Allopregnanolone is a neurosteroid naturally produced within the body, where it has a function in the regulation of brain activity and mood. It is synthesized from progesterone. This compound has attracted scientific and medical attention, leading to the development of new therapeutic agents based on its molecular structure and action.
The Brain’s Natural Mood Regulator
Allopregnanolone is a metabolite of the hormone progesterone. Its primary influence on the brain comes from its interaction with the GABA-A receptor system. Gamma-aminobutyric acid, or GABA, is the main inhibitory neurotransmitter in the central nervous system, responsible for reducing neuronal excitability and producing a calming effect.
The neurosteroid functions as a positive allosteric modulator of these GABA-A receptors. This means that allopregnanolone binds to a distinct site on the receptor, different from where GABA itself binds. This binding action enhances the receptor’s response to GABA, amplifying the natural calming signal. By making the brain’s primary “brake” more efficient, allopregnanolone helps to temper responses to stress and anxiety.
This mechanism is a natural part of the body’s system for maintaining neurological balance. The levels of allopregnanolone can fluctuate, for instance, during the menstrual cycle and pregnancy. During the third trimester of pregnancy, its concentrations rise significantly before dropping sharply after childbirth. These fluctuations are believed to play a part in the mood changes that can occur during these periods.
Approved Medical Formulations
The understanding of allopregnanolone’s role in brain chemistry has led to the development of specific, government-approved medications. These are not supplements but prescription drugs designed for precise therapeutic purposes. Two such medications are brexanolone (Zulresso) and zuranolone (Zurzuvae).
Brexanolone was the first medication of its kind approved by the U.S. Food and Drug Administration (FDA), specifically for the treatment of postpartum depression (PPD). PPD is a serious mood disorder that can occur in women after giving birth. The approval of brexanolone was a development because it offered a mechanism of action different from existing antidepressants.
Following this, zuranolone was developed as an oral medication. It is a synthetic analog of allopregnanolone, meaning it is chemically similar. The FDA has approved zuranolone for the treatment of both PPD and major depressive disorder (MDD) in adults.
The “Supplement” Distinction
A clear line exists between approved medical formulations of allopregnanolone and products marketed as supplements. Authentic allopregnanolone is a neuroactive steroid, and due to its effects on the brain, it is controlled as a prescription medication. It is not legally available for purchase over-the-counter as a dietary supplement in the United States.
Consumers searching online for “allopregnanolone supplements” will likely encounter products that are not what they seem. These are often precursors, such as pregnenolone or DHEA, which are hormones that the body can convert into other steroids. Other products may contain various herbal extracts that sellers claim can naturally boost the body’s own production of allopregnanolone.
It is important to recognize that these products are not the same as the regulated drug. The claims made about these supplements are often not supported by scientific evidence. Unlike FDA-approved medications, dietary supplements are not subject to the same requirements for proof of efficacy, safety, or manufacturing quality control. This lack of regulation can lead to variability in the purity and dosage of what is sold.
Administration and Safety Profile
The administration methods for approved allopregnanolone-based drugs are specific and reflect their safety considerations. Brexanolone (Zulresso) is administered as a continuous intravenous (IV) infusion over 60 hours. This procedure must be conducted in a certified healthcare facility, requiring the patient to be admitted to the hospital for the treatment.
This protocol is in place because of the drug’s safety profile. A primary risk associated with brexanolone is excessive sedation and the potential for a sudden loss of consciousness. To manage this risk, the FDA requires a Risk Evaluation and Mitigation Strategy (REMS) that mandates patients are monitored continuously by healthcare personnel and are not left alone with their infant.
Zuranolone (Zurzuvae) is an oral capsule taken once daily for 14 days. While this allows for at-home use, it comes with specific safety warnings. Common side effects include:
- Drowsiness
- Dizziness
- Fatigue
- Confusion
Because of these effects, patients are advised not to drive or operate heavy machinery for at least 12 hours after taking the medication.