side-effects

Mitochondrial disruption and systemic benzodiazepine side effects/tapering issues: pain, fatigue, brain fog, insomnia and anxiety

May 16, 2025 By Trudy Scott 19 Comments

A recent article published on Naturopathic Doctor News & Review, Mitochondrial Disruption Explains Systemic Benzodiazepine Side Effects, reports on new research that identifies a possible mechanism for wide-ranging side effects of these antianxiety medications. In addition to side-effects there can also be persistent withdrawal symptoms that continue after they have been tapered:

Benzodiazepines impair mitochondrial signaling across multiple systems in the body, not just GABA receptors in the brain. Mitochondria play a central role in regulating cell energy metabolism, hormone synthesis, oxidative stress balance, and immune response.

Disrupting these pathways has systemic consequences that explain the wide range of symptoms patients report during chronic use and withdrawal.

These findings offer a cellular mechanism for persistent fatigue, pain syndromes, cognitive impairment, and inflammatory symptoms that may continue after tapering.

Many medications impact the mitochondria but this new research has identified a new possible mechanism: tryptophan-rich sensory proteins (HsTSPO1) and reactive oxygen species.

In this blog I share more about HsTSPO1 and this new research, additional symptoms of benzodiazepine withdrawal, what we already know about mitochondria and anxiety, other medications and environmental toxicants that affect the mitochondria, and some key nutrients for mitochondrial support.

Benzodiazepines bind to tryptophan-rich sensory proteins (HsTSPO1)

This article from Virginia Commonwealth University, Researchers may have solved decades-old mystery behind benzodiazepine side effects, discusses the new study and HsTSPO1:

Benzodiazepines produce their therapeutic effect by binding with GABA_A receptors in the brain; however, the drug has an equally strong affinity to human mitochondrial tryptophan-rich sensory proteins (HsTSPO1), located on the outer membrane of mitochondria in cells.

This type of protein is linked to several neurodegenerative diseases, including Alzheimer’s, and researchers have suspected that HsTSPO1 may be involved in certain side effects of benzodiazepine drugs.

And “when valium and other benzodiazepines bind to HsTSPO1, they inhibit the protein’s ability to manage ROS (reactive oxygen species) levels in our cells … this both reduces the production and the neutralization of ROS.

This may help explain why such medications cause side effects over time

And the authors propose this: “The new insights into HsTSPO1’s function could help pharmaceutical companies develop improved benzodiazepines.”

I have a better idea and propose we create more awareness about how these and other medications affect the mitochondria. I believe all medications should include a warning about these mitochondrial effects, and that mitochondrial support should be included when these medications are prescribed and then tapered.

This may include a combination of the same nutrients used for neurodegenerative disorders caused by mitochondrial dysfunction – CoQ10, B-vitamins/NADH, L-carnitine, vitamin D, and alpha-lipoic acid. And should also include infrared sauna, red light therapy and other detox approaches.

Ideally, this awareness will increase the use of the amino acids GABA, tryptophan, 5-HTP and DPA (d-phenylalanine), and other nutritional approaches instead of long-term benzodiazepine prescriptions for anxiety, pain and sleep issues. More on that below.

Some of the many other symptoms of benzodiazepine withdrawal

This paper from 1994, The benzodiazepine withdrawal syndrome describes some of the many symptoms:

Physiological dependence on benzodiazepines is accompanied by a withdrawal syndrome which is typically characterized by sleep disturbance, irritability, increased tension and anxiety, panic attacks, hand tremor, sweating, difficulty in concentration, dry wretching and nausea, some weight loss, palpitations, headache, muscular pain and stiffness and a host of perceptual changes.

The mechanism is not addressed in the paper but in the light of this new research, it’s possible that tryptophan-rich sensory proteins, increased reactive oxygen species and mitochondrial dysfunction are factors.

Brain mitochondria: anxiety and fear

I first addressed mitochondrial dysfunction during the 2019 Anxiety Summit: Gut-Brain Axis. One of my guest experts, Tara Hunkin, NTP, CGP, RWP shared these highlights from this review paper – Anxiety and Brain Mitochondria: A Bidirectional Crosstalk:

Despite the established link between mitochondrial dysfunction and various psychiatric disorders, the contribution of mitochondria in anxiety disorders has not been extensively addressed.
Mitochondria are emerging as modulators of anxiety-related behavior, as evidenced both in animal and human studies.
There is a bidirectional link between mitochondria and anxiety. Mitochondrial, energy metabolism, and oxidative stress alterations are observed in high anxiety; conversely, changes in mitochondrial function can lead to heightened anxiety.

More recent research, published in 2024, The Emerging Role of Brain Mitochondria in Fear and Anxiety, supports this and proposes “a model in which mitochondrial function is critical for regulating the neural circuits that underpin fear and anxiety behaviors, highlighting how mitochondrial dysfunction can lead to their pathological manifestations.”

The new HsTSPO1 research builds on this research, identifying a possible mechanism and further supporting the oxidative stress connection.

On a side note, I’m really intrigued to learn more about these tryptophan-rich sensory proteins!

Other medications and environmental toxicants that impact the mitochondria

Keep in mind that it’s not only benzodiazepines that impact the mitochondria.

This 2023 paper, Drug-induced mitochondrial toxicity: Risks of developing glucose handling impairments, explores the correlation between potential mitochondrial dysfunction caused by selected medications, specifically looking at their effects on insulin signalling and glucose handling:

Drug classes such as statins, anti-diabetics, anti-epileptics, NSAIDs, anti-depressants, and certain antibiotics have been identified to induce mitochondrial toxicity.

This 2022 paper, Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature, states this:

Classes of environmental toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, and nanomaterials can damage the mitochondria in varied ways, with changes in mtDNA copy number and measures of oxidative damage the most commonly measured in human populations.

Amino acids and nutritional support: instead of benzos and before/during tapering

As I mentioned above, this awareness will hopefully increase the use of the amino acids GABA, tryptophan, 5-HTP and DPA (d-phenylalanine), and other nutritional approaches instead of long-term benzodiazepine prescriptions for anxiety, pain and sleep issues.

When it comes to tapering, it’s best to be nutritionally stable BEFORE starting to taper. This means eating real whole food that includes quality animal protein, healthy fats, fermented foods and organic vegetables and fruit; eating for blood sugar control; quitting sugar, gluten, alcohol and caffeine; addressing gut and adrenal health; addressing pyroluria and key nutritional deficiencies like low zinc, low iron, low vitamin D and more. This is all covered in my book.

Addressing neurotransmitter imbalances with amino acids before and during the tapering helps immensely too. And so does mitochondrial support.

And a reminder: tapering should always be done very very very slowly and under medical supervision with the prescribing doctor.

Additional resources when you are new to using GABA, tryptophan and other amino acids as supplements

As always, I use the symptoms questionnaire to figure out if low serotonin or low GABA or other neurotransmitter imbalances may be an issue.

If you suspect low levels of any of the neurotransmitters and do not yet have my book, The Antianxiety Food Solution – How the Foods You Eat Can Help You Calm Your Anxious Mind, Improve Your Mood, and End Cravings, I highly recommend getting it and reading it before jumping in and using amino acids on your own so you are knowledgeable. And be sure to share it with the practitioner/health team you or your loved one is working with.

There is an entire chapter on the amino acids and they are discussed throughout the book in the sections on gut health, gluten, blood sugar control (this is covered in an entire chapter too), sugar cravings, anxiety and mood issues.

The book doesn’t include product names (per the publisher’s request) so this blog, The Antianxiety Food Solution Amino Acid and Pyroluria Supplements, lists the amino acids that I use with my individual clients and those in my group programs.

If, after reading this blog and my book, you don’t feel comfortable figuring things out on your own (i.e. doing the symptoms questionnaire and respective amino acids trials), a good place to get help is the GABA QuickStart Program (if you have low GABA symptoms). This is a paid online/virtual group program where you get my guidance and community support.

If you are a practitioner, join us in The Balancing Neurotransmitters: the Fundamentals program. This is also a paid online/virtual program with an opportunity to interact with me and other practitioners who are also using the amino acids.

Wrapping up and your feedback

Are you aware that benzodiazepines and many other medications can play a role in mitochondrial disruption? And that this mitochondrial disruption is likely a factor when it comes to systemic benzodiazepine side effects and tapering issues such as pain, fatigue, brain fog, insomnia and anxiety (and more)?

Have you considered or used mitochondrial support when tapering one of the benzodiazepines and has this approach helped?

And has it helped to be nutritionally stable BEFORE tapering and using amino acids to help with tapering? What changes did you make and which amino acids helped?

If you’re a practitioner is this a topic you discuss and address with your clients/patients?

Please do share in the comments below.

I’m anxious about GABA side effects and feel like adding a bit of tryptophan before increasing GABA (to avoid overdoing it with either one)

September 6, 2024 By Trudy Scott 9 Comments

I have symptoms from both low GABA and low serotonin on your questionnaire. So I suspect I need to supplement with both. The main issues I have (anxiety, panic) are common to both deficiencies. I took a trial dose of 1 Gaba Calm and it seemed to help a bit. Should one continue increasing the dose of GABA or introduce some tryptophan next?

I am trying to avoid GABA side effects because now that I read your last post on tingling etc (which would be a huge trigger for me), I’m anxious about that.

I feel like adding a bit of tryptophan before increasing GABA and going up like that, one at a time. Versus going higher and higher with GABA since the symptoms are on both lists – in order to avoid overdoing it with one .

Does that make sense or do you still recommend doing one at a time (I just read on one of your blog posts that one should try one amino acid first before introducing another one)? Thank you!

Liz asked this great question on one of the blogs where I discuss how there can be an extremely large variation in dosing for GABA and how too much can cause a niacin-like flush and tingling.

Her concerns are very valid – especially for someone who is anxious – but I still recommend doing a trial of just one amino acid before introducing another. In today’s blog I share why this is my recommendation and why sometimes there is an exception to this recommendation (and how best to implement it).

My recommendation and her results

Liz is correct, I do always recommend doing a trial of one amino acid at a time before introducing the next one. I confirmed that this is still my recommendation and also reminded her that when “one GABA Calm seems to help a bit” it’s a positive sign. When I hear this it’s a big clue that you are on track and the next step is to continue to increase the GABA to determine if you’ll get even better results. I told her we are looking for a wow effect in a few days to weeks.

In case you’re wondering, she did increase just the GABA (without adding tryptophan) and shared “I’ve now increased to 2 GABA Calms and it helps a lot!”

With this kind of result she may decide to stay with just 2 GABA Calm or she may decide to increase yet again if this amount hasn’t substantially reduced her low GABA symptoms of physical tension, anxious thoughts, self-medicating with sugar or alcohol to relax, feelings of panic, pain etc. You can see all the low GABA symptoms here).

As always, I also reminded her what when you are new to the amino acids and other anxiety nutrition solutions like eating real whole food, quality animal protein, fermented foods, organic produce, healthy fats, gluten/sugar/caffeine removal, eating for blood sugar control, addressing gut health and pyroluria, my book “The Antianxiety Food Solution” is a great place to start. It’s a comprehensive approach – amino acids AND diet.

She has “been eating organic, gluten-free, whole foods for 10+ yrs” (this is a wonderful foundation). However the stress of the last few years has really gotten to her and she has been meaning to get my book to get some help with amino acids. Hopefully she now has a copy!

Why do I recommend doing a trial of one amino acid at a time before introducing the next one?

As she mentioned, she has overlaps with low GABA and low serotonin symptoms: “anxiety, panic.” This is not uncommon. Although they do differ – with low GABA it’s more physical and with low serotonin it’s more mental – it can often be challenging to figure out which neurotransmitter imbalance is the issue. Doing a trial of one of the amino acids and seeing/feeling the results provides the answer.

In this case, Liz discovered all or some of her anxiety was caused by low GABA levels. I say some, because it can be due to both low GABA and low serotonin. Once she has a good baseline of GABA and assuming she still has some lingering anxiety symptoms (and other low serotonin symptoms like PMS, anger, low mood, afternoon cravings etc – see them all here), she would then trial tryptophan without changing GABA dosing.

Laying in the tryptophan (after doing an initial trial) would help Liz know that low serotonin is also an issue for her.

And it would have all been challenging to figure out what was doing what had she done some GABA and some tryptophan and then more GABA and then more tryptophan.

Too much GABA and the adverse effects

Liz was understandably concerned about potential adverse effects of using too much GABA after reading this blog post: How much GABA should I use for my anxiety? It depends on your unique needs (and there is an extremely large variation in dosing). (This is the blog she commented on)

I’ve also published these blogs with similar messages:

Learning about adverse effects like this may make you feel more anxious rather than educated and empowered – hence her question about using tryptophan. However, too much tryptophan can also increase feelings of anxiousness and keep you awake (and it’s going to complicate the trial).

Knowing about vitamin C as an antidote often helps mitigate some of the anxious feelings but when it doesn’t then there may be an exception.

Why there may be an exception to my recommendation (and how best to implement it).

Typically when someone has profound fears that hold them back and stop them from using any of the amino acids, my recommendation is always to start with serotonin support as it can allay fears, worry, obsessing and ruminations about possible adverse effects.

In a situation like Liz describes, if anxious thoughts and worrying prevents her from increasing GABA, we would discuss all of the above and I’d help her decide what to do next:

Layer on tryptophan before she has found her ideal dose of GABA, without any change to GABA i.e. one change only. And then go from there to increase the GABA and eventually increase the tryptophan later if she needs to
Stop GABA and switch to tryptophan only and then come back to GABA. It isn’t ideal to lose the gains experienced, even when GABA only “seems to help a bit.”

The good news is that Liz felt comfortable enough increasing the GABA and saw the benefits. This may not be the case for everyone and the above are some options to consider.

A few GABA product options – a sublingual, a powder and a cream

Liz used Source Naturals GABA Calm lozenges (a good low dose of 125 mg). It’s one of the many products I recommend. Another one is Now GABA Powder (which does need to be measured out to provide a 125 mg typical starting dose). Keep in mind, some individuals need less to start.

When using GABA powder I have clients use a handy mini measuring spoon like this one (my Amazon link) and share more about how to measure out GABA powder on this blog).

For Source Naturals GABA Calm lozenges and Now GABA Powder:

You can purchase these from my online store (Fullscript – only available to US customers – use this link to set up an account).
If you’re not in the US, you can purchase these at iherb (use this link to save 5%).

Somnium GABA Cream is available in the US and elsewhere with international shipping. Read more about the product and who may benefit from using a cream, and grab my coupon code to save 15%.

Additional resources when you are new to using GABA and other amino acids as supplements

As always, I use the symptoms questionnaire to figure out if low low GABA or other neurotransmitter imbalances may be an issue.

Wrapping up and your feedback

I appreciate Liz for asking this question. I do hope this information has been helpful for you and for her too.

Now I’d love to hear from you – does any of this resonate with you? Have you felt anxious or fearful about increasing your dose of GABA? And how did you resolve it?

If you’re a practitioner is this how you advise your clients/patients?

Feel free to share and ask your questions below.

GABA supplementation may offer a new approach for the prevention and treatment of asthma (and it helps anxiety, ADHD and insomnia)

December 16, 2022 By Trudy Scott 12 Comments

If you’re already taking the amino acid GABA for physical anxiety, have you noticed if it’s also helping to ease your asthma symptoms too? This may sound surprising but research shows GABA may reduce inflammation and spasms and help with asthma symptoms via these mechanisms. What’s encouraging is the fact that GABA supplementation also helps with anxiety, obesity, ADHD and insomnia which commonly occur with asthma and can be associated with inflammation too. It’s so important to be addressing the root causes of asthma because of the many neuropsychiatric side-effects of asthma medications. This blog addresses all of these topics.

We’ll start with the research first. In this study, Effect of gamma-aminobutyric acid treatment on plasma substance P and calcitonin gene-related peptide levels in children with asthma, of 75 children with asthma, 36 children were in the GABA treatment group and received oral GABA (25-30 mg/kg per day) in addition to standard asthma medications.

The authors propose that airway inflammation may be a factor in asthma and GABA helps because it reduces SP (substance P) and CGRP (calcitonin gene-related peptide), easing neurogenic inflammation and tracheal spasms.

The conclusion of the study is that oral GABA:

can significantly decrease plasma levels of SP and CGRP in children suffering from acute asthma.

It may offer a new approach for the prevention and treatment of asthma.

(this is my best translation from the Chinese paper).

Dosing of GABA for asthma

The children in the study group received oral GABA of 25-30 mg/kg per day. For a 100 lb /45 kg child this would equate to 1125 mg -1350 mg of GABA per day.

As I always share, I don’t recommend using GABA based on the weight of the person and I consider this a high dose. For adults, 125 mg GABA is a good starting dose with 125 mg often used 2-4 times a day. For a child, ¼ to ⅓ this dose is typically good to start with. All that said, many adults and children with asthma and anxiety need higher doses than what they initially start with.

It’s also worth noting that the oral dose of GABA was swallowed so it’s possible (and very likely) that more was needed than if it was used sublingually or with the capsule opened or a powder or a liposomal form.

GABA is seldom recommended for asthma – more recent research supports this approach

This is not new research – the paper was published in 2013 – but I seldom see it discussed or hear about practitioners recommending GABA for asthma.

A more recent paper, Neuroimmune Pathophysiology in Asthma (published in 2021) supports this and discusses the role of neurotransmitters (including GABA and serotonin) and neuropeptides (including SP, CGRP and others) in asthma. The authors suggest “that regulating the effects of neurotransmitters and neuropeptides represents a potential novel approach for the treatment of asthma.”

Why we need to consider GABA – the neuropsychiatric side effects of asthma medications

Exploring the use of GABA and these approaches is especially important given the neuropsychiatric side effects of asthma medications. In this study (published in March this year), Neuropsychiatric adverse drug reactions induced by montelukast impair the quality of life in children with asthma

Neuropsychiatric ADRs (adverse drug reactions) were reported in 78 (62.4%) of 125 patients, who recovered when the drug was discontinued.

These were children of 3-18 years taking montelukast for the first time. The good news is that they recovered when the drug was stopped.

The bad news is there is no information on how many kids who have been prescribed this class of medication are subsequently prescribed psychiatric medications.

This concern needs to be considered for all asthma medications: there are similar adverse effects with antihistamine and inhaled corticosteroid medications.

GABA helps with other conditions where spasms are common

The study results are very encouraging and support what I see clinically with asthma and other conditions where spasms are common. These include

GABA helps with all of the above and the non-allergic comorbidities seen with asthma.

Asthma in children and non-allergic comorbidities (obesity, depression and anxiety, ADHD and insomnia)

As stated in this paper, Paediatric asthma and non-allergic comorbidities: A review of current risk and proposed mechanisms “It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population.” These include obesity, depression and anxiety, neurodevelopmental disorders (such as ADHD), sleep disorders and autoimmune diseases.

This paper looks at mechanisms and inflammation is a common theme except when it comes to anxiety and depression. Given that this paper was published this year and all that we now know about nutritional psychiatry and neuroinflammation and anxiety, it’s clearly lacking in this aspect.

Clinically, we see how GABA can help with obesity (and cravings or stress-eating), depression and anxiety, ADHD and insomnia, as illustrated by these case studies:

I see similar comorbidities (the occurrence of more than one disorder at the same time) in adults and GABA can be used safely with adults and children.

Asthma from a functional medicine approach

There is clearly more to asthma than only GABA. This this article on natural remedies for asthma covers diet (eat real good quality food and avoid junk food), nutrients like vitamin D, zinc and others, and allergens – and all this needs to be investigated and addressed with a functional medicine approach.

Dr. Axe does mention stress and anxiety being a trigger: “It’s well-known that stress increases the severity and frequency of asthmatic attacks because it hinders immune function and raises inflammation.” He mentions stress-reduction techniques and breathing. I say let’s add GABA to the mix too.

Resources if you are new to using GABA and other amino acids as supplements

If you are new to using GABA or any of the other amino acids as supplements, here is the Amino Acids Mood Questionnaire from The Antianxiety Food Solution (you can see all the symptoms of neurotransmitter imbalances, including low GABA and low serotonin).

There is an entire chapter on the amino acids and they are discussed throughout the book in the sections on gut health, gluten, blood sugar control, sugar cravings, self-medicating with alcohol and more.

Has GABA helped ease your physical anxiety and asthma symptoms too?

What about obesity/cravings, ADHD and insomnia as well?

Have you or one of your children been adversely impacted by asthma medications? If yes please share which medications and what symptoms were experienced.

What functional medicine and nutritional approaches have helped your asthma symptoms?

Feel free to post your questions and feedback in the comments below.

Balance Neurotransmitters for Pain and Anxiety: The Healing Pain Summit

September 11, 2015 By Trudy Scott 20 Comments

Joe Tatta is a Doctor of Physical Therapy and he is putting on The Healing Pain Summit which is focused on healing pain of all kinds using an integrated approach. Having practiced Physical Therapy for 20 years, Joe knows first-hand that pain is THE thing that will stop you in your tracks … completely. To help people with pain of all kinds Joe has brought together experts on:

Healing joint pain and muscle pain
How the foods you eat can cause you physical and emotional pain
Healing spiritual pain
Healing sexual pain

Here are just a few of the summit topics that may interest you:

Natural Ways To Heal Fibromyalgia
Your Adrenals and Pain: What is the Connection?
Solutions for Cancer Patients and Cancer Survivors

My interview will be: How Balancing Neurotransmitters Can Help Pain and Anxiety. I’ll be sharing new information on pain and the amino acids – something I don’t often talk about but can be a very powerful addition to a pain management program. I’ll cover how GABA, DPA/Endorphigen and tryptophan/5-HTP can help with various types of pain (and anxiety). I’ll also discuss some of the many mood and anxiety side-effects we can see with pain medications.

Here are some reasons for concern when it comes to pain medications:

Glucocorticoid medications like cortisone and prednisone can actually contribute to mood and cognitive issues. A 2014 paper titled Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects reports that

Severe neuropsychiatric consequences (including suicide, suicide attempt, psychosis, mania, depression, panic disorder, and delirium, confusion, or disorientation) have been reported to occur in 15.7 per 100 person-years at risk for all glucocorticoid courses, and 22.2 per 100 person-years at risk for first courses

NSAIDs (nonsteroidal anti-inflammatory drugs) such as ibuprofen are well known for causing injury and bleeding throughout the GI tract, but there now new evidence of an increased risk of a brain bleed when someone is also taking an SSRI. According to a Medscape article

The combination of antidepressants and nonsteroidal anti-inflammatory drugs (NSAIDS) is linked to an early increased risk for intracranial hemorrhage, regardless of the type of NSAID or antidepressant, new research shows.

Most worryingly, conditions requiring NSAIDs and antidepressants commonly coexist; 65% of adults with major depression also have chronic pain, with both morbidities sharing common psychological risk factors and neurobiological processes.

The good news is that amino acids can be a very powerful addition to a pain management program. One example is 5-HTP, an amino acid that raises serotonin levels. Anxiety, depression and increased pain can all be caused by low serotonin.

A paper published in 1998 and called 5-Hydroxytryptophan: a clinically-effective serotonin precursor reports that 5-HTP

easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.

You can register here https://gc182.isrefer.com/go/hpsreg/trudyscottcn/