Self-Blinded L-Theanine RCT
| Value tracked | Effect size d (λ, p, σ change) | Effect size d (λ, p, σ change) |
|---|---|---|
| 200 mg Caffeine (n=1, m=50) | 500 mg L-theanine (n=1, m=50) | |
| Log-score substance prediction[1] | −0.6 | −0.7 |
| Absorption | 0.61 (λ=13.3, p=0.00017, −0.072) | 0.04 (λ=1.38, p=0.77, −0.07) |
| Mindfulness | 0.58 (λ=11.8, p=0.0007, 0.021) | 0.12 (λ=0.72, p=0.89, −0.018) |
| Productivity | 0.58 (λ=28.9, p=1.3-12, 0.11) | −0.28 (λ=5.51, p=0.109, 0.03) |
| Creativity | 0.45 (λ=51, p=4.6-27, 0.09) | −0.12 (λ=5.05, p=0.14, −0.04) |
| Happiness | 0.27 (λ=10.6, p=0.002, 0.3) | 0.16 (λ=3.98, p=0.27, −0.155) |
| Contentment | 0.13 (λ=7.66, p=0.02, 0.47) | 0.25 (λ=6.83, p=0.04, −0.04) |
| Relaxation | −0.11 (λ=5, p=0.15, 0.42) | 0.12 (λ=1.5, p=0.74, 0.02) |
| Chastity[2] | −0.14 (λ=1.9, p=0.64, 0.11) | −0.03 (λ=1.15, p=0.8, 0.25) |
| Flashcard ease | 0.003 (λ≈∞, p≈0, −0.009) | −0.072 (λ=∞, p≈0, −0.01) |
| Flashcard ease factor | −0.039 (λ≈∞, p≈0, −32.7) | 0.0026 (λ=∞, p≈0, −18.9) |
| Flashcard new interval | 0.011 (λ≈∞, p≈0, −1.88) | −0.016 (λ=∞, p≈0, 3.1) |
| Time per flashcard[3] | 0.006 (λ≈∞, p≈0, 273.4) | 0.003 (λ=∞, p≈0, 13.66) |
L-Theanine is synergistic with caffeine in regards to attention switching[318] and alertness[319][320] and reduces susceptibility to distractions (focus).[320][321] However, alertness seems to be relatively subjective and may not be a reliable increase between these two compounds,[318] and increases in mood are either present or absent.[322][318][323] This may be due to theanine being a relatively subpar nootropic in and of itself pertaining to the above parameters, but augmenting caffeine’s effects; some studies do note that theanine does not affect the above parameters in and of itself.[324] Due to this, any insensitivity or habituation to caffeine would reduce the effects of the combination as L-theanine may work through caffeine.
L-Theanine does not appear to be synergistic with caffeine in regards to attention to a prolonged and monotonous task.[325]
—Kamal Patel, “Caffeine”, 2023
See also Examine, Wikipedia and Gwern.
Sitiprapaporn et al. 2018 test the effect of an unspecified quantity of L-theanine via Oolong tea on meditation on 10 university students (non-randomized, it seems). Data collected via EEG and indicates statistically significantly more alpha waves during meditation (although it is unclear how long the meditation was).
This paper is bad. The english is so horrendous it feels like I’m having a stroke while I’m reading it, but that would be fine if they were good at reporting methods, which they are not (missing amounts of L-theanine and duration of meditation, they also mention reading earlier in the article, which I assumed was the control activity, but it doesn’t come up again?). Also they report differences between scores, not effect sizes, and some figures are screenshotted images from a Windows Vista clustering application.
Examine agrees on the cognitive effects of l-theanine (if not on meditation specifically):
L-Theanine supplementation in the standard dosages (50-250mg) has been repeatedly noted to increase α-waves in otherwise healthy persons. This may only occur in persons with somewhat higher baseline anxiety[25][26] or under periods of stress (positive[14] and negative[27] results), but has been noted to occur during closed eye rest[5] as well as during visuospatial tasks[16] around 30-45 minutes after ingestion.[5][4] It appears that only the α-1 wave (8-10Hz) is affected, with no influence on α-2 wave (11-13Hz).[4]
Bill Willis, “Theanine”, 2022
Although I’m confused about the increased α-waves in “otherwise healthy patients”‽
Additionally, it notes that memory was slightly increased:
One study using a supplement called LGNC-07 (360mg of green tea extract and 60mg theanine; thrice daily dosing for 16 weeks) in persons with mild cognitive impairment based on MMSE scores, supplementation was associated with improved delayed recognition and immediate recall scores with no effect on verbal and visuospatial memory (Rey-Kim test).[17]
Bill Willis, “Theanine”, 2022
Experiment B: Self-Blinded RCT
This time I explicitely divided my meditation into a concentration part (first 15 minutes) and a mindfulness part (last 30 minutes).
Time for preparation: 93 minutes
Cost of l-theanine pills:
Cost of l-theanine pills:
Cost of empty capsules:
Notes during consumption:
1st dose: Made a mistake while filling the envelopes, accidentally deblinded myself.
19th dose: Took L-Theanine & did my routine, then took a nap and woke up 3 hours later.
43rd dose: Woke up with “brain fog”, meditation was dull & all over the place. Maybe because I’d been drying laundry in my room during the night? Also took nicotine later the day to kickstart some work on a project that needed to be finished.
Ran the experiment from 2023-06-22 to 2023-09-28, sometimes with pauses between samples.
I use the same statistical techniques as in the caffeine experiment, and start, as usual, with my predictions about the content of the pill:
>>> substances=pd.read_csv('../../data/substances.csv')
>>> experiment='B'
>>> substance='l-theanine'
>>> placebo='sugar'
>>> expa=substances.loc[substances['experiment']==experiment].copy()
>>> expa['datetime']=pd.to_datetime(expa['datetime'], utc=True)
>>> probs=np.array(expa['prediction'])
>>> substances=np.array(expa['substance'])
>>> outcomes=np.array([0 if i=='sugar' else 1 for i in substances])
>>> np.mean(list(map(lambda x: math.log(x[0]) if x[1]==1 else math.log(1-x[0]), zip(probs, outcomes))))
-0.705282842369643
This is not great. In fact, it’s slightly worse than chance (which would be about −0.693). Not a great sign for L-theanine, and, in fact, it gets worse. I use the generalized and compacted code from the last experiments to get the other results, and they don’t point a rosy picture for L-theanine:
>>> analyze('B', 'l-theanine', 'sugar')
absorption mindfulness productivity creativity happy content relaxed horny ease factor ivl time
d 0.040887 0.124170 -0.278448 -0.116001 0.164261 0.254040 0.119069 -0.031665 -0.072098 0.002561 -0.015955 0.003073
λ 1.378294 0.720780 5.517769 5.049838 3.983760 6.833004 1.496601 1.148131 inf inf inf inf
p 0.765758 0.894798 0.109735 0.146420 0.266491 0.045270 0.740705 0.813279 0.000000 0.000000 0.000000 0.000000
dσ -0.067847 -0.017736 0.039855 -0.043241 -0.155797 -0.046668 0.019655 0.251454 -0.016542 -18.901846 3.108518 13.660820
It worsens productivity and creativity (though not quite statistically significantly, but it’s on the way there), but at least it improves my mood somewhat (though those results, besides contentment, might as well be due to random chance). No clear effect sizes with the flashcards either.
So a hard pass on L-theanine, I think. Maybe it’s better when combined with caffeine?
I knew someone who (simplified) couldn’t use anxiolytics because their entire motivational structure was built on panic. If you chilled them out they couldn’t get to work on time, and would have rapidly gotten fired. I wonder how theanine’s effect on cognition/motivation changes based on an individual’s motivational structure.
I think this doesn’t apply to me: My model is that I lack energy in the morning, and theanine just makes me more tired.
I responded well to caffeine in another experiment.
I’ve personally gravitated towards adding hibiscus to regular tea for the boosted vasodilation and thus calming effect. Also seems to be good long term for blood pressure.
I have mild ADHD, which while not usually an issue in clinical practise, made getting through med school very hard until I was prescribed stimulants. Unsurprisingly it’s designed for people who are both highly intelligent as well as conscientious.
Ritalin, which is the only good stim available here, is almost intolerable for me even at the lowest available doses and longer acting formulations. It causes severe palpitations and anxiety, and I feel like absolute shit when it starts to wear off.
I tried a bunch of stuff to help, including things I’m embarrassed to admit, but I suffered for years until the serendipitous discovery that Earl Grey helped immensely. After consideration, I tried green tea and found it helped too, and now I’m confident that it’s the l-theanine that’s doing the heavy lifting, as normal tea or coffee only make things worse.
It’s made my life so much more bearable, and I strongly endorse it to anyone who has a need for being less anxious or happens to be on stimulants.
Neuroscientist Andrew Huberman uses and recommends theanine at bedtime to make it easier to get to sleep. I do, too. Theanine in pill or powder form, not from tea.
That seems better! I mostly took it in the morning, and I’m a night owl, so I sometimes felt becoming sleepier. Though I didn’t track this enough to be certain.
Edit: I found the post usefwl, thankmuch!!
Mh, was gonna ask when you were taking it. I’m preparing to try it as a sleep-aid for when I adjust my polyphasic sleep-schedule (wanting to go fm 16h-cycles potentially down to 9h) bc it seems potentially drowsymaking and has much faster plasma decay-rate[1] compared to alts. This is good for polyphasic if not want drowsy aft wake.
The data in [1] concerns 100mg tablets, however, and a larger dose (eg 400mg) may be longer. The kinetic model[2] they use will prob be good estimate of plasma concentrations even if adjust dose.
Questions is whether it’s good estimation for duration of action in the brain, esp given that it’s “single-compartment model” (the blood is one compartment, and the brain is another). My heuristic for whether plasma T predicts brain T is whether the molecule v easily passes the BBB (as melatonin does), since then I can guess that the curve for the brain will look similar to the curve for the blood, offset slightly down and to the right.
Hot tip, you can screenshot pdf equations (i rec Text Grab or Greenshot) and ask gpt-4-turbo (updated) to write it in latex and/or jupyter-notebook-compatible python[3].
Getting a tweakable python model for it was nontrivial after 35m of trying, so i’ll prob j wing it w 200mg 1h pre bedtime and do 3h sleep, and adjust bon feelings. ig the primary variable that determines how alert i feel upon waking up is getting the sleep-cycle timing right, and planning my wake-up routines (lights & text-to-speech-model as alarm) for j after I’ve done REM-sleep[4].
While I probably would feel alert if waking up in middle of REM-sleep (after emerging from deep), I want to avoid that bc studies show bad effects from targeted deprivation of REM (leaving other phases untouched).
Data point (not RCTs, more vulnerable to placebo):
Theanine before bed → wake up fewer times over night (previously a big problem for me, now pretty minor, theanine is only one reason of several)
Theanine before stressful appointments → noticeably more chill at appointments (but not as good as Halcion)
I’ve mostly heard people talking about l-theanine as something to complement caffeine rather than to take by itself.
This is interesting!
I would have guessed that the process of making tea is somewhat relaxing and almost all the “Contentment and Relaxing” properties of tea were due to placebo. Especially since culture seems to tell us that teas are a way to relax. This seems like solid evidence that L-Theanine is good for relaxing without the placebo effect. It comes at a productivity cost, but if relaxation is your goal maybe it is good and not too harmless!
Upvote, not least for my first ever sighting in the wild of the interrobang.