Synopsis

Source of validity: Scientific
Rating (out of 5): 2

Pregenolone is a neurosteroid and precursor to various hormones, including progesterone, cortisol, and DHEA. Interest in its potential for treating anxiety disorders stems from preclinical and early clinical studies suggesting that neurosteroids can modulate neurotransmitter systems involved in anxiety, particularly by enhancing GABAergic transmission in the brain. Some animal studies have demonstrated that pregnenolone and its metabolites exhibit anxiolytic-like effects, possibly through positive allosteric modulation of GABA_A receptors, which are also targeted by benzodiazepines.

Human data, however, are limited. A handful of small-scale clinical studies and case reports have investigated pregnenolone’s effects on anxiety and related symptoms in populations with schizophrenia, bipolar disorder, and PTSD. These studies sometimes report modest reductions in anxiety symptoms, but the findings are inconsistent and often confounded by the use of pregnenolone in combination with other medications. There are currently no large randomized controlled trials specifically evaluating pregnenolone as a monotherapy for primary anxiety disorders such as generalized anxiety disorder, panic disorder, or social anxiety disorder.

Overall, while there is a scientific rationale and some preliminary evidence suggesting that pregnenolone may influence anxiety pathways, the strength of evidence remains low and more robust clinical research is needed. Pregnenolone is not a first-line or widely recommended treatment for anxiety disorders at this time.

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