Posted by Tomatheus on December 23, 2005, at 2:28:05
In reply to Anyone have success with PREGNENOLONE?, posted by tecknohed on December 22, 2005, at 4:38:10
Tecknohed,
I experimented with pregnenolone when I was taking Wellbutrin and lithium, and I found it to have a moderate but relatively short-lasting antidepressant effect. Pregnenolone was one of dozens of supplements that I used to try to give myself a boost while on the Wellbutrin-lithium combo (I was partially responsive, but still struggled with depression to the extent that it was causing moderate - and occasionally severe - impairment in my daily activities), and it was one of the better supplements that I tried.
As far as my diagnosis and primary symptoms go, I have struggled with depression on an almost nonstop basis for the last six years. I was originally diagnosed with dysthymia, but I was rediagnosed as bipolar following the mood cycling I had in response to Paxil. Once I reached 60mg of Paxil, I basically cycled from mild hypomania to severe depression (with no euthymia in between) in "episodes" that lasted three to four days. Aside from that trial and a brief trial of Prozac, I've never had any (hypo)manic symptoms, not even while on non-SSRI antidepressants. The mood stabilizers I've taken so far have not been very helpful, but then again, even the non-SSRIs that I've taken have not done much to alleviate my depressive symptoms. I'm currently on Nardil monotherapy; I've been on it for 11 1/2 weeks, and I've been at 75mg for the last two weeks. I typically notice some slight improvement lasting for about two weeks after each dose increase, but other than that, I've basically felt mostly depressed while on the Nardil. I think I am finally getting some partial responsiveness on 75mg (that's not a result of the dose increase), but I'll see how it goes. So, there's my diagnostic and symptomatic explanation. I still prefer to look at it as an ongoing depression because that's the problem that I've struggled with both before meds and during most of my med trials (with the exception of some mild intermittent hypomania while on SSRIs), but feel free to look at it however you'd like.
At any rate, when I began experimenting with pregnenolone, I took one 50mg capsule daily. It boosted my mood and energy levels almost immediately, and the boost usually lasted for several hours (I would estimate 6-8 hours) or sometimes longer. On some occasions, it gave me enough of a boost that my depression was only slightly noticeable and caused virtually no functional impairment. When I tried sticking to this regimen daily, I seemed to develop a tolerance after several days (I think about five to seven, but I can't remember for sure; it was a while ago). After a while, I began rotating it with other supplements, taking it either alone or in combination with other supplements every few days. Basically, I just took as many supplements as I felt I needed every time moderate to severe depression was interfering with my ability to get crucial work done (remember that I was also still taking both Wellbutrin and lithium at the time). This turned out to be a disastrous way of managing my depression, and I wouldn't recommend it (especially in the long term), but that's another story. I did sometimes exceed the recommended pregnenolone dose of 50mg/day (I occasionally took two to three 50mg capsules a day on days when I felt extremely depressed), and it sometimes provided a better antidepressant effect without triggering hypomania or causing any other adverse effects. No matter how much pregnenolone I took, I didn't notice any feminizing hormonal effects (I'm a guy) or any other effects whatsoever other than an antidepressant effect.
As you may know, pregnenolone has reportedly been used with some success in treating memory problems, fatigue, and depression (Brownstein, 2004). It is known as a "mother hormone" because it is the precursor to all adrenal hormones, some of which include progesterone, DHEA, hydrocortisone, testosterone, and the estrogens (Brownstein, 2004). I actually think that there's a good possibility that pregnenolone "works" on depression by reducing MAO-A levels, possibly by increasing estrogen levels. This is really just a hypothesis of mine based on a little bit of research I've done, so please don't think I'm trying to pass my MAO-A idea off as an irrefutable fact. It is, however, one of several topics that I've sort of been researching and want to investigate further soon. So far, I have come across the abstract of one study that found that estrogen administration to rats (5mg/pellet) reduced MAO-A activity in the hypothalamus by 28 percent and in the amygdala by 21 percent (Holschneider et al., 1998). Another research article's abstract suggested that there is evidence that estrogens influence MAO levels (Chakravorty & Halbreich, 1997). Pregnenolone, like estrogen and the other adrenal hormones that are derived from pregnenolone, declines with age (Brownstein, 2004). Conversely, MAO-A levels increase with age (Hotamisligil & Breakfield, 1991). So, although the research I've done doesn't provide 100 percent conclusive evidence that pregnenolone exerts its antidepressant effects by reducing MAO-A levels (via estrogen), there is some evidence to support my hypothesis. Maybe there's even more, but I haven't really felt up to doing much research lately, unfortunately. Plus, I've got other things I've been putting off that I need to do, but that's enough rambling for me, at least for now.
I've read that you're taking Nardil (and I think you said you still are). Even though I haven't taken any supplements to try to augment Nardil (aside from melatonin, which worsened my depression), I don't think pregnenolone should pose a huge problem, as long as you go with the suggested dose. It may reduce MAO-A levels, but even if that is the case, remember that pregnenolone levels, estrogen levels, and even MAO-A levels vary from person to person. There is no specific MAOI warning on pregnenolone, but it does say to check with your doctor if you're taking prescription medications, so just take that info for what it's worth.
Tomatheus
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REFERENCES
Brownstein, D. (2004). Testimony on biologically identical hormone therapy: House subcommittee on human rights and wellness. Retrieved from http://reform.house.gov/UploadedFiles/brownstein%20testimony.pdf
Chakravorty, S. G., & Halbreich, U. (1997). The influence of estrogen on monoamine oxidase activity. Psychopharmacology Bulletin, 33, 229-33.
Holschneider, D. P., Kumazawa, T., Chen, K., & Shih, J. C. (1998). Tissue-specific effects of estrogen on monoamine oxidase A and B in the rat. Life Sciences, 63, 155-60.
Hotamisligil, G. S. & Breakfield, X. O. (1991). Human monoamine oxidase A gene determines levels of enzyme activity. American Journal of Human Genetics, 49, 383-92.
poster:Tomatheus
thread:591213
URL: http://www.dr-bob.org/babble/alter/20051208/msgs/591510.html