Pregnenolone Relieves Chronic Low Back Pain (human Study)

haidut

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After failing to find any effective treatments for the many ills that plague veterans, doctors are finally turning to older remedies successfully used back in the first half of the 20th century. Pregnenolone is one such remedy and I have been seeing more and more studies and ongoing trials with it for variety of conditions ranging from depression, to PTSD, to "addiction", to autism.
The study below showed that pregnenolone relieved chronic low back pain in military veterans. The protocol used was the same as the one for humans with schizophrenia and reached a maximum of 500mg daily in two doses during the last week. Pregnenolone administration raised serum levels of neurosteroids like allopregnanolone known to have anesthetic effects and this is the proposed mechanism the authors propose as explanation for pregnenolone's benefits.
Peat said a few times that chronic low back pain is linked to endotoxin and some of the neurosteroids derived from pregnenolone such as allopregnanolone, progesterone and 5a-DHP have known anti-endotoxin effects by blocking the 5-HT3 receptor. I think that may be the real mechanism of action, but regardless of the proposed explanation I am glad that mainstream medicine is finally starting to recognize pregnenolone's promise as a safe treatment for chronic conditions.

New Drug Discoveries Aim to Help Veterans, Others With Chronic Pain
"...Pregnenolone is a neurosteroid, which are endogenous molecules enriched in the brain, she said. They are synthesized de novo from cholesterol and are produced in the adrenal glands, gonads, and other peripheral tissues. They are neuroactive and and have pain-relieving properties. They are modulators of GABAAreceptors (proteins that were revealed as the potential target of a post-partum depression treatment a decade ago in experiments with mice) and NMDA receptors and others. They have at least 7 properties relevant to pain relief, as they are potentially neuroprotective, anxiolytic, anticonvulsant, antidepressant, anti-inflammatory, anti-apoptotic (protecting the nerves), and have anti-aggression properties. The study enrolled 41 veterans in a treatment group taking pregnenolone, and 41 in the placebo group. The primary endpoint was the mean weekly pain rating scales averaged from daily pain diaries. Neurosteroids and other small molecules were taken via blood samples. The dosage of pregnenolone for those in the treatment group was 50 mg twice a day for 1 week, then 150 mg twice a day for 1 week, then 250 mg twice a day for 2 weeks. The pregnenolone group did significantly better than the placebo group, with a 20% reduction in pain versus a 4% reduction in the placebo group. In addition, their low back pain ratings were inversely related with serum neurosteroid levels, suggesting that their lack of those neurosteroids could have been contributing to their pain. Additionally, they had reduced levels of pain interfering in work and activity."
 

Tarmander

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Lower back pain for me was always associated with Kidney distress. Preg being anti stress probably helping in that regard.
 

Mito

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Is the blood level of pregnenalone meaningful? If so what is an optimal blood level? The lab reference ranges vary (Lab Corp < 151 ng/dL, Mayo Clinic 33-248 ng/dL, Quest Labs 10-200 ng/dL).
 

x-ray peat

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what about back pain from a specific injury, like picking something up wrong. Is that still endotoxin related?
 

SOMO

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I actually had a really painful lower-back the past few days due to over-exercising + bad posture + housework/cleaning + taking care of elderly family members/other family stress.

Pain level was a 7 for last 2 days and getting worse.
I don't even get lower back pain normally, but I simply had the right blend of stressors to cause lower back pain this week.

It was getting sort of serious, I considered going to the chiropractor. Instead, I took 300g pregnenolone spaced throughout the day + applied a heating pad for 2 hours (simply laid on it and took a nap) and it was all gone by time I woke up.


I didn't even have Aspirin this week since I ran out a while ago. I think Aspirin's anti-inflammatory effect can be potent enough so that you don't notice physical exertion/muscle soreness as much when you exercise and you can push yourself too hard (which is what I did, which set me up for lower back pain for the rest of the week.) Over-exercising is a real thing.

N=1 anecdote, but I think pregnenolone + heat helped me with my soreness issues.
 
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haidut

haidut

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Is the blood level of pregnenalone meaningful? If so what is an optimal blood level? The lab reference ranges vary (Lab Corp < 151 ng/dL, Mayo Clinic 33-248 ng/dL, Quest Labs 10-200 ng/dL).

It is meaningful only in the sense that it shows adrenals are working well and releasing it (i.e. no Addison disease). I don't think it reflects tissue levels and beyound the age of 35 probably everybody can use a little extra to protect from stress.
 
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haidut

haidut

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what about back pain from a specific injury, like picking something up wrong. Is that still endotoxin related?

In that case probably not, but if the pregnenolone metabolites are indeed responsible for the pain relief then it should help in that case too.
 
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haidut

haidut

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I actually had a really painful lower-back the past few days due to over-exercising + bad posture + housework/cleaning + taking care of elderly family members/other family stress.

Pain level was a 7 for last 2 days and getting worse.
I don't even get lower back pain normally, but I simply had the right blend of stressors to cause lower back pain this week.

It was getting sort of serious, I considered going to the chiropractor. Instead, I took 300g pregnenolone spaced throughout the day + applied a heating pad for 2 hours (simply laid on it and took a nap) and it was all gone by time I woke up.


I didn't even have Aspirin this week since I ran out a while ago. I think Aspirin's anti-inflammatory effect can be potent enough so that you don't notice physical exertion/muscle soreness as much when you exercise and you can push yourself too hard (which is what I did, which set me up for lower back pain for the rest of the week.) Over-exercising is a real thing.

N=1 anecdote, but I think pregnenolone + heat helped me with my soreness issues.

Very interesting. You meant 300mg, not 300g, right? Did you use 100mg x 3 daily or did you break down in even smaller doses?
 

aguilaroja

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...
Peat said a few times that chronic low back pain is linked to endotoxin and some of the neurosteroids derived from pregnenolone such as allopregnanolone, progesterone and 5a-DHP have known anti-endotoxin effects by blocking the 5-HT3 receptor. I think that may be the real mechanism of action, but regardless of the proposed explanation I am glad that mainstream medicine is finally starting to recognize pregnenolone's promise as a safe treatment for chronic conditions.

New Drug Discoveries Aim to Help Veterans, Others With Chronic Pain
"...Pregnenolone is a neurosteroid...endogenous molecules enriched in the brain,...They are neuroactive and and have pain-relieving properties...They have at least 7 properties relevant to pain relief, as they are potentially neuroprotective, anxiolytic, anticonvulsant, antidepressant, anti-inflammatory, anti-apoptotic (protecting the nerves), and have anti-aggression properties. ...

Thanks @haidut. The study does not appear to have been published yet. I wonder what the rationale was for titrating up amount of pregnenolone. Perhaps it was fear of side effects.

AFAIK little has been done in looking at depleted metabolism as a main factor in chronic pain. As Dr. Peat reminds us, “Life is good for you.” Naylor does work in psychiatric “translation neuroscience.” The findings (outside this forum, not necessarily from Dr. Naylor) may be viewed through the filter that chronic pain is a psychiatric issue.
 
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haidut

haidut

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Thanks @haidut. The study does not appear to have been published yet. I wonder what the rationale was for titrating up amount of pregnenolone. Perhaps it was fear of side effects.

AFAIK little has been done in looking at depleted metabolism as a main factor in chronic pain. As Dr. Peat reminds us, “Life is good for you.” Naylor does work in psychiatric “translation neuroscience.” The findings (outside this forum, not necessarily from Dr. Naylor) may be viewed through the filter that chronic pain is a psychiatric issue.

Good points.
The titration protocol is a direct copy of the human studies with schizophrenia and autism. I guess they believe that 500mg daily doses are needed to elicit the increase in allopregnanolone needed for anesthetic effects, but that view is mistaken IMO since human doses with even 25mg progesterone showed robust elevations of 5a-DHP and allopregnanolone. In addition, lower doses of pregnenolone convert more easily into downstream steroids since higher doses tend to inhibit 3b-HSD as a form of negative feedback mechanism (as I posted in other threads). Optimal doses of pregnenolone in other human studies for mental illness and autism were found to be in 30mg-50mg daily range and one of the depression studies also had a group using 200mg-300mg daily and that group so no benefit. Given the high correlation between depression and chronic pain, as you pointed out, I would venture a guess that whatever (30mg-50mg pregnenolone dose) works better for depression should work better for pain too, but that remains to be tested.
 

aguilaroja

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Good points.
The titration protocol is a direct copy of the human studies with schizophrenia and autism. I guess they believe that 500mg daily doses are needed to elicit the increase in allopregnanolone needed for anesthetic effects
....I would venture a guess that whatever (30mg-50mg pregnenolone dose) works better for depression should work better for pain too, but that remains to be tested.

Thanks @haidut. I did not make the link with the previous research protocol, and await publishing of the Naylor result. Possibly there is also some “quantity bias” when clinician/researchers approach conditions that respond poorly to pharmaceuticals. How could relatively small amounts of bio-identical substances help when major pharmaceuticals are impotent?

Peter Himmel, M.D. did “pilot” work with pregnenolone & DHEA in the late 1990’s. I do not have the pregnenolone result handy, but recall the daily dosing was on the lower end. His work received attention only in the nutrition community. AFAIK he moved on to other work and received no further funding/encouragement for the metabolic support, despite significant success for difficult diagnoses.

A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome. - PubMed - NCBI
“Supplementation with DHEA to CFS patients lead to a significant reduction in the symptoms of CFS: pain (improved by 18%, p = 0.035), fatigue (decreased by 21%, p = 0.009)), activities of daily living (improved by 8.5%, p = 0.058), helplessness (decreased by 11%, p = 0.015), anxiety (decreased by 35%, p < 0.01), thinking (improved by 26%, p < 0.01), memory (improved by 17%, p < 0.05), and sexual problems (improved by 22%, p = 0.06) over the period of the trial.”
 
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haidut

haidut

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Thanks @haidut. I did not make the link with the previous research protocol, and await publishing of the Naylor result. Possibly there is also some “quantity bias” when clinician/researchers approach conditions that respond poorly to pharmaceuticals. How could relatively small amounts of bio-identical substances help when major pharmaceuticals are impotent?

Peter Himmel, M.D. did “pilot” work with pregnenolone & DHEA in the late 1990’s. I do not have the pregnenolone result handy, but recall the daily dosing was on the lower end. His work received attention only in the nutrition community. AFAIK he moved on to other work and received no further funding/encouragement for the metabolic support, despite significant success for difficult diagnoses.

A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome. - PubMed - NCBI
“Supplementation with DHEA to CFS patients lead to a significant reduction in the symptoms of CFS: pain (improved by 18%, p = 0.035), fatigue (decreased by 21%, p = 0.009)), activities of daily living (improved by 8.5%, p = 0.058), helplessness (decreased by 11%, p = 0.015), anxiety (decreased by 35%, p < 0.01), thinking (improved by 26%, p < 0.01), memory (improved by 17%, p < 0.05), and sexual problems (improved by 22%, p = 0.06) over the period of the trial.”

That's very interesting! This seems to be the only study by him on PubMed. If you find any of his results with pregnenolone please send over.
 

Soren

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Does anyone have any thoughts whether or not topical application of Pregnenolone or Progesterone would have a similar or possibly even a superior effect in combating lower back pain?
 

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