Can L-Theanine Cause Serotonin Syndrome Or Seizures?

In our latest question and answer, the pharmacist discusses whether or not L-theanine can cause seizures or precipitate serotonin syndrome.

Can L-Theanine Cause Serotonin Syndrome Or Seizures?
Jul 01, 2019

Phil asked

Can you let me know if there is anything in the medical literature or FDA adverse reports regarding L-Theanine precipitating serotonin syndrome or seizures? Also, can L-Theanine be used in concurrence with MAOI's?

At a glance

  • There is conflicting evidence regarding L-theanine and whether or not it could precipitate serotonin syndrome and/or seizures. While there are no reports of serotonin syndrome, it does have serotonergic effects. Additionally, animal studies show that it may decrease the frequency of certain types of seizures but increase the risk of others.


L-Theanine Stock Photo - Text - Chemical Formula - Green Powder

It can be extremely difficult to give definitive answers regarding the efficacy or side effects of over the counter supplements and herbal products simply due to the lack of high-quality studies regarding them.

As it concerns L-theanine, things are no different...studies are lacking. Making things more difficult is the fact that most studies that research L-theanine often utilize it in combination with other ingredients, like caffeine, making it challenging to deduce the effects of a single agent.

Nevertheless, we do have some reliable, albeit preliminary, information that has been published about l-theanine, and can, therefore, have a discussion regarding its potential therapeutic uses, adverse effects, etc...

In the next sections, I will discuss your questions in more detail, which are:

  • Can L-Theanine precipitate (i.e. cause) serotonin syndrome? (Maybe, since it can increase serotonin levels)
  • Can L-Theanine cause seizures? (Maybe, but studies are conflicting)
  • Can L-Theanine be used with MAOI's? (There may be an interaction, but there is a lack of drug interaction data to go off of)

First, I will start off by discussing what exactly L-Theanine is.

What Is L-Theanine?

L-Theanine Stock Photo On Black Background

Theanine is an amino acid that was originally discovered as a constituent in green tea in the late 1940s. While it is an amino acid, it is a non-protein one, and therefore, isn't classified as either essential or non-essential. Nevertheless, it is very similar in structure to the non-essential amino acid L-glutamine, as shown in the below image.

Comparing Molecular Structure Of Glutamine And Theanine - Side By Side

In green tea, in addition to its potential medicinal effects, it is thought to contribute to the umami taste of the beverage.

Since its discovery, L-theanine has been popularly used in over the counter supplements and used to treat a variety of conditions, including:

  • Anxiety and stress
  • Depression
  • Schizophrenia
  • Alzheimer's disease
  • Cancer
  • Inflammation/arthritis
  • Attention deficit-hyperactivity disorder (ADHD)

It also is used to improve cognitive performance.

How Is L-Theanine Produced?

As mentioned, L-theanine was first discovered as a component of green tea.

More recent studies have shown that green tea, on average, contains 1% to 3% theanine (98% of which is 'L-theanine while the other 2% is 'D-theanine', which isn't thought to be as active as L-theanine).

While L-theanine can be consumed via intake of tea, it is produced commercially (for use in supplements) via extraction from tea leaves or via chemical/biosynthesis.

What Does L-Theanine Do?

Green Matcha Theanine Powder

L-Theanine is thought to have a wide variety of actions and effects in the body.

Most studies report the following actions:

  • Increases concentrations of GABA
  • Increases concentrations of serotonin
  • Increases alpha activity in the brain
  • Increases concentrations of dopamine
  • Competes with L-glutamine for binding with glutamate receptors (i.e. acts as an antagonist)

All of the above are thought to contribute to L-theanine's effects.

Let's take the L-theanine's use in anxiety for example. While the physiology of anxiety is complex, studies have shown that L-theanine can decrease anxiety levels after supplementation. This is likely to do with L-theanine's ability to increase GABA, an inhibitory neurotransmitter, and serotonin, a neurotransmitter integral in mood regulation.

For depression, it is thought that theanine's antidepressant effects are related to its effects on the glutamatergic pathway (this mechanism may also be why L-theanine could have benefits for patients with dementia).

One study, researching L-theanine for its anti-anxiety and antidepressant effects, concluded the following:

  1. Theanine Monograph. ToxNET
  2. Acute effects of tea constituents L-theanine, caffeine, and epigallocatechin gallate on cognitive function and mood: a systematic review and meta-analysis. PubMed
  3. Inhibition by theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. PubMed
  4. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. PubMed
  5. 5-HTP Safety Concerns.
  6. L-Theanine intake increases threshold for limbic seizures but decreases threshold for generalized seizures. PubMed (Subscription Required)
  7. Nardil Prescribing Information. Pfizer
  8. Serotonin Syndrome. PubMed

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