Pregnenolone: A ‘Prohormone’ that May Help Relieve Depression

December 1, 2018

Are you concerned about your memory performance as you age? Maybe you are looking to boost your cognitive health and want to use natural sources to stay mentally sharp. Aside from brain foods that boost focus and memory, a steroid called pregnenolone is gaining attention for its potential neuroprotective effects.

Pregnenolone supplements are said to aid in the treatment of several health conditions, including depression, anxiety, schizophrenia and Alzheimer’s disease.

What does the scientific research suggest about the efficacy and safety of this supplement? Before you order a bottle, read up on the latest pregnenolone research. You may be surprised to find out how little is actually known about the uses of pregnenolone supplements for humans. There seems to be a lot of potential for it as a therapeutic agent, but there are some uncertainties that remain in question.

What Is Pregnenolone?

Pregnenolone is a prohormone that serves as a precursor (or “starting material”) for numerous steroids, including cortisol, progesterone, dehydroepiandrosterone (DHEA) and allopregnanolone. It’s used to make steroid hormones that play an important role in modulating brain activity and behavior. Steroids are also needed to regulate physiological activities like memory, mood, food intake, wakening and reproduction.

Pregnenolone is the main steroid that’s synthesized from cholesterol in humans and animals. It has three main sources of synthesis: the brain, adrenal glands and gonads. (1)

Studies show that this compound may have a role in regulating the mechanisms of anxiety and depression. There’s also evidence to suggest that pregnenolone administration is associated with improved performance on cognitive tasks and aging-related impairments. (2)

Health Benefits

Helps Improve Depression
May Reduce Symptoms of Schizophrenia
May Improve Memory
Potentially Reduces the Effects of THC

1. Helps Improve Depression

Research conducted in the last decade shows that pregnenolone may have beneficial effects on mood and cognition. In fact, it may work as a natural remedy for depression.

A 2014 randomized, double-blind and placebo-controlled trial conducted at the University of Texas Southwestern Medical Center in Dallas found that pregnenolone may improve depressive symptoms in patients with bipolar disorder or manic depression. When adults with bipolar disorder and depressed mood were randomized into two groups — one receiving 500 milligrams a day of pregnenolone and one receiving placebo — as a add-on therapy for 12 weeks, those taking the prohormone displayed greater depression remission rates. (3)

Another study involving patients with bipolar disorder or recurrent major depressive disorder and a history of substance abuse sought to determine whether or not pregnenolone is useful for improved cognition and mood. Seventy patients were randomly assigned to receive the prohormone or a placebo for eight weeks. The pregnenolone group ended up showing trends toward greater improvement compared to the placebo group. This suggests that the prohormone may be associated with some improvement in manic and depressive symptoms. However, it didn’t display major benefits for cognition in this study. (4)

2. May Reduce Symptoms of Schizophrenia

Because pregnenolone is a neurosteroid, it’s been studied for its potential therapeutic role for neuropsychiatric disorders, including schizophrenia.

In 2010, research published in the Journal of Clinical Psychiatry found that when patients with chronic schizophrenia or schizoaffective disorder were given 30 milligrams of pregnenolone a day for an eight-week period, they experienced significant reductions in symptoms. The patients also saw improvement in attention and working memory performance. (5)

In 2009, researchers at Duke University Medical Center’s Department of Psychiatry and Behavioral Sciences found that taking 500 milligrams of pregnenolone a day for an eight-week period led to significant improvements in symptoms of schizophrenia, such as the inability to feel pleasure (anhedonia), lack of speech and lack of emotions. (6)

3. May Improve Memory

Studies involving rodents have showed that pregnenolone positively affects learning and memory.

In 1992, researchers out of the Veterans Administration Medical Center in Saint Louis found that the administration of this prohormone to male mice improved memory when using a “footshock” experiment. Mice given pregnenolone and pregnenolone sulfate showed the best improvements in avoiding footback, or a mild electrical shock to the feet. (7)

A 2010 study published in the European Journal of Pharmacology suggests that intranasal administration of this neurosteroid improved memory and displayed central nervous system effects. (8)

Although evidence indicates that memory performance is correlated with pregnenolone levels in the brains of rodents, studies involving humans have mixed results. More research is needed to determine whether or not it can definitely improve memory and the cognitive health of humans. (9)

4. Potentially Reduces the Effects of THC

Because pregnenolone is an inactive precursor of all steroid hormones, it can modulate brain activity and behavior. This physiological activity may be helpful for patients who are dealing with drug dependence, especially cannabis.

Recent research suggests that THC, the psychoactive agent in cannabis and cannabis oil, significantly increases the synthesis of pregnenolone in the brain by activating a specific receptor called type-1 cannabinoid (CB1). Then, because pregnenolone acts as a signaling inhibitor for CB1, it reduces the effects of THC. This is called “negative feedback,” and it’s the brain’s way of protecting itself from the over-activation of receptors that are affected by THC and cannabis intoxication.

Although THC causes an increase in food cravings that can promote food intake and cause a decrease in memory performance, researchers found that pregnenolone administration actually blocked these behavioral changes in rodents.

When brain samples from rats were analyzed in a lab after being pre-treated with this neurosteroid, scientists found that the steroid significantly attenuated the effects of THC.

Researchers suggest that given its effects on THC and the side effects of cannabis use, pregnenolone may have supplementary advantages for the treatment of drug dependence. Unlike orthosteric antagonists that are used to treat drug addiction and tend to cause profound discomfort, aren’t well-tolerated by drug-dependent patients and can be overcome by taking higher doses of a drug, pregnenolone appears to be better tolerated and cannot be overcome by increasing drug intake. (10)

On top of that, this prohormone doesn’t appear to inhibit all CB1 receptor activities, so, in theory, you can still get CBD benefits when using cannabis medicinally and you won’t feel the psychoactive effects of THC.

However, more research in this area is needed to understand the potential of this neurosteroid for cannabis drug abuse. For one, studies have only been done in rodents or labs, and it’s difficult to administer the hormone to humans without it transforming to other steroids once it hits the bloodstream. Make sure to keep an eye out for more studies pertaining to this potential pregnenolone benefit.

Pregnenolone is also believed to be beneficial for arthritis, fatigue, endometriosis and aging-related disorders, but more research is needed on the efficacy of the hormone for these conditions before it can be recommended.

Dosage and How to Use

Pregnenolone supplements are available in capsule and tablet forms. Pregnenolone dosage varies, with 10- to 50-milligram supplements available and instructed to be taken one or more times daily. This is based on a health care professional’s recommendation.

These supplements are used to increase steroid hormone levels, including estrogen, testosterone and progesterone. They are also used to relieve signs of depression, reduce stress, promote restful sleep and improve fatigue. Pregnenolone is also used for weight loss. The scientific data pertaining to this neurosteroid and these health conditions is minimal and mostly conducted on rodents. That means we can’t be sure whether or not these supplements will actually benefit any of these concerns.

Keep in mind that pregnenolone supplements are not regulated by the United States Food and Drug Administration, and the safety of these supplements has not been proven with scientific research.

Risks and Side Effects

Little is known about the safety of taking pregnenolone supplements. There is some concern that this prohormone can cause steroid-like side effects, such as irritability, overstimulation, trouble sleeping, anxiety, anger, acne, mood changes, headaches, irregular heartbeat and hair loss.

People with hormone-sensitive conditions should not use these supplements, especially conditions that may worsen because of exposure to estrogen. Pregnenolone is converted into estrogen and other sex hormones by the body, so people with endometriosis, uterine fibroids, breast cancer and uterine cancer should consult their health care providers before using this type of supplement.

There isn’t any research to support the safety of pregnenolone use for women who are pregnant or nursing, so it should be avoided to be on the safe side.

In addition, these supplements should not be taken with any kind of hormones, like birth control pills, estrogen pills or testosterone pills, because they may cause too much of a particular hormone in your body.

Final Thoughts

Pregnenolone is a prohormone that serves as the starting material for numerous steroids, including cortisol, progesterone, DHEA and testosterone.
There are quite a few supplement companies that market it as an answer to health conditions like depression, anxiety, fatigue, insomnia, obesity and even hormone-related disorders like endometriosis. However, when you review the scientific evidence pertaining to these type of supplements, it’s clear that we really don’t know enough yet to make any appropriate recommendations.
Based on the research that is available, this prohormone neurosteroid seems to be effective for reducing symptoms of depression. It may also help improve memory, relieve symptoms of schizophrenia and reduce the effects of THC. However, more human studies are needed on these potential benefits.