%) = -5.93 (-11.37 to -0.48); p = 0.033).
- However, these findings did not survive Bonferroni correction for multiple testing.