Adults who microdose psychedelics report lower levels of depression and anxiety [pdf]
nature.com
nature.com
> We collected cross-sectional data between November 2019 and July 2020 from self-selected respondents recruited via media related to psychedelic use such as podcasts and online psychedelic research conference presentations.
This is already a significant bias in participants.
> Mental health was assessed with the questions “Do you currently have any psychological, mental health or addiction concerns?” Participants who endorsed concerns identified specific mental health and substance use categories from a drop down menu, and were allowed to select more than one category
So mental health is not actually accessed medically and simply self-reported.
To be clear I lack an informed opinion on microdosing psychedelics, but any study that picks its participant from a community engaging in X to study X but then uses the same community to sample their control group (for lack of a better expression) is questionable.
EDIT: Page 6 has a table that compare microdosers/non-microdosers and the latter was actually less likely to self-report *any* mental health or substance use problem by 5%. It's only when using the DASS-21 subscales that they can draw the conclusion that non-microdosers are more anxious, depressed or stressed. Their microdosers/non-microdosers ratio is also almost 1:1.
That said, I am supportive of more rigorous studies along these lines.
https://www.forbes.com/sites/amandasiebert/2021/03/03/larges...
That said, the reputation of any journal is a poor predictor of the impact of papers published in it, so you shouldn't judge. In fact that's why megajournals like nature scientific reports, plos one and peerj have become so popular.
> "Our results indicate health and wellness motives and perceived mental health benefits among microdosers, and highlight the need for further research into the mental health consequences of microdosing including studies with rigorous longitudinal designs."
It's not an unusual approach: 'We have some preliminary indications that X results in Y, but to confirm or reject this hypothesis we'll need more rigorous studies.'
It's basically going to be the centerpiece of a grant proposal to do that work.
What would be really interesting is to set up a double-blind placebo study comparing the results of using antidepressants (SSRIs etc.) with the results of using psilocybin at similar levels.
It would also be interesting to compare the results of a 'normal' psychedelic dose (full effect) taken once a month vs. the effects of daily microdosing or daily antidepressant use, again with a double-blind + placebo approach.
[0] Translate "scientists" into "the current scientific system between academic researchers and grant agencies"
Are these doses small enough that you don't notice the immediate effects?
The above comment study is pretty interesting, points to equivalent effectiveness.
> On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons. Larger and longer trials are required to compare psilocybin with established antidepressants.
For no significant difference in outcome, I'd much rather have two psilocybin sessions versus daily SSRI use.
For lsd this is generally under 15~20ug, though 5ug/10ug is generally what people dose at.
These dosages aren't well established with "proper studies" but I can say that people documenting there experiences seem to establish this pretty well. The psychonauts wiki is a good place for this type of information
I don't know how this compares to similar studies (if there are any similar studies) but microdosing is almost never done 3 weeks apart. That's usually the time frame done for macro dosing (but with multiple grams not mg).
Even the study at the top mentions that
>Reported microdoses identifed in observational research typically range from 5 to 20 μg of LSD and from 0.1 to 0.3 g of dried psilocybin mushrooms. Microdoses are most commonly used several times a week with various patterns of alternating days.
This is a lower tier Nature series journal where
Nature = flagship;
Nature XXXX (where XXXX is Neuroscience, Genetics, Methods, Metabolism…) makes up specialized second tier;
Nature Communications is a second or third tier non-specialized series journal (but still high impact)
Scientific Reports is nominal third or fourth tier.
But take this with a large dose of skepticism. The text, code, data, and metadata, are the true metrics if quality and generality of results.
And from my own work: if a study involves rodent models check if the authors studied just one type of mouse or rat. If so then consider most biological claims as provisional n=1 efforts. Unfortunately the reductionist mindset has won the day and last five decades. This is almost always true in neuroscience and genomics, fields in which well over 90% of science relies on the C57BL/6 mouse or the SD rat. As a result, claims may be exceedingly fragile—like doing all human studies with a single clone of one specific human.
Yes, it is nuts.
Rwilliams@uthsc.edu
The results of this study are people like to do whatever they are into.
Do we know this or do we "know" this?
Having another study, even a self reported one like this, doesn't degrade the scientific body of knowledge, it adds to it. The fact that there have been other studies doesn't make doing another worthless.
I also think a lot of people here are discounting the fact that this study would typically be very hard (or impossible) to administer at such a large scale, especially in such a short amount of time.
In my mind, the important questions here are:
Are the benefits of massive scale studies worth the trade-offs of self-reporting?
What can we do to reduce or eliminate those trade-offs?
Imagine the scientific value of having easily created, easily administered, massive studies be easily accessible to any research group. If the research data can be made even a little bit more reliable, that's hugely valuable.
I really don't see how it's valuable. I don't even believe my friends when they talk about how much micro-dosing benefits them (and this is coming from someone who is a huge supporter of psychedelics). People are really good at making themselves believe what they want to believe.
There are also plenty of tests and measurements that can be given over an app that don't rely solely on subjective self reporting too though. For instance: reflexive tapping tests, wearable health telemetry, memory tests, etc., etc.
I'm excited to see researchers taking advantage of tech to speed up studies and make research more feasible in general. More research means more insights and advancements in the long run for all of us.
Yes. The simple corollary to Bayes theorem: all observations, even biased ones, improve your knowledge of the world.
But it doesn't say anything about efficiency. A single photodiode mechanically scanned behind a pinhole can capture the same image as an image sensor behind a lens, but it takes millions of times longer. A self-reporting survey will say something, but it will be very noisy. How many self-report surveys would it take to match an actual double-blinded study with double digit participants? What if the answer is "hundreds"? Should we wait a century for all these surveys to be done before even attempting data analysis? (After all, surveying the same set of people over and over won't give you additional data. You need to wait for some of the survey respondents to die) What about all the people in the preceding 99 years who, perhaps reasonably, look at a stack of fifty self-reported surveys that all say the same thing, and come to an incorrect conclusion? Science is right eventually, not right right now.
You say that "millions" of participants should be useful, almost automatically. Why should that be the case? If you're off by an order of magnitude somewhere in your stack of assumptions, the data could be noisy enough that you need to be sample from a population of a hundred billion. If the data is bad enough or biased enough then even a large survey wouldn't be powered enough without a world population ten times bigger.
I don't disagree that there are issues with self-reported data, but I do disagree with saying that a large set of self-reported data is worthless.
I also didn't say millions, I said massive. Which in the case of research like this could be the difference of 40k participants (through an app) and 100 participants (clinically). While the size of the data set isn't everything, it does matter. With 40k participants you could aggressively invalidate 30k of them and still have 100 times as many data points for statistical validity as that clinical study. The clinical study would also cost more and take much more time to implement.
> How many self-report surveys would it take to match an actual double-blinded study with double digit participants? What if the answer is "hundreds"?
I don't know, but how many more can be easily done now if technology is used like it was here? What if doing 100s in the same amount of time is now feasible? What if it takes far fewer than your arbitrary assumption of 100s of studies? What if it only takes 1 study with 100x the participants?
No one here is advocating for stopping double-blinded studies. Why not both?
> If you're off by an order of magnitude somewhere in your stack of assumptions, the data could be noisy enough that you need to be sample from a population of a hundred billion.
Why would you assume that it would be off by an order of magnitude? That seems about as likely as the data being perfectly accurate (that is, very unlikely).
And why 100 billion? It seems like you're just throwing out arbitrarily large numbers here.
> Should we wait a century for all these surveys to be done before even attempting data analysis?
This study took less than a year, and because it was automated, could likely be run concurrently with others. Why would it take a century?
> surveying the same set of people over and over won't give you additional data. You need to wait for some of the survey respondents to die.
Why would they survey the same set of people for the same study? There's a lot of people in the world.
I know you've decided for some reason that it would take 100 billion people, and that 100s of studies would need to be done to compare to even one clinical study. I know that for some reason you think that would take a century instead of in parallel.
Consider for a second that if you're wrong on any of those magically large and arbitrary numbers, this might actually have some value to the world instead of dismissing it out of hand.
Again, no one is suggesting any fewer clinical, double blinded, etc. studies. Doing studies this way has some potentially very large upside, and it can be easily used in tandem with those other studies to speed up research and gain much larger data sets.
Yes it has trade-offs. We can be aware of those without throwing out the whole idea.
There are well over 200 highly diverse lines of mice that could be split into isogenic cases and controls by sex, age, and any other instrumental variable (diet, enrichment).
We have many objective ways to quantify rodent health and behavior. Admittedly, there is no “happiness” metric that is translationally relevant to humans, but at least with rodents we can critically evaluate what goes on in the CNS at molecular and synaptic levels with and without drug X.
Mice and rats are in the same Supraprimate superoder (the euarchonta) with monkeys and apes. They are also fine for rigorous case-control studies of drug effects, IF and ONLY IF the study includes a high level of genetic variation among the rodents that will model hunan genetic and biochemical diversity. Unfortunately, typical rodent studies of just a single inbred type of mouse or rat are of modest translational relevance to humans.
> This is already a significant bias in participants.
In my experience, these pro-psychedelic conferences and associated discussion venues have already concluded that microdosing is a positive, to the point that they’re actively hostile to any information to the contrary.
Psychedelic forums and even threads on HN and Reddit can be extremely hostile to anyone arriving with negative anecdotes about their personal microdosing experiences. When people report negative effects there’s a rush to blame them for dosing too high or too low, or for having counterfeit substances, or any other number of easy outs to dismiss the negative anecdotes. There’s almost no room for discussion of people who aren’t convinced that microdosing is a positive.
https://elifesciences.org/articles/62878
Article summarizing it:
https://www.forbes.com/sites/amandasiebert/2021/03/03/larges...
Saddly from my experience self-reported is about as accurate as any medical professional. When I was actively seeing professional help it always started off filling out PHQ-9, adding up the numbers and seeing the sum in the range of depression.
I was never officially told I've been diagnosed with anything but it was enough to where I've gone through a plethora of psychiatric medication.
0 - https://www.researchgate.net/publication/287756303_Psilocin_...
This study has a solid methodology, and concluded that microdosing positive effects look significantly similar to placebo.
Given psychedelic agonistic activity on the 5ht2b receptors, chronic use is advised against because of the possibility of significant injury to the heart.
Fen-phen, notorious for causing heart failure, had the same mechanism of action. Phentermine and its analogs are still in use, but fenfluramine was found to be lethally dangerous, because of significant agonistic activity at 5ht2b receptors.
It remains to be seen if the dose makes the poison, but chronic stimulation of the receptors would seem to be inadvisable, given that the benefits of microdosing aren't distinguishable from placebo, according to a well designed study.
Full, heroic doses every 6 months have a proven positive effect, so treat yourself to a trip under the right conditions if you're wanting a boost to creativity and calming of the inner chatter.
https://en.wikipedia.org/wiki/Fenfluramine
https://en.wikipedia.org/wiki/5-HT2B_receptor
https://www.hopkinsmedicine.org/news/newsroom/news-releases/...
The work of Dr. David Nutt is phenomenal. He is an advocate for science and for ending the absurd war on drugs.
Johns Hopkins is doing stellar work as well, using extremely rigorous and institutionally impeccable methodology to investigate psychedelics as treatment for some of the most pernicious conditions affecting the human mind.
While I'm hopeful that psychedelics may prove to be a treatment for some mental health issues, but this study doesn't tell us much.
A lot of people here are discounting the fact that this study would typically be very hard (or impossible) to administer at such a large scale, especially in such a short amount of time.
In my mind, the important questions here are:
Are the benefits of massive scale studies worth the trade-offs of self-reporting?
What can we do to reduce or eliminate those trade-offs?
Imagine the scientific value of having easily created, easily administered, massive studies be easily accessible to any research group. If the research data can be made even a little bit more reliable (direct mobile health-kit measurements for example), that's hugely valuable.
A simple way of thinking about this is that you're almost always making a trade off between quality and quantity when you collect data, with enough quantity you can hope to overcome some of the quality concerns. For instance our study also included a finger tapping test (analysis will be in an upcoming paper). This would have traditionally be administered in a lab by a technician by placing electrodes on a persons thumb and forefinger and asking them to tap them together. It is a validated practice for measuring Parkinson's symptoms or neuromuscular integrity. We can easily replicate something like this on a mobile app.
Obviously doing it this way might result in noisier or less reliable data because there isn't a technician standing next to them helping them to get it right. Over time we have improved this by adding better instructions, addressing training effects and providing better instructions. We also collect data like screen resolution and phone model with each response so we can account for people who switch devices between tests or device-specific issues. And having datasets measured in the thousands means that a lot of these confounders come out in the wash, which isn't the case with study populations measured in the tens.
We're picking up the pace on our technical development. Version 2 of the app will be out in the next week or two; we planned to get it out before this paper was published, but they surprised us with a very fast turn-around on the proofs. One of our goals is to make this type of research more agile, in a similar way that the software industry moved from waterfall project management to more rapid iterations. If the cost of designing and deploying a study is low enough, and data can get back fast enough, researchers can do more rapid pilot studies and iterations, and more quickly make adjustments to add new scales and assessments.
On the subject of direct HealthKit measurements that's also a trend that we're excited about. The new version of our app will read from HealthKit and Google Fit, and we will be adding more integrations to other wearables and passively collected data with a privacy-by-design approach. We'll also be moving towards a design where users can consolidate different feeds of data and assessments that they are interested in collecting for intrinsic reasons, and then choose to make these available to different research projects.
As for myself, it helped me get over a mountain of grief after a rough childhood. I feel like there's no way I'd be where I am or forgive as much as I have unless I had taken them.
No, they're not addictive. No, you can't take them repeatedly within a short time span. Yes, they're decriminalized/legalized in many areas.
There is no way to guarantee the outcome the first time, that's why medical expert supervision is important, especially for people with mental issues/baggage.
That is all being said by person who did shrooms few times, alone, laying with closed eyes and the journey inward and back, with dissolution and later recomposition of every sense and part of my being as a bonus. By far the strongest experience in my life. It was absolutely amazing and beyond positive. But I don't have any mental or childhood issues and am very balanced person who knows himself pretty well (also thanx to these experiences).
That said, we... - took smaller doses - went with a beginner friendly strain - dosed in a calm, trusting setting - had guides that ensured our safety
Don't take these things lightly, and they'll treat you well.
found the replicant
Really, where have you heard this. I have only heard myths about this. Do we have any collections of data for these cases?
Something that is interesting is one of the lead researchers in the area professes that the disclaimer about psychotic episodes due to psychedelics in research is not based on any study more of a fear of tainting the study outcomes.
On the subject of bad trips (or the better term "challenging experiences"), Roland Griffith's lab at Johns Hopkins has found that people who had "bad trips" on psilocybin often actually experienced better long term improvements. Sometimes the best way out is through, and these medicines appear to help people confront issues that they have a hard time facing through standard approaches.
https://www.hopkinsmedicine.org/news/media/qanda_griffiths.h...
There are also people who end up in a psych ward for the rest of their lives without ever taking hallucinogens.
I am not a researcher so I wouldn't be able to "see" or figure out these things or know what to look for myself, unfortunately.
But this is Nature, a well-respected journal, no?
I'm surprised that they're essentially posting clickbait studies...
I don't see anything in the study that claims anything other than the truth? It's not like it's saying "Microdosing will make you happy".
The title is literally "Adults who microdose psychedelics report health related motivations and lower levels of anxiety and depression compared to non-microdosers"
It then tells you how the research was done, and what the statistics were. This isn't a random news website saying "Chocolate prevents cancers" or something.
Take a drive down skid row. Or look at Haight-Ashbury in the 70's.
If you've done any psychedelics you would be foolish to not notice that they can drive a person insane under the right circumstances.
And no I wasn't talking about "drugs" I was talking about psychedelics and their targeted use/dosage. I made the counter claim to provide evidence that psychedelics cause permanent psychosis. No one seems to be able to produce such evidence, and your point of casually linking homelessness to drug use may be all fine in a grand sense but with respect to the topic at hand it just looks like a red herring.
That's not to say that microdosing can't be useful. But I think it's possibly quite dangerous for some people. My evidence of that is knowing people who have done too much acid, and meeting plenty of street people in Haight-Ashbury who do acid.
I've seen a friend of mine going deeper and deeper into that hole.
He's asked for evidence and you've responded with a claim. Do you have any evidence to back this claim up?
>I've seen a friend of mine going deeper and deeper into that hole.
This is an anecdote. It does not constitute scientific evidence.
Here's a bunch of real people suffering from it: https://old.reddit.com/r/HPPD
You can definitely overdo psychedelics and fuck up your mind if you are careless with them. Maybe read up a bit on erowid, dmtnexus, shroomery, plenty of warnings from people who went to deep. Don't be stupid and naive.
Microdosing may seem harmless, but it also means taking psychedelics every day for long periods. I wouldn't do more than 2 weeks, you gotta have to function without the drug at some point, can't imagine dosing LSD for a year and then stopping will be pleasant. But your mileage might vary... I just have way to much respect for psychedelics to take them every day.
I had mental issues afterwards largely in line with those I had beforehand.
there you go, fwiw
This has zero relevance to microdosing.
I know two people who did this, and they both got very weird and ended up putting themselves in dangerous situations from their questionable judgement, years after they stopped even. One flipped his car while drunk and tripping and got seriously injured, but he made serious lifestyle changes. Months later he had a psychotic break and got arrested naked in the street. He is mostly better however he is still a shell of his former self. The other ended up getting addicted to heroin and overdosed several years later. Could just be selection bias and clustering of risky behaviors, but I believe the LSD played some role (possibly related to an interaction between LSD and SSRIs).
I think there are a lot of potential therapeutic benefits that should be studied, but clandestine microdosing is still risky as its practically impossible dose accurately and many people who think they are microdosing are taking doses that exceed the perceptual threshold because they don't think it's working if they don't feel it. Taking 5mcg LSD 3x week is probably mostly safe. Taking 40mcg once a quarter is also probably mostly safe. Taking an unknown 10-40 mcg 3x week seems like it could be entering the danger zone.
(Please learn about volumetric dosing if you're considering microdosing - it at least allows consistency. Fractions of blotter are inherently inconsistent because blotter concentration is not homogenous.)
Yes. He's a pretty normal dude.
The term "acid casualty" exists for a reason. I've known a few people that over-indulged and became detached weirdos and never came back.
It's not a 'wives tale' as someone here said. Take acid by all means. Just know that you could become a despondent ghoul if you go too hard and frequently.
It's basically a window into a malfunctioning brain. You bounce back when it wears off, but you can definitely change from tripping too much. Have you never met someone who has done too much acid?
None of this tells me whether or not people who have the time and money to microdose are simply in a situation more conducive to mental wellbeing.
Every morning I wake up relaxed, refreshed and it stays the same through the day.
Before that I used to do something similar with shrooms but in the morning. Always had that odd feeling I was borderline of starting to trip even with very low micro doses.
But my experience in both cases is pretty similar to what people usually say about micro dosing.
Google is one thing, reading and interpreting the papers is another. What matters to me is that I feel great, regardless.
Caveat: anecdote is not data and all that...
The effects you are describing are those of sativa strains, know for the 'head high' and creativity boost.
For example, I always had the same understanding of indica as you described, and I would solely buy indica gummies. They would give me a pretty "heavy" high, full body but mostly in my head, and I would wake up lethargic and often with a headache. I switched to a "sativa" of the same brand, and got a very nice full body high, but much lighter, very relaxing, and would sleep very well and wake up feeling refreshed.
Anyway, all that to say, different strains have different effects, and often the description from the dispensary can give you a good idea of the effects they are intended to have.
Can you get an 'indica oil' then? Pure THC oil is different than plant matter.
It’s marketing, nothing more.
The strain does not make a huge difference to me, Indica does not much make of difference, I still get somewhat energized by it. It is quite unusual that I get the opposite effect from other people but I know I'm not the only one.
I had really stressful workplace environment, it helped me immensely. I feel good effects today as well.
Compass Pathways' Phase IIb psilocybin trial shows reduced depression symptoms - https://news.ycombinator.com/item?id=29169160 - Nov 2021 (119 comments)
One think pointed out when I stumbled about similar papers before was:
The reduction of depression, anxiety, stress from micro-dosing are rediculus small compared to the effects of a more healthy live style and environment. Even just taking a walk in nature for 10min a day often had many times stronger positive effects.
I also have not read this study yet judging from a few comments it's not really randomized or blinded or anything.so the takeaways are very minimal.
How much is this "medium dose"? In all likelihood it's not a microdose, which is what is under discussion. It's well known that higher doses can have lasting effects.
Respect part is about wasting people's time (if knowingly).
The danger part is the same as with any other misleading information, which can lead people to consume damaging amounts of dangerous substances for now good reason (at least not better than just eating cucumbers instead).
I'll address a few of the comments made here so far below, but feel free to reply with more questions (or reach out directly, email in bio) and I'll try to get back to them throughout the day.
There are a lot of comments re-iterating concerns already covered in the limitations section of the paper. It's clear that an observational approach like this cannot establish causality and that self-selected recruitment can introduce bias, and the paper acknowledges this. RCTs will happen on this subject, but there aren't many significant ones published yet, and other types of evidence also provide value.
The subject of microdosing is one where the community practice and experimentation is far ahead of where the science is, which is different from research into regulated medicines where drugs are either not on the market or prescribed by doctors. There are a lot of health-related topics like this that are understudied where practice within a community that is not served by mainstream medicine moves forward slowly through anecdotes and informal discovery processes. Think not just about stigmatized subjects like psychedelics, but also about chronic disease communities, biohackers, athletes, etc. Sometimes alternative therapies and bottom-up health practices like these end up being validated by the scientific community, and other times the relative lack of rigor leads to years of people taking harmful or fruitless approaches. Bringing a more scientific lens to what people are already doing and speeding up the feedback loop with the research community is a big part of what we're doing with our company.
For microdosing specifically, there is a lot to discover by gathering evidence on motivations, demographics, and methods of real-world usage. The paper linked to above brings new insights into these topics, and is the first published research looking at the practice of stacking. One advantage of a large (n=8703) observational approach like this is that it helps pull signals from the noise to help inform further study.
The patient-reported data on depression and anxiety comes form the standardized DASS-21 scale which is a widely used self-report tool in psychological research. In addition to this data, we also included various quantitative cognitive tasks in the app (data will be analyzed in upcoming papers, stay tuned). While this data isn't collected in a controlled environment our approach collects data from so many participants that we have power across various demographics and methods of use. We also encouraged non-microdosers to participate, and the relatively low burden of participating meant that many submitted data throughout the study period.
Otherwise you've got a bunch of people who are the sorts of people who are going to try microdosing. Of course they're going to answer questionnaires in a way that scores them as less depressed. Firstly because they're less depressed people (can be bothered to work out how the hell to get hold of the stuff) and secondly because they're not stupid and know what sorts of answers will influence the score in what direction).
Totally did not read the paper. Someone tell me I'm wrong please!
Microdosing isn't going to alter your ability to reason.
But, I have been microdosing over the past few years.
Happy to answer any questions.
The schedule is 5 on, 2 off, and it's taken in conjunction with B3 (Niacin) and Lion's Mane (a non-psychoactive mushroom). All together, the mix promotes neurogenesis.
Combined with tools like meditation, exercise, and a supportive environment, it can do wonders to help re-construct toxic patterns built from long-term depressions and anxieties.
What is the propensity for addiction - can you stop whenever you want to? When last did you stop and for how long?
Sorry for so many questions but this is not a trivial matter and you graciously offered to answer.
I imagine they would be the best guage of the total net effect.
I wonder if this is a new phenomenon or just an undiagnosed one.
However, the idea that there could be chemicals like psilocybin or modafinil or piracetam that used to be in our produce seems highly implausible.
But my friend showed me a study a while back of turmeric supplementation and how it can be comparable and in some cases more effective than prozac: https://pubmed.ncbi.nlm.nih.gov/23832433/
I started taking 450-900mg daily and noticed an increase in optimistic perspective and seeing "the point" of doing things during rut of burnout after quitting my last job. Just my story. This is not health advice.
Psychedelic microdoser: "Because I'm a balloon."
Throwamon's explanation is good too. When someone asks a question with an obvious affirmative answer, a popular answer is an inquisitive "yes?". Only the thing being questioned in that case isn't the answer, its the doubt in the mind of the speaker who asked.