Supplementary Neurosteroid May Reduce Pain

Novel, ‘Non-Habit Forming’ Medication May Reduce Low Back PainNancy A. Melville – Apr 2019  [It’s actually a supplement, not a “medication”.]

A novel, “non-habit-forming” neurosteroid appears to be effective and well tolerated in the treatment of chronic low back pain, new research suggests.

I’ve been exploring the benefits of supplementary neurosteroids for a while, but mainly as a remedy for my chronic anxiety. I’m thrilled to learn they could also ease pain a little.

In a double-blind, randomized controlled trial of almost 100 Iraq/Afghanistan-era veterans, those treated with a pharmaceutical-grade tablet formulation of pregnenolone showed “significant and meaningful reductions” in low back pain intensity ratings at 6 weeks compared with their peers who received matching placebo, investigators report.  

The active treatment group also showed greater reductions than the placebo group in two pain-interference domains.

In addition, “those who were randomized to the pregnenolone group had a 2.6-times greater likelihood of obtaining a 20% reduction in their pain,”

That sounds at least as good as many of the new fancy and outrageously expensive pharmaceuticals.

Anti-inflammatory Properties

The research team at Duke University Medical Center and the Durham VA Medical Center in North Carolina have been exploring biomarkers of posttraumatic stress disorder (PTSD) among Iraq and Afghanistan veterans.

They previously showed that serum levels of allopregnanolone, an endogenous progesterone metabolite and downstream metabolite of pregnenolone, were inversely associated with symptoms of depression, anxiety, and low back pain.

I’ve been taking 300mg of OTC pregnenolone daily for over a month and so far it seems to be keeping my anxiety down to tolerable levels.

But this is after years of effort to mentally reduce/redirect my anxiety, so it’s “tolerable” only because I’ve trained myself to control my thoughts. I still need a little more help when that inner biochemical “panic button” is constantly being pushed.

I haven’t had an “anxiety meltdown” since I started taking it, and if it’s useful for my pain as well, that would be a double bonus.

Subsequent research has linked allopregnanolone, a positive allosteric modulator of gamma-aminobutyric acid-A (GABAA) receptors, with analgesic and anti-inflammatory and neurotrophic properties.

Investigators enrolled 94 Iraq or Afghanistan-era veterans (90% male) in the 6-week study, which included a 4-week treatment period. The participants were randomly assigned to fixed escalation of pregnenolone up to 500 mg per day (n = 45) or to matching placebo (n = 49).

Significant improvements with pregnenolone vs placebo were also shown in pain interference scores during normal work (P = .040) and general activity (P = .031).

In addition,

  • 51.2% of those in the pregnenolone group reported having at least a 20% improvement in pain symptoms
  • compared with 28.6% of those in the placebo group (odds ratio, 2.62).

These aren’t miraculous drugs for pain, but they’re still available OTC from health food stores. Having access to this supplement without having to beg a doctor for it is a huge plus these days.

New Pain Intervention?

The primary outcome was average pain intensity ratings from a daily pain diary in which 24-hour average pain severity scores were recorded on an 11-point Likert score.

Those who received pregnenolone showed significantly greater reductions in low back pain compared with placebo on pain diary scores (P = .024) and pain recall (P = .010).

Pregnenolone may thus represent a new intervention for pain conditions that is safe, well-tolerated, non-habit-forming, and potentially efficacious for the alleviation of pain symptoms,” the investigators note.

Allopregnanolone does many different things in the brain. It is possible that its GABAA receptor activity is an important contributing mechanism of action, as well as its anti-inflammatory effects,” she said. “


Allopregnanolone also enhances neurogenesis, and it is neuroprotective in a number of animal models.”

This sounds like a much more promising avenue than the “nerve growth factor inhibitors” they are trying to develop as profitable pharmaceuticals.

Given a choice, I much prefer drugs/supplements that “enhance neurogenesis” rather than those that are “growth factor inhibitors”. This just seems like simple common sense.

Pregnenolone was custom-synthesized to meet FDA standards for purity for this study. Over-the-counter formulations of pregnenolone are not required to meet this standard,” she said.

Dietary supplements sold over-the-counter are generally not pharmaceutical-grade, and they are not infrequently contaminated with other products that are not listed on the label,” Marx added. Therefore, “over-the-counter use of pregnenolone is not recommended.”

While these concerns are valid, they assume pharmaceutical products are different and we’ve recently seen just how adulterated, defective many generic drugs are as well.

David Craig, PharmD, clinical pharmacologist said, “Clearly there was a noticeable difference between pain intensity in the pregnenolone group versus the placebo group, but why was there a difference is the real question,” said Craig, who was not involved with the research.

These days, I doubt pain patients care much about “how” a possible supplement can help their pain. When the alternative is unrelieved suffering, we’ll take anything we can get and worry about the aftereffects later. And if we notice them at all we may still decide that the “cost-benefit” of side effects versus pain relief makes it worth it.

“It would be interesting to see the researchers conduct another prospective study looking at prednisone versus pregnenolone versus placebo, which could answer the question of whether the pregnenolone is acting as a ‘natural’ anti-inflammatory agent to reduce back pain,” he said.

“I think the intervention they used is interesting and potentially innovative, but I have concerns about the acute/chronic use of pregnenolone, as much of what it is and does in the human body is unknown,” he said.

Strange that they never express such concerns over the acute/chronic use of pharmaceuticals, even though much of what they do in the human body is unknown as well.

But without the profit motive, criticism becomes more honest.

“I have concerns about using OTC products that are potentially unpure, unsafe, and lack studies to support their efficacy,” he said.

Well, I have concerns about using all the generic and even some branded prescription drugs these days. I’ve previously posted articles that show how corrupt the practices are in the countries that provide most of our raw ingredients for medications:

American Pain Society (APS) 2019: Abstract 274. Presented April 5, 2019.

2 thoughts on “Supplementary Neurosteroid May Reduce Pain

  1. GZB

    You are so right, patients are willing to try anything that would possibly help relieve the unrelenting torture that is chronic pain. I was asked recently by an anti opioid do gooder if I would be willing to give up opioids if another option presented itself. My answer was that I didn’t care if they were made of green beans! How do we drive this point home ?
    I’m scheduled for another spinal steroid session. Does this crap not prove that we are only seeking some relief?

    Liked by 1 person


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