Pregnenolone is a steroid hormone produced from cholesterol, and it’s the parent of the rest of your sex and adrenal hormones (DHEA, cortisol, aldosterone, estradiol, estrone, estriol, progesterone, and testosterone). Because it’s the parent of all of them, it tends to have a balancing effect on both pathways. Mostly it gets made in the adrenal glands, but it also gets produced in the ovaries and testes, and in a few other places—including the brain.

Like all hormones, pregnenolone decreases with age. Correlation is not causation, but is it possible that less pregnenolone might be implicated in age-related memory decline?

How Pregnenolone Affects Neurons

Throughout our lives, our brains have the ability to grow new neurons and form new synaptic connections—this is called neuroplasticity.

Pregnenolone directly stimulates this process—via the growth of new neurons, enhancing myelination (the formation of the nerves’ fatty protective covering), and protecting nerves from toxicity, or toxin-induced cell death. It even helps neurons to repair themselves after such toxicity or damage has occurred.

How Pregnenolone Affects Concentration

In addition to protecting and nurturing the nerve cells and fostering their connections with one another, pregnenolone is also excitatory; that is, it stimulates the neurons’ activity. Specifically, this means it decreases the activity of the calming neurotransmitter GABA, and stimulates the NMDA receptors. The NMDA receptor deals with two primary neurotransmitters: glutamate, the neurotransmitter that stimulates it, and glycine, the neurotransmitter that calms it down. Stimulation causes a calcium channel to open, while calming it down closes the calcium channel. Calcium in this case is carrying an electrical charge… so think of it like a bolt of electricity. Pregnenolone will also encourage release of dopamine, the neurotransmitter involved in focus and often inhibited in times of high stress.

These activities are good, to a point—like anything else, there can be too much of a good thing. Stimulation of the brain can enhance motivation and concentration, but overstimulation of the NMDA receptor for someone who already has excitotoxicity (from chemical exposure, say,) can worsen existing problems. Also, less GABA and more dopamine for someone who is already anxious can certainly increase anxiety. 

How Pregnenolone Affects Learning and Memory

Pregnenolone also enhances learning and memory.

This may be because it enhances release of acetylcholine, the primary neurotransmitter responsible for the formation of new memories. (Acetylcholine is the target for many Alzheimer’s drugs, including Aricept.)

It may also be because, as mentioned above, it enhances focus.

It may even be because it enhances deep sleep, and sleep deprivation can profoundly affect memory formation. (However, pregnenolone often interferes with sleep, too; this may be because it can enhance anxiety in some people, which is often a major cause of insomnia.)

The Upshot

There are an impressive number of studies on the effects of pregnenolone on cognition. If you’re interested in trying it, though, I’d highly recommend getting your levels checked to make sure you’re a good candidate for supplementation, and starting low to avoid overshooting. Aside from possible sleep and anxiety issues, too much pregnenolone often manifests with the same symptoms as too much DHEA or testosterone, including acne, oily skin, and even abnormal hair growth. Because it is a precursor for cortisol, I also would recommend monitoring your levels during treatment and stopping once you’ve achieved sufficiency or reached your treatment goals, as long-term usage can set you up for dependency.