Reducing Sedative and Addictive Side Effects of Anti-Anxiety Drugs Benzodiazepines (Xanax, Valium, etc.) with L-Theanine, Pregnenolone, and DHEA

One of the mainstay drug families that doctors prescribe for patients with anxiety are a class of GABA receptor drugs called benzodiazepines. For people who are using these drugs to get to sleep, a strong sedative effect may be helpful. But if you are trying to counter conditions such as panic attacks, PTSD, and high arousal from stress inducing situations while you are awake, the sedative effects may be a big problem. They are one of the main reasons why these drugs carry warning labels regarding operating heavy machinery.

The sedative effects can leave a person in a drugged-up “sleepy and stupid” state in which it is better they not drive. Some people have to modify their schedules and activities because of the adverse effect that the sedation can have on their ability to do mentally complicated tasks such as those involved in many professions. Such dilemmas are particularly a problem for the many patients who are advised to use higher and higher dosages as they build up tolerance to these drugs and may have to take them all day long to avoid suffering major anxiety attacks.

Fortunately there are some supplement available that can counteract anxiety and can reduce the need for benzodiazepines. For many, they may help keep the daily dosages of benzodiazepines lower than they otherwise would be. Some may find they no longer need benzodiazepines except during very high-stress situations on an infrequent basis. That’s a big win because the addiction potential for this class of drugs is huge.

L-Theanine Works Similarly To Benzodiazepines But Without Sedation and Addition Side Effects

As I’ve discussed previously, there are some great options for anxiolytic (anti-anxiety) therapy that can be found in natural supplements. My article L-Theanine for Anxiety, Insomnia, and Depression discusses some of the very helpful properties and research findings regarding the tea extract L-Theanine, an amino acid which also helps favorably modulate the GABA response in the body to reduce anxiety but without the sedation and tolerance side effects common to benzodiazepines. The tolerance problem is a major one as it leads many long-term users of benzodiazepines to become physiologically addicted to them. That article also discusses several other promising supplements with similar beneficial anti-anxiety effects on the GABA receptors in the brain.

Pregnenolone Reduces Anxiety and Benzodiazepine Sedative Side Effects

It turns out that the human hormone pregnenolone has a big impact on anxiety. I’ll highlight findings from three studies that illustrate that pregnenolone supplements can help in treatment of anxiety conditions and that low pregnenolone is suspected as a contributing factor in anxiety disorders.

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One study entitled Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation shows that pregnenolone appears to significantly counteract the sedative effects of diazepam (Valium). This means it likely also will counter those effects with benzodiazepine medications in general since the varying types work by the same mechanism. In this 2004 study by the University of California San Francisco (UCSF) School of Medicine, researchers experimented in a group of 17 volunteers using small dosages of pregnenolone at 15 mg for two weeks followed by 30 mg per day for two weeks. The same group also was treated with a placebo for four weeks with a “washout period” of four weeks between experiments to allow hormone levels to return to normal. The study group patients used the benzodiazepine drug diazepam (Valium) to treat their anxiety.

The researchers found that there was a strong effect of the pregnenolone on reducing the sedative effect and a smaller effect at reducing the amnestic (memory-impairing) effect. Anxiety control was unaffected, meaning the diazepam worked about the same with or without pregnenolone in terms of its effects on perceived anxiety.

At 15 mg to 30 mg per day, the dosages used in this study are quite small for most people. Many people who supplements with hormones to restore them to optimal levels are using 50 mg of 100 mg of pregnenolone per day. Some people may need upwards of 200 mg per day of pregnenolone supplements to achieve optimal levels of the hormone. Body mass and general health certainly have an effect on this and might help some make a good guess at an initial dosage, but blood tests to monitor the effects are the best way to adjust dosage.

Low Pregnenolone Levels in Patients with Anxiety Disorders

A study by the University of Alberta entitled Low pregnenolone sulphate plasma concentrations in patients with generalized social phobia found that male patients with generalized anxiety disorder or generalized social phobia, both of which are conditions for which benzodiazepines are often prescribed, had markedly lower blood levels of pregnenolone.

This finding suggests that people suffering from chronic anxiety should get their pregnenolone hormone level checked to see if they may be suffering from an easily and inexpensively treated hormone deficiency that could be worsening their anxiety. How easy and cheap? If you shop around, you can typically find that a dosage of 50 mg of pregnenolone per day can easy be had for less than $3 per month. I’ve used Swanson Health Products and Life Extension supplements containing pregnenolone myself and found them to be inexpensive and effective for boosting pregnenolone levels as shown by blood test results.

High-Anxiety Schizophrenia Patients Have Lower Pregnenolone

Another study tying low pregnenolone to aggravated anxiety was run by Israeli researchers comparing healthy control subjects to patients with schizophrenia. In their study Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects, they measured pregnenolone and DHEA levels via blood tests. They found that schizophrenia patients tend to have lower pregnenolone and somewhat higher DHEA levels than control patients. What is most interesting, however, is that they observed a strong correlation between high levels of anxiety and low levels of pregnenolone in the schizophrenia patients.

How Might I Use Pregnenolone for My Anxiety?

Combined with the previously study and how low pregnenolone levels are relatively common, a good approach for people with anxiety problems may be to start a small dosage around 10 mg to 50 mg per day of pregnenolone before or in conjunction with any other anti-anxiety treatment and then to check the pregenolone levels in their blood after a couple of months. Then adjust the dosage upwards or downwards depending upon the levels founds and the effect being observed. Life Extension’s guidance on optimal hormone levels is that both men and women do best with pregnenolone levels between 100 to 170 nanograms/dL.

As with several other hormones (notably progesterone, often used in medication for women), pregnenolone has the potential to be converted into cortisol which could keep you awake at night. Some people notice this effect, others do not. One thing you can do to help with this if it happens to you is to take the pregnenolone in the morning.

Another step is to add DHEA supplements as they are known to help mitigate the stress-related effects of cortisol and appear to be beneficial for most people with low, normal, high, or inconsistent cortisol levels. Starting with a 25 mg per day dosage would be conservative. There are many studies of DHEA usage at 50 mg or higher dosages for long terms in patients with depression or other health conditions that show DHEA is very beneficial and the side effect risks are small.

Abnormal Hormone Levels May Worsen Anxiety

Levels of sex hormones such as pregnenolone, DHEA, and testosterone are also well known to drop drastically starting in most people by the time they reach age 30. It is well known from vast quantities of medical research that aging humans tend to have lower levels of these sex hormones and that supplementing with them exerts a protective effect on the brain and other organs. Thus it is quite common for those interested in optimal health and lifespan to get their sex hormone levels tested via blood tests and to supplement to restore them to youthful levels.

As you may know, pregnenolone can be converted in the body into DHEA. Thus it’s possible that a person may need to supplement with both pregnenolone and DHEA to get low levels of pregnenolone corrected. Otherwise, the body may simply convert more of the newly available pregnenolone from the supplements into more DHEA to shore up low levels of that hormone. While that would probably still be beneficial for nearly everybody, it’s best to have healthy levels of both hormones. To get a better understanding of the ways the body can convert many important hormones from one to another, there is a helpful chart showing how the human body converts steroid hormones between different forms.

DHEA is believed to also have an anti-anxiety effect and to help fight depression, but the mechanisms may be different from pregnenolone. DHEA is often discussed as having an “anti-cortisol” effect by blunting the stress response caused by elevated levels of the hormone cortisol. With some “anti-cortisol” drugs and supplements, you have to be cautious because they can make matters worse for people who have low cortisol levels. DHEA appears to be beneficial for most people regardless of their cortisol levels and in fact is often recommended for people with low or high cortisol or no cortisol problem at all.

High cortisol levels are common in people with chronic stress conditions. When they are not treated to get them under control, often people will ultimately suffer from damaged adrenal glands overworked by pumping out so much cortisol for so long. Then their cortisol levels crash and they develop symptoms of illnesses such as chronic fatigue syndrome (CFS), fibromyalgia (FMS), adrenal fatigue, and PTSD (post-traumatic stress disorder). Long-term elevations of cortisol from high stress can also damage the brain as discussed in Chronic Stress Kills: High Cortisol Levels Damage the Brain, May Lead to Shorter Life and Neurodegenerative Diseases Such As Alzheimer’s and Parkinson’s.

People who have progressed to severe cortisol deficiency due to long term stress and anxiety or other taxing conditions that damaged the adrenal glands may be especially likely to suffer pregnenolone deficiency because pregnenolone is one of the hormone precursors for cortisol. Many people who are advised to take cortisol replacement therapies such as IsoCort or hydrocortisone would probably also benefit from supplemental pregnenolone.

In one case of severe cortisol deficiency of which I’m aware, even 200 mg per day of supplemental pregnenolone was still not enough to get the measured blood level up to the optimal range from 100 to 170 nanograms/dL. Therefore I suspect that some people suffering from low cortisol related medical conditions could need even 300 mg or more per day of pregnenolone plus cortisol supplementation to attain optimal levels of pregnenolone and cortisol.

More Benefits of Pregnenolone and DHEA

Even in people without anxiety problems, there are many studies that show pregnenolone and DHEA supplementation are beneficial to health. In 2010 alone there were about 380 published research papers on DHEA, so the amount of research in this area is way too much to cover in this short article. I’d suggest you read Enhancing Cognitive Function with Pregnenolone and
Why DHEA May Be the Best-Validated Anti-Aging Supplement for more information.

Best to Get All Sex Hormones Tested

Anybody following a long-term hormone supplementation program should get all of their sex hormones checked periodically, at least once per year. Pregnenolone and DHEA can convert into testosterone, DHT, estradiol, and other estrogens. Some people, particularly overweight men, suffer from low levels of pregnenolone, DHEA, and testosterone but very high estradiol and other estrogens. Pregnenolone and DHEA supplementation could in theory worsen the high levels of estrogens unless other supplements (DIM, I3C, etc.) or medicines (aromatase inhibitors such as Arimidex) are used to prevent the conversion of testosterone into estradiol.

If you’re overweight, don’t assume that you have an estrogen problem even though that is really common especially for men in their 40’s and older. High stress leading to high levels of cortisol can also trigger weight gain even in people with healthy estrogen levels.

A good place to start to learn about comprehensive hormone testing for men and women is the Life Extension article Male and Female Hormone Testing: An Underutilized Tool for Maintaining Optimal Health.

Men and women have very different hormone profiles. Two good references to understand more about hormone restoration using supplements and medicines with routine monitoring via blood tests are the articles Female Hormone Restoration and Male Hormone Restoration.

A great reference for understanding blood test results in general with optimal ranges listed for many hormones is the article Blood Testing Protocols. For DHEA, it recommends an optimal level of 500 to 600 micrograms/dL for men and 250 to 380 micrograms/dL for women. For pregenolone, it recommends 100 to 170 nanograms/dL for men and women. The list also includes recommended ranges for many other test results, so be sure to consult it when you look over your own blood test results.

Cancer Patients Be Extra Cautious About Hormone Replacement Programs

Some hormone-dependent cancers could be worsened by elevated levels of certain hormones, particularly estrogen (e.g., certain breast cancers) and DHT (e.g., certain prostate cancers). If you suspect or know that you may have cancer, certainly don’t start any kind of hormone supplementation program without discussing it with your doctor and getting hormone blood tests. Many cancers are not hormone sensitive, but there is no general rule of thumb when it comes to breast and prostate cancers become some are and some are not.

Since pregnenolone and DHEA can convert into estrogen and DHT, there is at least a theoretical basis for elevated cancer risk in people who already have hormone-sensitive tumors. However, it appears that to date there is no research showing that pregnenolone or DHEA supplementation raises the risk for cancer in general.

Overall, supplementation with pregnenolone and DHEA is very safe for most people. But you may run across a lot of warnings that worry you. Some governments like to force warning labels or even bans on these hormones because of overly alarmist fears about them. Please read State of California Decrees Strong Warning Labels on DHEA and Pregnenolone for more details about the truth behind the hyped-up paranoia being fueled by government. Many government health care policies are designed to reward big pharma lobbyists by helping to push expensive, profitable, and dangerous drugs over what are usually much less expensive and much safer hormones and supplements. It’s my belief that is one of the major factors behind the governmental alarmism over these hormones despite solid research showing they are highly beneficial and have very little risk when used appropriately.

Further Reading

L-Theanine for Anxiety, Insomnia, and Depression

Chronic Stress Kills: High Cortisol Levels Damage the Brain, May Lead to Shorter Life and Neurodegenerative Diseases Such As Alzheimer’s and Parkinson’s

Tired All the Time for Months or Years? Here’s A Resource With Many Possible Explanations.

Depressed But Antidepressants Don’t Work? Adrenal Fatigue or Neurotransmitter Imbalances May Be Responsible.

Cortisol Imbalances May Cause Weight Gain, Depression, Anxiety, and Insomnia

Theanine: An Amino Acid from Tea Has Numerous Health-Protecting Effects

Quick Relief from Anxiety and Stress Without Tranquilizer Drugs

Widely Used in Europe… Natural Sedative Restores Youthful Sleep

How Chronic Insomnia Destroys Skin Health


These statements have not been evaluated by the Food and Drug Administration. The products mentioned in this post and on this website are not intended to diagnose, treat, cure or prevent any disease. The information presented here is for educational purposes and does not constitute medical advice. Please obtain medical advice from qualified healthcare providers. Pursuant to FTC regulations, please be aware some of the links herein may be affiliate iinks. If you click on them and complete a purchase, this website may earn a commission.

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