Non-Opioid Medication May Reduce Pain

Novel, ‘Non-Habit Forming’ Medication May Reduce Low Back PainNancy A. Melville – Apr 2019

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

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.

I’m excited about this because pregnenolone is an over-the-counter supplement available to us all.

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,” lead investigator Jennifer Naylor, PhD, Durham Veterans Affairs Health Care System in North Carolina, told Medscape Medical News.

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.

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

Amid stepped-up efforts to treat pain with nonpharmacologic methods, the current researchers focused on the effects of pregnenolone in chronic low back pain.

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).

Patients who were currently taking opioids were excluded. While use of other medications were allowed, the regimens were required to have been stable for 4 weeks prior to study entry.

Other exclusions included epidural steroids, facet blocks, nerve blocks, or other invasive procedures to reduce low back pain in the 3 months prior to the start of the study.

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).

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).

There were no serious adverse events in either group.

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.

While pregnenolone is available over the counter, the researchers used a pharmaceutical-grade tablet formulation for the study.

“We know from our prior work that when we give patients pregnenolone in tablet form that it increases the levels of allopregnanolone by fivefold,” Naylor said.

This is certainly a powerful intervention if it can result in such dramatic changes.

“What’s really interesting about this is if we can determine whose blood levels of allopregnanolone are lower, we might be able to use pregnenolone to increase levels that might have been deficient to begin with,” she added.

This is an interesting idea: some people may be deficient in allopregnanolone, which would make them more pain-sensitive in general. I wonder if that could be part of my problem with pain.

Postpartum Depression Treatment?

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.”

Pregnenolone, meanwhile, currently does not have FDA approval for any indication, and Marx cautions that unregulated over-the-counter formulations are not recommended for the treatment of pain.

When so many doctors are no longer allowed to treat pain effectively with opioids, the recommendation to avoid potentially helpfulunregulated over-the-counter formulations” seems ridiculous in light of the desperate situation we’re in.

Concerns and Questions

Commenting on the findings for Medscape Medical News, David Craig, PharmD, clinical pharmacologist with the Moffitt Cancer Center, Tampa, Florida, said he agrees with the cautionary approach regarding pregnenolone, and noted several questions about the neurosteroid and its effects.

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.

When patients suffer pain every single day for years on end, are not allowed to use opioids, and then finally find something that eases it, they won’t care why it works.

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.

In addition to efficacy questions, Craig noted that more needs to be learned about longer-term safety effects.

What about the long term safety effects of all the “new” pharmaceutical non-opioid medications urged upon us, like the prescription gabapentoids (which pregnenolone may be related to)?

And, even more importantly, what about the “safety effects” of constant pain? (see Bodily Damage from Uncontrolled Chronic Pain for a long list)

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

7 thoughts on “Non-Opioid Medication May Reduce Pain

  1. Flutterby

    Personally, prednisone sucks ass at controlling pain (just from my personal standpoint). I’m wondering if pregnenlone is better tolerated because it’s closer to the endogenous form (allopregnenolone)? Plus, if they’re seeing more neuroprotective properties from pregnenlone, that would be a huge benefit vs gabapentinoids.

    Liked by 1 person

    1. Zyp Czyk Post author

      I started taking pregnenolone as a supplement and it seems to help my anxiety a little bit. My pain is so variable that it’s almost impossible to know whether it’s affected, but I haven’t had bad anxiety since I started taking it… of course, that could just be coincidence. So many times, I find something that seems to work for a while, and then it’s back to the same old symptoms :-(


      1. Flutterby

        Yup, especially as we age and our body chemistry changes. I’m so POed right now after my appointments today with the oncologist, who isn’t allowed to write prescriptions for opiates, and the social worker who can’t seem to get the rehab center that coordinates the housekeeping service but thinks therapy would be helpful, AND the palliative care doctor who has never had more that a damned stubbed toe! Omg, I was ready to scream by the time I left. And the cancer is already in my bones.

        Liked by 1 person

          1. Flutterby

            Well, let’s say enough pain meds. I was force tapered to half my original dosage of fentanyl March – May of last year, and I had just finished weaning off of the tramadol that I had been taking for 18 years when the cancer showed up. I got the a-ok from my primary care and they gave me a new prescription. Now they’re having trouble getting the prior approval for my hydromorphone, which was prescribed to take up the excess pain that the lack of fentanyl was causing. Oh, and the oncologist at the MGH Cancer Center at Cooley Dickinson hospital is FORBIDDEN from writing prescriptions for opioids, especially if patients come in already taking them.

            Another problem is that even though I told the palliate care doctor I was doing much better when taking the 100 mcg/hr patches, he wants to wait and see how much pain is the cancer pain before we mess with anything (I’m a rapid metabolizer – once upon a time up until February 2014, I was changing the patches every 48 hours, but oh no, we can’t be doing that anymore). He also understands that the reason for having the hydromorphone on board is because the patches are way too weak for my pain.

            Hopefully they can get this straightened the eff out because I hurt like hell and I can’t sleep laying down.

            Liked by 1 person

            1. Zyp Czyk Post author

              I find your matter-of-fact attitude astonishing – you sound so reasonable in a situation that would have me yelling and cursing and hating life. When even cancer pain is left untreated… its like they want you to find opioids on the street! I would have no idea how to do that, but desperation can make us very creative.

              I really, really hope the situation improves as the doctors get to know you better and realize you’re not just a “drug seeker” for kicks. Keeping my fingers crossed for you…

              Liked by 1 person

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