cognitive

I feel so dependent on my nightly “cocktail” of GABA, 5-HTP, melatonin and Ambien for insomnia – how do I reduce them?

May 2, 2025 By Trudy Scott 3 Comments

I have had insomnia for years. I have used GABA Calm with good results and also 5-HTP, melatonin and Ambien. Recently I discovered I have mild sleep apnea and have made huge progress in modifying my night awakening.

With my sleep apnea issues addressed, I would like to try to reduce my supplements and the Ambien… but the thought of this causes more anxiety. I feel so dependent on my nightly “cocktail”.

What is the best way to reduce the fear of withdrawal and my nagging brain that tells me I “need” these things?

Many thanks for all the wonderful information you share!

Lynn asked this on one of the blogs and since it’s a common question I’m sharing my feedback in this new blog post. I’m pleased to hear she has discovered sleep apnea is a factor as it’s not always checked and it definitely can cause disrupted sleep and waking in the night.

There is no need to taper amino acids and melatonin but I typically have clients gradually reduce them, one at a time, especially when they are concerned and are not sure how much they may still be helping.

She has a nagging feeling she still needs these supplements, feels dependent on them and feels anxious about stopping. All of this, in conjunction with the fact that stopping a sleep medication such as Ambien can also cause rebound insomnia has me advising a go-slow approach in a situation like this. Also, Ambien does need to be tapered very slowly and under medical supervision, so she would need to keep this in mind too.

A go-slow approach and one amino acid at a time

Lynn may still need one or more of the GABA, 5-HTP and/or melatonin and we don’t want to lose any gains.

As mentioned above, there is no need to taper amino acids and melatonin but I typically have clients gradually reduce them, one at a time, especially when they are concerned and are not sure how much they may still be helping.

I would start with assessing other low GABA symptoms and other low serotonin symptoms and if there are none, start with reducing either GABA or 5-HTP over a few weeks, watching for worsening sleep or other symptoms showing up. She could then do the same with melatonin.

As a reminder, other than sleep issues (with physical tension at night), these are low GABA symptoms: feeling anxious with physical-tension and stiff-and-tense-muscles, overwhelm, feelings of panic, and the need to self-medicate to calm down, often with alcohol but sometimes with carbs and sugary foods. You can also experience anger, rage and agitation, poor focus, intrusive thoughts/overactive brain, spasms, visceral pain/belly pain with IBS and more. You can read the entire list of low GABA signs and symptoms here.

With low serotonin, we see sleep issues with ruminating thoughts and worry (at night too), and fears, phobias, ruminations, obsessing, feelings of panic, perfectionism and lack of confidence, low mood, rage, anger and irritability.

Lynn has a nagging feeling she still needs these supplements, feels dependent on them and feels anxious about stopping. All this is a clue she may still need them or at least need one or more to some extent. Doing a reverse-trial of reducing each one, one at a time, with careful tracking is my approach.

I would tackle the above amino acid and melatonin reduction – if she decides to go ahead with it – only AFTER she has worked with her prescribing doctor on a slow taper on the Ambien. Stopping a sleep medication such as Ambien can cause rebound insomnia/discontinuation syndrome and she may find she does still need nutritional support to tide her over the Ambien taper period. This may be the same as she is currently using or she may even need to adjust upwards on one or more.

Ambien: dependence, withdrawal, rebound insomnia, slow tapering, falls and memory issues

Ambien/Zolpidem “is a non-benzodiazepine receptor modulator primarily used in the …short-term treatment of insomnia aimed at patients with difficulty falling asleep,” increasing “GABA inhibitory effects leading to sedation.”

I seldom see it used short-term i.e. 7 to 10 days. With longer-term use, “this drug has a high potential for overuse and daily dependence” and “withdrawal symptoms may occur if the zolpidem dose is tapered off rapidly or discontinued.”

Other factors to be aware of:

Complex sleep behaviors can occur after using zolpidem, such as sleep-driving, sleep-walking, and engaging in activities while not fully awake
Changes in behavior and abnormal thinking have been reported after zolpidem administration. In addition, patients have demonstrated aggressiveness and extroversion uncommon for the person’s usual behavior
Worsening of depression or suicidal ideation may occur with zolpidem therapy

I encourage you to read the article here and be fully informed.

This 2024 paper supports that “long-term use of Zolpidem may lead to drug tolerance, dependence, rebound phenomena, and withdrawal symptoms, making discontinuation difficult.” Other concerns include: dizziness, headache, falls, and cognitive decline.

Many of the papers published prior to 2023 do not report many of these issues, however awareness is growing. This 2024 paper, Case report: Additional grounds for tighter regulation? A case series of five women with zolpidem dependence from a Brazilian women-specific substance use disorder outpatient service, also reports adverse effects in women such as “memory and social impairment, falls, seizures” and “withdrawal symptoms, including rebound insomnia, social impairment, and craving.”

The authors recommend tighter regulation, stating that: “The surge in zolpidem prescriptions, driven by its perceived safety and low abuse potential compared to benzodiazepines, may lead to a global health issue of dependence.”

Because of much of this it’s important to work with the prescribing doctor on doing a very slow taper under their medical supervision. She may need to adjust her amino acids up during the taper period if her sleep gets worse in the short-term. And then do the taper approach I mentioned at the start of this blog.

With these safety, dependence and withdrawal issues, I would love to see GABA, tryptophan/5-HTP and/or melatonin (and other nutritional and functional medicine approaches), addressing sleep apnea and lifestyle factors/sleep hygiene be considered as the first approach for sleep issues – instead of Ambien/Zolipdem.

Additional resources when you are new to using GABA, 5-HTP 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

I appreciate Lynn for asking this question and want to acknowledge that she is wise to be cautious and have concerns about the best way to tackle this. And she may find she does have a physical dependence on the Ambien.

Have you found that GABA, 5-HTP and/or melatonin helped/helps with your sleep issues?

And is sleep apnea a factor for you too?

And have you been prescribed Ambien and had any of the issues mentioned?

And how have you adjusted your amino acids and other sleep supplements as you’ve tapered your sleep medication?

Feel free to share your feedback and ask your questions below in the comments section.

Low lithium questionnaire and how we use lithium orotate with the amino acids

August 19, 2022 By Trudy Scott 44 Comments

This is the low lithium questionnaire that I use with new clients in order for us to figure out if a trial of low dose lithium, in the form of lithium orotate, may be helpful. The hallmark of low lithium is a rollercoaster of emotions. Keep in mind that this is just one of 12 questionnaires that I have my clients complete. Many of the following symptoms can have multiple causes, the labs may relate to other deficiencies and the conditions have other root causes. This questionnaire simply provides additional evidence that lithium orotate may help.

We typically do a lithium orotate trial, starting with 5 mg once a day, and going up to 10 mg twice a day. We do this after we have started trialing the respective amino acids for low serotonin, low GABA, low endorphins, low catecholamines and low blood sugar. A big clue that lithium orotate may be helpful (when many of the symptoms below are checked off) is when the amino acids for low serotonin (tryptophan or 5-HTP), low GABA (GABA or theanine), low endorphins (DPA or DLPA), low catecholamines (tyrosine or DLPA) and low blood sugar (glutamine) are not as effective as expected (based on the amino acids mood/neurotransmitter questionnaire).

Low lithium questionnaire

Symptoms
Mood swings (a rollercoaster of emotions)
Addictions and/or cravings
Depressed
Low self-esteem
Boredom
Easily distracted
Rebellious, disruptive behavior and/or aggressiveness
Irritability
Restless/internal anxiety (similar to low serotonin worry/ruminating anxiety)
Restless/external anxiety (similar to low GABA physical anxiety)
Anxiety ups and downs (fluctuations)
Melancholic pessimism
Suicidal thoughts
Disorganized with planning difficulties
Focus issues/ADHD
Insomnia
Procrastination and/or no initiative
Jack of all trades, master of none
Impulsive and/or lacking tact
Poor insight
Risky behavior
Cognitive issues
Migraines or cluster headaches

Effectiveness of amino acids
The amino acids for low serotonin, low GABA, low endorphins, low catecholamines and low blood sugar are not as effective as expected (based on the amino acids mood/neurotransmitter questionnaire)

Labs
Low white blood cell count
Low red blood cell count
Anemia
Low platelet count

Conditions
Anorexia nervosa
Heart disease (heart arrhythmias, history of heart attack)
Raised blood sugar or diabetes
Kleptomania
Alcoholism
Alzheimer’s disease
Fibromyalgia
Bipolar II
Gout
Hyperthyroidism
Nearsightedness or glaucoma
Herpes infections (current or prone to them)

If you are new to low dose lithium / lithium orotate

As I share in this blog, Upping my tryptophan and lithium orotate have been absolutely profound for me: I’ve been depression free and anxiety free for over a year, I’ve used lithium orotate with many clients and use it when folks have mood swings and anxiety ups and downs. It’s harder for the amino acids to work when there is a moving goal post and lithium orotate evens things out.

You can read Katrin’s wonderful results: “Upping my tryptophan dose and also including and upping the dose of lithium orotate has been absolutely profound for me. I’m off my SSRI/antidepressant (which I was off and on for a number of years). I’ve been depression/anxiety free for over a year. So fantastic.”

The above blog also includes additional information on the differences between low dose lithium / lithium orotate and prescription lithium carbonate. The latter is used at much higher doses and does have side-effects.

One of the many ways lithium works is via the impact on neurotransmitter production. This paper, Potential Mechanisms of Action of Lithium in Bipolar Disorder, states this: “At a neuronal level, lithium reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission.” It also increases protective proteins such as BDNF (brain-derived neurotrophic factor), helps reduce oxidative stress and is neuroprotective. This paper is referring to lithium carbonate and not lithium orotate but until we have more research on lithium orotate, I feel comfortable extrapolating, given what I’ve seen clinically with lithium orotate.

I’ve also blogged about low dose or microdose lithium here: Microdose lithium formulation is capable of halting signs of advanced Alzheimer’s and improving cognition. In a study published in 2020, “a team of researchers has shown that, when given in a formulation that facilitates passage to the brain, lithium in doses up to 400 times lower than what is currently being prescribed for mood disorders is capable of both halting signs of advanced Alzheimer’s pathology and of recovering lost cognitive abilities.” In this study, they used lithium citrate in similar doses as the lithium orotate i.e 3.2 mg to 6.4 mg NP03 based on 70kg of body weight (which is around 154.3 lbs).

Resources if you are new to using the amino acids as supplements (and where to get lithium orotate)

If you are new to using any of the 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).

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.

You can find the amino acid products I use and a number of different lithium orotate products in my online Fullscript store.

Do you resonate with any of the above and have you used lithium orotate with success?

Was the rollercoaster of emotions and fluctuating anxiety a hallmark for you before using lithium orotate?

If you’re a practitioner, do you use lithium orotate with your clients or patients?

If you have questions please share them here too.

SSRI/antidepressant impact on the microbiome, discontinuation syndrome and safe tapering

October 16, 2021 By Trudy Scott 2 Comments

Antidepressants can have an antibiotic effect, causing dysbiosis and impacting serotonin, GABA and dopamine production. This can cause psychiatric symptoms and even suicidal thoughts or behaviors. Various SSRI (selective serotonin reuptake inhibitors) and SNRI (serotonin norepinephrine reuptake inhibitors) have more of an effect than others. And the top known side effects for SSRIs are gut symptoms: nausea, diarrhea and vomiting.

These medications are seldom prescribed with informed consent and can cause severe psychological, cognitive, physical and neurological withdrawal side effects (also known as discontinuation syndrome). A functional medicine and nutritional approach using 5-HTP, GABA, theanine and glycine can often be used to smooth the taper process.

Dr. Achina Stein addresses all this in her interview, SSRI Impact on the Microbiome and Safe SSRI Tapering, on The Anxiety Summit 5: Gut-Brain Axis.

We cover the following:

Antibiotic effect of antidepressants: dysbiosis and impacts on serotonin/GABA/dopamine
Withdrawal/discontinuation syndrome symptoms of SSRIs and benzodiazepines
5-HTP, GABA, theanine and glycine to smooth the taper process

Here are a few snippets from our interview.

We start with a discussion on the antibiotic effect of antidepressants and a review of this paper – Serotonin Reuptake Inhibitors and the Gut Microbiome: Significance of the Gut Microbiome in Relation to Mechanism of Action, Treatment Response, Side Effects, and Tachyphylaxis.

Dr. Stein comments on this study sharing how SSRIs affect the gut and microbiome in many different ways:

“This paper is important. It’s one of several papers that talk about how the SSRIs or serotonin reuptake inhibitors affect the gastrointestinal tract. And as you know, the gastrointestinal tract is really full of serotonin.
SSRIs, as well as other psychotropic medications, actually exert an antibiotic effect, which can have a direct consequence in disrupting the integrity and stability of the gut microbiome.
And the ones that are most likely to do that are Sertraline, fluoxetine, and paroxetine in that order. And it’s followed by fluvoxamine, escitalopram, and citalopram, having the least impact.
What they’re noticing is that this antibiotic effect actually results in dysbiosis.
The top known side effects for SSRIs are gut symptoms: nausea, diarrhea, vomiting.
We know that the gut microbiome has a significant effect on emotions, behaviors, and metabolic changes.
And it’s involved in the metabolism of drugs, and this combination is what really causes psychiatric symptoms and even suicidal thoughts or behaviors.”

She also talks about the bidirectional gut-brain connection/communication, the microbiome and short-chain fatty acids (which are a common theme you’ll hear throughout the summit):

“There is this huge connection between the gut microbiome and the brain.
And there’s also other indirect communication pathways because we’ve always wondered, well, how does this happen that the gut is connected to the brain?
So the other pathways which are more indirect are the hypothalamic-pituitary-adrenal axis.
And there’s also an immune-mediated connection where there’s a communication between short-chain fatty acids and microglia in the brain.
So short-chain fatty acids are the main metabolites produced by the microbiota in the large intestine through bacterial fermentation of indigestible polysaccharides, which are dietary fiber and resistant starch. And they possess neuroactive properties. So they influence the communication between these short-chain fatty acids between the gut and the microglia of the brain.
And it’s a bidirectional communication too.”

And we talk about tachyphylaxis or the poop-out effect of antidepressants.

The discussion on the SSRI (selective serotonin reuptake inhibitors) and SNRI (serotonin norepinephrine reuptake inhibitors) discontinuation syndrome (or withdrawal symptoms) is eye-opening and sobering, Here are just a few of the many psychological symptoms that she says patients may experience when tapering:

I’m just going to read them off because I think it’s important for people to know: mood swings, unstable moods, hypomania, hyperarousal, anxiety, medication-induced agitation – which is described as being caffeinated – impulsive behavior, aggression, irritability, crying spells, lowered mood or depression.

Dr. Stein also shares the many cognitive, physical and neurological side effects, and how she works with her patients with a functional medicine and nutritional approach to try and mitigate the side effects. She likes to use 5-HTP, GABA, theanine and glycine to smooth the taper process.

We also have a lengthy discussion about informed consent and the fact that it’s not happening and should be.

We do a deep dive into all this and much more.

The interviews that dove-tail well with this topic are as follows:

My interviews, GABA & Tryptophan: Gut-Anxiety Connections and Glutamine, DPA and Tyrosine for Anxiety and Sugar Cravings. The amino acids help during the tapering process and help you make the dietary changes.
Thiamine Deficiency in Anxiety and Gut Health (Part 1 and 2) with Chandler Marrs. She talks about how medications can deplete thiamine. Could this contribute to some of the severe discontinuation syndrome symptoms we see?
Anxiety, Gut-Brain Communication and Diet with David Perlmutter, MD, FACN, ABIHM. This one gives you an excellent overview of the gut-brain communication and fermented foods, short-chain fatty acids and histone deacetylases (HDACs).
Gut-Brain Axis and Mental Health with Peter Bongiorno, ND, LAc. This is also a great overview on the mental health impacts of the microbiome. He goes deep into serotonin and GABA production mechanisms.

I encourage you to tune in if you have:

Anxiety & feel overwhelmed & stressed by little things
Panic attacks &/or obsessive thoughts or behaviors
Social anxiety/pyroluria
Phobias or fears (flying, spiders or even driving on a highway)

And also if you suffer from…

Food sensitivities, IBS/SIBO, parasites or gallbladder issues
Constipation, diarrhea, bloating, gas, pain & other digestive issues
Leaky gut, a leaky blood-brain barrier or vagus nerve issues

Join us if you are also an emotional eater with intense sugar cravings (and know you suffer from low blood sugar), experience insomnia, low mood, PMS, poor focus and/or low motivation.

This is THE online event to learn about the powerful individual amino acids – GABA, theanine, tryptophan, 5-HTP, glutamine, DPA and tyrosine – to quickly ease anxiety and help with gut symptoms while you are dealing with other root causes which take longer to address. (They also help with cravings as with this example, and sleep and immunity).

With research-based anxiety nutritional solutions and practical steps, you can determine your root causes, ease your anxiety and prevent it from coming back so you can feel on top of the world again!

If you are a practitioner, please join us too and find advanced solutions for your clients or patients too!

You’ve heard me say the Anxiety Summit has been called “a bouquet of hope!” My wish for you is that this summit is your bouquet of hope!

I hope you’ll join me and these incredible speakers, be enlightened and find YOUR solutions!

Here’s to no more anxiety and you feeling on top of the world again!

Learn more/purchase now

How have antidepressants impacted your gut and digestion?

Have you experienced discontinuation syndrome when tapering from an SSRI or SNRI or benzodiazepines? And have diet and the amino acids helped smooth the taper process?

Feel free to post your questions here too.

5-HTP benefits both adopted daughters who had prenatal exposure to alcohol: they are happier, more focused and can stay on task

March 5, 2021 By Trudy Scott 10 Comments

A grateful mom, Besty, posted wonderful feedback on the 5-HTP and ADHD blog. She shared how 5-HTP benefits both her adopted daughters who had prenatal exposure to alcohol i.e. exposure to alcohol while in the womb. When using the supplement 5-HTP, an amino acid precursor to serotonin, both girls are happier, more focused and can now stay on task. Here is the feedback Besty shared on the blog:

After listening to Dr. Michael Murry’s interview on your Anxiety Summit, I decided to try 5-HTP on my 18-year-old daughter (a senior in high school) who was adopted at 5 years of age. She has always had some issues with focus, but she has never been medicated for this. She has had some learning struggles. She was exposed to alcohol in the womb, so some of her learning difficulty has been attributed to this.

She started 5-HTP in December and doesn’t ever want to miss a day on it. She says that she can better complete her assignments because it helps her to “stay on task”.

Even on days that she is not in school, she wants to take it, because it makes her feel happier.

Because she has done so well on it, her 23-year-old biological sister (also adopted) started on it. She was also exposed to alcohol while in the womb and has some learning struggles. She is in college. She also doesn’t want to miss a day, because she says that “it keeps her on her toes,” which she says means that it “keeps me focused,” when she is working on her school work.

I am so thankful that I learned about this therapy through your summit!

I thanked Besty for her kind words and for sharing this wonderful outcome both her daughters experienced. I love hearing stories like this and I am sharing this as a blog post so more folks are inspired and have hope.

Prenatal exposure to alcohol: the adverse effects, and impacts on serotonin and dopamine

This 2012 paper, Moderate prenatal alcohol exposure and serotonin genotype interact to alter CNS serotonin function in Rhesus monkey offspring, describes fetal alcohol spectrum disorder (FASD):

Fetal alcohol spectrum disorder (FASD) is associated with a range of adverse effects that can be observed in children prenatally exposed to alcohol.
Fetal alcohol syndrome (FAS), which includes growth retardation, craniofacial anomalies, CNS dysfunction, and cognitive and behavioral impairments, is the most serious of the FASD outcomes of prenatal alcohol exposure.
Alcohol-related neuro-developmental disorder (ARND) is the term used to describe prenatally alcohol-exposed children with problems that are primarily neurobehavioral, including cognitive effects, hyperactivity, impulsivity, reduced attention span, and lack of inhibition.

It appears these young girls may fall into the ARND category with their reduced attention span and cognitive issues, and some possible neurobehavioral issues. I’m not, however, aware if a diagnosis was made. I’m also not aware if hyperactivity, impulsivity and lack of inhibition have been issues too.

This paper also discusses the research on prenatal alcohol exposure and deficiencies in the serotonergic neurotransmitter system, and the possibility that genetic factors might predispose someone to fetal alcohol effects during a sensitive period. These are primarily genes affecting serotonin production. The authors also report that prenatal exposure to alcohol also affects dopamine levels.

Addressing neurotransmitter imbalances with tryptophan, 5-HTP and tyrosine

We don’t often associate low serotonin with ADHD (attention deficit and hyperactivity disorder) and poor focus but the research and clinical outcomes like this one (and the other success story below with 5-HTP melts) is very promising.

If you are new to addressing neurotransmitter imbalances with targeted amino acids you may find these blogs helpful:

Using tryptophan to address low serotonin eases worry, rumination, anxiety and negative self-talk. Keep in mind that some folks do better with tryptophan and some do better with 5-HTP.
ADHD: 5-HTP melts have been a miracle for one of my adopted kids. I summarize the role of serotonin in ADHD, the interplay with dopamine and the use of oral tryptophan (a serotonin precursor similar to 5-HTP). And this is the blog post that Besty commented on.
We typically consider the use of tyrosine to address low dopamine (one of the catecholamines), leading to better focus, good energy and better motivation so you are more likely to finish tasks. It also improves mood.

Questions I still have about the 5-HTP trials

I have these questions I posed to Betsy and hope to hear back as I feel these answers may be helpful as you navigate your trials with 5-HTP (for yourself or your loved ones):

Which product are they using and how much is helping?
Did your daughters make any other changes (diet or other supplements) at the same time?
What have they tried over the years to help with focus and learning issues?
Why did you initially decide to trial 5-HTP with your younger daughter?
Did your younger daughter encourage her older sister to trial 5-HTP too?
Did either daughter have any of the classic low serotonin symptoms too: worry-type of anxiety, ruminations, OCD, fears, PMS, irritability, insomnia, afternoon/evening cravings, anger issues, lack of confidence? And did the 5-HTP help with any of these symptoms too?
Were some of the classic low serotonin symptoms a factor when it came to lack of focus? For example, did the worrying or feelings of fear or insomnia contribute to the inability to stay on task and keep focused?

I’ll report back once I get Besty’s feedback. But keep in mind that dosing/timing doesn’t really matter as the doses that work for her daughters are unique to their own biochemistry and needs.

Additional resources when you are new to using GABA, 5-HTP 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.

Wrapping up and your feedback

Have you found that 5-HTP (or tryptophan) helps your child (who was exposed to alcohol in the womb) with focus and ADHD symptoms? Are they happier when using one of these serotonin precursors?

If you’re a practitioner working with children or adults who have had prenatal exposure to alcohol, have you had good results with 5-HTP or tryptophan?

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

Microdose lithium formulation is capable of halting signs of advanced Alzheimer’s and improving cognition

February 7, 2020 By Trudy Scott 59 Comments

In a new study, a team of researchers has shown that, when given in a formulation that facilitates passage to the brain, lithium in doses up to 400 times lower than what is currently being prescribed for mood disorders is capable of both halting signs of advanced Alzheimer’s pathology and of recovering lost cognitive abilities.

The above snippet is from a press release published in January 2020 on Science Daily: Can lithium halt progression of Alzheimer’s disease? Keep in mind that this is an animal study but the results are so promising. I’m also very intrigued by the delivery method (more on that below).

In order to give this microdosing context, a typical adult prescription is 900-1800mg lithium carbonate/day. I reached out to the lead author for clarification about the dosing of this new formulation and lead researcher Dr. Cuello shared this with me:

I calculate that our lithium dosage is 285 times lower concentration than the 900 mg dose (based on 70 kg of body weight) and 570 times lower than the 1800 mg dose.

This translates to around 3.2 mg to 6.4 mg NP03 based on 70kg of body weight (which is around 154.3 lbs).

NP03 is a disease-modifying nano dose formulation of lithium citrate which is used sublingually. I assume it’s not yet commercially available.

Also from the press release: “our findings show that microdoses of lithium in formulations such as the one we used, which facilitates passage to the brain through the brain-blood barrier while minimizing levels of lithium in the blood, sparing individuals from adverse effects, should find immediate therapeutic applications.”

Here is a link to the actual paper: NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats

Can we compare NP03 to low dose lithium orotate?

What is really interesting is that low dose lithium in the form of lithium orotate is commonly recommended by integrative practitioners for anxiety, mild mood swings, brain fog, ADHD and insomnia. I have found it to be extremely beneficial for many of my clients and have used it personally with success (for brain fog and insomnia).

Just how much lithium orotate is low dose? Typical doses are 5-10 mg per day, increasing to 20mg per day.

Can we compare NP03 to low dose lithium orotate? It’s too early to know for sure but we I believe we can start to make extrapolations, especially given that both are very low doses.

Integrative psychiatrist, Dr. James Greenblatt, MD has written extensively about low dose lithium orotate for the above purposes and for Alzheimer’s too. In this article, Lithium: The Cinderella Story About a Mineral That May Prevent Alzheimer’s Disease, he shares that

Scientists first became interested in the use of lithium for treating neurodegenerative disorders when they observed that bipolar patients using lithium therapy seemed to have lower rates of cognitive decline than peers on other medications.

He writes how an enzyme called Glycogen Synthase Kinase-3 (GSK-3) – a serine/threonine protein kinase – normally plays a major role in neural growth and development and how lithium

works as a direct GSK-3 inhibitor… halting inappropriate amyloid production and the hyper-phosphoryation of tau proteins before they become problematic.

If all this fascinates you as much as it does me, Dr. Greenblatt writes more about lithium orotate in his excellent book: “Nutritional Lithium: A Cinderella Story: The Untold Tale of a Mineral That Transforms Lives and Heals the Brain” (my Amazon link).

Lithium deficiency and the onset of Alzheimer’s disease: a 2025 study

Update August 8, 2025:

A new animal study, Lithium deficiency and the onset of Alzheimer’s disease (and published Aug 2025), supports the above, concluding that lithium orotate is “a potential approach to the prevention and treatment of Alzheimer’s disease.” The authors share this about lithium in the brain:

endogenous lithium is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, lithium was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to Alzheimer’s disease. Lithium bioavailability was further reduced in Alzheimer’s disease by amyloid sequestration.

The authors explored the role of endogenous lithium in the brain (i.e. lithium within the brain) by depleting it from the diet of wild-type and Alzheimer’s disease mouse models and found that:

Reducing endogenous cortical lithium by approximately 50% markedly increased the deposition of amyloid-β and the accumulation of phospho-tau, and led to pro-inflammatory microglial activation, the loss of synapses, axons and myelin, and accelerated cognitive decline.

It’s exciting that they found that lithium orotate, “a lithium salt with reduced amyloid binding, prevents pathological changes and memory loss in Alzheimer’s disease mouse models and ageing wild-type mice.” And this paper also mentions the fact that these “effects were mediated, at least in part, through activation of the kinase GSK3β.”

They conclude that:

These findings reveal physiological effects of endogenous lithium in the brain and indicate that disruption of lithium homeostasis may be an early event in the pathogenesis (cause) of Alzheimer’s disease. Lithium replacement with amyloid-evading salts [such as lithium orotate] is a potential approach to the prevention and treatment of Alzheimer’s disease.

Given the concerns with the toxicity of high dose prescription lithium carbonate, I appreciate that this was addressed:

An important limitation in the treatment of aged individuals with pharmacological doses of lithium [i.e. lithium carbonate] is kidney and thyroid toxicity. It is encouraging that toxicity could not be detected following long-term treatment of ageing mice with a low dose of lithium orotate.

Alzheimer’s and cognitive decline have many root causes

Keep in mind that Alzheimer’s and cognitive decline have many root causes that must be considered. This may include inflammation, stress and candida, and even insecticide exposure.

The best Alzheimer’s book is “The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline” by Dr. Dale Bredeson (my Amazon link). He doesn’t mention lithium orotate so I look forward to hearing his thoughts on this new research. [I’ll come and update the blog when I do]

You can read about some of Dr. Bredesen’s work here: Alzheimer’s disease, mercury and mycotoxins.

Benzodiazepines have also been linked to increased Alzheimer’s risk which is why a nutritional approach for anxiety is the best approach. Let’s use the amino acids like GABA (for physical anxiety), and tryptophan (for worry and fears), as well as dietary changes and improving gut health instead of anti-anxiety medications (more on these below).

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

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

If you need serotonin support, the Serotonin QuickStart Program is a good place to get help. This is also a paid online/virtual group program where you get my guidance on using tryptophan and 5-HTP safely, and community support during 5 LIVE Q&A calls. You can sign up to be notified when the next live launch of this program is happening.

Wrapping up and your feedback

I look forward to human clinical trials of NP03. Dr. Cuello “ believes that there is an excellent opportunity to launch initial clinical trials of this formulation with populations with detectable preclinical Alzheimer’s pathology or with populations genetically predisposed to Alzheimer’s, such as adult individuals with Down Syndrome.”

I also look forward to human clinical trials of lithium orotate for Alzheimer’s disease. And I would love to see lithium orotate compared to NP03 in future research.

In the meantime I feel this research is exciting because it supports so much of what is being seen clinically with lithium orotate.

Have you used lithium orotate with success? How much has helped you and have you seen cognitive benefits? What about a more even mood, better sleep and less anxiety?

And have you or a family member seen improvements with the Bredesen protocol?

Nutrients for dementia: could they help during benzodiazepine withdrawal?

September 19, 2014 By Trudy Scott 29 Comments

Half Coconut and Flower on Bamboo Mat

Could certain nutrients help with memory and cognitive issues, and the “pseudo-dementia” symptoms so many people experience when withdrawing from benzodiazapines?

In a recent article I shared the new research on benzodiazepines being linked to increased Alzheimer’s risk and other serious concerns.

Alison, who was featured in the Boston Globe story, commented on the above blog post:

I am only 29 years old, and I developed what I refer to as pseudo-dementia once I developed a tolerance to benzodiazepines and it got worse once the drug was stopped. From what I have seen from others recovering from and in tolerance to benzodiazepines, cognitive functioning and memory can get hit hard and actually mimic dementia. I wonder if the symptoms these elders are experiencing are true Alzheimer’s, or a side effect/withdrawal effect.

This really got me thinking. She makes an excellent point. It may well be that the symptoms they are seeing in the study are a side effect/withdrawal effect, rather than true Alzheimer’s disease and may be reversible. It surprises me that the study authors have not commented on this since cognitive effects are well documented in the literature.

Here are a few examples I found:

“Benzodiazepines revisited—will we ever learn?” Published in Addiction in 2011

“The review noted a series of adverse effects that continued to cause concern, such as cognitive and psychomotor impairment. In addition, dependence and abuse remain as serious problems. Despite warnings and guidelines, usage of these drugs remains at a high level.”

“Benzodiazepine harm: how can it be reduced?” Published in British Journal of Clinical Pharmacology in January this year (2014)

“Adverse effects comprise sedation subjectively and cognitive and psychomotor impairment objectively. Complex skills such as driving can be compromised… Withdrawal and dependence have excited particular concern, and even polemic. Perhaps a third of long term (beyond 6 months) users experience symptoms and signs on attempting to withdraw – anxiety, insomnia, muscle spasms and tension and perceptual hypersensitivity.”

I was not able to find much in the literature on pseudo-dementia. I did see it listed on the benzo.org.uk site but not elsewhere in relation to benzodiazapines.

I did find this paper “Pseudo-dementia: A neuropsychological review” which is presumably something different (as it refers to depression/dementia). This part may be applicable: “ ‘The pseudo component’ which denotes the actual lack of the neurodegenerative dementia” and the fact that it can be reversed.

This all inspired me to do some digging on dementia. If what they are seeing in participants of the British Medical Journal is not true dementia, it’s very encouraging to think that recovery is possible.

There are some very powerful foods and nutrients that help certain people with dementia and I wonder if they would also help with the benzodiazepine-induced pseudo-dementia:

Not all of the above would work for everyone because of biochemical individuality, and there are mixed results in the literature, but it’s worth assessing for possible deficiencies and addressing overall nutrient status.

It would be wonderful to think that benzo recovery can be improved in the areas of cognition, memory and “pseudo-dementia.”

Interestingly, many of these above nutrients are also factors in anxiety and/or depression and may be related to why someone sought help and was prescribed benzos initially.

P.S. There nutrients are great for overall brain function so anyone could benefit from one or more of them. I actually take 20mg of lithium orotate a day and it helps keep my post-menopausal brain sharp and focused.

P.P.S. I have recently learned that many people in benzo withdrawal do not tolerate supplements so please USE CAUTION and work with your health practitioner. I will do a part 2 follow up to this blog listing foods high in these nutrients in case you feel more comfortable and do better with a food based approach.