Neuropsychiatric Disorders

Medical Studies on Pregnenolone – Neuropsychiatric Disorders


Pregnenolone has been shown to exert positive effects on the brain. For example, it improves memory and learning, helps maintain a healthy mood and supports the modulation of cognitive functions.

Memory Support at Any Age

Numerous studies over the past three decades have shown that even low-dose pregnenolone supplementation helps to support memory – long-term memory in particular. In addition, pregnenolone protects the body from age-related cognitive problems while promoting nervous system health. Incidentally, healthy younger people who are frequently exposed to stressful situations can also benefit from this function of pregnenolone, as this substance supports optimal mental performance by preventing neuronal damage.

Other Applications

Sub-optimal pregnenolone levels have been associated with mood disorders, cognitive decline, anxiety and panic attacks, schizophrenia or dementia, psychosis and cannabinoid-related dysfunctions. Studies have attributed some of the beneficial effects of pregnenolone to the direct effect of pregnenolone, while other effects can be attributed to substances metabolized from pregnenolone, such as DHEA, progesterone and their derivatives. Of particular interest is the fact that pregnenolone can promote neurogenesis; a property that can be especially useful in neurodegenerative diseases.

Medical Studies on Pregnenolone – Immune System

The Neuroactive Steroid Pregnanolone Glutamate: Anticonvulsant Effect, Metabolites and Its Effect on Neurosteroid Levels in Developing Rat Brains

2021-12 Kudova E, Mares P, Hill M, Vondrakova K, Tsenov G, Chodounska H, Kubova H, Vales K

Pregnanolone glutamate (PA-G) is a neuroactive steroid that has been previously demonstrated to be a potent neuroprotective compound in several biological models in vivo. Our in vitro experiments identified PA-G as an inhibitor of N-methyl-D-aspartate receptors and a potentiator of γ-aminobutyric acid receptors (GABAARs).

Longitudinal proneuroactive and neuroactive steroid profiles in medication-free women with, without and at-risk for perinatal depression: a liquid chromatography-tandem mass spectrometry analysis

2020-11 Deligiannidis KM, Kroll-Desrosiers AR, Tan Y, Dubuke ML, Shaffer SA

Neuroactive steroids (NAS) are derivatives of cholesterol or steroidal precursors made in the gonads, adrenal gland, placenta and brain. We characterized longitudinal plasma proneuroactive and NAS in healthy perinatal comparison women (HPCW), women at-risk for perinatal depression (AR-PND), and women with PND with/without comorbid anxiety. We hypothesized that AR-PND women who either did or did not go on to develop PND would have elevated NAS concentrations as compared to HPCW and that NAS would be correlated to depressive and anxiety symptoms.

Augmentation of endogenous neurosteroid synthesis alters experimental status epilepticus dynamics

2020-09 Lucchi C, Costa AM, Senn L, Messina S, Rustichelli C, Biagini G

Neurosteroids can modulate γ-aminobutyric acid type A receptor-mediated inhibitory currents. Recently, we discovered that the neurosteroids progesterone, 5α-dihydroprogesterone, allopregnanolone, and pregnanolone are reduced in the cerebrospinal fluid of patients with status epilepticus (SE). However, it is undetermined whether neurosteroids influence SE.

BV-2 microglial cells respond to rotenone toxic insult by modifying pregnenolone, 5α-dihydroprogesterone and pregnanolone levels

2020-09 Avallone R, Lucchi C, Puja G, Codeluppi A, Filaferro M, Vitale G, Rustichelli C, Biagini G

Neuroinflammation, whose distinctive sign is the activation of microglia, is supposed to play a key role in the development and progression of neurodegenerative diseases. The aim of this investigation was to determine levels of neurosteroids produced by resting and injured BV-2 microglial cells.

Stress and drug abuse-related disorders: the promising therapeutic value of neurosteroids focus on pregnenolone-progesterone-allopregnanolone pathway

2019-10 Tomaselli G , Vallée M

The pregnenolone-progesterone-allopregnanolone pathway is receiving increasing attention in research on the role of neurosteroids in pathophysiology, particularly in stress-related and drug use disorders. These disorders involve an allostatic change that may result from deficiencies in allostasis or adaptive responses, and may be downregulated by adjustments in neurotransmission by neurosteroids.

Neurosteroid levels in patients with bipolar disorder and a history of cannabis use disorders

2017-12 Van Enkevort E, Filbey F, Marx CE, Park J, Nakamura A, Sunderajan P, Brown ES

In animal models, levels of the neurosteroid pregnenolone increase after tetrahydrocannabinol (THC) administration and pregnenolone appears to attenuate the brain effects of THC. Given these interactions between pregnenolone and THC, we evaluated baseline neurosteroid levels in participants with a history of a cannabis use disorders (CUDs).

A role of endogenous progesterone in stroke cerebroprotection revealed by the neural-specific deletion of its intracellular receptors

2017-11 Zhu X, Fréchou M, Liere P, Zhang S, Pianos A, Fernandez N, Denier C, Mattern C, Schumacher M, Guennoun R

Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult.

Pregnenolone can protect the brain from cannabis intoxication

2014-01 Vallée M, Vitiello S, Bellocchio L, Hébert-Chatelain E, Monlezun S, Martin-Garcia E, Kasanetz F, Baillie GL, Panin F, Cathala A, Roullot-Lacarrière V, Fabre S, Hurst DP, Lynch DL, Shore DM, Deroche-Gamonet V, Spampinato U, Revest JM, Maldonado R, Reggio PH, Ross RA, Marsicano G, Piazza PV

Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated.

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