Allopregnanolone
The Neurosteroid Behind Calm, Sleep & Emotional Stability
Allopregnanolone is a powerful neurosteroid derived from progesterone, with critical roles in brain function, mood regulation, sleep, and anxiety control.
Unlike classic hormones that act on glands and tissues, neurosteroids like allopregnanolone act directly on the brain—particularly the GABA-a receptors, which are responsible for calming neural activity.
How Allopregnanolone Is Made
Synthesized from progesterone in the brain & peripheral nervous system.
Follows this basic pathway:
- Cholesterol → Pregnenolone → Progesterone → Allopregnanolone
- Enzymes involved: 5α-reductase and 3α-hydroxysteroid dehydrogenase
What Allopregnanolone Does in the Brain
Enhances GABA-A receptor activity
Produces calming, anti-anxiety effects
Promotes deep sleep
Supports slow-wave and REM sleep
Stabilizes mood,Reduces depression, irritability, and panic
Helps prevent neuroinflammation and cognitive decline
Supports memory, Linked to cognitive clarity and reduced “brain fog”
Low Allopregnanolone Levels May Contribute To:
- Insomnia or disrupted sleep
- Chronic anxiety or panic attacks
- PMDD (premenstrual dysphoric disorder)
- Postpartum depression
- PTSD and trauma-related disorders
Therapeutic Uses & Clinical Relevance
Postpartum Depression - Zulresso (brexanolone) – synthetic IV allopregnanolone approved by FDA
PMDD or perimenopause - Bioidentical oral micronized progesterone increases allopregnanolone
Mood and sleep support
How to Support Natural Allopregnanolone Production
- Supplement with oral micronized progesterone (100–200 mg at bedtime)
- Support cholesterol metabolism (healthy fats, B5, magnesium)
- Reduce chronic stress and cortisol dominance, which can suppress neurosteroid production
- Ensure adequate sleep and light exposure, which regulate neurohormone synthesis
Summary
Allopregnanolone is a calming, mood-stabilizing neurosteroid produced from progesterone. It plays a key role in regulating anxiety, sleep, memory, and emotional well-being. Declining levels during perimenopause, postpartum, or chronic stress states are linked to insomnia, mood disorders, and heightened emotional sensitivity. Optimizing progesterone—especially oral bioidentical forms—can help restore allopregnanolone and improve overall brain health.
