LSD microdosing does not appear to improve mood or cognitive ability: study
psypost.org
psypost.org
> The researchers found that the higher dose of LSD (26 μg) produced a small decrease in false alarm rates for recognizing fearful emotions and a small decrease in feelings of social rejection. The higher dose of LSD also produced heightened feelings of vigor and some participants who received the higher dose reported feeling a modest “high” during the drug sessions.
Then the following paragraph: > Under these limited conditions, the effects did not differ from placebo.
If the study was placebo controlled, doesn't the first paragraph contradict the second?
I'd also like to point out 1) that modest decreases in negative emotions (implied by the first paragraph) over a period of time can cumulatively alter one's perception of life for the better pretty significantly and 2) most microdosing protocols use 25ug, which is the high end of dosing for this study.
A person with a chemical imbalance cannot "just snap out of it", nor is it just a feeling of depression. There is a range of symptoms symptomology to go along with the diagnosis of true depression [1]. If left untreated, depending on severity, this can lead to suicide, delusional thinking, schizoid breaks, homelessness and very often self treatment with illicit drug use.
[1] https://www.mayoclinic.org/diseases-conditions/depression/sy...
That isn’t necessarily a bad thing, but it’s probably not worth criticizing a study that is looking in a different subset domain of interest.
I criticized the article. Not the study. The study authors believed the limitation was so important they put it in the title.
> If left untreated, depending on severity, this can lead to suicide, delusional thinking, schizoid breaks, homelessness and very often self treatment with illicit drug use.
I am current in most of these states; homeless, suicidal, and just suffered psychosis during a covid infection and dealing with an odd perception of reality. Talking to people about their sadness I know, luckily, most people do not know what depression is. There is such large gap between mental health and mental illness.
Be well.
Like you wake up feeling great and ready for the day, prepare your breakfast while thinking about all the cool things you want to do during the day, then you sit down and start crying for no reasons, and you’re now in the worst mood ever with very little control over how you feel. The whole thing is really violent.
The chemical imbalance idea is an oversimplification of what is going on. There is evidence that giving a serotonin agonist helps symptoms of depression, giving a dopamine agonist helps ADHD symptoms, a dopamine antagonist helps with some symptoms of schizophrenia, etc. Therefore, you want to conclude that if blocking (or increasing) a neurotransmitter relieves symptoms, that the person did not have the right levels of the neurotransmitter in the first place, thus, a chemical imbalance. The problem with this idea is that simply changing the levels of a neurotransmitter does not necessarily cause a clinical effect. Take depression, once you start taking an SSRI, your serotonin levels start to increase right away, but you will not see the mood enhancing effects for a couple of weeks. This is likely because there are issues with serotonin receptors, and the flood of extra serotonin helps to reset them. For schizophrenia, if too much dopamine was the answer, we would expect to see increases in its metabolites, but we do not. More likely, there is a problem in the pathway that projects dopamine from the midbrain to the forebrain, which causes it to not function properly as negative feedback, therefore allowing over-activity of dopamine pathways from the midbrain to the limbic areas.
I personally believe this is why many invidivuals report post-trip lessening of depression or anxiety, cessation of smoking or other addictive behaviors such as gambling, and even improvement of cluster personality disorders symptoms in some cases. It's not an inherent neurological trait, but a complex interaction in the way that you view the self and society. Psychedelics allow people to view situations and experiences in a way they've never viewed them before, and in a way this is giving a key to a perspective that they've never heard before but resonates deeply with them, helping to initiate serious change.
https://www.science.org/content/blog-post/how-antidepressant...
That’s why ketamine works better than they do, and why they take weeks to take effect unlike Adderall that’s near instant for ADHD.
“We removed any expectations that this was a psychedelic drug,” de Wit explained. “Because in the real world, people’s expectations can strongly influence their responses.”
The goal is to know whether the drug itself actually leads to improved mood & cognition, without any prior bias. I don’t know why you’d want to include expectational effects. Why is a placebo controlled study not well suited? If you don’t have a control group, you can’t know if the results are due to the drug, or due to hopes or “contact high” as they put it.
Michael Pollan points out a few of the factors that make studying psychedelics hard in How to Change Your Mind. For macrodoses, there's the obvious problem that you probably know whether you got placebo (he mentions a control drug that gives people "chills" but even that is pretty obviously not LSD)
But the bigger issue is that LSD has a huge dynamical set of effects that depend heavily on mindset, expectations, environment, and probably randomness. It's not as straightforward a casual mechanism as say, aspirin. The positive effects of psychs can't be isolated from the supportive environment, the coaching from staff, etc - doing those things wrong can easily negate - or even reverse! - the effect (i.e. bad trips)
With the ongoing war on drugs and the abysmal outlook of just hacking the charm of psychedelics to make people into dispassionate monsters or work robots, I don't think we are on the right road to what the substances can do for society.
Also, not everyone needs to trip. Fact. In most cultures that do have psychedelic substance rituals they are used by individuals that need to go to a shaman and sort out a complication such as loss, sickness, or mental disorder. Usually the shaman is the designated tripper for the community and that lifestyle is not considered to be a super sweet gig or constant party.
Drugs being illegal has relegated them to parties, which I think is the wrong way to look at mind altering chemicals. Not that getting high as fuck at a party can't be super fuckin' fun but it commodifies the experience in a way that does a lot of harm that could be avoided without prohibition. Decriminalizing everything would open the door to building those structures into society and some places in the world have had good results with decriminalization and legalization.
This a million times. We could build, "safe places" where people could productively use things like LSD and this activity could contribute to a body of active research. This might be a, "net loss" for society but you know what's even worse? Teenagers having a foundational spiritual experience sullied by being arrested or by being in the company of unsympathetic others. This ends up contributing to crime statistics (which is useful for the establishment, isn't it?) but does little in the way of furthering our understanding of the brain or cultural pharmacology; what to say of spirituality or freedom.
It's also so bloody wasteful. Such a goddamned waste of magic and potential. The psychedelic brats with their dad's credit cards and the anal retentive aggressor lizards trying to steal my prostate energy.
Hand's off!
Lol. Sorry, I read this but somehow did not read this last sentence. I don't know or even know if I want to know what this statement really means to you because I love it so much and I'm afraid that if you told me it might lose it's magic. If this is a serious comment and you want to clarify though, I'll take it completely seriously and deal with whatever the outcome is. Either way, shine you crazy diamond. Genuinely I think that might be one of the best sentences I've ever read.
I'm in that age range and among those people, and my observation is that we already do (and have for a while) mind-altering chemicals at scale. Alcohol is ancient, mind-altering, and very widely used. Caffeine is ubiquitous. Something like 1 in 6 Americans is on an antidepressant. Birth control is popular and has mood-altering effects. I think you'd be hard pressed to find anyone that doesn't consume some form of mind/mood altering substance with regularity.
I would personally put alcohol and psychedelics in roughly the same ballpark of altered mental state. The effects are different, but the degree of difference between one's "normal" self and the altered self are roughly equivalent.
I don't think they're some panacea, but I would wager that if we replaced alcohol with psychedelics, we'd probably be in a better place. Not because psychedelics are some kind of fairy dust, but because alcohol is damaging in almost every sense you can imagine. It's hard on the body, it causes people to make poor decisions, and it leads to a lot of deaths due to the prior.
I've seen neoliberalism co-opt surfing, folk music, skateboarding, rock n' roll, sex, punk rock, tight jeans, baggy jeans, EDM, being gay, and being black in commercials and having recognized a pattern I really, really shudder to think what LSD culture will be like when it's sold alongside Baker skateboards and ripped mom jeans at Zumiez at the mall. I don't think it will be harmful at all but that's just the thing (...) all the, "revolutionary" potential will get sidelined and that's worse than a few dead Supermen or a few acid dropouts. Che Guevara t-shirts come to mind.
You remember those robots things from X-Men: Days Of Future Past? How they could absorb the, "magic potential" of the mutant they targeted? What happens when the man, "absorbs" the chemical and spiritual potential of LSD, Mescaline, 5-MeO-DMT, or Psilocybin? What happens when we offend the gods by turning them into consumer products?
The fact that they “removed any expectations that this was a psychedelic drug” is tantamount to removing the agency.
https://scholarsarchive.byu.edu/intuition/vol13/iss2/10/
However, the fact that they did not test this on depressed patients is, well, depressing. When someone has depression, it is very easy to know when it leaves.
Dosing acid every morning will do absolutely nil for you if you're just going to continue doing what you always did. You're going to do it with a little bit of an expanded mind, have comparably better creative and abstract thought streams, maybe get to see small glimpses of how your subconscious works during your daytime routine, and appreciate details and life itself more. You might also start interpreting too much into your experience or experience placebo effects.
Nothing of that is permanent, and nothing will change, until you actually start to use it with clear intent as a tool to accelerate forming of new habits and thought patterns for yourself, which is MUCH harder than it sounds like. What LSD is really good at is opening up the flood barriers of your subconscious mind and removing filters off your perception, which then leads to exactly the effects you can use for benefit - that every experience you make while under the influence is immediately ingrained into your neural pathways 100x stronger than usually, and your stream of thought and inner monologue is very.. "clear" and accessible, so you can also apply this effect to your own inner unconscious monologue. This is for example where trauma is continued within yourself. You might have noticed that, if you let your mind chat and run unchecked and unwatched, sometimes it will start to form thoughts and inner monologue that resembles closely how you were treated by your parents in early childhood.
Coupled with downsides of microdosing (and yes, there are downsides), it is a really delicate venture to undertake and you will need good knowledge and experience of psychedelics, psychology and a clear and direct intent, plan and motivation, or you are bound to end up just routinely microdosing for no purpose whatsoever and fuck up your brain chemistry for a while.
Would recommend to some, but definitely not as a routine activity. Max 1 week.
I hear you, but "a few weeks" and N of 1 isn't enough to determine that something isn't placebo.
> Coupled with downsides of microdosing (and yes, there are downsides)
Yeah - I feel like every drug user on hacker news is like the pinnacle of mental health or something because there's a whole batch of people called the mentally ill for whom I can never recommend microdosing, lest they have a panic attack or manic episode.
But sure! Psychedelics are all upside! /s
Sure do. The immediate effects are anything but a placebo, but there is.. gigantic room for interpretation left open regarding actual persistent long-lasting benefits. It's a little bit like the hen and egg problem with psychedelics.. if there's anything that probably always holds true to some extent, it's that you will gain more insight into yourself - whether that is helpful then again depends on what you make out of it.
Intent... if you have none, you leave the room for interpretation open to delusions.
People who experience a placebo effect also think whatever they're given is definitely effective.
If we want to talk about placebo, we really need to define the original purpose. I've heard countless of reasons to microdose by now, most of them are hokum to begin with. I think I did a pretty good job at describing what microdosing is actually useful for: Speeding up the forming of new habits and thought patterns, which is really really difficult and simply taking a small dose of LSD with your morning coffee isn't going to do anything and not going to produce immediate favorable and persistent effects, unlike for example Adderall would, aside of gaining a little bit of a deeper understanding on subconscious processes during your daytime routine.
If you're going to do it, it has to have a very, very clear purpose that also matches the effective profile of LSD, and even then the outcome is not guaranteed. A close friend of mine did not heed these warnings and now suffers from an, arguably, microdosing-induced panic disorder. Is this still a placebo? Possibly, but the effects of psychedelics are anything but a placebo, and their potential power is absolutely insane - but the utility, or harm potential, is directly correlated to what you do with it. Psychedelics are unlike any other substance class. The effects are not predictable like e.g. coffee is, they will send your deepest subconscious workings straight up into aware consciousness and you may not like what you see.
Physical effects of LSD are well documented: More physical endurance, for example.
100%.
> I.e. if your friend took sugar water that you told them had LSD, would they have the same panic disorder?
I see what you're saying. Extremely unlikely, because the effects of psychedelics are not caused by simple knowledge of ingestion. I know this, because I once got sold bad LSD, with close to zero active ingredient, yet I assumed it was a very strong dose, and there were no effects whatsoever. Generally, adding to this, the effects of psychedelics are so extremely strong and all-encompassing this is completely out of the question. Don't take my word for it, ask anyone with experience or read experience reports.
> And also not just the one friend of course, but repeated across many trials.
Sorry, I'm not an expert in this field, I'm a software engineer. Just wanted to share my subjective experiences.
FYI I have microdosed and it felt great but I wasn’t trying to tease out an effect. I think there’s a decent chance that the lift I got was because I felt mischevious, like, i just took some fing acid this morning and here I am at work. Solid lift.
If there is some effect, then a blinded study should show a response. It doesn’t come down to ‘magic’ that works only if you know you’re taking the actual thing and have the right set and setting. By your own example, a blinded study that was run without the important steps you mention should correspondingly show people with both positive and negative effects which would appear in results. If you don’t have these results, then you have a bunk field that is just pseudoscience. Now this study may or may not be of that good a quality, but it goes in the evidence pile.
> Sorry, I'm not an expert in this field, I'm a software engineer. Just wanted to share my subjective experiences.
It’s clear that you’re sharing your subjective experiences, but that is not at all how you presented it, you presented it as though the study is wrong because of your experience. The study could be wrong, but the study is (at least ostensibly) attempting to follow the scientific method. Your dogmatic defence of a technique you clearly believe in (and to be clear, I don’t want to invalidate the benefit you say you have received from it) does not in any way contribute positively to what the objective of science is - to get to the truth.
The broader picture here is that if there are high quality studies that demonstrate that micro dosing has some minor, or even significant effects on subjective experience when appropriately blinded, then it is a field for further study and potential adoption into therapy or other areas in controlled situations. If it shows nothing, then it is like the whole field of pseudoscience where the labours and efforts of people and mis allocation of resources to something that provides no benefit (and, on a re-run of history may never be developed, as opposed to science, which would come out the same way)
Absolutely not. To be clear, I'm not arguing against this study. In fact I absolutely believe the results to be conclusive and am trying to offer a possible explanation based on my experiences.
I very well understand what a placebo is (or, at least, sufficiently enough), maybe the misunderstanding of my intentions behind commenting made it seem like I didn't. With the knowledge that I am arguing for the study and not against it, maybe my comments will make sense in a different way now.
Approaching microdosing as you mention (and as I did) - with a clear goal and very intentionally is the key. But I could never really tell if I made the choices I wanted (not eating a candy bar or something) because the LSD was affecting my thinking or because I had taken the time to set my intentions clearly for the day. Would doing the ritual of microdosing but not taking the LSD have the same effect? I'm not sure. I found the LSD acts as a symbol and a way to signify the day as meaningful and keep my intentions top of mind. Parsing out what part of "success" was attributable to the chemicals and what was attributable to the ritual is very difficult. But in the end, does it matter how it works if it helped change habits?
Me neither. All I know is that the substance is extremely powerful, and beneficial if applied correctly.
> But in the end, does it matter how it works if it helped change habits?
:)
People claim ketamine + "integration therapy" is harmless but it makes the therapy so much more expensive if you have to sit in a room with a medical professional paid by the hour. And a lot of depressed people are not rich.
I was talking about microdosing LSD, although now I wonder if there is such a thing with Ketamine as well. You might like to hear that the country I live in is taking steps to have Ketamine therapy for depression covered by universal basic healthcare soon.
This term disturbs me. Is there really an encoded idealism that says, "just start taking a dose of X" and forget about it? Or am I just misunderstanding this?
No follow up therapy? No behavior modification? No treatment protocol? When do you ever get to a point where you're no longer consuming therapeutics, or is that the end game? Just find the right one and take it forever?
> with Ketamine as well
A known side effect is long term bladder damage. This is precisely the reason I find the logic of "fire-and-forget" around these drugs disturbing.
Regarding your other statements, they mirror very closely what I've also described.
After my first trip I became capable of discerning and understanding lyrics in songs. I am on the spectrum and had a lot of trouble with that prior, but it's as if a path was unblocked.
When I microdosed sclerotia I found that many of my ADHD symptoms were gone. In particular it was far easier to get things done because I didn't feel that I was inertial i.e. prior to that I felt that I needed to put a lot of effort to change my trajectory and start doing things but after that I could "just do it". I know that time moved a lot more slowly and I got things done significantly faster than otherwise.
You can't know 100% unless someone actually swaps your stuff with a placebo, especiall with something that is so hard to measure.
There’s this thing called the placebo crisis going on at the moment, which is making it harder and harder to validate drug candidates: because medicine is improving, people’s faith in it is increasing, which in turn increases the strength of the placebo effect, which raises the bar for drug candidates.
What downsides did you find?
There is no way someone can know if a drug is placebo when self dosed. I have attempted to do placebo tests on my self with some high dose supplements and it means I blind myself to what I am taking by having someone else give me the supplements not telling me if it is the real thing or the placebo. After you do that get back to us.
> Psychedelics bring up your subconscious processes into aware consciousness, and do so to lesser extent even at microdoses.
I would say this is a fantasy born in the sixties. How do you know something was brought up from your subconscious or a delusion created from the medication. You would have to know what was in your subconscious to know it came from there. So this to me is just more woo woo talk.
> Coupled with downsides of microdosing (and yes, there are downsides), it is a really delicate venture to undertake and you will need good knowledge and experience of psychedelics, psychology and a clear and direct intent, plan and motivation, or you are bound to end up just routinely microdosing for no purpose whatsoever and fuck up your brain chemistry for a while.
That does not seem workable for depression. I have to say I am currently struggling with suicidal thoughts and can barely get out of my van do to anything.
Might there be some neurogenesis with LSD, possibly through increasing BDNF https://pubs.acs.org/doi/10.1021/acsptsci.0c00099 But can all depression be cured with neurogenesis and therapy? Who knows.
Ketamine has this same property of neurogenesis, as does prozac https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360216/
There are definitely performance enhancing drugs out there - effects and side effects might not make them viable/worthwhile for everyone - but saying it's mostly placebo is just plain wrong.
Either way, why are you wasting this on making more money for your boss? It's much better spent having a fun weekend on the beach with friends, going for a hike in the woods (if you're highly experienced and can safely manage a solo trip), or literally anything else.
There's something to be said for a little bit all the time being as valid as a lot every now and then. They're focused on different effects and facets of life.
In my mind it's 'doing large doses all the time' that's generally a problem (and even then only from a 'hey, you might need to work on yourself a bit and take a deep look at why you're doing that' perspective).
But it's not like you can compulsively load up adderall pills into a pipe to turn into a puddle.
The huge issue I see with tweakers is that they smoke that shit like a joint and will tell you that they're doing it for medical reasons. Hilarious if it wasn't for what that does to you.
Sola dosis facit venenum (The dose makes the poison)
Also, Adderall (Amphetamine) != Methamphetamine. That is like saying Ethylene Glycol (a common car anti-freeze) is the same as Ethanol (drinking alcohol) or that Peroxide is the same as distilled water. In fact, the substances I listed above are more molecularly similar than methamphetamine and amphetamine.
From my understanding, meth made in quality controlled, lab tested, legally controlled, and medically administered and monitored dosages has amazing results for the conditions it treats. Commonly, dosages are in the 2mg - 20mg range vs. the multiple GRAMS of meth + whatever leftover reaction byproducts in recreational usages.
Also, stimulant medications have a higher safety profile than many OTC medications, so take that for what it's worth.
The people I know who have made such a distinction haven't done both. The people I know who have done both tell me that they have essentially the same effects.
> Also, stimulant medications have a higher safety profile than many OTC medications, so take that for what it's worth.
Yeah, I think a lot of OTC medications are essentially grandfathered in to drug policies and would require a prescription if they came out new today.
Have you ever tried both, though? Once you factor out the faster uptake due to that methyl group, it's essentially impossible to tell which is which at equivalent, medicinal doses.
Would one be able to tell a difference at a much higher dosage? What about when compared to an equivalent dosage of another CNS like methylphenidate or cocaine?
I never dared risk much higher dosages, so I wouldn't know.
> What about when compared to an equivalent dosage of another CNS like methylphenidate or cocaine?
In my experience, one can definitely tell the difference between (meth)amphetamine and methylphenidate / cocaine, at any dose. They are by no means that different, though, and I wouldn't be surprised if a person with no previous exposure to either would struggle to do so. Other CNS stimulants, like nicotine and caffeine, are more obviously different.
This is all purely anecdotal, though I have skimmed studies which also claimed as much, so those might be worth looking into.
And that's exactly why this study is bogus. Here are the two tests which they used to "measure" cognitive ability. See anything wrong here?
https://en.wikipedia.org/wiki/Digit_symbol_substitution_test
https://upload.wikimedia.org/wikipedia/en/2/20/LSDaffinities...
I do like having full blown ego death once in a while but just as much I like to just take the edge off at a music fest and not have a bad trip
no one cares
I do not dose often. I’ve done lsd 5 times total
I definitely was outside my body but maybe what I call ego death isn’t as intense as a full blown trip?
I didn't do it to increase productivity, I did it to experiment. I was the same me, minus negative thinking for 48 hours. I felt lighter and happier. It was like a medicine.
Wish I could try it again but it's so hard to find.
Though even if it's snake oil, its pretty cheap snake oil. The cost ends up being around $1 every 3 days which is pretty reasonable.
--- CONFLICT OF INTERESTS HdW has served as scientific advisor to Schedule | Therapeutics, Gilgamesh Pharmaceuticals and Awakn Life Sciences, and she serves on the Board of Directors of PharmAla. None of these are directly related to this study. The other authors declare no conflicts of interest. ---
HdW being Harriet de Wit, the lead on the study.
Who sits on the Board of Directors of PharmAla [1].
PharmAla according to their website manufacture clinical-grade MDMA and novel (_patentable_) MDXX compounds for the scientific research community.
Compounds that it could easily be argued are threatened by LSD for therapeutic purposes.
...I wonder why the original PsyPost article doesn't mention this.
/Snark
First, the study size appears to be so small (about 20 people for placebo, and for each of the two dose regimens) that it's not really that indicative one way or the other.
Second, reading through the journal's articles on Google Scholar definitely shows it has a bias towards the traditonal 'addictive and dangerous drugs' mentality such as alcohol, heroin, marijuana, cocaine, meth, etc. Interesting, a search for 'Adderall' turns up 1 result, and a search for 'methamphetamine' turns up 327 results on Google Scholar (using advanced search and limiting to this journal). Heroin gets 445 results, oxycodone gets 35 results. All in all this looks like a journal for researchers who approach the subject from an abuse-centric perspective, basically the Nancy Reagan approach to drug addiction issues.
If you want a more balanced overview from a more general journal, try this:
https://www.nature.com/articles/nature.2012.10200
> "The powerful hallucinogen LSD (lysergic acid diethylamide) has potential as a treatment for alcoholism, according to a retrospective analysis of studies published in the late 1960s and early 1970s. . . Of 536 participants in six trials, 59% of people receiving LSD reported lower levels of alcohol misuse, compared to 38% of people who received a placebo. “We were surprised that the effect was so clear and consistent,” says Krebs. She says that the problem with most studies done at that time was that there were too few participants, which limited statistical power. “But when you combine the data in a meta-analysis, we have more than 500 patients and there is definitely an effect,” she says. In general, the reported benefits lasted three to six months. Their findings are published today in the Journal of Psychopharmacology."
Now does this address the best option for therapeutic use? Is one strong dose followed by therapy best for alcoholics? Could microdosing be a means for alcoholics to continue to resist the urge to drink over longer periods of time? Those sound like good topics to study.
As far as those who want to use drugs and alcohol recreationally, vs. those who want to use the police and courts and prisons to enfore their view of what are the acceptable substances to ingest, I'll side with the former, though I'd advise them to adopt the "less is more" mentality.
So far, there is quite a bit of evidence that two sessions of psilocybin dosing in a controlled environment does provide permanent relief for anxiety, depression and PTSD symptoms.
I have a lot of other anecdotal evidence that this is also the case in less.. controlled settings.
What evidence?
If I've missed your point, I think you need to unpack "bullshit" before anyone can take your comment seriously.
Nootropics, and many nutritional supplements generally, have the same problem.
believe in yourself or become owned by the world.
ignorance may be the price to pay but the alternative is worse
It definitely improves creativity.
It is possibly the explanation for the Flintstones House, which isn’t in SV.
It induces oxidative stress which is not necessarily a good thing.