If this is a real effect, why didn't we discover it decades ago? 'Common plant used in folk remedies turns out to be useful therapeutic' gives us aprin and digitoxin in the mid 19th century but nobody notices lavender until the 21st.
Silexan isn't really new, I've stumbled on it and tried it in my insomnia research... over 5 years ago? I think examine.com recommended it. Pills didn't do anything for me but lavander oil seemed to help a little and it smells nice anyways, so I still use it occasionally, but in all fairness mostly when entertaining. To note, I don't think my problem is anxiety - if anything, I'm lately leaning towards ADHD.
One of the cons at that time was that lavander aromatherapy was supposed to build tolerance. I take it it's not a concern anymore?
(speaking of things that work even though nobody ever talks about them, maybe a post on inositol in the future?)
Presumably a placebo treatment for anxiety would wear off once you've been doing it so long that it's part of your baseline daily pill pack, rather than this exciting new thing that you're trying.
"I’m not sure how to even think about the difference between a placebo anxiety cure and a real anxiety cure."
Assuming equal effects, there is no difference between a placebo anxiety cure and a non-placebo anxiety cure. Where the ailment is itself a psychological symptom, the amelioration of that symptom is the goal of treatment, and it is not a failure mode for the treatment also to be psychological (as it mostly is in psychotherapy.)
Of course, the caveat above is important: "assuming equal effects."
I'll go further: although we factor out placebo effects in good RCTs, they are fully present in clinical practice. So even non-placebo drugs are often working partly by placebo in the clinical setting.
I'll go further yet: the above observations hold not only for psychological ailments, like anxiety, but for those we think of as physiological, like viral infections. The immune system is known to respond, often strongly, to psychological factors, so placebos effects are often at play in the administration of drugs for physiological ailments in a clinical setting.
Lesson: While it makes perfect sense to adopt the mindset of a "war on placebo effects" for RCTs in which the goal is to assess a drug, it makes no sense to continue that war into the clinical setting.
Is Silexan substantially different from what I would get if I asked for a lavender-oil extract in the supplements aisle at a national drug store chain?
I've come to understand my anxiety more deeply in the quest to defang it and I might be at a good point to try something like this. It would be really nice if it works quickly because I mostly have occasional outbursts or short 5-7 day stretches of anxiety and I'm bad at taking something regularly. I intensely hated cipralex! It made me feel like a sexless zombie!
I should make a habit of tracking my anxiety levels more regularly in Daylio and then try this!
Do you find a difference in those patients who it worked for with to respect to their internal awareness of their anxiety and symptoms?
1. How could silexan affect the cognitive performance and overall health in the short and in the long run?
2. Isn't lavender an estrogenic hormone disruptor?
3. Should silexan pair well with other supplements, such as L-theanine and/or sceletium?
4. Is it specifically helpful for GAD, or also for other forms of anxiety (such as panic attacks)?
5. To what extent should a silexan user be concerned about the rebound anxiety or other negative effects to their affect (e.g. emotional blunting) when discontinuing the supplement, lowering its dosage, or maintaining the same dose?
Scott, would you expect other lavender preparations (e.g. off-the-shelf herbal teabags containing lavender, or fresh-picked lavender leaves steeped or otherwise processed in a home kitchen) to have a comparable effect on anxiety, or would you expect the effect to be isolated to the pharmaceutically produced pills?
Is this available in the UK? I got off the tube a stop early while reading this to get it at Holland & Barret. Didn't have it. The Amazon link with delivery from US means it would be over £100.
Is there any specific evidence that patients don't mean-revert after some number of months? That's the problem I have with just about all these sorts of things.
How do people with lavender allergies react to this? Is it like [nut] allergies where inhaling [nut] wood smoke and even eating refined [nut] oil are okay?
I tried 80 mg silexan daily for GAD for a couple months. I've found the effect to be barely perceptible, and even that could be placebo. By comparison, I find that a small dose of a benzo (0.25 mg alprazolam) has an obvious impact. So I'm pretty skeptical of this analysis showing Silexan outperforming benzos. To be fair I only take benzos sparingly, so I've never developed any sort of tolerance.
FWIW, I recall an older Scott post promoting pregabalin for GAD based on result showing it outperformed SSRIs. Based on that recommendation I also tried pregabalin for a few months, and had maybe only a small positive impact (the main result was that I felt pleasantly drunkish for a day or so at the start). Then larger studies came out and showed that pregabalin really isn't all that effective for GAD.
My point here being, we should be skeptical about any data showing a drug outperforms benzos, especially when the mechanism isn't clear. People take benzos recreationally to chill out - see the million rap songs that reference Xanax. Until I see some rapper talk about getting fucked up on lavender extract, I will remain skeptical.
Probably irrelevant, but I do have a terrible sense of smell. If lavender does act through smell, this would explain why it didn't work for me. I'm skeptical of the smell theory, but do with that information what you will.
You might want to change the link to the Amazon version of the Silexan supplement; the part after /dp/B007TYY2JA/ is unnecessary and might contain undesirable tracking stuff etc. And if it contained an affiliate link (not sure whether it does), you might have to indicate that somewhere.
I got pretty excited while reading this until I clicked on the link to buy and realized that I had already tried this several years ago with no discernible effect. Which is funny, because SSRIs work *great* for me. I struggle a bit more with OCD than GAD though, so maybe that's the reason.
I have to say, given the background rate of this sort of thing, it's really refreshing to see a rundown of a drug or supplement which concludes that it's pretty likely that it's actually useful or worthwhile.
How is this the first time I've heard of this one! Just ordered it, arriving tomorrow, let's see how it goes! I'd say I have some anxiety most of the time, but its not bad enough for me to consider chronic use of Benzos or SSRIS. I'm totally functional, generally happy and high-energy, so I'm not too eager to put up with side-effects or addiction risk.
I've tried both Benzos and Phenibut, and they make me feel wonderfully calm, but I've heard too many horror stories to consider chronic use. I've tried some other supplements (Ashwagandha, L-Theanine), but they didn't have any obvious effect. I've tried Kratom years ago, and it sort of worked but it was more of a mild-cozy-high than just reducing anxiety, and I've heard accounts about bad withdrawals as well, plus it's mostly illegal now. I've tried Pregabalin but it just made me dizzy.
I haven't tried SSRIs as I haven't met anybody that hasn't had at least some side-effects (emotional blunting/weight-gain/reduced-sex-drive), and you can't just give it a shot as they take a month to work and and a month to taper off.
Silexan sounds too good to be true, but I'm excited now, hope it works!
One thing to consider is losing your sense of smell (anosmia) is strongly linked to depression. Depressed people have worse sense of smell, and completely losing your sense of smell puts you at risk of depression. The link is also true for people born without a sense of smell.
Once you factor in that smell is an extremely emotionally evocative sense, is related to memory, enjoying food, and even some social functions, the anosmia-depression connection doesn't look so odd.
I'm not one to put much stock in aromatherapy, but the smell-anxiety-depression link is a point in its favor.
(1) I'm not surprised this is by a German company; due to Anthroposophism (yes, really) and other hippy-dippy (sorry if that sounds dismissive, I can't think of a better catch-all term) stuff, Germans are surprisingly really into things like biodynamics.
(2) So this means if you buy their supplement, it will be properly manufactured and have the exact dosages of active ingredient they claim and be consistent between batches, because German. It also means that it could be along the same lines as homeopathy, because German: https://en.wikipedia.org/wiki/Commission_E
(3) Which means I'd have no qualms recommending, say, skin creams (https://www.drh.ie/) but supplements to replace pharmaceutical drugs? Ehhhh, maybe not so much.
(4) Lavender, as noted above, is a big deal in aromatherapy. Lavender is traditionally used for sleep aid and relaxing and easing anxiety. Of course, it also is recommended in traditional usage for anything that might ail you:
"Lavender essential oil is one of the most popular and versatile essential oils used in aromatherapy. Distilled from the plant Lavandula angustifolia, the oil promotes relaxation and believed to treat anxiety, fungal infections, allergies, depression, insomnia, eczema, nausea, and menstrual cramps.
In essential oil practices, lavender is a multipurpose oil. It is purported to have anti-inflammatory, antifungal, antidepressant, antiseptic, antibacterial and antimicrobial properties, as well as antispasmodic, analgesic, detoxifying, hypotensive, and sedative effects."
(6) So does this mean this wonder supplement is ringing snakeoil bells for me? Yes, but I can't 100% rule out that it does work. This may be a case like St. John's Wort, or it may be snakeoil.
But at the very least, if you take this, you'll smell of lavender and that's a soothing scent! (Also, while I applaud their thoroughness in testing every last possibility, I do wonder how on earth you would abuse lavender supplements; you take so much you smell like a detergent factory? https://methodproducts.co.uk/products/wild-lavender-concentrated-laundry-detergent/ )
The lavender pills didn't have much affect on me, but I didn't know it might take some weeks for the affect to kick in, so I'll try again. The topical oil does for sure help me fall asleep faster.
I'm curious Scott if you've had experience prescribing hydroxyzine for anxiety? It's an antihistamine and I only just learned about it. It's helping me simultaneously with allergies and anxiety.
And trazodone has been a miracle for sleep. Why would a person prescribe Ambien-type sleep meds when trazodone exists? Do people ever prescribe trazodone for anxiety? I tried taking it a lower dose during the day and it worked fine for anxiety for me.
I honestly thought you were building up to a punchline of "This is completely implausible, and here's how one can be appropriately skeptical of such claims." And in my defense, you led with a mention of The Daily Mail. And the same dude writing all the papers and being a coauthor on a couple of the meta-analyses?
April Fools?
But it sounds like you think there's something to it, so I clicked the link. Unfortunately my library doesn't have access to the Carlat Report. What are those effect sizes? Are those the standardized mean differences?
It doesn't seem like a stretch to say that this effect size is implausible. Look at the comparison to benzos.
The idea of the placebo effect in something like this has always amused me. That medicine didn't help your anxiety, you just think it did! You're not really calm, you just think you're calm!
I used to follow SSC before it was shut down. I've always enjoyed Scott's analyses. I re-discovered Scott recently via his critique of Ivermectin. I appreciate this specific article is not about Ivermectin. However, Scott made similar remarks in that particular analysis to this analysis. I am leaning toward the belief that Scott was wrong on his findings relating to Ivermectin. The point being that we should be careful not to downplay a study because it comes from big pharma as much as we should blindly accept a study because it comes from big pharma.
I've provided a link about Ivermectin (below) to show the level of Interference by NGOs (supposed third parties) in studies. Given how easily meta-analyses lead Scott to draw a conclusion that I now feel is wrong, I would encourage all of us to be more open minded and more careful in how we analyse meta-analyses.
To add to this, a senior medical authority (an MD specifically) whom I personally know well advised me that a large published study had confirmed the effectiveness of Ivermectin this year. I do not have a link to it but he's a very credible source.
This is the video (an open letter) about Ivermectin where one participant admits to undermining Ivermectin and to taking a bribe.
Scott cited a study that investigated addiction risk. Do we know of any reason to be concerned about any other health risks from taking this? Liver damage, interference with other drugs, other psychological risks, nutritional stuff, anything really?
Scott how likely do you think the specific brand is to make a difference? In Australia it looks like I could order the CalmAid brand but there's another local brand I could order for cheaper (still 80g Selexan in soft capsules: https://seremind.com.au/what-is-seremind/ ), so I'm wondering whether it's worth the additional cost for CalmAid or not.
There are millions of people taking supplements but 99.999% of that potential data goes to waste instead of being incorporated into studies and surveys. There has to be some low cost way to harvest the data. Nootroflix seems like a good idea for that but the execution needs improvement.
Scott, you might want to correct this statement: "Nobody is sure about the mechanism of action, but it probably involves serotonin 1A receptors, the same receptors blocked by mediocre anti-anxiety medication buspirone and some of the newer antidepressants."
Buspirone, along with related compounds, is an agonist at the 5-HT1A receptor. (It does not block the receptor, it simulates it.) It gets complicated because there are both post-synaptic 5-HT1A receptors as well as pre-synaptic 5-HT1A autoreceptors. The latter reduce secretion of 5-HT into the synapse, resulting in less 5-HT activity, including possibly at the post synaptic receptor. Another complication is that Buspirone is technically a high affinity partial agonist, which basically means it stimulates the receptor, but might in theory block the effect of other full agonists. But it would not be characterized as an antagonist.
It isn't quite clear where silexan fits into this. Kasper's study showed binding to the 5-HT1A receptor but it's not proven to act as an agonist as far as I can tell. He seems to believe it is and may be right.
A common drug that acts as a 5-HT1A antagonist is the beta-blocker pindolol. There was hope that by blocking pre-synaptic auto-receptors it might block negative feedback by SSIRs on serotonin output and thus increase the effectiveness of SSRIs, but that does not seem to have panned out.
Given your large reach, Scott, why don't you help organize a crowd-sourced cross-over study? Figure out how to make placebo version of these pills. Have people randomize themselves into blocks of time. Do daily anxiety measures using whatever app/website you prefer. I bet you could easily get 50+ volunteers with your reach.
Your article "Melatonin: Much More Than You Wanted To Know" totally changed my relationship to melatonin for the better. And since then, I've been much more open to glaring holes in my map of OTC meds. For $10 I'm willing to give this a shot.
Does anyone know how this drug is prepared? I assume there is some processing to change the ratio of constituents, as unprocessed lavender oil is toxic internally. All I have for now is: “a novel, well-defined preparation from Lavandula angustifolia for oral use” (Kasper 2014).
I was proscribed a low dosage of Quetiapine (40mg) to help me sleep and a side effect is that my anxiety is noticeably better. Not sure why the Cartlat Report says "too many side effects" for anxiety treatment.
"Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things" - except the name "Kasper" literally means "clown" in German...
As a former Office Director for Epidemiology, Postmarketing and Statistics at FDA for seven years, I have a few comments on the notion that Silexan may work and is without risk. First, in general, dietary supplements are not manufactured in a consistent and safe manner in that they are not required to meet any Good Manufacturing Requirements and have often been shown to have contaminants and varying dose. Second, do existing cited studies adequately identify adverse events --doubtful. Third, a well done RCT is needed for efficacy-requires adequate blinding and sample size. Forth, there is no doubt that placebo effect was operative in the cited studies. So caveat emptor for both the prescriber (recommender) and consumer.
I think I have a slightly higher prior when it comes to discounting good methodology in sponsored studies, but the cost does seem so low that trying Silexan is worth it.
Does anyone know if silexan is available in a vegetarian formulation? Unfortunately the softgels are made with gelatin (which is pretty much universally animal derived)
Anything that starts with a Daily Mail link has a tendency to update my priors away from whatever the link is claiming - I would hope that reputable professors could also find slightly more reputable papers to get interviewed in. (I will grant that the Carlat Report very much looks like a reputable source here.)
(If something's topical and an expert gets interviewed by all the papers including the Daily Mail, I won't count it against them, but if the only paper covering a story is the Mail then that's sometimes useful information to know.)
Lavender oil may be an endocrine disruptor. “Some of the components had varying degrees of estrogenic or anti-androgenic properties, as shown by their effects on estrogen receptor alpha and androgen receptor activities in human cells.” https://factor.niehs.nih.gov/2019/9/feature/3-feature-lavender/index.htm
I’m not sure what the literature might say about this, but I bought some because it’s cheap and can’t hurt. Been taking 160mg for about 4 days. Today, I noticed only at the end of the day that I fully forgot to take my second dose of Dexedrine. I was still feeling the effects, and I was fully focused on my work all day. I found it a little odd. If it keeps up, I might be able to reduce my dose.
This is the only change I’ve made. I did have two off Dexedrine days rather than one over the weekend, but I’ve had multiple days off before and recently without a similar effect. I’m not sure if there is any good reason that would be the effect, but I thought it might be meaningful.
Have been taking 160mg for 6 days. Haven't noticed much so far besides Lavander burps, which I don't mind. I'll keep at it for a while as the studies showed it started to work after a week.
Hm, I wonder how (or if) this affects the microbiome? From a cursory search it seems that lavender generally and linalool in particular are antimicrobial. Though perhaps 80mg is quite a small amount and quickly spreads out so wouldn't be in sufficient concentration to do much for very long?
At any rate, we're giving this a try, thanks for the inspiration!
I have a question that I don't see being discussed much. Continued availability. From what I can see, the only way to get this is through "Nature's Way Calmaid" and a similar product "Lavela ws 1265" both made by Schwabe. This single point of failure worries me.
Just before I wrote this comment, the option to buy a single pack was removed from amazon and can now only bought as a 12 pack.
I do not know much about the company. How much can we trust that these will keep being affordable/available? It seems prudent to wonder if they would double the price given the promising results+monopoly.
People may use Silexan to reduce/get off anti-anxiety meds. If this stops being available/affordable, their old meds may not work quite as well when they get back on it. That is a difficult decision to make.
Does anyone have any other thoughts about this?
Specifically - Has anybody here been using Schwabe(Nature's Way) products for many years? If so, can you vouch for availability/affordability?
Finally got around to trying this. Took a single 80mg capsule of what brand was recommended around the time my daily amphetamine (30mg, ER) was at Cmax.
Within a couple hours my sinuses were suffused with the scent of lavender with every breath. I didn't notice any improvement. Couple hours later, I was markedly more depressed and anxious than usual, and in comparison to yesterday, without any perceptible origin.
I had suspected that the SERT and 5-HT 1A effects might interact with the stimulant therapy, and it'd appear that was right. I'm susceptible to CNS overstimulation and while the muscle tension added by Silexan wasn't overly concerning, it plus the _added_ anxiety was uncomfortable and seemingly counterproductive.
I suppose the adverse effects could be nocebo, but I wasn't particularly anxious about taking it by the time I did. On the contrary, I was hoping it would help considering I'd been anxious the last few days. If anything, the stiffness and discomfort in my wrists and knees made itself known in and of itself rather than that being the product of consciously monitoring for effects. I'll pass on further trials! 😅
Note that this is of course an atypical reaction. I have the Met/Met COMT mutation that reduces monoamine clearance, and the serotonin agonism that Silexan causes through 5-HT 1A and SERT reuptake inhibition increases dopamine activity. (Initially going on amphetamine proved difficult and resulted in borderline rhabdomyelosis. I only successfully initiated it by titrating up from 1mg by the milligram every few days.)
I'm late to this party, but wanted to share that I was curious whether the reported trial results hold up to independent reanalysis. So I asked the senior researcher on this work Prof Roland von Känel if he would be willing to share the patient-level data. Prof Känel responded very kindly, and passed the question on to Schwabe Pharma, which apparently controls the data from their clinical trials, and their representative told me that the data cannot be shared as a matter of company policy. (For context, I am a medical researcher at a well-known university.)
The Psychiatrist on Youtube Dr. Tracey Marks has a video on it and says it works by increasing serotonin and Blocks NMDA receptors and Glutamate and thus helping GABA do its thing. It is implied by blocking NMDA you also get more BDNF. She doesn't state where she got this info but seems like a legit doctor.
And you are correct it is only in the GAD subset. Silexan is best thought of as a med - depakote and bupropion were derived from plants - and suffers the same limitations (industry sponsored, limited authorship) and strengths (large sample size) as other psych meds
In the _The Carlat Report_ podcast, I am seeing something quite concerning. They're saying that, while stuff like Silexan, SSRIs and benzos sometimes work for people who are _just starting treatment_, for people who have _treatment resistant_ anxiety, nothing seems to work.
> KELLIE: OK but this podcast is on treatment resistant anxiety disorder. And that was my frustration – I found nothing that worked! Does Silexan work in treatment resistant cases?
>
> AIKEN: Not that we know of. It has a large effect, but that’s in people just starting treatment. Treatment resistant anxiety is defined much like treatment resistant depression – failure to have a meaningful response to 1-2 therapies, usually antidepressants. And here’s where things get interesting, although not very inspiring. The paper you’re holding looked at whether adding something to an SSRI to could work when anxiety doesn’t respond to SSRIs. And like you said they concluded that nothing worked. And most of those studies involved which medication?
>
> KELLIE: Let me see… quetiapine, quetiapine, olanzapine…. Quetiapine. IN fact of the dozen studies they looked at over half of them involved atypical antipsychotics, and they didn’t work.
Also:
> But I have to acknowledge that Silexan – despite it’s large effect size – has never been studied in treatment resistant anxiety.
I just read this Aella repost from a while back. Maybe it’s not the lavender that helps, but the burps? TLDR she thinks her year long anxiety issues were actually gas, and they went away when she drank soda water and burped.
Given background odds, a 50% chance it works really well is pretty confident, I think.
I like everything about your analysis except your presumption that a big-named researcher would necessarily be male!
50%? You sounded way more confident than that in the post, at least to me!
Although, I guess, it would be a great deal even if it worked less well than SSRIs, given how side effects appear more manageable.
How serious is the miscarriage risk? Asking for someone with heightened anxiety due to a series of miscarriages.
If this is a real effect, why didn't we discover it decades ago? 'Common plant used in folk remedies turns out to be useful therapeutic' gives us aprin and digitoxin in the mid 19th century but nobody notices lavender until the 21st.
Silexan isn't really new, I've stumbled on it and tried it in my insomnia research... over 5 years ago? I think examine.com recommended it. Pills didn't do anything for me but lavander oil seemed to help a little and it smells nice anyways, so I still use it occasionally, but in all fairness mostly when entertaining. To note, I don't think my problem is anxiety - if anything, I'm lately leaning towards ADHD.
One of the cons at that time was that lavander aromatherapy was supposed to build tolerance. I take it it's not a concern anymore?
(speaking of things that work even though nobody ever talks about them, maybe a post on inositol in the future?)
Presumably a placebo treatment for anxiety would wear off once you've been doing it so long that it's part of your baseline daily pill pack, rather than this exciting new thing that you're trying.
"I’m not sure how to even think about the difference between a placebo anxiety cure and a real anxiety cure."
Assuming equal effects, there is no difference between a placebo anxiety cure and a non-placebo anxiety cure. Where the ailment is itself a psychological symptom, the amelioration of that symptom is the goal of treatment, and it is not a failure mode for the treatment also to be psychological (as it mostly is in psychotherapy.)
Of course, the caveat above is important: "assuming equal effects."
I'll go further: although we factor out placebo effects in good RCTs, they are fully present in clinical practice. So even non-placebo drugs are often working partly by placebo in the clinical setting.
I'll go further yet: the above observations hold not only for psychological ailments, like anxiety, but for those we think of as physiological, like viral infections. The immune system is known to respond, often strongly, to psychological factors, so placebos effects are often at play in the administration of drugs for physiological ailments in a clinical setting.
Lesson: While it makes perfect sense to adopt the mindset of a "war on placebo effects" for RCTs in which the goal is to assess a drug, it makes no sense to continue that war into the clinical setting.
Is Silexan substantially different from what I would get if I asked for a lavender-oil extract in the supplements aisle at a national drug store chain?
I've come to understand my anxiety more deeply in the quest to defang it and I might be at a good point to try something like this. It would be really nice if it works quickly because I mostly have occasional outbursts or short 5-7 day stretches of anxiety and I'm bad at taking something regularly. I intensely hated cipralex! It made me feel like a sexless zombie!
I should make a habit of tracking my anxiety levels more regularly in Daylio and then try this!
Do you find a difference in those patients who it worked for with to respect to their internal awareness of their anxiety and symptoms?
Five important questions:
1. How could silexan affect the cognitive performance and overall health in the short and in the long run?
2. Isn't lavender an estrogenic hormone disruptor?
3. Should silexan pair well with other supplements, such as L-theanine and/or sceletium?
4. Is it specifically helpful for GAD, or also for other forms of anxiety (such as panic attacks)?
5. To what extent should a silexan user be concerned about the rebound anxiety or other negative effects to their affect (e.g. emotional blunting) when discontinuing the supplement, lowering its dosage, or maintaining the same dose?
could i take silexan on top of SSRIs? ( i take fluvoxamine)
Scott, would you expect other lavender preparations (e.g. off-the-shelf herbal teabags containing lavender, or fresh-picked lavender leaves steeped or otherwise processed in a home kitchen) to have a comparable effect on anxiety, or would you expect the effect to be isolated to the pharmaceutically produced pills?
Is this available in the UK? I got off the tube a stop early while reading this to get it at Holland & Barret. Didn't have it. The Amazon link with delivery from US means it would be over £100.
Is there any specific evidence that patients don't mean-revert after some number of months? That's the problem I have with just about all these sorts of things.
Is this in replacement of lavender or lavender oil? Why not at least suggest or talk about the natural source.
How do people with lavender allergies react to this? Is it like [nut] allergies where inhaling [nut] wood smoke and even eating refined [nut] oil are okay?
Downside/upside if you take this without suffering from anxiety?
"finding no red flags example “other bias”, ie it was funded by the drug company"
Red flag _except_ other bias? (Also, i.e.?)
I tried 80 mg silexan daily for GAD for a couple months. I've found the effect to be barely perceptible, and even that could be placebo. By comparison, I find that a small dose of a benzo (0.25 mg alprazolam) has an obvious impact. So I'm pretty skeptical of this analysis showing Silexan outperforming benzos. To be fair I only take benzos sparingly, so I've never developed any sort of tolerance.
FWIW, I recall an older Scott post promoting pregabalin for GAD based on result showing it outperformed SSRIs. Based on that recommendation I also tried pregabalin for a few months, and had maybe only a small positive impact (the main result was that I felt pleasantly drunkish for a day or so at the start). Then larger studies came out and showed that pregabalin really isn't all that effective for GAD.
My point here being, we should be skeptical about any data showing a drug outperforms benzos, especially when the mechanism isn't clear. People take benzos recreationally to chill out - see the million rap songs that reference Xanax. Until I see some rapper talk about getting fucked up on lavender extract, I will remain skeptical.
Probably irrelevant, but I do have a terrible sense of smell. If lavender does act through smell, this would explain why it didn't work for me. I'm skeptical of the smell theory, but do with that information what you will.
You might want to change the link to the Amazon version of the Silexan supplement; the part after /dp/B007TYY2JA/ is unnecessary and might contain undesirable tracking stuff etc. And if it contained an affiliate link (not sure whether it does), you might have to indicate that somewhere.
I got pretty excited while reading this until I clicked on the link to buy and realized that I had already tried this several years ago with no discernible effect. Which is funny, because SSRIs work *great* for me. I struggle a bit more with OCD than GAD though, so maybe that's the reason.
I have to say, given the background rate of this sort of thing, it's really refreshing to see a rundown of a drug or supplement which concludes that it's pretty likely that it's actually useful or worthwhile.
I worry that it sounds like a monster from Dr Who.
How is this the first time I've heard of this one! Just ordered it, arriving tomorrow, let's see how it goes! I'd say I have some anxiety most of the time, but its not bad enough for me to consider chronic use of Benzos or SSRIS. I'm totally functional, generally happy and high-energy, so I'm not too eager to put up with side-effects or addiction risk.
I've tried both Benzos and Phenibut, and they make me feel wonderfully calm, but I've heard too many horror stories to consider chronic use. I've tried some other supplements (Ashwagandha, L-Theanine), but they didn't have any obvious effect. I've tried Kratom years ago, and it sort of worked but it was more of a mild-cozy-high than just reducing anxiety, and I've heard accounts about bad withdrawals as well, plus it's mostly illegal now. I've tried Pregabalin but it just made me dizzy.
I haven't tried SSRIs as I haven't met anybody that hasn't had at least some side-effects (emotional blunting/weight-gain/reduced-sex-drive), and you can't just give it a shot as they take a month to work and and a month to taper off.
Silexan sounds too good to be true, but I'm excited now, hope it works!
If it blocks serotonin 1A receptors like some SSRIs, would you expect an effect on depression?
I'm convinced to try it myself. Any particular capsules I should look for to mitigate the lavender burps?
One thing to consider is losing your sense of smell (anosmia) is strongly linked to depression. Depressed people have worse sense of smell, and completely losing your sense of smell puts you at risk of depression. The link is also true for people born without a sense of smell.
Once you factor in that smell is an extremely emotionally evocative sense, is related to memory, enjoying food, and even some social functions, the anosmia-depression connection doesn't look so odd.
I'm not one to put much stock in aromatherapy, but the smell-anxiety-depression link is a point in its favor.
(1) I'm not surprised this is by a German company; due to Anthroposophism (yes, really) and other hippy-dippy (sorry if that sounds dismissive, I can't think of a better catch-all term) stuff, Germans are surprisingly really into things like biodynamics.
(2) So this means if you buy their supplement, it will be properly manufactured and have the exact dosages of active ingredient they claim and be consistent between batches, because German. It also means that it could be along the same lines as homeopathy, because German: https://en.wikipedia.org/wiki/Commission_E
(3) Which means I'd have no qualms recommending, say, skin creams (https://www.drh.ie/) but supplements to replace pharmaceutical drugs? Ehhhh, maybe not so much.
(4) Lavender, as noted above, is a big deal in aromatherapy. Lavender is traditionally used for sleep aid and relaxing and easing anxiety. Of course, it also is recommended in traditional usage for anything that might ail you:
"Lavender essential oil is one of the most popular and versatile essential oils used in aromatherapy. Distilled from the plant Lavandula angustifolia, the oil promotes relaxation and believed to treat anxiety, fungal infections, allergies, depression, insomnia, eczema, nausea, and menstrual cramps.
In essential oil practices, lavender is a multipurpose oil. It is purported to have anti-inflammatory, antifungal, antidepressant, antiseptic, antibacterial and antimicrobial properties, as well as antispasmodic, analgesic, detoxifying, hypotensive, and sedative effects."
(6) So does this mean this wonder supplement is ringing snakeoil bells for me? Yes, but I can't 100% rule out that it does work. This may be a case like St. John's Wort, or it may be snakeoil.
But at the very least, if you take this, you'll smell of lavender and that's a soothing scent! (Also, while I applaud their thoroughness in testing every last possibility, I do wonder how on earth you would abuse lavender supplements; you take so much you smell like a detergent factory? https://methodproducts.co.uk/products/wild-lavender-concentrated-laundry-detergent/ )
The lavender pills didn't have much affect on me, but I didn't know it might take some weeks for the affect to kick in, so I'll try again. The topical oil does for sure help me fall asleep faster.
I'm curious Scott if you've had experience prescribing hydroxyzine for anxiety? It's an antihistamine and I only just learned about it. It's helping me simultaneously with allergies and anxiety.
And trazodone has been a miracle for sleep. Why would a person prescribe Ambien-type sleep meds when trazodone exists? Do people ever prescribe trazodone for anxiety? I tried taking it a lower dose during the day and it worked fine for anxiety for me.
A market has just been created on Manifold Markets: https://manifold.markets/AlvarodeMenard/will-an-independent-rct-study-evalu
I honestly thought you were building up to a punchline of "This is completely implausible, and here's how one can be appropriately skeptical of such claims." And in my defense, you led with a mention of The Daily Mail. And the same dude writing all the papers and being a coauthor on a couple of the meta-analyses?
April Fools?
But it sounds like you think there's something to it, so I clicked the link. Unfortunately my library doesn't have access to the Carlat Report. What are those effect sizes? Are those the standardized mean differences?
It doesn't seem like a stretch to say that this effect size is implausible. Look at the comparison to benzos.
I mean...really!
The idea of the placebo effect in something like this has always amused me. That medicine didn't help your anxiety, you just think it did! You're not really calm, you just think you're calm!
I used to follow SSC before it was shut down. I've always enjoyed Scott's analyses. I re-discovered Scott recently via his critique of Ivermectin. I appreciate this specific article is not about Ivermectin. However, Scott made similar remarks in that particular analysis to this analysis. I am leaning toward the belief that Scott was wrong on his findings relating to Ivermectin. The point being that we should be careful not to downplay a study because it comes from big pharma as much as we should blindly accept a study because it comes from big pharma.
I've provided a link about Ivermectin (below) to show the level of Interference by NGOs (supposed third parties) in studies. Given how easily meta-analyses lead Scott to draw a conclusion that I now feel is wrong, I would encourage all of us to be more open minded and more careful in how we analyse meta-analyses.
To add to this, a senior medical authority (an MD specifically) whom I personally know well advised me that a large published study had confirmed the effectiveness of Ivermectin this year. I do not have a link to it but he's a very credible source.
This is the video (an open letter) about Ivermectin where one participant admits to undermining Ivermectin and to taking a bribe.
https://www.bitchute.com/video/vIvTklLi7f5x/
I do appreciate this article isn't about Ivermectin. My focus is about improving using past analyses.
Scott cited a study that investigated addiction risk. Do we know of any reason to be concerned about any other health risks from taking this? Liver damage, interference with other drugs, other psychological risks, nutritional stuff, anything really?
Scott how likely do you think the specific brand is to make a difference? In Australia it looks like I could order the CalmAid brand but there's another local brand I could order for cheaper (still 80g Selexan in soft capsules: https://seremind.com.au/what-is-seremind/ ), so I'm wondering whether it's worth the additional cost for CalmAid or not.
There are millions of people taking supplements but 99.999% of that potential data goes to waste instead of being incorporated into studies and surveys. There has to be some low cost way to harvest the data. Nootroflix seems like a good idea for that but the execution needs improvement.
Scott, you might want to correct this statement: "Nobody is sure about the mechanism of action, but it probably involves serotonin 1A receptors, the same receptors blocked by mediocre anti-anxiety medication buspirone and some of the newer antidepressants."
Buspirone, along with related compounds, is an agonist at the 5-HT1A receptor. (It does not block the receptor, it simulates it.) It gets complicated because there are both post-synaptic 5-HT1A receptors as well as pre-synaptic 5-HT1A autoreceptors. The latter reduce secretion of 5-HT into the synapse, resulting in less 5-HT activity, including possibly at the post synaptic receptor. Another complication is that Buspirone is technically a high affinity partial agonist, which basically means it stimulates the receptor, but might in theory block the effect of other full agonists. But it would not be characterized as an antagonist.
It isn't quite clear where silexan fits into this. Kasper's study showed binding to the 5-HT1A receptor but it's not proven to act as an agonist as far as I can tell. He seems to believe it is and may be right.
A common drug that acts as a 5-HT1A antagonist is the beta-blocker pindolol. There was hope that by blocking pre-synaptic auto-receptors it might block negative feedback by SSIRs on serotonin output and thus increase the effectiveness of SSRIs, but that does not seem to have panned out.
What about just stuffing your pillow with lavender blossoms? Where I live you can't swing a dead cat without hitting a lavender farm.
Given your large reach, Scott, why don't you help organize a crowd-sourced cross-over study? Figure out how to make placebo version of these pills. Have people randomize themselves into blocks of time. Do daily anxiety measures using whatever app/website you prefer. I bet you could easily get 50+ volunteers with your reach.
It's worth mentioning that the quotes at the beginning of the article are from Peter Volz, who also has a significant conflict of interest.
Source: https://pubmed.ncbi.nlm.nih.gov/29150713/
In your second paragraph the hyphenation is 'Hans-Peter Volz', not 'Hans Peter-Volz'.
Your article "Melatonin: Much More Than You Wanted To Know" totally changed my relationship to melatonin for the better. And since then, I've been much more open to glaring holes in my map of OTC meds. For $10 I'm willing to give this a shot.
Does anyone know how this drug is prepared? I assume there is some processing to change the ratio of constituents, as unprocessed lavender oil is toxic internally. All I have for now is: “a novel, well-defined preparation from Lavandula angustifolia for oral use” (Kasper 2014).
I was proscribed a low dosage of Quetiapine (40mg) to help me sleep and a side effect is that my anxiety is noticeably better. Not sure why the Cartlat Report says "too many side effects" for anxiety treatment.
When I read that title, I thought "Silexan" is a language and "Lavenders Game" is the translation of "anxiety" into that language. Inglish is hard!
"Professor Kasper seems like as legitimate and respectable a researcher as you can get for these kinds of things" - except the name "Kasper" literally means "clown" in German...
As a former Office Director for Epidemiology, Postmarketing and Statistics at FDA for seven years, I have a few comments on the notion that Silexan may work and is without risk. First, in general, dietary supplements are not manufactured in a consistent and safe manner in that they are not required to meet any Good Manufacturing Requirements and have often been shown to have contaminants and varying dose. Second, do existing cited studies adequately identify adverse events --doubtful. Third, a well done RCT is needed for efficacy-requires adequate blinding and sample size. Forth, there is no doubt that placebo effect was operative in the cited studies. So caveat emptor for both the prescriber (recommender) and consumer.
I think I have a slightly higher prior when it comes to discounting good methodology in sponsored studies, but the cost does seem so low that trying Silexan is worth it.
Results so far: I strongly dislike burping lavender. However, I do feel fairly calm, so...
LavENDER'S GAME. Nice.
Does anyone know if silexan is available in a vegetarian formulation? Unfortunately the softgels are made with gelatin (which is pretty much universally animal derived)
Niacin - a B vitamin (works very well) and other natural remedies - this is a non commercial site: http://doctoryourself.com/anxiety.html
Anything that starts with a Daily Mail link has a tendency to update my priors away from whatever the link is claiming - I would hope that reputable professors could also find slightly more reputable papers to get interviewed in. (I will grant that the Carlat Report very much looks like a reputable source here.)
(If something's topical and an expert gets interviewed by all the papers including the Daily Mail, I won't count it against them, but if the only paper covering a story is the Mail then that's sometimes useful information to know.)
Lavender oil may be an endocrine disruptor. “Some of the components had varying degrees of estrogenic or anti-androgenic properties, as shown by their effects on estrogen receptor alpha and androgen receptor activities in human cells.” https://factor.niehs.nih.gov/2019/9/feature/3-feature-lavender/index.htm
Where is this obtained, for a trial? Can it be ordered online?
Whoops!
Lavender oil was one of the few things that was able to counteract caffeine induced sleep maintenance insomnia. This was my best theory about it: https://www.reddit.com/r/DNA/comments/kj7ztm/caffeine_anxiety_sleep_disruption_and_snp/
I can't figure out how to buy it in either Turkey or Russia :(
I just wanted to mention that I loved the stand up crow comedian, in case you've been unsure about using sporadic memes.
I’m not sure what the literature might say about this, but I bought some because it’s cheap and can’t hurt. Been taking 160mg for about 4 days. Today, I noticed only at the end of the day that I fully forgot to take my second dose of Dexedrine. I was still feeling the effects, and I was fully focused on my work all day. I found it a little odd. If it keeps up, I might be able to reduce my dose.
This is the only change I’ve made. I did have two off Dexedrine days rather than one over the weekend, but I’ve had multiple days off before and recently without a similar effect. I’m not sure if there is any good reason that would be the effect, but I thought it might be meaningful.
Have been taking 160mg for 6 days. Haven't noticed much so far besides Lavander burps, which I don't mind. I'll keep at it for a while as the studies showed it started to work after a week.
Hm, I wonder how (or if) this affects the microbiome? From a cursory search it seems that lavender generally and linalool in particular are antimicrobial. Though perhaps 80mg is quite a small amount and quickly spreads out so wouldn't be in sufficient concentration to do much for very long?
At any rate, we're giving this a try, thanks for the inspiration!
I have a question that I don't see being discussed much. Continued availability. From what I can see, the only way to get this is through "Nature's Way Calmaid" and a similar product "Lavela ws 1265" both made by Schwabe. This single point of failure worries me.
Just before I wrote this comment, the option to buy a single pack was removed from amazon and can now only bought as a 12 pack.
I do not know much about the company. How much can we trust that these will keep being affordable/available? It seems prudent to wonder if they would double the price given the promising results+monopoly.
People may use Silexan to reduce/get off anti-anxiety meds. If this stops being available/affordable, their old meds may not work quite as well when they get back on it. That is a difficult decision to make.
Does anyone have any other thoughts about this?
Specifically - Has anybody here been using Schwabe(Nature's Way) products for many years? If so, can you vouch for availability/affordability?
The current amazon link no longer works.
Finally got around to trying this. Took a single 80mg capsule of what brand was recommended around the time my daily amphetamine (30mg, ER) was at Cmax.
Within a couple hours my sinuses were suffused with the scent of lavender with every breath. I didn't notice any improvement. Couple hours later, I was markedly more depressed and anxious than usual, and in comparison to yesterday, without any perceptible origin.
I had suspected that the SERT and 5-HT 1A effects might interact with the stimulant therapy, and it'd appear that was right. I'm susceptible to CNS overstimulation and while the muscle tension added by Silexan wasn't overly concerning, it plus the _added_ anxiety was uncomfortable and seemingly counterproductive.
I suppose the adverse effects could be nocebo, but I wasn't particularly anxious about taking it by the time I did. On the contrary, I was hoping it would help considering I'd been anxious the last few days. If anything, the stiffness and discomfort in my wrists and knees made itself known in and of itself rather than that being the product of consciously monitoring for effects. I'll pass on further trials! 😅
Note that this is of course an atypical reaction. I have the Met/Met COMT mutation that reduces monoamine clearance, and the serotonin agonism that Silexan causes through 5-HT 1A and SERT reuptake inhibition increases dopamine activity. (Initially going on amphetamine proved difficult and resulted in borderline rhabdomyelosis. I only successfully initiated it by titrating up from 1mg by the milligram every few days.)
The link for the brand you recommend patients no longer works.
i bought a tin of assorted vitamins, and i tell my body what type of placebo i'm eating each day, seems to work wonders
Hi,
I'm late to this party, but wanted to share that I was curious whether the reported trial results hold up to independent reanalysis. So I asked the senior researcher on this work Prof Roland von Känel if he would be willing to share the patient-level data. Prof Känel responded very kindly, and passed the question on to Schwabe Pharma, which apparently controls the data from their clinical trials, and their representative told me that the data cannot be shared as a matter of company policy. (For context, I am a medical researcher at a well-known university.)
Just published large German sleep study with positive results for lavender, more effective than benzos:
https://www.mdpi.com/2227-9032/11/1/77
The Psychiatrist on Youtube Dr. Tracey Marks has a video on it and says it works by increasing serotonin and Blocks NMDA receptors and Glutamate and thus helping GABA do its thing. It is implied by blocking NMDA you also get more BDNF. She doesn't state where she got this info but seems like a legit doctor.
Excellent article. Agree with that limitation. The reference for the 0.87 effect size was from a paper that had no industry ties (or Kasper ties):
https://pubmed.ncbi.nlm.nih.gov/27861196/
And you are correct it is only in the GAD subset. Silexan is best thought of as a med - depakote and bupropion were derived from plants - and suffers the same limitations (industry sponsored, limited authorship) and strengths (large sample size) as other psych meds
In the _The Carlat Report_ podcast, I am seeing something quite concerning. They're saying that, while stuff like Silexan, SSRIs and benzos sometimes work for people who are _just starting treatment_, for people who have _treatment resistant_ anxiety, nothing seems to work.
> KELLIE: OK but this podcast is on treatment resistant anxiety disorder. And that was my frustration – I found nothing that worked! Does Silexan work in treatment resistant cases?
>
> AIKEN: Not that we know of. It has a large effect, but that’s in people just starting treatment. Treatment resistant anxiety is defined much like treatment resistant depression – failure to have a meaningful response to 1-2 therapies, usually antidepressants. And here’s where things get interesting, although not very inspiring. The paper you’re holding looked at whether adding something to an SSRI to could work when anxiety doesn’t respond to SSRIs. And like you said they concluded that nothing worked. And most of those studies involved which medication?
>
> KELLIE: Let me see… quetiapine, quetiapine, olanzapine…. Quetiapine. IN fact of the dozen studies they looked at over half of them involved atypical antipsychotics, and they didn’t work.
Also:
> But I have to acknowledge that Silexan – despite it’s large effect size – has never been studied in treatment resistant anxiety.
I just read this Aella repost from a while back. Maybe it’s not the lavender that helps, but the burps? TLDR she thinks her year long anxiety issues were actually gas, and they went away when she drank soda water and burped.
https://aella.substack.com/p/anxiety-and-the-path-of-least-resistance-5f6