Overview
Pregnenolone has nothing to do with being pregnant, and everything to do with well-being.
Pregnenolone is the master steroid hormone from which whole
families of other hormones are made. For example, testosterone,
estrogens, progesterone, and cortisone, are all derivatives of
pregnenolone. But pregnenolone is also an important brain neurosteroid
— a hormonal substance that is formed and accumulated in the
nervous system and is active there. As such, pregnenolone is
involved in learning and memory, aggression and epilepsy, and
modulation of responses to stress, anxiety and depression.
Pregnenolone has a long history of use as a drug and supplement. It has been shown to have a wide range of beneficial actions
for people who are sick or under stress. These include:
- ameliorating arthritis (300 mg/day)
- countering fatigue (50-100 mg/day)
- generally improving the quality of life.
These effects occur after about two weeks of pregnenolone usage.
Many scientific studies provide evidence that pregnenolone can:
- enhance memory
- reduce stress
- lessen depression
- control ‘bipolar disorder’
- reduce schizophrenic symptoms.
Read Pregnenolone Monograph
Pregnenolone is a prohormone used by the body to produce other steroid hormones, such as testosterone, estrogens, progesterone,
cortisone, and many others. But pregnenolone is also an important brain neurosteroid
— that is, a hormonal substance that is both formed and accumulated in
the nervous system and is active there. As such, pregnenolone is
involved in learning and memory, aggression and epilepsy, and
modulation of responses to stress, anxiety and depression.
What we can’t tell you
In
the U.S. and some other industrialized countries, government agencies
like the U.S. Food and Drug Administration have adopted censorship as a
method for intensifying their control over supplement users and their
suppliers. Thus, FDA regulations prohibit us from telling you that any
of our products are effective as medical treatments, even if they are, in fact, effective.
Accordingly, we will limit our discussion of pregnenolone to a brief summary of relevant research, and let you draw your own
conclusions about what medical conditions it may be effective in treating.
History
Before
it was pushed aside by the promotion of other hormones, pregnenolone
had been shown to have a wide range of beneficial actions for people
who were sick or under stress. These included ameliorating arthritis,
countering fatigue, and generally improving the quality of life.
Experiments
in the 1940s showed that 50-100 mg/day of pregnenolone given to factory
workers resulted in improved production rates, less fatigue, and an
increase in happiness and well-being. Pilots reported also reported
less fatigue and an improved ability to fly airplanes. These effects
occurred after about two weeks of pregnenolone usage.
Also
during the 1940s, rheumatoid arthritis was successfully treated with
pregnenolone. At 300 mg/day for 40 days patients experienced “a
significant decrease in joint pain, tenderness, and spasticity, with
improved strength and range of motion”.
In
the 1950s, however, a raft of new stimulants, painkillers and
anti-inflammatories hit the market, and pregnenolone simply got swept
into the backwaters of the pharmaceutical world as the medical
profession got caught up in the excitement of new drugs and the money
they bring in. It was later discovered that the long-term use of these
newer drugs led to serious side effects, but by then pregnenolone had
become an unfashionable research topic.
During the past two decades, however,
pregnenolone and its sulfate ester have been receiving renewed
attention. Many scientific studies give strong experimental support to
claims that pregnenolone can be used to enhance memory and reduce
stress. There is also evidence that it lessens depression, controls ‘bipolar disorder’, and reduces schizophrenic symptoms.
Overview
The
term ‘neurosteroid’ was introduced in the 1980s to refer to
pregnenolone and other steroids that can be produced in the brain.
Since then, hundreds of studies have been published about these
substances and their potential value as treatments for psychiatric
illnesses.
Pregnenolone is made from cholesterol in many tissues of the body besides the brain. Pregnenolone is the master steroid hormone from which whole families of other hormones are made, including the corticoids,
androgens, estrogens, and progestins.
When
pregnenolone is taken orally much of it is absorbed from the digestive
tract. Some of it is immediately converted to pregnenolone sulfate
which dissolves in the circulating blood, some of it remains
unconverted and is thought to be transported in the blood by a carrier
protein. When it reaches the brain, some of the circulating
pregnenolone and pregnenolone sulfate passes through the
blood-brain-barrier into the nervous system, Hence, oral supplements of pregnenolone can elevate the concentrations of pregnenolone and pregnenolone sulfate in the brain
beyond what the brain would do on its own.
whereupon further conversion of pregnenolone to its sulfate is carried out.
Memory
Experiments have clearly shown that pregnenolone is a powerful stimulator of memory formation. So strong is the effect that significant memory-enhancing effects have been seen in mice when just a few dozen molecules
of pregnenolone sulfate are injected into certain regions of the brain.
But
does pregnenolone really enhance memory when you take it orally?
Incredible as it may seem, neither the medical research establishment
nor the supplement industry has bothered to do a clinical study and
publish the results. The studies that were performed and published in
the 1940s showed definite improvements in mental functions, but they
did not specifically measure memory enhancement.
One study of memory enhancement is said to
have been done recently at the St. Louis School of Medicine, USA: 500
mg pregnenolone or a placebo were given to volunteers three hours
before they performed standard memory tests. “Pregnenolone resulted in
improved memory in both men and women, improved spatial memory and
perception in men, and improved verbal recall memory in women.” The work, however, has not been published in a medical journal.
But
we do not have to wait for formal studies to be done before we can reap
the memory benefits which pregnenolone presumably has to offer — this
supplement is available, affordable, and safe to use in the amounts
that are typically recommended for memory enhancement: 50 to 500
mg/day.
Anxiety
Studies in patients with anxiety disorders have shown that higher anxiety levels correlate with lower pregnenolone levels
in the blood. More to the point, experiments with mice demonstrated that when pregnenolone sulfate is administered directly to the brain,
anxiety symptoms decrease. But at very high doses (10 to 100 times the effective dose), mice experienced increased anxiety.
The one published clinical study that has been done in humans used very low oral doses of pregnenolone (15-30 mg/day) and
showed no effects on anxiety, thereby establishing a lower bound on the effective dose range. In view of the studies on mental function done in the 1940s,
these results suggest that anxiety therapy using pregnenolone may require doses in the range of 50-200 mg/day.
Depression and manic-depression (‘bipolar disorder’)
It was reported in 1994 that patients with bipolar disorder have depressed pregnenolone levels in their cerebrospinal fluid.
Since then, dozens of studies have been performed in mice and rats in
an effort to understand how neurosteroids affect brain function. Many
investigators have concluded that these substances hold great promise
as treatment options for psychiatric illnesses, including depression
and bipolar disorder.
Yet, to the discredit of the psychiatric profession, only one clinical
trial has been conducted to test this concept and the results have not
been published.
Fortunately,
the snail’s pace at which the medical world moves is no obstacle to
people who want to use pregnenolone. They can easily and safely buy
pregnenolone and try it for themselves, and many do — in the U.S. at
least, where the right of individuals to buy it is protected by an act
of Congress.
Schizophrenia
Researchers
investigating the detailed mechanism by which pregnenolone influences
brain function consider pregnenolone a promising treatment for
schizophrenia, drug abuse and dementia.
In
a clinical trial conducted in 2005, schizophrenia patients were given
pregnenolone for 8 weeks in escalating doses from 100 to 500 mg/day.
During the trial the researchers reported that patients “who have been
on the higher dose (500 mg/d) have felt better, with an improved sense
of energy. Even when blinded to treatment, high-dose patients have
asked to remain on pregnenolone.” But the results of the study remain
unpublished as of 2007.
Schizophrenia
is a complex illness for which the causal factors may vary somewhat
from one patient to another. One would expect that optimum treatments
would vary somewhat also. Pregnenolone may be a useful therapy for some
patients and not for others. It would be nice to have some clinical
data to use as a guide, but the psychiatric profession’s lack of
interest in exploring ‘outside the box’ makes it unlikely that we will
have this data any time soon. Schizophrenia patients must therefore try
pregnenolone on their own if they want an answer to the question “Is
pregnenolone right for me?”
Conclusion
Are pregnenolone supplements useful for the conditions and purposes mentioned above? We aren’t allowed to tell you, so you
should take a look at some of the references cited here, and then decide for yourself.
Review articles
A clear, non-technical overview of pregnenolone as a supplement is the one by PDR Health. A slightly more technical discussion of pregnenolone and its relationship to other steriods is available in the Wikipedia. The article on the Intelegen website offers a broad perspective.
Warning:
Pregnenolone should be avoided by those who are at risk for hormonally
related cancers, or who are lactating or pregnant.
References
[1] PDRhealth website
[2] Pregnenolone and Mental Function Intelegen.com website
[3] CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI. Biol Psychiatry. 1994 May 15; 35(10):775-80 George MS, Guidotti A, Rubinow D, Pan B, Mikalauskas K, Post RM
[4] Pregnenolone for Bipolar II disorder: Community ratings Revolution Health website. 2005
[5] A DOSE-FINDING STUDY OF PREGNENOLONE IN PATIENTS WITH SCHIZOPHRENIA Schizophr Bull. 2005 Apr; 31(2):183-575 A. J. Savitz, K. E. Carpiniello, S. M. Silverstein
[6] Rates of sterol synthesis and uptake in the major organs of the rat in vivo. J Lipid Res. 1981 May; 22(4):551-69 Turley SD, Andersen JM, Dietschy JM
[7] The regional brain distribution of the neurosteroids pregnenolone and pregnenolone sulfate following intravenous infusion. J Steroid Biochem Mol Biol. 1997 Jul; 62(4):299-306 Wang MD, Wahlström G, Bäckström T
[8] Neurosteroids: deficient cognitive performance in aged rats depends on low pregnenolone sulfate levels in the hippocampus. Proc Natl Acad Sci U S A. 1997 Dec 23; 94(26):14865-70 Vallée M, Mayo W, Darnaudéry M, Corpéchot C, Young J, Koehl M, Le Moal M, Baulieu EE, Robel P, Simon H
[9] Neurosteroids
and cholinergic systems: implications for sleep and cognitive processes
and potential role of age-related changes. Psychopharmacology (Berl). 2006 Jun; 186(3):402-13 George O, Vallée M, Le Moal M, Mayo W
[10] Pregnenolone sulfate enhances post-training memory processes when injected in very low doses into limbic system structures:
the amygdala is by far the most sensitive. Proc Natl Acad Sci U S A. 1995 Nov 7; 92(23):10806-10 Flood JF, Morley JE, Roberts E
[11] Neuroactive steroid levels in patients with generalized anxiety disorder. J Neuropsychiatry Clin Neurosci. 2001; 13(3):396-8 Semeniuk T, Jhangri GS, Le Mellédo JM
[12] Low pregnenolone sulphate plasma concentrations in patients with generalized social phobia. Psychol Med. 2002 Jul; 32(5):929-33 Heydari B, Le Mellédo JM
[13] Differential anxiolytic effects of neurosteroids in the mirrored chamber behavior test in mice. Brain Res. 1997 Mar 28; 752(1-2):61-71 Reddy DS, Kulkarni SK
[14] Pregnenolone and pregnenolone sulfate, alone and with ethanol, in mice on the plus-maze. Pharmacol Biochem Behav. 1994 Aug; 48(4):893-7 Melchior CL, Ritzmann RF
[15] Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology. 2004 May; 29(4):486-500 Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM
[16] [Effects of sigma receptor ligands on psychiatric disorders] Nihon Shinkei Seishin Yakurigaku Zasshi. 2003 Oct; 23(5):187-96 Kamei H, Noda Y, Nabeshima T, Yamada K
[17] The antidepressant-like effect induced by sigma(1)-receptor agonists and neuroactive steroids in mice submitted to the forced
swimming test. J Pharmacol Exp Ther. 2001 Sep; 298(3):1269-79 Urani A, Roman FJ, Phan VL, Su TP, Maurice T
[18] Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics. Neuropsychopharmacology. 2006 Jun; 31(6):1249-63 Marx CE, Stevens RD, Shampine LJ, Uzunova V, Trost WT, Butterfield MI, Massing MW, Hamer RM, Morrow AL, Lieberman JA
[19] Pregnenolone Wikipedia website
[20] Dietary Supplement Health And Education Act of 1994 Website of the Commission on Dietary Supplement Labels
