Pregnenolone: Mixed Results in Real Trials
Pregnenolone sits at the top of the body's steroid chain and is sold as a supplement. Placebo-controlled trials have tested it for bipolar depression, back pain, schizophrenia and drug craving. Some found benefits. Others found none.
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How Does Pregnenolone Work?
Pregnenolone is the major steroid precursor in humans (Meieran 2004). Taking it raises levels of two brain-active steroids made from it: allopregnanolone, which enhances GABA-A receptor responses, and pregnenolone sulfate, a positive modulator of NMDA receptors (Marx 2014).
In a University of Michigan study, 16 adults took a single 400 mg dose and 15 took placebo before brain scanning. Higher allopregnanolone was linked to lower amygdala and insula activity and stronger amygdala-prefrontal connectivity, which tracked with lower self-reported anxiety (Sripada 2013).
A Bordeaux team reported in Science (2014) that THC substantially increases pregnenolone synthesis in the brain through the CB1 cannabinoid receptor, and that pregnenolone then acts as a signaling-specific inhibitor of CB1, damping several THC effects. That work was done in laboratory animals, not people.
In a small UCSF pilot, volunteers who had taken pregnenolone for 4 weeks were noticeably less sedated by a single dose of diazepam than those on placebo (5 vs 6 people). The authors read this as possible antagonism at the GABA-A benzodiazepine site. It has not been tested at scale.
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What the Data Shows
Key Takeaways
- Pregnenolone is the major steroid precursor in humans, and animal studies show it also acts directly on the brain (PMID 14749094).
- In 80 adults with bipolar depression, add-on pregnenolone titrated to 500 mg/day for 12 weeks gave 61% remission vs 37% on placebo on a self-report scale, though not on the clinician-rated scale (PMID 24917198).
- In 94 Iraq- and Afghanistan-era veterans, 4 weeks of escalating doses up to 500 mg/day reduced chronic low back pain more than placebo (PMID 32119096).
- In 120 people with schizophrenia, 8 weeks did not improve cognitive scores but did improve functional capacity (PMID 25030803).
- In Yale pilots of people with alcohol or cocaine use disorder, 300 or 500 mg/day reduced stress- and cue-provoked craving in the lab (PMID 36445398, 36358943).
- Trials at doses up to 500 mg/day for 4-12 weeks reported it was well tolerated (PMID 24917198, 32119096).
- Whether it helps healthy people. The one trial in healthy adults found no effect on mood, memory or sleep quality at 15-30 mg/day (PMID 14749094).
- Long-term safety. The longest trial on this page lasted 12 weeks.
- What it does to testosterone, estrogen or DHEA in supplement users. None of the trials here used sex hormones as an outcome.
- How it interacts with sedatives. A pilot of 11 people found less diazepam sedation after 4 weeks of pregnenolone (PMID 14749094).
- Whether the pilot results replicate. Several trials enrolled fewer than 60 people, and the schizophrenia trials disagree with each other (PMID 19339966, 25030803).
- Whether it blunts cannabis intoxication in people. That effect comes from animal work (PMID 24385629).
Frequently Asked Questions
What is pregnenolone?
Pregnenolone is a steroid the body makes itself, and it is the major steroid precursor in humans (PMID 14749094). It is also called a neurosteroid because it acts on the brain in animal studies. Taking it raises allopregnanolone and pregnenolone sulfate, two steroids that act on GABA-A and NMDA receptors (PMID 25030803). It is sold as a dietary supplement.
Does pregnenolone help with depression?
One randomized trial points that way for bipolar depression. Among 80 adults, add-on pregnenolone titrated to 500 mg/day for 12 weeks produced 61% remission against 37% on placebo on a self-report scale, but the clinician-rated scale showed no remission difference (PMID 24917198). One trial is not proof, and the doses were high.
Does pregnenolone improve memory?
The trials disagree. In healthy volunteers, 15-30 mg/day for 4 weeks did nothing for mood or memory (PMID 14749094). In schizophrenia, a 120-person trial found no cognitive gain (PMID 25030803), while a 58-person trial reported better attention and working memory at 30 mg/day but not at 200 mg/day (PMID 20584515).
Is pregnenolone safe to take?
In trials lasting 4 to 12 weeks, doses up to 500 mg/day were reported as well tolerated (PMID 24917198, 32119096). We found no published long-term safety trial. A small pilot found 4 weeks of pregnenolone reduced sedation from diazepam (PMID 14749094), so people on sedatives or hormone-sensitive treatments should involve their doctor.
Does pregnenolone raise testosterone?
That is not established. Pregnenolone sits upstream of the other steroid hormones (PMID 14749094), but none of the trials on this page used testosterone, estrogen or DHEA as an outcome. They tracked neurosteroids such as allopregnanolone and symptoms instead (PMID 24917198). A blood test is the only way to know what it does in one person.
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Pregnenolone is a hormone precursor. Talk to a clinician before taking it, especially with a hormone-sensitive condition or alongside sedatives.
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