Neurosteroids for Anxiety Disorders

Neuroactive Steroid Levels in Patients With Generalized Anxiety DisorderThe Journal of Neuropsychiatry and Clinical Neurosciences – 2001

Anxiety isn’t just a state of mind, it’ s physical state of the body too.

Several neurotransmittersystems have been suspected to play a role in the pathophysiology of GAD [generalized anxiety disorder].  Various lines of research suggest dysregulation of the gamma-aminobutyric acid (GABA A )/ benzodiazepine (BZ) receptor complex.

These findings include decreased numbers and sensitivities of BZ receptors in patients with GAD and successful pharmacologic treatment of GAD with agents that target the GABA A / BZ receptor (e.g., benzodiazepines).  

But if you have pain severe enough to be on opioid therapy, you are not allowed to take benzodiazepines (like Ativan, Xanax, Valium).

Dealing with the disability brought on by chronic pain and the inability to earn a living, having to give up many previously pleasurable activities, and becoming socially isolated by lack of ability to participate in group activities IS anxiety-producing.

So it’s ironic that the most effective medication to tame that anxiety is forbidden to us.

A number of compounds termed neuroactive steroids (NAS) that have intrinsic activity on the GABA A / BZ receptor have been characterized. 

These compounds include the

  • progesterone metabolite 5-pregnan-3-ol-20-one (allopregnanolone; ALLO),
  • pregnenolone sulfate (PREGS), and
  • dehydroepiandrosterone sulfate (DHEAS).

In animal models, positive allosteric GABA A receptor modulators such as ALLO display anxiolytic activity, whereas negative GABA A allosteric modulators such as DHEAS may exhibit anxiogenic activity.

The aim of this study was to compare serum levels of ALLO, PREGS, and DHEAS between healthy control subjects and medication-free patients with GAD and no other concurrent psychiatric diagnosis.


Subjects: Eight male patients with GAD and eight healthy male control subjects.


  • The average level of ALLO in patients with GAD (3.780.92 ng/ml) was lower compared with control subjects (9.919.27 ng/ml) but did not reach statistical significance
  • Levels of PREGS were significantly lower in patients than in control subjects
  • There was no significant difference in the levels of DHEAS between patients and control subjects

Both pregnenolone sulfate (PREGS), and dehydroepiandrosterone sulfate (DHEAS) are available OTC.

I take both and get them from, but the usual caveats about uncontrolled supplements hold: you can’t be sure if you’re getting what’s on the label.


The finding of statistically significant lower levels of PREGS in patients with GAD is consistent with in vitro binding experiments, which found PREGS to act as an agonist on the GABA A receptor at low concentrations, and with in vivo experiments, which found that intraperitoneal administration of low-dose PREGS to mice can lead to a reduction of anxiety.

And it’s not just for mice.

The reason you’ve seen so many posts about neurosteroids lately is that I’m investigating ways to ease my constant low-level anxiety and prevent episodes of crippling fear.

From the information I found, I thought pregnenolone was worth a try. I’m especially enthusiastic about anything I can do myself, or at least without a prescription.

So I started taking 300mg pregnenolone (or at least that’s what the label says) every day, first thing in the morning on an empty stomach, on July 19 this year. It’s been almost 4 months and I haven’t had a serious anxiety attack since then. That’s a good sign, so I remain hopeful.

I still have days with that familiar tension and knot under my sternum, but I can keep my balance if I just don’t let myself think about anything too “real” in my life.

However, in those experiments it was also noted that PREGS could act as a GABA A receptor antagonist and functional anxiogenic agent at higher doses.

Although the lower level of ALLO in patients was only statistically suggestive, the direction of the results would indicate a decrease in an endogenous anxiolytic agent and lower agonist activity at the level of the GABA A /BZ receptor in patients with GAD.

The clinical relevance of our results is supported by findings of abnormal cerebral spinal fluid (CSF) and serum levels of NAS in patients with major depressive disorder .

It has been observed that selective serotonin reuptake inhibitors (SSRIs) normalized these abnormal NAS levels, possibly by altering the kinetics of enzymes involved in NAS metabolism.  On the basis of preliminary reports on the efficacy of SSRIs in GAD, we suggest, and are currently testing the hypothesis, that treatment with SSRIs normalizes NAS levels in GAD patients.

The relevance of plasma levels of neurochemicals to central nervous system activity is always difficult to determine. It has been shown, however, that PREGS crosses the blood–brain barrier, a finding that supports the clinical relevance of plasma PREGS alterations.

our findings are suggestive of different levels of certain neuroactive steroids in patients with GAD. These findings will require confirmation in a larger study.

6 thoughts on “Neurosteroids for Anxiety Disorders

  1. Erin

    I take this too but at much, much, much lower levels. I only take 10 mg daily. I’m curious if maybe you meant to say 30 Mg? It does help but can have some serious trade offs. Liver problems, increased cancer risks if it your family has a history of specific types of cancer. So I’m trying to keep my dosage a bit lower.

    Liked by 1 person

      1. Zyp Czyk Post author

        I think you might be confusing pregnenolone with prednisone, which is a corticosteroid (not neurosteroid). That “steroid” has entirely different functions and has terrible side effects when taken in high doses consistently.

        I also didn’t understand the different classes of steroids (which also include anabolic and catabolic steroids) but I’ve learned there’s a huge difference between those groups.

        I appreciate your concern for my wellbeing!


    1. Zyp Czyk Post author

      In my desperation, I do take 300 daily and if I’m feeling really awful, even 500.

      I assume it’s safe because the study used 500mg of “medicinal grade” pregnenolone and I figure the unregulated OTC supplements would be much weaker, even if they supposedly contain 500mg.

      I haven’t looked into safety, mainly because my depression/anxiety gets so persistently bad I want to kill myself. But now that you’ve made me aware of this downside…

      I really feel that I wasn’t biologically designed properly to survive, so I tend to grasp for any solution that works now, and worry about the long term only if I can even foresee myself surviving long term.


  2. leejcaroll

    why cant you take those meds with the pain meds? I also wonder about the effects of neurosteroids. Not sure if have same action but when I am on steroids, low dose for short time I become the green hornet or whoever he is that is mildmannered and then within seconds amass of anger and strength Got so mad one time at a lady in bank forget what she was doing I actually called over the security guard so I would make sure I didnt follow thru on the feeling that I may need to hit her, Never felt that way before absent the steroid.

    Liked by 1 person

    1. Zyp Czyk Post author

      I’m so grateful for your concern – it’s so kind of you to care about my health.

      I think you’re confusing pregnenolone with prednisone, which is a corticosteroid. Neurosteroids are hormones like estrogen, progesterone, testosterone, and DHEA (which I also take).

      Occasionally I take 5mg of prednisone before bed, after days of activity that I know will result in a huge inflammatory response the next day. It helps tremendously in that role, but I know not to take it too often because that steroid truly is harmful.

      It also gives me energy along with pain relief, so I wish I could take it all the time, but it’s literally too good to be true. I know the long term side effects are awful, so I save it to prevent only the worst days of pain.

      Your hugs are appreciated!



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