1. I think the active ingredient is linalool, but I don't know much about this or why you can't just give that to people.
2. No, it's not just about which neurotransmitter system you affect, it's about how you affect it. Both SSRIs and LSD affect serotonin, but in very different ways.
"Natural products, including essential oils and their components, have been used for their bioactivities. Linalool (2,6-dimethyl-2,7-octadien-6-ol) is an aromatic monoterpene alcohol that is widely found in essential oils and is broadly used in perfumes, cosmetics, household cleaners and food additives. This review covers the sources, physicochemical properties, application, synthesis and bioactivities of linalool. The present study focuses on the bioactive properties of linalool, including anticancer, antimicrobial, neuroprotective, anxiolytic, antidepressant, anti-stress, hepatoprotective, renal protective, and lung protective activity and the underlying mechanisms. Besides this, the therapeutic potential of linalool and the prospect of encapsulating linalool are also discussed. Linalool can induce apoptosis of cancer cells via oxidative stress, and at the same time protects normal cells. Linalool exerts antimicrobial effects through disruption of cell membranes. The protective effects of linalool to the liver, kidney and lung are owing to its anti-inflammatory activity. On account of its protective effects and low toxicity, linalool can be used as an adjuvant of anticancer drugs or antibiotics. Therefore, linalool has a great potential to be applied as a natural and safe alternative therapeutic."
In general, you shouldn't just rub on or inhale or swallow essential oils, but linalool is used amongst other things as a food additive so it must be safe for consumption. I don't know the level of linalool that would be effective as a medication versus how much is toxic, so perhaps that is part of the reason why you can't just stick the oil in a capsule and give it to people:
I spent some time looking at the silexan papers (https://gwern.net/doc/psychiatry/anxiety/lavender/index) and I couldn't find any evidence that it's *not* linalool or that linalool essential oil from other plants like thyme shouldn't work, and there's plenty of work on linalool itself, not to mention that there are anxiolytic claims for other plants which contain linalool.
So I bought some and have been alternating between brand-name silexan CalmAid™ and a random linalool essential oil off Amazon, and I can't tell any difference in the effect - although they both have very distinct tastes/aftertastes so I have no idea how to run a self-blinded experiment there. (Linalool is not the 'lavender' taste of silexan, so if I added a lavender component, I may just be recreating silexan; if one could *remove* linalool from silexan instead, I think it would still burp the same lavender flavor, but I dunno how one would do that.)
No I was referring to the imagined researcher in this statement -- "Usually there will only be one academic institution or team that’s really committed, and if it has a prestigious leader, his name will be on all of the papers."
Is there really a "right" way to use pronouns in this context? I guess you could say "his/her/their/[xir...]" but it starts to get cumbersome. "their" works but can be confusing in some contexts (is "their" referring to the leader, or the team/institution?). I sometimes alternate "his" and "her" (which is also convenient if you're discussing two hypothetical people simultaneously)--but in an isolated example like this, ofc you can't tell if that is what Scott is doing.
It's easy enough to say "the name" -- this has always been a pet peeve of mine as a woman scientist. It's not that hard to fix and younger women need to stop thinking they're unusual if they go into STEM.
“The name” sounds wrong; “their name” sounds like he’s referring to the team; “her name” is the sort of construction Scott very commonly uses, but would be a bit odd here since researcher he’s indirectly talking about is male.
It’s really helpful for clarity and elegance to be able to use gendered pronouns in a generic non-gendered way in a piece of writing. I can see why you might have a problem with someone using only male pronouns in this way, but if they’re used interchangeably, what’s the problem?
I would actually be willing to bet (money) that Scott uses female pronouns in this way more often than male, precisely for the reason that even if you split it 50-50, then 50% of the time some people will think you only use male ones.
Given that it’s a useful linguistic construction and it seems like the ideal outcome would be if it became established practice to split it 50-50, I think it would be nice not to criticise people who are indifferent to whether they use male or female pronouns in this way as if they’re staunch advocates of only using male ones!
I think "Their name" works in this sentence because the antecedent is clearly the leader - they're the noun closest to the pronoun and the only one that makes sense in context.
"Usually there will only be one academic institution or team that’s really committed, and if it has a prestigious leader, that name will be on all of the papers."
Couldn't we say "that name" instead of "the" or "their"? I am almost certain that "that" is the appropriate option here and it doesn't have the issues of "the" or "their". Perhaps it has different issues I am unaware of?
In this context that would be genuinely ambiguous as to which name was meant. 'That person's name' would work. But in this case, the context- that this is a real situation, with a male researcher- justifies the use of 'he'.
I would use "their" there without a moment's thought, and I imagine the singular "name" would eliminate any confusion about the referent. It wouldn't cross my mind that it might be referring to some kind of scientist team name like "Raiders".
Scott, you can solve this the way Douglas Hofstadter did in Metamagical Themas. Just use she and her for the ambiguous pronouns. Save everyone a bit of energy.
Do you honestly think that anyone with brains enough to read this blog assumes that women are less capable than men in research? This is about language, style and concision, not about bias. Sheesh!
It is possible to simultaneously believe that men and women are equally capable and to refer to an unnamed big researcher as male without thinking about it, particularly when there is a hisorical prevalence of a particular gender in that position.
The point is to consciously write so as (a) not make that automatic choice, and (b) make it less likely for others to do so.
When you say "Silexan might cause miscarriage during pregnancy and they should avoid it until this has been investigated better." does that mean that somebody in a trial was pregnant and miscarried, that for some reason they think it has a defined mechanism of action that harms pregnancy, or just to avoid accidentally recommending something bad to pregnant women without any actual reason why it's bad?
Not trying to be accusatory, but I see lots of things that "may have risk against pregnant women" and am curious, especially given it's so early in development overall
The guidelines around essential oils and pregnancy seem to be "anything the mother consumes can cross over to the foetus via the placenta so since we don't really know the effects, better not to use them".
So don't take the capsules, but you can use the oils in diffusers to smell them, which may help reduce anxiety anyway:
"Guidelines for using essential oils while pregnant
First off, avoid using essential oils during the first trimester. The first trimester is the most critical period during pregnancy, and any risk of exposing the fetus to a toxic substance should be avoided at all costs.
But in your second or third trimesters, keep the following safety protocols in mind when you’re using approved essential oils.
Don’t ingest essential oils
Even if you aren’t pregnant, essential oils aren’t meant to be taken orally unless under the direct supervision of an expert or physician. Many essential oils can pose toxicity risks when ingested — for you and, potentially, your baby.
Focus on aromatherapy
In general, most medical experts agree that aromatherapy is a safer option for pregnant people as opposed to topical applications. This simply means that you should use your essential oils in a diffuser rather than applying them to your skin."
You shouldn't use essential oils in early pregnancy because they could potentially cause uterine contractions or adversely affect your baby in their early developmental stages, explains Jill Edwards, N.D., an Oregon-based doctor of naturopathic medicine who specializes in prenatal care.
More research needs to be conducted on the topic, but it's always better to be safe than sorry. Pregnant women should also avoid aromatherapy products and treatments in the first trimester, since essential oils are the key ingredients used in aromatherapy.
Essential Oils in the Second and Third Trimesters
"In the second and third trimesters, some essential oils are safe to use, as your baby is more developed," Edwards adds. These include lavender, chamomile, and ylang ylang—all of which calm, relax, and aid sleep. Here are some tips:
Stick with quality essentials oils from a reputable brand unadulterated, advises the International Federation of Professional Aromatherapists (IFPA).
Only use essential oils externally because ingesting them may cause miscarriage, lead to preterm labor, or negatively affect your fetus.
Dilute essential oils with a carrier oil—like olive oil or coconut oil—before applying to the skin. "
There is no shortage of advice from authorities telling pregnant women what not to do. Very little of it, including advice against taking medication or supplements during pregnancy is based on scientific or statistical proof. All of this seems very CYA to me or possibly paternalistic. With a few exceptions, based on large registry numbers looking at various agents, there is minimal ATTRIBUTABLE risk to offspring or pregnancies due to various medications commonly employed. . For some reason psychiatric medications or supplements are singled out for being easily dispensed with during pregnancy. Meanwhile women are left with the choice of feeling incredible angst and guilt if anything goes wrong with her pregnancy (which on a statistical basis is far more likely to happen due to inherent risk of pregnancy than to anything they ingest), or suffer with untreated anxiety for the duration.
I mean, it *is* CYA, for both the doctor *and* the mother. If you don't warn them, and they take the medication (with your knowledge) and something bad happens with the pregnancy who do you expect will take the heat for that once the mother finds out the drug she was taking may have been a contributing factor in the complications? How upset will the mother be at that point, with the classic 'why didn't anybody tell me'?
You can't just lie about it (including a lie of omission), you have to give the woman the information to make her own choice (suggesting doctors shouldn't even *tell* the woman for her own good sounds 'paternalistic' to me but YMMV).
I do agree that women having unwarranted feelings of guilt when something goes wrong in a pregnancy is a problem, but you tackle that issue on it's own merits not by hiding potentially important information from the mother, especially since those feelings of guilt can crop up even if she was not engaging in any potential risk factors.
I capitalized attributable because it has a specific definition in this context. Many of the Supposedly possible risks can be attributed to the medication because those some risks are overwhelmingly inherent in pregnancy itself. Unless this context is explained to the expectant mom they are not being given appropriate informed consent.
For that matter, risks associated with no treatment need to be explained to give an accurate picture. Untreated anxiety and depression have been associated with higher rates of low birth weight, prematurity and failure to bond. how many pregnant moms to be are given that information from their busy ob rather as opposed to a list of dont’s? I can tell you from treating these scared women, not nearly all of them.
All the women I know who became mothers were right grateful for every shred of information, advice, and even informed speculation they could pry out of their OBs -- whether or not "scientifically proven" (whatever that means). They were all big girls, and could make up their own minds perfectly comfortably on whether or not to take the advice, how much weight they wanted to put on this speculated risk versus this other inconvenience, et cetera.
Maybe the paternalistic attitude here is yours, in that you would appear to fear the poor women will be overwhelmed by too much information, or incapable of mustering up the gumption to reject advice they don't find persuasive -- in short, be not so good at adulting.
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.
I disagree with the assumptions here - there are dozens of folk remedies that probably have some chemical basis, and we still haven't gotten around to investigating most of them. Research into St. John's Wort as an antidepressant is only a few decades old. A good example from outside of psychiatry is artemisinin, an ancient Chinese folk remedy for malaria that was isolated and inducted into the regular medical system in the 1970s.
I have suspicions that Chinese herbal medicine might have a number of other legitimately valuable compounds here and there which haven't been discovered so far because most Western researchers aren't familiar with them, and most Chinese medical research is of very low quality. There are lots of studies on traditional Chinese medicine which turn up positive results, but don't really mean much because the research is untrustworthy. But just because the research is untrustworthy doesn't mean that the treatments *don't* do anything. Some interventions, like accupuncture and moxibustion, which could be replicated anywhere if they worked without the need for specific plants or extracts, have already been tested to death and we can be pretty sure they don't work. But there's nothing strange about plants having real medicinal effects, and I think the herbal side of Chinese medicine is still mostly uncharted by modern science.
There's also the question of side effects and toxicity. Anyone can collect herbs and brew up a tea. If your symptoms are bad and the net effect is positive you will continue even if it's slowly trashing your liver.
Herbal medicine uses plant names as if they are indivisible units but any random plant is likely to have hundreds or thousands of different molecules that are biologically active in humans humans. The cultivars we eat are special cases that have had their worst toxins cleaned up and food value bumped up over the years.
Conventional pharmacology aims to isolate an active molecule and maybe alter it a bit to ramp up its function - and make it patentable! - which eliminates an array of potentially problematic molecules from the product.
I'm not really a chemistry person (or a lab person, or a physical world person, or a useful person at all), but it seems insane we've ever isolated any useful chemicals from plants at all! How do you actually know which one has the effect without trying thousands? Do you actually just try thousands?
You actually just do try thousands, yes. And look for ones that have similar structures to chemicals that are known to be active/chemicals in the body. But a lot of psychoactive compound research in the midcentury was chemists isolating compounds and testing them on animals (and sometimes themselves!) based on structural similarities.
And it's fairly unlikely that you're not a useful person if you know how to read and write coherently, by the way.
Oh I don't doubt I *could* be useful, but I concern myself with my silly little numbers and functions and stay away from the messy stuff that affects the real world. But that doesn't mean I can't be curious! Its incredible that they managed to work out so many useful molecules back in the day. I mean, it feels crazy that we have a good understanding of molocules regardless, but the brilliant inferences which are necessary amaze me. The lab sciences are marvels of human intelligence and ingenuity
Tens of thousands, typically, for even a modest drug, and probably millions for each entire new classification of drug.
It isn't completely blind, though. Some discoveries come from careful observation of the natural world, e.g. for antibiotics plants and fungi are rich potential sources, since they must fight off bacterial invasion the way we do, e.g. penicillin is a natural compound synthesized by a mold to kill invading bacteria, and was discovered when Fleming noticed some nasty mold was wiping out his nice bacterial cultures.
Others these days are driven by understanding of the target biomolecule -- you want to inhibit this enzyme, and knowing its structure or that it's homologous to some other enzyme inhibited by this class of molecules -- gives you a lead on what types of compounds (in terms of their chemical structure) might have a hope of working. The most famous case of this that comes to mind are the protease inhibitors introduced in the 90s that changed AIDS from pretty much a death sentence to something far more manageable. Supposedly these were deliberately designed to interfere with a key assembly step of HIV protease, an enzyme the virus needs to reproduce[1].
Some drugs are developed by observing unexpected side effects of other drugs -- Viagra is famous this way, it was originally being studied for treating heart failures, and only in human trials did somebody notice all the men were getting lots of stiffies. Amphetamine was discovered by someone trying to improve on ephedrine as a bronchodilator.
Many leads come from follklore and folk medicine, e.g. aspirin derived from the folk remedy of willow bark tea, quinine was discovered in bark used by Peruvian natives to control malaria, and of course all of the the various cocaine derivatives come from the folk use of the coca plant.
In addition, every big pharma firm maintains a giant library of many thousands of compounds that have been synthesized for prior projects that they will routinely test against new targets just on the off chance one might work.
It is nevertheless incredibly arduous, the major reason for the high cost of new drugs, and many people have struggled to make it more efficient. Many have pinned their hopes on computer modeling, either abstract or by actually simulating the chemistry, but this has so far proven fairly disappointing, or at least far less useful than was hoped 40 years ago[2].
You might think that if you know the shape and reactivity desired, because you've completely characterized the receptor let us say, you could just tell the organic chemist to go make a molecule of this particular size and shape, with this and such kind of reactive group hanging off it. And sometimes that kind of works -- certainly it's a big part of optimizing a molecule once it seems promising.
But first of all, a molecule's reactivity in vivo is often an exquisite balance of many more factors than just its shape and most obviously functional groups. How flexible it is, how its reactivity changes with changes in shape or pH or the microenvironment of a protein's active site all turn out to often matter a lot, and we are very poor at predicting any of those characteristics for any molecule more complex than, say, water. And secondly, organic chemists can rarely fully explore the geometric and chemical possibilities for molecules. We synthesize compounds fairly crudely, by mixing them up and supplying heat. But biochemically molecules are synthesized far more directly, like construction equipment stacking this on top of that and welders solidifying the links. Nature is capable of synthesizing weirdly complex molecules, with 3D shapes and connections that defy the lab. So although we have made progress on identifying candidate shapes, there is still a big role for natural substances, synthesized by plants and unicellular organisms, because they explore a part of the space of molecules of a given size that are still difficult or impossible for us to explore synthetically[3].
----------------
[1] The AIDS virus codes for *all* its proteins to be made in one long strand, like model parts on a runner, and the protease is what snips them apart into separate protein strands that can become functional. Without the protease, the virus cannot reproduce because while all the parts can be made, they cannot be assembled into a whole functioning virus.
[2] One of the more spectacular failures was IBM's Watson Health, which aimed to bring the awesome power of AI to things like diagnosing cancer, identifying promising drug targets, and so on.
It ended up failing miserably at all these tasks, and people are still not entirely sure why, except that doing well at this particular pattern matching seems to require some magic pixie dust that is common enough in the human cerebrum that we rather take it for granted, but which is very, very difficult to program, perhaps because we don't even really know what it is.
This is all incredible stuff! It's really amazing what humans managed to accomplish with it. But what was the process of finding, say, just penicillin? Like you see the fungus killing bacteria, how do you know what it's doing to accomplish that?
You don't have to be a big pharma company to screen new drug compounds. There are companies with large libraries of compounds that will run your assay on tens of thousands of candidates and identify any positive hits. You then take those positive hits and look at their kinase maps for possible drug-drug interactions and specificity, and do some other analyses. (Something druggable needs to be able to survive the stomach if it's going to be orally administered. It needs to be soluble in something we can give humans. It needs to be stable, etc.)
The trick is to develop a meaningful assay. There's always an assumption in vitro that the experimental setup you're using will translate in a meaningful way to a full human system. And since you're basically ignoring every other system when you take a single cell type, that's bound to be a confounding factor. For example, you're studying breast cancer so you take breast cancer cells. Except what about other cell infiltrates that are often found in tumors, like tumor-associated macrophage, fibroblasts, etc? Extrapolating from simple models out to complex systems is where it becomes surprising that we find anything at all.
I will say that I don't think drug screening is the determining factor in driving drug development costs. A phase I clinical trial runs into the millions of USD, and a phase III trial is at least tens of millions. Within that, the per-patient cost for the trial will probably be north of $10k/patient (depending on the indication), plus large clinical monitoring costs, data management, drug manufacturing and P&L, pharmacovigilance, PK, IVRS, and stats, to name a few.
Once you think you have isolated something you can start seeing how it combines to arrays of different chemicals to get clues about its structure and similarities with other known molecules. It's a long process.
As far as I know it has been used for a long time in Europe as a folk remedy. The etymology of the name “lavender” comes from French, prior to that from Latin “lavare” meaning “to wash.” Basically implying “everything should be washed with this in the water,” which is a high level of remedization. The interwebs says it goes back to Ancient Greece & Rome.
For what it's worth, amethyst (purple quartz) is named for the Greek belief that it was protective against inebriation.
In this case, we can be certain from the basic chemistry and physics of the situation that there is no such protective effect, but it's still named amethyst.
Yeah, but only if you align the crystals properly with your personal magnetic field. That's why it doesn't work for some people, they haven't done the alignment properly. Plus misaligned amethyst can give you smelly farts, but I guess if you just got addicted to meth you have bigger problems now anyway.
See Vitamin D. The problem isn't identifying them, it's working out if, and especially when they work. For every plant X, maybe the roots work, maybe the leaves. Maybe this supplier is just bad, or they skipped a certain step when processing. Maybe it helps, but only for a subset of people. Maybe it helps, but only for a subset of the condition. Dosage. Interactions.
Just recently came out the mother of all meta-analyses on whether coffee is healthy or not. Care to guess the result? Coffee is very good, but only when filtered. If pot-boiled it keeps certain oils that dramatically increase cholesterol. Espresso is so-so. We still aren't clear if decaf has the same benefits. And that's freaking coffee!
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?)
Inositol was third from the bottom in my old nootropics survey ( https://slatestarcodex.com/2016/03/01/2016-nootropics-survey-results/ ). I agree it seems to work for a small subset of people - I recently saw someone speculate mostly for people with PCOS, though I can't confirm this.
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.
After around 2 months of regular lavender pill usage, it still feels like this exciting new thing that has made my headspace immensely better - so this might be the strongest placebo yet devised /s
"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.
I'd argue that most of the benefit of having drugs that "really" do something instead of relying on the placebo effect is that they still work after the drug isn't exciting or new anymore. There's lots of stuff that seems to intensify the placebo effect, and much of it won't be present after a few weeks of home use.
I'm a huge fan of RCTs and finding drugs that have a reproducible physiological effect independent of psychological factors.
Having said that, I also believe that psychological effects, while highly variable in several dimensions (I suspect I'm a low responder), can sometimes be surprisingly large and enduring.
For example, with many viral infections, it wouldn't surprise me if psychological effects could kick your immune system into high gear, with the outcome that the infection is overcome and you're effectively cured. No worry about anything wearing off there.
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?
Doesn't lavender oil contain strong hormone disruptors? Presumably taking the unprocessed oil would supply not enough Silexan or too much everything else.
After further investigation: apparently standard lavender-oil extracts are marketed as "not intended for human consumption". And after trying half a drop, I agree with that take.
You can put dried lavender flowers in desserts. It pairs decently with sweet & lemony, ie lemon cake with lavender-infused icing. Not sure about dose there.
There will have been more of the active ingredients in a single drop of extract than in a slice of lavender-iced cake. I've seen them steam-distilling lavender oil and you have to put in a lot of flowers to get out an appreciable amount of oil. The essential oil is about a hundred times more concentrated than the plant. Eating the flowers is fine but pure essential oils are for external use only.
Lavender tea is known for its calming effect. You can also smoke or vape lavender, erowid has several articles on it. I do it occasionally (not a fan of putting smoke in my lungs if I can help it) when I'm feeling very anxious and it has a small but noticeable effect -- feels very nice and calm. I smoked CBD once and I'd say the effect is similar.
Lavender has some sort of gynochromastia causing interaction, especially with topical application or in detergents. Or this was in the news years ago at least.
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?
I agree that we're not likely to see funded studies which answer my question, but that's not what I'm asking – just Scott's current expectation of whether there's a reason to believe the effect is linked to it being in pill form or not.
My guess is that you would have to drink a *lot* of tea to get the same dosage as one of the prepared pills (to the extent that it may not be possible or healthy to do so) but I haven't done any research to support that.
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.
The brand name for the German manufacturer is Lasea and it would seem it can be ordered online in the UK, this site is selling a pack of 56 capsules for £26.41 (ex. post and packing costs):
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.
Some patients surely do to some degree; not all will though, else there wouldn’t be demand for a treatment for persistent anxiety.
Isn’t this captured by comparing the intervention with a control arm? Whatever the rate of mean-reversion, you measure that in the control group. (You also capture any placebo effect, you don’t need to measure the two components separately). The delta between the control and the intervention arm is the actual effect of the intervention.
Silexan is prepared directly from lavender plants and because it's taken orally, it's easier to consume in capsule form instead of drinking the oil. It's got a brand name just because they have a standardized process that delivers a reliably standard dose.
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?
Potential upside: you figure out you have undiagnosed anxiety by suddenly not feeling anxious, and noticing the difference from your regular state.
(Which is not to say this is the optimal way to learn that; but I could totally see a generally side-effect-free anti-anxiety med becoming a recreational drug passed around between friends and college roommates, in much the same way that adderall / methylphenidate is, and people coming to learn they have anxiety from said recreational experience.)
So if I snort a line of coke and feel amazing, like I can do anything, then it turns out I was suffering from depression and low self-esteem all along?
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.
Well, biology. Which is what is so frustrating. Lavender did nothing for you, but for someone else it might work via placebo, and for another person again it might be the best thing they ever tried.
How effective a drug is is always going to depend on your own specific physiology. For instance, I was surprised to see st johns wort near the bottom of the results of the nootropics survey that got posted here recently, because SJW is one of the more dramatically effective over the counter substances I've taken.
Yeah, I am constantly surprised by studies showing much lower benzo effect sizes than I would expect. I think it's a combination of -
1. Lots of people gain tolerance to benzos, and lots of studies are done after they've gained tolerance.
2. The psychiatric establishment hates benzos, and is constantly trying to convince people not to use them, and lots of studies are from people trying to show that look, safer alternatives are just as good!
3. Because benzos are a known effective drug, everyone who wants to prove that their own drug is great needs to show that it's better than benzos, so they rig studies to prove this and then those studies go into meta-analyses to show that benzos have a low effect size.
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.
For what it's worth, I did a round of research on a whole range of supplements for anxiety several years ago and the results on lavender pills was really the only one with fairly clear benefit from studies that weren't complete garbage. L-theanine may be a not so close second.
Here are two different articles about essential oils for anxiety, and lavender, rose and chamomile seem to be the only ones in common for both articles. I don't know how much is medicinal effect and how much is just that smelling something pleasant and floral inclines you to relax and takes your mind off the stressful situation (I mean, if I was sitting in the waiting room of a mental health centre, I'd appreciate something that smelled nice in the air):
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.
"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."
Yes, and if you look into those studies, the places that report great effects are also the places that have a lot of parasite infections. Countries that don't have the same don't report the same (except, apparently, Florida but then again, it's Florida).
Well, we tried that. I mean, as a species and a culture. For most of the past 40,000 years we have been pretty credulous when it comes to the possibility of cures and fixes that the pros might have overlooked. This is why the practitioners of the Hermitic cult did a thriving business in cures among the Romans. It's why alchemy was so broadly studied for centuries. It's why medicine used to prescribe bleeding for infectious disease and trephining (later lobotomy) for psychiatric illness, because the need for *something* was urgent and...well, it might work. A guy I know who's very experience said he observed some darn persuasive and dramatic effects...so let us keep an open mind! And so on. Very understandable, very human, but the long-term consequences were not good.
It's only since a small subset of us started practicing Presbyterian-level hard-ass fanatic inhumane skepticism sometime in the late 1600s, and habituated ourselves to believe *nothing* unless backed up by data triple-checked at every point, that we have started to make significant progress. More has been learned about medicine in the past 200 years than the previous 20,000, and this is not because people prior to that time lacked interest, intelligence, or opportunity -- what they lacked was a sufficiently harsh truth-verification culture, so that even good work was set on top of prior error and thereby vitiated.
It seems very regrettable that this should be the only way, but it seems to be. Apparently the human ability to fool one's self, to mistake motivated rationalization for reasoning, to cherry pick the data and be blind to disappointing facts, is *so* powerful that we cannot make sustained progress and also give ourselves the benefit of the doubt. Our minds need to be so firmly closed that only the hardest possible empirical evidence can pry them open a crack, or otherwise we degenerate into superstitutious fools who are prey to every variety of shamanism and mass delusion imaginable.
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?
Do not take Seremind® if you are allergic to lavender oil or any of the other ingredients in this medicine.
Do not take Seremind® if you have impairment of hepatic (liver) function.
Warnings and precautions
Seremind® is not recommended during pregnancy or breastfeeding, as its safety during pregnancy or breastfeeding has not been established.
Seremind® contains sorbitol. If you have been told by your doctor that you are intolerant to some sugars, contact your doctor before taking this product. Not recommended in children and adolescents under 18 years of age."
So it seems if you have liver troubles, don't use this. There seems to be contradictory information about essential oils and the liver, with one set of data saying they absolutely can be toxic, and other studies saying they have beneficial effects.
Basically, don't take big doses, be careful about ingestion, and if you have any doubts, then don't:
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.
The ingredients claim that it's the patented Silexan and not their own formulation, so it might be worth trying it and see if it has any effects before you go to the more expensive brand:
"Seremind® is available in packs of 28 and 56 capsules. The active ingredient is lavender oil 80 mg. Seremind® also contains rape seed oil, sorbitol, glycerol, gelatin, purified water and annatto. Note: Seremind® does not contain egg, peanuts, soy beans, tree nut products, yeast, gluten, artificial colours, flavourings or preservatives."
"INGREDIENTS
Silexan™ English Lavender (Lavandula angustifolia) Essential Oil 80 mg
Other Ingredients: canola oil, gelatin (softgel), glycerin, sorbitol, annatto extract color
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).
"Silexan was found to contain 36.8% of linalool and 34.2% of linalyl acetate. Other components of the lavender essential oil present in substantial quantities include monoterpene alcohol lavandulol, its ester lavandulyl acetate, and bicyclic monoterpenoids borneol, eucalyptol (1,8-cineole) and camphor. Linalool also demonstrated anxiolytic properties in several animal models, and possessed stress-relieving effect in humans under the experimental stress. Studies on molecular mechanisms of pharmacological effects of lavender essential oil revealed that its effect on CNS could be attributed to the inhibition of voltage dependent calcium channels. Unlike some other monoterpenes found in the lavender essential oil, linalool and linalyl acetate significantly inhibited voltage dependent calcium channels. In another study, lavender essential oil was demonstrated to possess affinity to the NMDA receptor and SERT. Binding to NMDA receptor was also observed for major constituents of lavender essential oil linalyl acetate and linalool, while only linalool demonstrated significant binding to SERT. Further results of the clinical, randomized, placebo-controlled, double-blind, cross-over study on healthy men using positron emission tomography technology suggested that the anxiolytic effect of lavender essential oil (given as Silexan) could be attributed to the serotonergic system changes, particularly at the 5-HT1A receptor level".
It seems to be the meta-study Scott mentions above.
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.
Weight gain, increased risk of diabetes seem like they are pretty common. A web search of Seroquel + diabetes will return lots of hits “Ambulance Chasers Are Us” lawyers.
As Gunflint said, high risk of metabolic complications later. I also think you're pretty lucky if 40 mg works consistently without building any tolerance - most people will need more, and get worse SEs. Keep in mind that the FDA refused to approve Seroquel for sleep (and fined the company millions of dollars for promoting it for sleep), not because it didn't work but because they thought it was too dangerous to be worth it - see https://www.justice.gov/opa/pr/pharmaceutical-giant-astrazeneca-pay-520-million-label-drug-marketing
"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.
Silexan is manufactured by Schwabe, which is GMP-certified, and regulated as a German OTC medicinal product.
Most of the studies cited here did monitor for adverse events. The Yap meta-analysis sums up the findings as "In the analyzed 5 studies, adverse events, attributable to silexan use, consisted mainly of gastrointestinal problems such as nausea, eructation or breath odour, and diarrhea. A number of patients also reported having headaches in the 2015 study by Kasper et al.41 Nevertheless, the number of patients that experienced these mild adverse events comprised of a small percentage of the sample size. No serious adverse event was found to be linked to the use of silexan." There were also several studies specifically designed to investigate potential adverse events that the researchers were worried about, like https://academic.oup.com/ijnp/article/24/3/171/6029371 investigating abuse potential, and https://www.sciencedirect.com/science/article/pii/S0022395620310311 investigating driving performance.
The RCTs I discussed above are double-blind and have several hundred patients. I'm not sure why you expect placebo effect to be operative in these double-blinded studies. I was generally impressed with the blinding procedure - they even went so far as to make the placebo taste of lavender!
In general, I think that the fear around contaminants in supplements is incompatible with the fact that 76% of Americans take supplements and yet medical emergencies from supplement contamination are extremely rare. When they do happen, they tend to be because the supplement itself was questionable - some kind of weird stimulant or marijuana substitute made out of a bunch of random things thrown together - rather than because somebody's vitamin pill had a contaminant in it. I think if worrying about contaminants made people even 0.1% more likely to prefer benzodiazepines to herbal anxiolytics, it would have costs > benefits.
Yeah, it's German, so they're going to be *very* rigorous and scrupulous about exact formulations and contaminants. Buying other supplements is "you pays your money and you takes your chance" but to be fair to the German woo merchants, if they say it has 100 ppm of magicberry in every capsule, by gum it will do!
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.
>(Also freezing it is sugested to help with the burps)
Huh weird. I don't think it makes me burp more than usual honestly, its more like in any microburp you might have during the day I smell some lavander now hah, whereas I wouldn't notice them before.
Anyway, I'm on day 8 now and still haven't noticed anything too obvious.
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.
Yeah, you got a giggle out of me. :)
1. I think the active ingredient is linalool, but I don't know much about this or why you can't just give that to people.
2. No, it's not just about which neurotransmitter system you affect, it's about how you affect it. Both SSRIs and LSD affect serotonin, but in very different ways.
There seems to be a Chinese study on linalool, but I'm not forking out £42.50 to read it:
https://pubs.rsc.org/en/content/articlelanding/2021/fo/d1fo02120f/unauth
"Natural products, including essential oils and their components, have been used for their bioactivities. Linalool (2,6-dimethyl-2,7-octadien-6-ol) is an aromatic monoterpene alcohol that is widely found in essential oils and is broadly used in perfumes, cosmetics, household cleaners and food additives. This review covers the sources, physicochemical properties, application, synthesis and bioactivities of linalool. The present study focuses on the bioactive properties of linalool, including anticancer, antimicrobial, neuroprotective, anxiolytic, antidepressant, anti-stress, hepatoprotective, renal protective, and lung protective activity and the underlying mechanisms. Besides this, the therapeutic potential of linalool and the prospect of encapsulating linalool are also discussed. Linalool can induce apoptosis of cancer cells via oxidative stress, and at the same time protects normal cells. Linalool exerts antimicrobial effects through disruption of cell membranes. The protective effects of linalool to the liver, kidney and lung are owing to its anti-inflammatory activity. On account of its protective effects and low toxicity, linalool can be used as an adjuvant of anticancer drugs or antibiotics. Therefore, linalool has a great potential to be applied as a natural and safe alternative therapeutic."
In general, you shouldn't just rub on or inhale or swallow essential oils, but linalool is used amongst other things as a food additive so it must be safe for consumption. I don't know the level of linalool that would be effective as a medication versus how much is toxic, so perhaps that is part of the reason why you can't just stick the oil in a capsule and give it to people:
https://www.webmd.com/skin-problems-and-treatments/ss/slideshow-essential-oils
I spent some time looking at the silexan papers (https://gwern.net/doc/psychiatry/anxiety/lavender/index) and I couldn't find any evidence that it's *not* linalool or that linalool essential oil from other plants like thyme shouldn't work, and there's plenty of work on linalool itself, not to mention that there are anxiolytic claims for other plants which contain linalool.
So I bought some and have been alternating between brand-name silexan CalmAid™ and a random linalool essential oil off Amazon, and I can't tell any difference in the effect - although they both have very distinct tastes/aftertastes so I have no idea how to run a self-blinded experiment there. (Linalool is not the 'lavender' taste of silexan, so if I added a lavender component, I may just be recreating silexan; if one could *remove* linalool from silexan instead, I think it would still burp the same lavender flavor, but I dunno how one would do that.)
Given background odds, a 50% chance it works really well is pretty confident, I think.
Agreed. My starting point is ~10% chance of efficacy for any new psychiatric medication
I like everything about your analysis except your presumption that a big-named researcher would necessarily be male!
If you mean this big-named researcher, he looks quite male (and ludicrously big-named) to me: https://cluster.meduniwien.ac.at/mnc/general-information/members/people/persons-details/?pers_id=346
"o. Univ. Prof. Dr. h. c. mult. Dr. med. Siegfried Kasper"
No I was referring to the imagined researcher in this statement -- "Usually there will only be one academic institution or team that’s really committed, and if it has a prestigious leader, his name will be on all of the papers."
Is there really a "right" way to use pronouns in this context? I guess you could say "his/her/their/[xir...]" but it starts to get cumbersome. "their" works but can be confusing in some contexts (is "their" referring to the leader, or the team/institution?). I sometimes alternate "his" and "her" (which is also convenient if you're discussing two hypothetical people simultaneously)--but in an isolated example like this, ofc you can't tell if that is what Scott is doing.
It's easy enough to say "the name" -- this has always been a pet peeve of mine as a woman scientist. It's not that hard to fix and younger women need to stop thinking they're unusual if they go into STEM.
“The name” sounds wrong; “their name” sounds like he’s referring to the team; “her name” is the sort of construction Scott very commonly uses, but would be a bit odd here since researcher he’s indirectly talking about is male.
It’s really helpful for clarity and elegance to be able to use gendered pronouns in a generic non-gendered way in a piece of writing. I can see why you might have a problem with someone using only male pronouns in this way, but if they’re used interchangeably, what’s the problem?
I would actually be willing to bet (money) that Scott uses female pronouns in this way more often than male, precisely for the reason that even if you split it 50-50, then 50% of the time some people will think you only use male ones.
Given that it’s a useful linguistic construction and it seems like the ideal outcome would be if it became established practice to split it 50-50, I think it would be nice not to criticise people who are indifferent to whether they use male or female pronouns in this way as if they’re staunch advocates of only using male ones!
I don't think it's a big deal to bring this up. I think it's a worthwhile question and not an ad hominem attack at all.
I think "Their name" works in this sentence because the antecedent is clearly the leader - they're the noun closest to the pronoun and the only one that makes sense in context.
How do you feel about "that"?
"Usually there will only be one academic institution or team that’s really committed, and if it has a prestigious leader, that name will be on all of the papers."
Couldn't we say "that name" instead of "the" or "their"? I am almost certain that "that" is the appropriate option here and it doesn't have the issues of "the" or "their". Perhaps it has different issues I am unaware of?
Personally, in this particular instance, I'd use "that person's name" -- both gender-neutral and quite clear.
In this context that would be genuinely ambiguous as to which name was meant. 'That person's name' would work. But in this case, the context- that this is a real situation, with a male researcher- justifies the use of 'he'.
Women don't think that. Since men are now the minority in higher education, if anything we need to encourage young *men*.
Generic "his" jumped out at me, too.
I would use "their" there without a moment's thought, and I imagine the singular "name" would eliminate any confusion about the referent. It wouldn't cross my mind that it might be referring to some kind of scientist team name like "Raiders".
I think the "imagined" researcher is actually Kasper, and that's why the pronoun was used that way.
He/she, his/her are non-binary pronouns. Sometimes they refer to the gender of the antecedent, sometimes they are for general, non-gendered use.
Scott, you can solve this the way Douglas Hofstadter did in Metamagical Themas. Just use she and her for the ambiguous pronouns. Save everyone a bit of energy.
The ludicrosity of the maganominality is a peculiarity of the Austrian culture. Also known as "Titelhuberei".
Do you honestly think that anyone with brains enough to read this blog assumes that women are less capable than men in research? This is about language, style and concision, not about bias. Sheesh!
It is possible to simultaneously believe that men and women are equally capable and to refer to an unnamed big researcher as male without thinking about it, particularly when there is a hisorical prevalence of a particular gender in that position.
The point is to consciously write so as (a) not make that automatic choice, and (b) make it less likely for others to do so.
talk about missing the woods for the trees
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.
The evidence presented in the post is pretty substantial, but the priors are pretty low, so a 50% posterior seems reasonable to me in that context.
As far as nootropics go, 50% odds of being equal to SSRIs seems quite high. I wasn't expecting such a high number.
How serious is the miscarriage risk? Asking for someone with heightened anxiety due to a series of miscarriages.
I don't know, but there are plenty of anti-anxiety meds and supplements without that risk, I think it's easier just not to take it in that situation.
When you say "Silexan might cause miscarriage during pregnancy and they should avoid it until this has been investigated better." does that mean that somebody in a trial was pregnant and miscarried, that for some reason they think it has a defined mechanism of action that harms pregnancy, or just to avoid accidentally recommending something bad to pregnant women without any actual reason why it's bad?
Not trying to be accusatory, but I see lots of things that "may have risk against pregnant women" and am curious, especially given it's so early in development overall
This article tells you all about essential oils and risks during pregnancy:
https://www.mother.ly/life/essential-oils-not-use-pregnancy/
I believe it’s an inference based on secular beliefs about the side effects of lavender oil as used in traditional medicine.
The guidelines around essential oils and pregnancy seem to be "anything the mother consumes can cross over to the foetus via the placenta so since we don't really know the effects, better not to use them".
So don't take the capsules, but you can use the oils in diffusers to smell them, which may help reduce anxiety anyway:
"Guidelines for using essential oils while pregnant
First off, avoid using essential oils during the first trimester. The first trimester is the most critical period during pregnancy, and any risk of exposing the fetus to a toxic substance should be avoided at all costs.
But in your second or third trimesters, keep the following safety protocols in mind when you’re using approved essential oils.
Don’t ingest essential oils
Even if you aren’t pregnant, essential oils aren’t meant to be taken orally unless under the direct supervision of an expert or physician. Many essential oils can pose toxicity risks when ingested — for you and, potentially, your baby.
Focus on aromatherapy
In general, most medical experts agree that aromatherapy is a safer option for pregnant people as opposed to topical applications. This simply means that you should use your essential oils in a diffuser rather than applying them to your skin."
https://www.parents.com/pregnancy/my-body/pregnancy-health/essential-oils-during-pregnancy-whats-safe-and-what-to-avoid/
"Essential Oils in the First Trimester
You shouldn't use essential oils in early pregnancy because they could potentially cause uterine contractions or adversely affect your baby in their early developmental stages, explains Jill Edwards, N.D., an Oregon-based doctor of naturopathic medicine who specializes in prenatal care.
More research needs to be conducted on the topic, but it's always better to be safe than sorry. Pregnant women should also avoid aromatherapy products and treatments in the first trimester, since essential oils are the key ingredients used in aromatherapy.
Essential Oils in the Second and Third Trimesters
"In the second and third trimesters, some essential oils are safe to use, as your baby is more developed," Edwards adds. These include lavender, chamomile, and ylang ylang—all of which calm, relax, and aid sleep. Here are some tips:
Stick with quality essentials oils from a reputable brand unadulterated, advises the International Federation of Professional Aromatherapists (IFPA).
Only use essential oils externally because ingesting them may cause miscarriage, lead to preterm labor, or negatively affect your fetus.
Dilute essential oils with a carrier oil—like olive oil or coconut oil—before applying to the skin. "
There is no shortage of advice from authorities telling pregnant women what not to do. Very little of it, including advice against taking medication or supplements during pregnancy is based on scientific or statistical proof. All of this seems very CYA to me or possibly paternalistic. With a few exceptions, based on large registry numbers looking at various agents, there is minimal ATTRIBUTABLE risk to offspring or pregnancies due to various medications commonly employed. . For some reason psychiatric medications or supplements are singled out for being easily dispensed with during pregnancy. Meanwhile women are left with the choice of feeling incredible angst and guilt if anything goes wrong with her pregnancy (which on a statistical basis is far more likely to happen due to inherent risk of pregnancy than to anything they ingest), or suffer with untreated anxiety for the duration.
I mean, it *is* CYA, for both the doctor *and* the mother. If you don't warn them, and they take the medication (with your knowledge) and something bad happens with the pregnancy who do you expect will take the heat for that once the mother finds out the drug she was taking may have been a contributing factor in the complications? How upset will the mother be at that point, with the classic 'why didn't anybody tell me'?
You can't just lie about it (including a lie of omission), you have to give the woman the information to make her own choice (suggesting doctors shouldn't even *tell* the woman for her own good sounds 'paternalistic' to me but YMMV).
I do agree that women having unwarranted feelings of guilt when something goes wrong in a pregnancy is a problem, but you tackle that issue on it's own merits not by hiding potentially important information from the mother, especially since those feelings of guilt can crop up even if she was not engaging in any potential risk factors.
I capitalized attributable because it has a specific definition in this context. Many of the Supposedly possible risks can be attributed to the medication because those some risks are overwhelmingly inherent in pregnancy itself. Unless this context is explained to the expectant mom they are not being given appropriate informed consent.
For that matter, risks associated with no treatment need to be explained to give an accurate picture. Untreated anxiety and depression have been associated with higher rates of low birth weight, prematurity and failure to bond. how many pregnant moms to be are given that information from their busy ob rather as opposed to a list of dont’s? I can tell you from treating these scared women, not nearly all of them.
All the women I know who became mothers were right grateful for every shred of information, advice, and even informed speculation they could pry out of their OBs -- whether or not "scientifically proven" (whatever that means). They were all big girls, and could make up their own minds perfectly comfortably on whether or not to take the advice, how much weight they wanted to put on this speculated risk versus this other inconvenience, et cetera.
Maybe the paternalistic attitude here is yours, in that you would appear to fear the poor women will be overwhelmed by too much information, or incapable of mustering up the gumption to reject advice they don't find persuasive -- in short, be not so good at adulting.
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.
I disagree with the assumptions here - there are dozens of folk remedies that probably have some chemical basis, and we still haven't gotten around to investigating most of them. Research into St. John's Wort as an antidepressant is only a few decades old. A good example from outside of psychiatry is artemisinin, an ancient Chinese folk remedy for malaria that was isolated and inducted into the regular medical system in the 1970s.
I have suspicions that Chinese herbal medicine might have a number of other legitimately valuable compounds here and there which haven't been discovered so far because most Western researchers aren't familiar with them, and most Chinese medical research is of very low quality. There are lots of studies on traditional Chinese medicine which turn up positive results, but don't really mean much because the research is untrustworthy. But just because the research is untrustworthy doesn't mean that the treatments *don't* do anything. Some interventions, like accupuncture and moxibustion, which could be replicated anywhere if they worked without the need for specific plants or extracts, have already been tested to death and we can be pretty sure they don't work. But there's nothing strange about plants having real medicinal effects, and I think the herbal side of Chinese medicine is still mostly uncharted by modern science.
There's also the question of side effects and toxicity. Anyone can collect herbs and brew up a tea. If your symptoms are bad and the net effect is positive you will continue even if it's slowly trashing your liver.
Herbal medicine uses plant names as if they are indivisible units but any random plant is likely to have hundreds or thousands of different molecules that are biologically active in humans humans. The cultivars we eat are special cases that have had their worst toxins cleaned up and food value bumped up over the years.
Conventional pharmacology aims to isolate an active molecule and maybe alter it a bit to ramp up its function - and make it patentable! - which eliminates an array of potentially problematic molecules from the product.
I'm not really a chemistry person (or a lab person, or a physical world person, or a useful person at all), but it seems insane we've ever isolated any useful chemicals from plants at all! How do you actually know which one has the effect without trying thousands? Do you actually just try thousands?
You actually just do try thousands, yes. And look for ones that have similar structures to chemicals that are known to be active/chemicals in the body. But a lot of psychoactive compound research in the midcentury was chemists isolating compounds and testing them on animals (and sometimes themselves!) based on structural similarities.
And it's fairly unlikely that you're not a useful person if you know how to read and write coherently, by the way.
Oh I don't doubt I *could* be useful, but I concern myself with my silly little numbers and functions and stay away from the messy stuff that affects the real world. But that doesn't mean I can't be curious! Its incredible that they managed to work out so many useful molecules back in the day. I mean, it feels crazy that we have a good understanding of molocules regardless, but the brilliant inferences which are necessary amaze me. The lab sciences are marvels of human intelligence and ingenuity
Tens of thousands, typically, for even a modest drug, and probably millions for each entire new classification of drug.
It isn't completely blind, though. Some discoveries come from careful observation of the natural world, e.g. for antibiotics plants and fungi are rich potential sources, since they must fight off bacterial invasion the way we do, e.g. penicillin is a natural compound synthesized by a mold to kill invading bacteria, and was discovered when Fleming noticed some nasty mold was wiping out his nice bacterial cultures.
Others these days are driven by understanding of the target biomolecule -- you want to inhibit this enzyme, and knowing its structure or that it's homologous to some other enzyme inhibited by this class of molecules -- gives you a lead on what types of compounds (in terms of their chemical structure) might have a hope of working. The most famous case of this that comes to mind are the protease inhibitors introduced in the 90s that changed AIDS from pretty much a death sentence to something far more manageable. Supposedly these were deliberately designed to interfere with a key assembly step of HIV protease, an enzyme the virus needs to reproduce[1].
Some drugs are developed by observing unexpected side effects of other drugs -- Viagra is famous this way, it was originally being studied for treating heart failures, and only in human trials did somebody notice all the men were getting lots of stiffies. Amphetamine was discovered by someone trying to improve on ephedrine as a bronchodilator.
Many leads come from follklore and folk medicine, e.g. aspirin derived from the folk remedy of willow bark tea, quinine was discovered in bark used by Peruvian natives to control malaria, and of course all of the the various cocaine derivatives come from the folk use of the coca plant.
In addition, every big pharma firm maintains a giant library of many thousands of compounds that have been synthesized for prior projects that they will routinely test against new targets just on the off chance one might work.
It is nevertheless incredibly arduous, the major reason for the high cost of new drugs, and many people have struggled to make it more efficient. Many have pinned their hopes on computer modeling, either abstract or by actually simulating the chemistry, but this has so far proven fairly disappointing, or at least far less useful than was hoped 40 years ago[2].
You might think that if you know the shape and reactivity desired, because you've completely characterized the receptor let us say, you could just tell the organic chemist to go make a molecule of this particular size and shape, with this and such kind of reactive group hanging off it. And sometimes that kind of works -- certainly it's a big part of optimizing a molecule once it seems promising.
But first of all, a molecule's reactivity in vivo is often an exquisite balance of many more factors than just its shape and most obviously functional groups. How flexible it is, how its reactivity changes with changes in shape or pH or the microenvironment of a protein's active site all turn out to often matter a lot, and we are very poor at predicting any of those characteristics for any molecule more complex than, say, water. And secondly, organic chemists can rarely fully explore the geometric and chemical possibilities for molecules. We synthesize compounds fairly crudely, by mixing them up and supplying heat. But biochemically molecules are synthesized far more directly, like construction equipment stacking this on top of that and welders solidifying the links. Nature is capable of synthesizing weirdly complex molecules, with 3D shapes and connections that defy the lab. So although we have made progress on identifying candidate shapes, there is still a big role for natural substances, synthesized by plants and unicellular organisms, because they explore a part of the space of molecules of a given size that are still difficult or impossible for us to explore synthetically[3].
----------------
[1] The AIDS virus codes for *all* its proteins to be made in one long strand, like model parts on a runner, and the protease is what snips them apart into separate protein strands that can become functional. Without the protease, the virus cannot reproduce because while all the parts can be made, they cannot be assembled into a whole functioning virus.
[2] One of the more spectacular failures was IBM's Watson Health, which aimed to bring the awesome power of AI to things like diagnosing cancer, identifying promising drug targets, and so on.
https://www.statnews.com/2021/03/08/ibm-watson-health-sale/
It ended up failing miserably at all these tasks, and people are still not entirely sure why, except that doing well at this particular pattern matching seems to require some magic pixie dust that is common enough in the human cerebrum that we rather take it for granted, but which is very, very difficult to program, perhaps because we don't even really know what it is.
[3] Derek Lowe has a small rogue's gallery here:
https://www.science.org/content/blog-post/some-natural-product-weirdness
This is all incredible stuff! It's really amazing what humans managed to accomplish with it. But what was the process of finding, say, just penicillin? Like you see the fungus killing bacteria, how do you know what it's doing to accomplish that?
You don't have to be a big pharma company to screen new drug compounds. There are companies with large libraries of compounds that will run your assay on tens of thousands of candidates and identify any positive hits. You then take those positive hits and look at their kinase maps for possible drug-drug interactions and specificity, and do some other analyses. (Something druggable needs to be able to survive the stomach if it's going to be orally administered. It needs to be soluble in something we can give humans. It needs to be stable, etc.)
The trick is to develop a meaningful assay. There's always an assumption in vitro that the experimental setup you're using will translate in a meaningful way to a full human system. And since you're basically ignoring every other system when you take a single cell type, that's bound to be a confounding factor. For example, you're studying breast cancer so you take breast cancer cells. Except what about other cell infiltrates that are often found in tumors, like tumor-associated macrophage, fibroblasts, etc? Extrapolating from simple models out to complex systems is where it becomes surprising that we find anything at all.
I will say that I don't think drug screening is the determining factor in driving drug development costs. A phase I clinical trial runs into the millions of USD, and a phase III trial is at least tens of millions. Within that, the per-patient cost for the trial will probably be north of $10k/patient (depending on the indication), plus large clinical monitoring costs, data management, drug manufacturing and P&L, pharmacovigilance, PK, IVRS, and stats, to name a few.
Chemists have a bunch of techniques for separating components of mixtures out. For an idea, this is one of the classic techniques:
https://en.wikipedia.org/wiki/Thin-layer_chromatography
Once you think you have isolated something you can start seeing how it combines to arrays of different chemicals to get clues about its structure and similarities with other known molecules. It's a long process.
As far as I know it has been used for a long time in Europe as a folk remedy. The etymology of the name “lavender” comes from French, prior to that from Latin “lavare” meaning “to wash.” Basically implying “everything should be washed with this in the water,” which is a high level of remedization. The interwebs says it goes back to Ancient Greece & Rome.
For what it's worth, amethyst (purple quartz) is named for the Greek belief that it was protective against inebriation.
In this case, we can be certain from the basic chemistry and physics of the situation that there is no such protective effect, but it's still named amethyst.
I, for one, have never gotten drunk wearing amethyst, so there's that.
Actually, it protects you from meth addiction.
Yeah, but only if you align the crystals properly with your personal magnetic field. That's why it doesn't work for some people, they haven't done the alignment properly. Plus misaligned amethyst can give you smelly farts, but I guess if you just got addicted to meth you have bigger problems now anyway.
See Vitamin D. The problem isn't identifying them, it's working out if, and especially when they work. For every plant X, maybe the roots work, maybe the leaves. Maybe this supplier is just bad, or they skipped a certain step when processing. Maybe it helps, but only for a subset of people. Maybe it helps, but only for a subset of the condition. Dosage. Interactions.
Just recently came out the mother of all meta-analyses on whether coffee is healthy or not. Care to guess the result? Coffee is very good, but only when filtered. If pot-boiled it keeps certain oils that dramatically increase cholesterol. Espresso is so-so. We still aren't clear if decaf has the same benefits. And that's freaking coffee!
Also, the compounds in a plant vary because of variety and growing conditions.
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?)
Inositol was third from the bottom in my old nootropics survey ( https://slatestarcodex.com/2016/03/01/2016-nootropics-survey-results/ ). I agree it seems to work for a small subset of people - I recently saw someone speculate mostly for people with PCOS, though I can't confirm this.
Maybe not large enough doses? The psychoactive effects start pretty high, and very close to certain side effects *ahem*explosivediarrhea*ahem*.
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.
Lots of real treatments for anxiety also stop working after a few weeks, though :(
After around 2 months of regular lavender pill usage, it still feels like this exciting new thing that has made my headspace immensely better - so this might be the strongest placebo yet devised /s
"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.
I'd argue that most of the benefit of having drugs that "really" do something instead of relying on the placebo effect is that they still work after the drug isn't exciting or new anymore. There's lots of stuff that seems to intensify the placebo effect, and much of it won't be present after a few weeks of home use.
I'm a huge fan of RCTs and finding drugs that have a reproducible physiological effect independent of psychological factors.
Having said that, I also believe that psychological effects, while highly variable in several dimensions (I suspect I'm a low responder), can sometimes be surprisingly large and enduring.
For example, with many viral infections, it wouldn't surprise me if psychological effects could kick your immune system into high gear, with the outcome that the infection is overcome and you're effectively cured. No worry about anything wearing off there.
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?
Doesn't lavender oil contain strong hormone disruptors? Presumably taking the unprocessed oil would supply not enough Silexan or too much everything else.
After further investigation: apparently standard lavender-oil extracts are marketed as "not intended for human consumption". And after trying half a drop, I agree with that take.
You can put dried lavender flowers in desserts. It pairs decently with sweet & lemony, ie lemon cake with lavender-infused icing. Not sure about dose there.
There will have been more of the active ingredients in a single drop of extract than in a slice of lavender-iced cake. I've seen them steam-distilling lavender oil and you have to put in a lot of flowers to get out an appreciable amount of oil. The essential oil is about a hundred times more concentrated than the plant. Eating the flowers is fine but pure essential oils are for external use only.
Dried lavender is also very good in scrambled eggs.
Lavender tea is known for its calming effect. You can also smoke or vape lavender, erowid has several articles on it. I do it occasionally (not a fan of putting smoke in my lungs if I can help it) when I'm feeling very anxious and it has a small but noticeable effect -- feels very nice and calm. I smoked CBD once and I'd say the effect is similar.
Lavender has some sort of gynochromastia causing interaction, especially with topical application or in detergents. Or this was in the news years ago at least.
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)
I was wondering the same thing. Any interactions to look out for?
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?
Isn't the issue that funding natural non-profitable sources much harder than a "here's your proprietary blend of the natural thing marked up 10x"?
I agree that we're not likely to see funded studies which answer my question, but that's not what I'm asking – just Scott's current expectation of whether there's a reason to believe the effect is linked to it being in pill form or not.
My guess is that you would have to drink a *lot* of tea to get the same dosage as one of the prepared pills (to the extent that it may not be possible or healthy to do so) but I haven't done any research to support that.
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.
I find iherb to be very reliable AND reasonable shipping cost wise to Europe and they carry it: https://iherb.com/pr/nature-s-way-calmaid-clinically-studied-lavender-30-softgels/43054 (I must have spent high 4 figures there over the years!)
Spam: you and I can get both get a discount using coupon CIF501
Cheers! 💪
The brand name for the German manufacturer is Lasea and it would seem it can be ordered online in the UK, this site is selling a pack of 56 capsules for £26.41 (ex. post and packing costs):
https://www.pharmasana.co.uk/lasea-weichkapseln-56-st-05489632
The dosage seems to be 80mg of lavender oil, so Kalms do their own version which is available from Boots:
https://www.boots.com/kalms-lavender-one-a-day-14-capsules-10211103
That's one-a-day, but Scott's review says two a day are more effective.
Thanks! :)
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.
Some patients surely do to some degree; not all will though, else there wouldn’t be demand for a treatment for persistent anxiety.
Isn’t this captured by comparing the intervention with a control arm? Whatever the rate of mean-reversion, you measure that in the control group. (You also capture any placebo effect, you don’t need to measure the two components separately). The delta between the control and the intervention arm is the actual effect of the intervention.
Is this in replacement of lavender or lavender oil? Why not at least suggest or talk about the natural source.
Silexan is prepared directly from lavender plants and because it's taken orally, it's easier to consume in capsule form instead of drinking the oil. It's got a brand name just because they have a standardized process that delivers a reliably standard dose.
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?
I don't think there would be an upside.
Cheers. Always been curious about that. I won't mess about.
Potential upside: you figure out you have undiagnosed anxiety by suddenly not feeling anxious, and noticing the difference from your regular state.
(Which is not to say this is the optimal way to learn that; but I could totally see a generally side-effect-free anti-anxiety med becoming a recreational drug passed around between friends and college roommates, in much the same way that adderall / methylphenidate is, and people coming to learn they have anxiety from said recreational experience.)
So if I snort a line of coke and feel amazing, like I can do anything, then it turns out I was suffering from depression and low self-esteem all along?
Some amazon reviews are saying it's good for sleep
"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.
I actually tried Silexan before benzos, so I don't think that was the issue.
Well, biology. Which is what is so frustrating. Lavender did nothing for you, but for someone else it might work via placebo, and for another person again it might be the best thing they ever tried.
The post suggest 160mg saying 80mg is not recommended.
How effective a drug is is always going to depend on your own specific physiology. For instance, I was surprised to see st johns wort near the bottom of the results of the nootropics survey that got posted here recently, because SJW is one of the more dramatically effective over the counter substances I've taken.
Yeah, I am constantly surprised by studies showing much lower benzo effect sizes than I would expect. I think it's a combination of -
1. Lots of people gain tolerance to benzos, and lots of studies are done after they've gained tolerance.
2. The psychiatric establishment hates benzos, and is constantly trying to convince people not to use them, and lots of studies are from people trying to show that look, safer alternatives are just as good!
3. Because benzos are a known effective drug, everyone who wants to prove that their own drug is great needs to show that it's better than benzos, so they rig studies to prove this and then those studies go into meta-analyses to show that benzos have a low effect size.
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.
You can reduce it further since the description part of the link is just fluff. This works equally well: https://www.amazon.com/dp/B007TYY2JA/
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 mean, I might be totally wrong. I have been before!
For what it's worth, I did a round of research on a whole range of supplements for anxiety several years ago and the results on lavender pills was really the only one with fairly clear benefit from studies that weren't complete garbage. L-theanine may be a not so close second.
Here are two different articles about essential oils for anxiety, and lavender, rose and chamomile seem to be the only ones in common for both articles. I don't know how much is medicinal effect and how much is just that smelling something pleasant and floral inclines you to relax and takes your mind off the stressful situation (I mean, if I was sitting in the waiting room of a mental health centre, I'd appreciate something that smelled nice in the air):
https://www.medicalnewstoday.com/articles/324478#other-essential-oils
https://www.healthline.com/health/anxiety/essential-oils-for-anxiety#essential-oils-for-anxiety
I worry that it sounds like a monster from Dr Who.
I've thought the same about the household appliance brand Proctor Silex.
The Golgothian Sylex in MTG was a doomsday device.
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?
Buspirone doesn't have much 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!
Ah yes! Sounds like a reasonable hypothesis. :)
And now, a riddle:
Q. What do you call alternative medicine that works?
A. Medicine.
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.
"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."
Yes, and if you look into those studies, the places that report great effects are also the places that have a lot of parasite infections. Countries that don't have the same don't report the same (except, apparently, Florida but then again, it's Florida).
Well, we tried that. I mean, as a species and a culture. For most of the past 40,000 years we have been pretty credulous when it comes to the possibility of cures and fixes that the pros might have overlooked. This is why the practitioners of the Hermitic cult did a thriving business in cures among the Romans. It's why alchemy was so broadly studied for centuries. It's why medicine used to prescribe bleeding for infectious disease and trephining (later lobotomy) for psychiatric illness, because the need for *something* was urgent and...well, it might work. A guy I know who's very experience said he observed some darn persuasive and dramatic effects...so let us keep an open mind! And so on. Very understandable, very human, but the long-term consequences were not good.
It's only since a small subset of us started practicing Presbyterian-level hard-ass fanatic inhumane skepticism sometime in the late 1600s, and habituated ourselves to believe *nothing* unless backed up by data triple-checked at every point, that we have started to make significant progress. More has been learned about medicine in the past 200 years than the previous 20,000, and this is not because people prior to that time lacked interest, intelligence, or opportunity -- what they lacked was a sufficiently harsh truth-verification culture, so that even good work was set on top of prior error and thereby vitiated.
It seems very regrettable that this should be the only way, but it seems to be. Apparently the human ability to fool one's self, to mistake motivated rationalization for reasoning, to cherry pick the data and be blind to disappointing facts, is *so* powerful that we cannot make sustained progress and also give ourselves the benefit of the doubt. Our minds need to be so firmly closed that only the hardest possible empirical evidence can pry them open a crack, or otherwise we degenerate into superstitutious fools who are prey to every variety of shamanism and mass delusion imaginable.
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?
Seremind website:
"Contraindications
What you need to know before you take Seremind®?
Do not take Seremind® if you are allergic to lavender oil or any of the other ingredients in this medicine.
Do not take Seremind® if you have impairment of hepatic (liver) function.
Warnings and precautions
Seremind® is not recommended during pregnancy or breastfeeding, as its safety during pregnancy or breastfeeding has not been established.
Seremind® contains sorbitol. If you have been told by your doctor that you are intolerant to some sugars, contact your doctor before taking this product. Not recommended in children and adolescents under 18 years of age."
So it seems if you have liver troubles, don't use this. There seems to be contradictory information about essential oils and the liver, with one set of data saying they absolutely can be toxic, and other studies saying they have beneficial effects.
Basically, don't take big doses, be careful about ingestion, and if you have any doubts, then don't:
https://lindseyelmore.com/effects-of-essential-oils-on-the-liver/
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.
The ingredients claim that it's the patented Silexan and not their own formulation, so it might be worth trying it and see if it has any effects before you go to the more expensive brand:
"Seremind® is available in packs of 28 and 56 capsules. The active ingredient is lavender oil 80 mg. Seremind® also contains rape seed oil, sorbitol, glycerol, gelatin, purified water and annatto. Note: Seremind® does not contain egg, peanuts, soy beans, tree nut products, yeast, gluten, artificial colours, flavourings or preservatives."
"INGREDIENTS
Silexan™ English Lavender (Lavandula angustifolia) Essential Oil 80 mg
Other Ingredients: canola oil, gelatin (softgel), glycerin, sorbitol, annatto extract color
CalmAid® Does Not Contain
Sugar
Salt
Yeast – Derived Ingredient
Gluten
Corn
Dairy Products
Artificial Flavors
Wheat
Preservatives"
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.
I tried something like this once and nobody stuck to it. I expect even fewer people would be willing to put in the work to make it actually blinded.
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).
This study states:
https://www.nature.com/articles/s41598-019-54529-9
"Silexan was found to contain 36.8% of linalool and 34.2% of linalyl acetate. Other components of the lavender essential oil present in substantial quantities include monoterpene alcohol lavandulol, its ester lavandulyl acetate, and bicyclic monoterpenoids borneol, eucalyptol (1,8-cineole) and camphor. Linalool also demonstrated anxiolytic properties in several animal models, and possessed stress-relieving effect in humans under the experimental stress. Studies on molecular mechanisms of pharmacological effects of lavender essential oil revealed that its effect on CNS could be attributed to the inhibition of voltage dependent calcium channels. Unlike some other monoterpenes found in the lavender essential oil, linalool and linalyl acetate significantly inhibited voltage dependent calcium channels. In another study, lavender essential oil was demonstrated to possess affinity to the NMDA receptor and SERT. Binding to NMDA receptor was also observed for major constituents of lavender essential oil linalyl acetate and linalool, while only linalool demonstrated significant binding to SERT. Further results of the clinical, randomized, placebo-controlled, double-blind, cross-over study on healthy men using positron emission tomography technology suggested that the anxiolytic effect of lavender essential oil (given as Silexan) could be attributed to the serotonergic system changes, particularly at the 5-HT1A receptor level".
It seems to be the meta-study Scott mentions above.
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.
Weight gain, increased risk of diabetes seem like they are pretty common. A web search of Seroquel + diabetes will return lots of hits “Ambulance Chasers Are Us” lawyers.
As Gunflint said, high risk of metabolic complications later. I also think you're pretty lucky if 40 mg works consistently without building any tolerance - most people will need more, and get worse SEs. Keep in mind that the FDA refused to approve Seroquel for sleep (and fined the company millions of dollars for promoting it for sleep), not because it didn't work but because they thought it was too dangerous to be worth it - see https://www.justice.gov/opa/pr/pharmaceutical-giant-astrazeneca-pay-520-million-label-drug-marketing
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...
Darn!
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.
👍
Thanks for your comment.
Silexan is manufactured by Schwabe, which is GMP-certified, and regulated as a German OTC medicinal product.
Most of the studies cited here did monitor for adverse events. The Yap meta-analysis sums up the findings as "In the analyzed 5 studies, adverse events, attributable to silexan use, consisted mainly of gastrointestinal problems such as nausea, eructation or breath odour, and diarrhea. A number of patients also reported having headaches in the 2015 study by Kasper et al.41 Nevertheless, the number of patients that experienced these mild adverse events comprised of a small percentage of the sample size. No serious adverse event was found to be linked to the use of silexan." There were also several studies specifically designed to investigate potential adverse events that the researchers were worried about, like https://academic.oup.com/ijnp/article/24/3/171/6029371 investigating abuse potential, and https://www.sciencedirect.com/science/article/pii/S0022395620310311 investigating driving performance.
The RCTs I discussed above are double-blind and have several hundred patients. I'm not sure why you expect placebo effect to be operative in these double-blinded studies. I was generally impressed with the blinding procedure - they even went so far as to make the placebo taste of lavender!
In general, I think that the fear around contaminants in supplements is incompatible with the fact that 76% of Americans take supplements and yet medical emergencies from supplement contamination are extremely rare. When they do happen, they tend to be because the supplement itself was questionable - some kind of weird stimulant or marijuana substitute made out of a bunch of random things thrown together - rather than because somebody's vitamin pill had a contaminant in it. I think if worrying about contaminants made people even 0.1% more likely to prefer benzodiazepines to herbal anxiolytics, it would have costs > benefits.
Yeah, it's German, so they're going to be *very* rigorous and scrupulous about exact formulations and contaminants. Buying other supplements is "you pays your money and you takes your chance" but to be fair to the German woo merchants, if they say it has 100 ppm of magicberry in every capsule, by gum it will do!
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)
Incredibly annoying and unnecessary that they are only selling this in gelatin capsules
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
Lavender oil is also linked to breast growth in boys: https://www.nih.gov/news-events/news-releases/lavender-tea-tree-oils-may-cause-breast-growth-boys
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 :(
Not sure if it's a legit product but this is what I found in Russia: https://www.evalar.com/products/russia/Lavender/
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.
What is the expiry date on them?
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.
Can I ask what the expiry date on these are?(Also freezing it is sugested to help with the burps)
November 2024.
>(Also freezing it is sugested to help with the burps)
Huh weird. I don't think it makes me burp more than usual honestly, its more like in any microburp you might have during the day I smell some lavander now hah, whereas I wouldn't notice them before.
Anyway, I'm on day 8 now and still haven't noticed anything too obvious.
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