Evidence Update: Anxitane (L-theanine) for Anxiety in Dogs (and Cats)

In late 2014, I reviewed the evidence for Anxitane (l-theanine), an amino acid from the tea plant reported to have benefits for dogs with anxiety. At that time, my conclusion was:

The theoretical reasoning behind the potential value of l-theanine for treatment of anxiety in dogs is plausible, which means it could work. The research in humans shows some weak evidence for a possible benefit, but the evidence is not sufficient to allow firm conclusions. Likewise, the research evidence in dogs is limited and weak, and it is not possible to say with any confidence whether or not l-theanine has a meaningful benefit for dogs with anxiety. It could work, but at this point we don’t know if it actually does.

Since the product is likely safe, there is little risk in trying it in dogs with anxiety. However, without stronger evidence for a benefit, it should not be viewed as a substitute for therapies with better evidence of efficacy.

I was recently asked to see if there had been any new studies that might clarify the value of this product. In humans, there haven’t been any major changes. A more recent review of the human literature reported that “few short-term benefits were reported with l-theanine alone.” Some studies reported reduced tension and anxiety, but others did not confirm this and found negative effects on cognition as well as an increase in headaches. A variety of positive effects on attention, cognition, and memory were reported for the combination of l-theanine and caffeine, but this is not relevant to veterinary patients due to the risks of caffeine in dogs and cats, and this would not be relevant to the use of l-theanine for anxiety anyway.

Here are a few additional veterinary studies not included in my last review.

Kern L. La transmission de la peur. In: La communications. Collection Zoopsychiatrie. Beata C. ed. Marseille, Solal Editeurs, 2005:191-6. (translation provided by the manufacturer of Anxitane)

This is not a new study but one that has only been published in French in a book on animal behavior, not in a peer-reviewed journal. The manufacturer of Anxitane has made it available as part of the marketing efforts for the product.

This was not really a clinical trial so much as a “try-it-and-see” report. Essentially, owners gave the l-theanine for two months to dogs they felt had a wide variety of behaviors assumed to be related to fear. The veterinarians then evaluated the dogs’ behavior at intervals (at the beginning, at 15 days, 30 days, and 60 days after starting the Anxitane) and decided whether they had improved. Not surprisingly, given the lack of bias controls in this study, the assessment was that the behavior improved.

Dramard V. Kern L. Hofmans J. et al. Clinical efficacy of l-theanine tablets to reduce anxiety-related emotional disorders in cats: A pilot, open-label clinical trial. 6th IVBM Conference. 2007. Riccione, Italy.

This is not actually a new publication since 2014, just one I hadn’t seen previously. It was also another “try-it-and-see” report rather than a controlled clinical trial. 33 cats with a wide variety of symptoms assumed to be due to anxiety were given l-theanine and then the owners and vets subjectively rated whether these were improved. The caregiver placebo effect, and numerous other potential confounders and sources of error, make the results of this study pretty unreliable. Funding was not disclosed, but one of the authors is an employee of the manufacturer of Anxitane.

Pike AL. Horwitz DF. Lobprise H. An open-label prospective study of the use of l-theanine (Anxitane) in storm-sensitive client-owned dogs. J of Vet Behav. 2015;4(10):324-31.

In this study, owners of dogs with storm phobia were recruited online and from general veterinary practices. Owners rated their dogs’ symptoms before and after using the supplement for at least 4 weeks or 5 storm events. Improvements were noted on most, but not all, behaviors measured. However, as the authors themselves acknowledge, the lack of the standard clinical trial bias controls (randomization, blinding, and placebo control group) made the results highly susceptible to caregiver placebo effects. The study was funded by the manufacturer of Anxitane.

Michelazzi M. Berteselli GV. Talamonti Z. et al. Efficacy of L-Theanine on noise phobias in dogs: preliminary results. Veterinaria (Cremona). 2015;29(2):53-9.

This study randomly assigned 10 dogs with noise phobia to receive behavioral therapy and Anixtane or just behavioral therapy. Assessment was by owner questionnaire and both owners and investigators were unblinded. There was no placebo or positive control. The funding source was not disclosed. Most behaviors measured improved over time in both groups. Some appeared to improve more in the animals given Anxitane while others, and the overall score, did not differ between the groups. Due to the subjective assessment and lack of controls, this study is at high risk of bias.

Bottom Line
While the basic principle that l-theanine might have clinically useful effects based on its biochemistry is plausible, there is still little compelling evidence it actually helps patients in the real world. A handful of studies have been done in humans, and the systematic reviews that have assessed them do not find strong evidence of benefit for anxiety in people. There have also been a handful of veterinary studies. Most of these are uncontrolled, unblinded, and use relatively subjective measures of outcome, and most are funded by the manufacturer. All appear to show benefits, but all are at high risk of bias. No significant risks have yet been seen, though headaches and some negative effects on mental function have been reported in humans.

All of this leaves us right where we were four years ago. Could work, might work, not sure if it does work, probably doesn’t do much harm. The frustrating thing is that the first low-quality attempt to study l-theanine for anxiety in dogs was reported by the manufacturer 13 years ago. Since then, the company has funded a few more unblinded, uncontrolled studies, but no high-quality, properly controlled clinical trials.  The product has been on the market for 9 years, yet the company has not funded such a study, nor has any independent research been published that accounts for the limitations of the existing literature. This is an all-too-typical pattern I have previously illustrated this way:

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31 Responses to Evidence Update: Anxitane (L-theanine) for Anxiety in Dogs (and Cats)

  1. Robin Wenham says:

    Maybe helpful to insert “massive profit” in the graphic illustration of the life cycle?

  2. Jerold Sorbel says:

    Is there any drug that actually relieves anxiety in dogs and not just turn them into zombies?

  3. George Butel says:

    Because I have a parrot, I watch for studies dealing with substances that show promise as safe anxiolytics for birds. I have wondered about theanine for a long time, having seen it recommended by those on the “holistic” bandwagon a couple of decades ago, a recommendation based, apparently, on the work of two well-known scientists, They Say, and Everybody Knows. Two fairly recent works on theanine caught my attention.

    The first, on rats, a Chinese study last year, surprised me a little. The verbiage at the beginning of their paper suggests that Yan, et al, might not have been totally dispassionate about the effects of theanine to begin with, judging by their apparent uncritical acceptance of other work, but they did add to the biochemical basis for theanine’s activities. (Let me point out, though, that this was published in a Hindawi journal.)
    “L-theanine administration had decreased serum glucose probably by inhibiting intestinal SGLT3 and GLUT5 mRNA expression in rats. Dietary fatty acids uptake might be suppressed by downregulating GPR120 and FABP2 transcripts in the intestine of rats. Meanwhile, intestinal transporters responding to AAs absorption were upregulated by L-theanine administration. Our data provide theoretical basis for further investigation of L-theanine and nutrients interaction.” (https://www.hindawi.com/journals/bmri/2017/9747256/).

    The other paper, from a multi-national group, also provides some biochemical rationale for physiological effects of theanine, this time in broilers. This study seemed to be of decent quality, and also brings up an issue that’s bothered me for a long time–the possibility of adverse effects, in this case, from higher doses–might be of concern. I don’t recall seeing any of the advocates of its use on birds worry much about “inconsequential” matters such as what an actual reasonable dosage might be. Saeed, et al, found, “Supplementing broiler diet with L-theanine reduced (p = 0.02) total serum cholesterol contents while increased HDL. Further analysis revealed lower relative serum cytokines (IL-2 and INF-g) and reduced mRNA expression of TNF-a and IL-6 in thymus, and IFN-g and IL-2 in spleen in the treated group. Moreover, supplementation with 200 mg/kg of L-theanine improved antioxidant status in blood by increasing SOD, GSH-Px, and relative CAT levels. It is concluded that the optimum supplementation level of L-theanine is 200 mg/kg of diet because it resulted in improved performance parameters in broilers. However, higher levels of L-theanine (300 mg/kg diet) may have deleterious effects on performance and health of broiler chickens.”

    Neither of those had anything to do with measuring anxiolytic activity, but modulation of important physiological processes such as blood pressure cannot be ignored. Would it be conceivable that better BP and lipid levels might make a human—or another animal—feel better, and, thereby, less anxious?
    Theanine is metabolized in humans this way: “L-theanine is rapidly absorbed and seems to be hydrolyzed to ethylamine and glutamic acid. A minor part of L-theanine is retained in erythrocytes. Kinetics and urinary excretion of L-theanine, ethylamine, and glutamic acid are comparable after both treatments. Thus, functional effects of L-theanine intake may result from L-theanine, ethylamine, or glutamic acid.” (Scheid, et al, 2012: https://academic.oup.com/jn/article/142/12/2091/4630725)

    Even if the substance is an effective anxiolytic, it isn’t something that one should start adding teaspoons of to a dog’s food (or even to one’s own food.) Since green tea is well-known as a source of theanine, some pet owners might be tempted to administer green tea extract, without thinking about the caffeine that’s present in most extracts. Or, they might decide to use a supplement such as that from Solaray or Thompson, both of which are sold as L-theanine, but which also contain green tea leaf (not likely enough to worry about, though.)
    There is a fascinating review of its effects in an article in the Asian Pacific Journal of Tropical Biomedicine last year. Warning; take a grain of sodium chloride (or, better, potassium chloride) before reading it though. It appears almost as though Adhikary and Mandal are promoting its use to cure all diseases known to mankind.

    There is no law against being cautious. Based on that one finding in the case of poultry, I would be extremely careful with dosage if I were going to use it.

  4. Andria says:

    Great summary – thanks for this!:) Quick error to report in the paragraph above “Bottom line”. The first sentence reads “This study randomly assigned 10 dogs with noise phobia to receive behavioral therapy and anxiety…” – assuming it should be “…with Anxitane…”.

  5. skeptvet says:

    There are many medications which can be used for anxiety, and their effects are highly variable between dogs. Serious side effects are uncommon, but sedation does occur with some medications in some dogs, and which often it improves with continued use, it can limit the usefulness of some drugs in some patients. The best we can do at this point is combine behavior modification therapy with trials of medications based on the specific needs and reactions of each individual patient.

  6. Is L-theanine completely safe? I have a lil pup. So i was thinking will it be harmful for lil puppy?

  7. skeptvet says:

    Nothing is “completely safe,” but so far there haven’t been any reports of side effects in dogs, and the only adverse effects reported in people have been mild (e.g. headaches), so the risk is probably very low.

  8. My cat has anxiety problem. What can i do for him?

  9. skeptvet says:

    I would recommend seeing a board-certified veterinary behaviorist to help get a comprehensive understanding of your cat’s issues, their causes, and the best combination of methods to help solve them. This is a lot of work, but there simply are not cheap, quick fixes to serious behavior problems.

    Good luck!

  10. Kate says:

    I read a Facebook post yesterday from a veterinary behaviorist who said that a speaker at the Veterinary Behavior Symposium at the AVMA meeting had presented research indicating that a specific probiotic strain can be effective against anxiety in dogs and that Purina will be coming out with a probiotic product this fall for anxiety. Do you have any details about this research?

  11. skeptvet says:

    Haven’t seen this. Let me know if you can find a link to the original study.

  12. Kate says:

    Here is a link to the abstract of the talk at the Veterinary Behavior Symposium. I will keep an eye out for a published study.


  13. AKBAR WIGUNA says:

    Thanks for your share very nice, Maybe helpful to insert “massive profit” in the graphic illustration of the life cycle?

  14. cindy says:

    Hi, I came across your article when searching for l-theanine for dogs. We have a maltese mix male, 25#, who is about 9 years old. We adopted him when he was 2, so I don’t know what his life was like before that. The whole time we have had him, he has barked at thunder (and motorcycles, and lawnmowers); we live in SW Florida so during the rainy season, we have a LOT of thunder. It’s not only that the incessant barking is annoying, he just seems to be frenzied. Our vet who has since retired mentioned trying l-theanine a couple years ago. I decided to try it now.
    The past 2 days we have had huge thunderstorms lasting a couple of hours. It may be placebo effect on my part, but my husband and I both think he is a little calmer with it. He may bark a couple of times, but it is not the incessant running back and forth, barking till he’s hoarse. I’m trying to decide if I should give it daily, or just when I see a storm coming?

  15. skeptvet says:

    It is used both ways, but I don’t think there are any studies showing whether it works better for storms if given continuously. Most treatments for storm phobia are given as needed, so it probably makes sense to try that first.

  16. Vicky says:

    I would find it immensely useful if you reported on the use of anti anxiety products e.g. Zyklene and the like. We have 2 very reactive dogs and have tried a range of these ‘medications’ without success. We have yet to try CBD oil but that may be next in the list – that or fluoxetine.

  17. skeptvet says:

    I have covered a few, though not specifically Zylkene. You might find this literature summary interesting:

    Clinical bottom line

    There is currently no evidence to show that alpha-casozepine is effective as an anxiolytic when administered to dogs shortly (minutes to a few days) before exposure to an anxiety provoking stressor. There is limited and weak evidence to suggest that it may have a role to play in reducing anxiety in dogs over the medium to longer term but the available evidence is of low quality and / or high risk of bias, with confounding variables providing alternative explanations for the findings. More research is needed in this area.

  18. Kim says:

    Hi there: My neighbor suggested I try L-theanine. She said the vet formula (Anxitane) contains mannitol which she said was an unnecessary diuretic. So, she just gets the amino acid supplement. I am ordering some today from amazon. Our 5-year old miniature aussie has anxitey and has been treated with prozac which no marked improvement. We have also worked very hard with him and several trainers and a DVM with psychology credentials. He has participated in agility classes and obedience training three times without much improvement. It seems very little we do improves his mood and behavior. I walk him 1.25 miles daily and throw a tennis ball for 5-minutes three to five times a day. He is fine for 20 minutes (no barking) but then reverts to barking at almost no stimulus. He barks at everything, including us and is driving us crazy. He barks at our friends when visiting to the point we cannot have them over because he inhibits conversation. We love him and want to help him. How much of this L-theanine should we administer. My neighbor suggested 200 mgs daily.

  19. margie ridgen says:

    I used CBD Oil for my dogs when we go to our Vet. They are so excited when we go outside. I gave them CBD Oil 15 to 30 minutes prior. CBD oil for our pets can treat health issues such as digestive or upset tummy, inflammation, joint pain or even allergies.
    I tried this in my dog, I gave it when I know he faced a stressful situation.
    And as I done researching, I came across to this article about Cannabis and Mj blimburnseeds.com/cannabis

  20. Nadine says:

    With this breed I think the amount of exercise he described is way too low. They need to be walked a good 3 miles daily because they require like three hours of exercise. We even resorted with ours to using the treadmill but the most effective thing is tearing him out with a brother or sister to run with who is just as energetic.

    Miniature Aussies seem to suffer from a really high anxiety level. They’re really not meant I think to be in homes with people coming in and out but I meant to be an area as they were intended with many other animals and a few people. That was our experience with a mini Aussie we had and I got to the point where it was protective enough where it was biting people.

  21. Joanne says:

    My cat is on Prozac for letterbox use and had breakout incidences this winter. We used Solequin then Anixtane and I think both increased the incidences. I can’t find that they interfere with Prozac but if they can interfere with nutritional absorption or uptake, perhaps they can interfere with Prozac absorption.

  22. v.t. says:

    I would think Solliquin to be nearly useless (it’s a proprietary ‘blend’, with green tea, etc, yuck!)

    Have you kept a log of sorts of kitty’s behavior and during times of stress/changes to help you determine potential triggers? Have you ruled out health issues with your vet such as cystitis, colitis, arthritis, pain issues?

  23. Jiff says:

    I have a geriatric dog with cognitive dysfunction. We’ve tried a number of supplements and pharmaceuticals to treat her anxiety but almost everything increased it (or it didn’t do anything – except Gabapentin it works somewhat). After reading this article a year ago I decided to give it a shot. Got a bottle from a health food store and immediately saw a huge improvement in her behavior provided I give it to her on an empty stomach. No more panting and pacing for hours on end with her ears pinned against her head, walking and walking lost in her mind until her ass end gives out and she collapses into an exhausted heap. Now when she is tired she lays down and takes a nap! That is a novel idea to a CCD dog. She’s currently just shy of 16 and is 50lbs. I give her 100mg once or twice a day on an empty stomach. For anyone out there like myself desperately searching for one last thing to try before the euthanasia decision is made, give it a shot. I know my n-1 anecdotal evidence isn’t science but this brought her back to us.

  24. Jeff Deats says:

    We have two dogs, a Labradoodle (Standard Poodle-Black Lab mix) and English Bulldog, each weighing about 60 lbs., which we have used L-Theanine for different anxiety applications.
    The Labradoodle has some separation anxiety, and if you have owned one you will know that their hyperactivity “pup-years” extend into 2-4 years of age. She is very loving but would often knock down our grand-daughter. She is also very sight prey active and continually barked and chased our pet cats or squirrels outside through the window. We have given her 100 mg capsules / once daily in her treats for about 6 months. It has been extremely successful, calming her, but never making her drowsy.
    When getting groomed we sometimes gave another dose. The effects begin within 30 minutes and seem to last bout 6 hours.
    The English Bulldog has less anxiety issues, although separation from me for a day (his primary owner) is an issue. But nail trimming is extremely bad time for him; I believe his previous owner miss-used a drommel tool on him. While it does have the same calming affect without drowsiness, There may have been a negative reaction after a few days on taking it daily; he had some episodes of shaking, not quite like full body seizures, but shivering. This happened on a few occasions before we make the connection and quit using it on him

  25. Alice says:

    My rescue dog has many issues around reactivity, fearfulness, anxiety, fear aggression, all of which improved with hard work and behaviour modification. I decided to try anxitane as I thought it wouldn’t do any harm. It’s not been a miracle and I didn’t expect to see any changes and didn’t for around 2 months but she did improve in lots of ways. With her reactivity it seemed like I had more time to get her attention and intervene, she seemed to have a better threshold for triggers, she just seemed a little more secure in herself. These aren’t major changes but for us they make a big difference. We recently ran out and she was off of them for a short period and her behaviour change was noticeable. Very irritable, quick to react, hard to recover even with all of the usual methods I use to help her calm down. It took around a month for her to settle again. There are still many issues we help her manage and I know it’s not going to help with major fears like fireworks but our everyday life has improved. The only problem is it is getting quite expensive and I am wondering if human version L-Theanine would have the same effect but need to research ingredients. To me it is worth it. It won’t be the same for everyone and I didn’t realise how much it was helping until she was off of it. It helps take the edge off and there haven’t been any negative effects. I think it’s worth trying if you have an anxious pup or are waiting for outside behavioural help.

  26. Steve Danzis says:

    Have you looked at this NIH study on L-theanine? It seems like solid support for the benefits. I give my cattle dog a theanine supplement sold for humans to help with his separation anxiety, and it really does keep him calmer (as witnessed through the nannycam), unlike all the dog calming supplements I’ve tried, along with a worthless Thundershirt. (If you chalk this up to the placebo effect, then why wouldn’t those other products work as placebos?)

  27. skeptvet says:

    To begin with, a study in humans is of questionable relevance when looking at behavioral problems in dogs since the differences between species, in terms of behavioral capacity, issues and context, are pretty different.

    The results in this study were also not very compelling. As the authors state, no difference from placebo in several measures of stress and a borderline difference (significance P<0.05 and these values 0.46-0.499) in others.
    "When score reductions in the stress-related symptoms were compared between L-theanine and placebo administrations, changes in the PSQI sleep latency, sleep disturbance, and use of sleep medication subscales were significantly greater (p = 0.0499, 0.046, and 0.047, respectively), while those in the SDS and PSQI scores showed a non-statistically significant trend towards greater improvement (p = 0.084 and 0.073, respectively), during the L-theanine period compared to placebo."

    No difference from placebo for cognitive function,
    "When score changes were compared between the L-theanine and placebo administrations, no significant difference was found for any cognitive function."

    Recent systematic reviews of the human research overall are equivocal-
    “Our findings suggest that supplementation of 200-400 mg/day of L-THE may assist in the reduction of stress and anxiety in people exposed to stressful conditions. Despite this finding, longer-term and larger cohort clinical studies, including those where L-THE is incorporated into the diet regularly, are needed to clinically justify the use of L-THE”

    “L-theanine (MD: -0.49, 95% CrI: -6.54 to 5.57) did not outperform a placebo for the treatment of anxiety in terms of statistical certainty. ”

    Overall, the “maybe but not clear” conclusion is pretty much the same.

    As for the caregiver placebo effects with different treatments, lots of things influence our perceptions of effectiveness besides the true action of the treatment. People experience more placebo effects with injections than pills, with expensive placebos than with cheap ones, and when the provider is confident or formally dressed rather than hesitant and casually dressed. There are plenty of reasons why you dog might seem, or even be, different with one and not another besides a true biological effect. That’s why we need studies instead of just relying on individual trial and error for every patient.

    I hope your dog continues to do well, and I hope at some point we have solid evidence to support this treatment so we can know for sure if it is useful.

  28. Susan Moore says:

    I have a 16 month old Cockapoo that I adopted in December 2023 (4 months ago). He demonstrates some reactive behavior as well as fairly severe separation anxiety. My vet has recommended that he see a Veterinary Behaviorist. The behaviorist she recommends charges $1000+tax for a 90 minute consultation and I simply cannot afford this. My vet has also recommended that he wear a pheromone collar to help with the anxiety. I have worn the collar on him even though the scientific evidence that this is effective is really no better than that of the L-Theanine supplement and I noticed no difference in his behavior after wearing the collar for 30 days. I have spoken with a couple of dog owners in my neighborhood who have used L-Theanine on their dogs for treatment of anxious behavior who sing it’s praises, so I am willing to give it a try. I understand that there is no solid evidence to support the success of this supplement and also there seems to be no evidence of harmful side effects. Considering this, and the amount of positive testimony from dog owners who have tried it, it makes sense to me to at least try L-Theanine supplements rather than putting my pup on prescription fluoxetine medication at such a young age, and for which there is proven evidence of negative side effects. I have purchased a bottle of 125mg. chewable tablets and I am wondering what the dosage should be for a 22lb. dog.

  29. L says:

    You should have gone with the Prozac or considered Anafranil. With some behavioral therapy and time (at least 6 months) often they can be tapered off of it and may only need an occasional prn of Trazadone or the like.

    Discuss with your vet, maybe you can get a refund on that bottle if you haven’t opened it, and your vet advises against.
    Not a vet but have owned a dog with thunderstorm phobia and separation anxiety that had a positive response to Anafranil and only needed it less than a year.

  30. L says:

    I meant Clomicalm (doggie version of Anafranil)

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