Cosmos asked:
Does this drug provide significant improvement in memory as some have claimed? If I have to I would dissolve the pill in water and spray it intra-nasally to get the most effects, but I'm wondering whether anyone can substantiate this claim. It's reasonably inexpensive from some retailers and I would be willing to try it myself if it's indeed worth the money, time and effort to do so.Save yourself the money, time and effort
. Some companies have been hyping pregnenalone for years now, based almost entirely on one animal experiment involving pregnenalone sulfate
injected directly into various brain structures. The nature of the test itself was such that I'm not sure that I'd want to take the stuff even if it panned out in humans: it showed that mice whose brains were shot up with pregnenalone were more likely to 'learn' to avoid taking the 'wrong' arm of a T-maze after being subjected to a foot-shock active avoidance program than if they did not receive the injection. This of course
could be the result of 'better' 'learning,' but it could also simply be the result of greater pain sensitivity (for instance).
More importantly: even this result were truly the result of 'learning,' I doubt that this is a very healthy thing to replicate in yourself. The study found pregnenalone most effective when injected into the amygdala: in fact,
10 000 times more potent than when injected into the hippocampus, a locus more classically related to working memory and the transfer of short-term into long-term storage. As the full text of the paper notes, "
There ismuch evidence supporting the hypothesis that processing of sensory data in the amygdala assigns emotional significance to it and, when the stimuli are aversive, elicits behavioral, autonomic, and humoral responses typical of what is commonly known as fear (unconditioned). The amygdala is possibly the central station where unconditioned (eg foot shock) and conditioned stimuli (eg buzzer sound) meet. The most reasonable interpretation of the human translation would be that you'd be more fearful of trying something again if you got a negative result the first time. If you were rejected by an attractive person after approaching him or her, or got beaten up after walking through a park, you might live in fear of ever trying the same thing again. This hardly marks pregnenalone as a supplement to enhance human potential
.
In any case, two clinical trials have now been performed which appear to demonstrate that pregnenalone -- at least when taken orally at doses typical of existing supplements or higher -- does not yield significant cognitive benefits in humans. The first trial had two parts: an open (unblinded) dose-ranging study of pregnenalone in men aged 20-88 at doses from 0 to 500 mg, and a second (blinded) arm at 150 mg/day for 12 weeks in older men only (average age 69). The unblinded study seemed to show that "performance on Trails B (a test of visuospatial ability and speed of central processing) improved with increasing doses of pregnenalone", but it's hard to be sure that this was not just a placebo effect because it was a short-term, unblinded study. In the double-blind trial, pregnenolone in older men led to a
trend toward a Trails B improvement and an increase in libido, but the result was not statistically significant, and overall memory, wellbeing, and other parameters were not improved. In summarizing their own results in a later review, the researchers simply said that the study "failed to demonstrate any effects on strength or memory."
In the second trial, "normal volunteers received pregnenolone and placebo for 4 weeks each (15 mg PO per day x2 weeks followed by 30 mg PO per day x2 weeks, vs. placebo x4 weeks) in a within-subject, double-blind, cross-over design, with a 4 week drug-free washout period separating the two arms. ... Pregnenolone was generally well-tolerated but, by itself, had no significant effects on mood, memory, self-rated sleep quality, or subjective well-being."
Since most pregnenalone supplements contain doses from 25-150 mg, I suggest that it is not an effective cognitive-enhancement supplement. I know of no studies taking it nasally, however -- but again, I'm not sure that I would
want to increase my tendency to 'learn' from negative reinforcement except under specific, carefully-controlled conditions.
To your health!
AOR
Flood JF, Morley JE, Roberts E. 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.
Sih R, Morley JE, Kaiser FE, Herning M. Effects of pregnenolone on aging. J Investig Med. 1997 Sep;45(7):348A.
Morley JE, Unterman TG. Hormonal fountains of youth. J Lab Clin Med. 2000 May;135(5):364-6.
Morley JE, Unterman TG. Hormonal fountains of youth. J Lab Clin Med. 2000 May;135(5):364-6.
Meieran SE, Reus VI, Webster R, Shafton R, Wolkowitz OM. Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation. Psychoneuroendocrinology. 2004 May;29(4):486-500.
Edited by AORsupport, 20 April 2004 - 08:34 PM.
