Does Microdosing actually work?

Improving creative flexibility using three molecules

The research of Psychedelics has mostly focused on clinical angles (PTSD, Depression et cetera) using large (macro) doses under supervision of a psychiatrist. Yet fewer studies have investigated microdoses of psychoactive compounds, despite its popularity as a believed cognitive upgrade. I myself, as is fashionable of late, have done a little research of my own.

This idea of using compounds as smart drugs is not new. The movie Limitless is often suggested to be based on the drug Modafinil (otherwise known as Provigil), and the use of amphetamine based pharmacological compounds for studying is so widespread at this point, to call it fringe would be disingenuous. Over the years, psychedelics in particular, have been used for the belief they may enhance productivity, creativity and cognitive flexibility — but how legitimate is this claim really if there are few scientific studies which validate it? In technology, the space I’ve worked for all of my career, microdosing psychoactive compounds was frequently suggested as a performance-enhancing-drug of sorts, a cognitive edge in a domain where edges can mean billions, but could this have all been a hallucination in itself?

Over the years, I’ve gone through periods of micro dosing (both LSD and Psilocybin) to see if it would improve all kinds of cognitive functioning, and had some mixed results. My experiences, obviously, were all anecdotal — there was no real way I could have proved a benefit either way. If you’d put a gun to my head — I’d have said the results were positive? But this was likely me just telling myself a story about it more than a real, interoceptive assessment.

First though, before you read on, the usual caveats apply to something like this. It goes without saying, don’t use illegal substances, don’t do things without a doctor’s oversight, abide by the laws that govern the jurisdictions in which you live, and only engage in these activities, should you wish, where it is legal and safe to do so — none of this should be considered medical advice, obviously. But most of all, If you have any sense of mental illness or psychosis, or even simply increased vulnerabilities to mental disorders, which you’d find out by seeing a professional, you should take the doctors route, have a discussion about it, and my advice, is to steer clear from loading up your mind with mysterious compounds, because there can be some real consequences, many of which, “will not be a vibe”.

That out of the way, those who have experience or are curious about microdosing and its effects on creativity, I want to offer my own personal experiences because I think I came across something kind of interesting.

Microdosing poorly

My first attempt on micro dosing (years back) was using 1/50th of a dose of LSD. This dosage was both practical and easy to administer; a drop (or tab) of LSD in a 50 ml dropper bottle means that each drop is roughly 1/50th, it makes application pretty simple. This level of dosing is supposedly imperceptible. I found otherwise.

In the first week, I noticed a profound elevation in mood (I was in a much better mood) and would describe my interactions with conflict and adversity much less destabilising. If you think of going about your day and coming in contact with something that usually annoyed you (or someone who annoyed you) the difference between microdosing and not was that the internalisation of that annoyance seemed less impactful, like having a ball thrown at you in a snow jacket, you know it hit you — but it’s just not that big a deal. This effect, I found, was noticeable. I was, as the zen buddhists say, the rock on which the waves break; unfazed.

The downside? My eyes were watery, and also, I got minor headaches. There is also this kind of fuzziness to visual sensations; I suspect the headaches and the ocular disturbances are related. From inside my head, i the world was shaking a little, it was harder to focus on a specific object, even though, objectively, this wasn’t true. The conclusion I came to was that my senses were actually totally fine, and my vision was fine, but my conscious interpretation of that experience was disrupted. In many ways, if you have ever done a large, macro-dose of psychedelics, and just dial it back about 50 times, that’s more or less the feeling. This is why, I suspect, the effects were not down to placebo alone. The similarity between large and small doses were the same, just vastly reduced. A bit more speculatively, maybe this has something to do with the whole predictive processing theory that people like Andy Clarke and Anil Seth discuss when talking of Consciousness, but this is just a guess.

On the headaches though, they weren’t bad enough to deter me, just very, very minor. The mood elevation seemed well worth the downside. I’m just stating the side effects because it was present, and consistently so, as was the eye watering, and I want to be authentic about my experiences.

LSD method: When and how

In terms of when I used this method, I used a dropper bottle for dosage in the morning, more or less within 90 minutes of waking up, and took nothing else with it, nothing special anyway. Over time, as I found myself supplementing my diet with other things, I noticed no real interaction effects worth noting.

More generally, I just felt happier throughout the day.

Using the LSD 1/50th protocol, I used it every second day for maybe 6–12 week periods. But honestly, after the second week, I noticed the effects were totally gone and started to question how molecules might deteriorate over time, especially given the LSD was in water. I also noticed, as time went on, the feeling of happiness started to dissipate. Essentially, all the upsides vanished after a few months of use.

There are some moderately grounded theories about why this could occur, which essentially come down to the following

1. LSD works (primarily) on these 5-HT2A receptors, (serotonin receptors) and after repeated exposure, they might have become desensitised or down-regulated, and this change could persist over longer usage.
2. LSD changes brain connectivity and neuroplasticity, so maybe the brain adjusts to some new baseline “set point” in terms of how it responds to stimuli.
3. Maybe the P450 enzymes, which are involved in drug metabolism changed due to factors like diet, meaning other lifestyle factors I had going on were messing with these enzymes changing the effects?
4. And yes, heat and air. Maybe the storage of said LSD droppers degraded over time.

Either way, I don’t really know why it stopped working but it did. So I simply moved on with my life, until I got to Austin.

So Paul Stamets gets on stage…

Each year, at the music, movie and interactive conference known as SXSW, the conference decides on a theme which will inform some of the conference tracks. When I went with my wife, a few years back, that theme was Psychedelics, specifically, the industrialisation of the Psychedelic economy.

As many were beginning to suspect, much like with Cannabis, as attitudes changed both politically and scientifically about the psychedelic compounds that were moving beyond illicit substances to research properties, would an industry that could be monetised, naturally follow? If so, what opportunities would emerge?

Arguably, two figures have brought psychedelics into the mainstream in recent years, Michael Pollen, whose book “How to change your mind” seemed to break the back of Psychedelic stigma when it came out in 2018, and Paul Stamets, one of the most vocal supporters of the benefits of mushrooms, who suggests they can be useful from everything to solving the colony collapse disorder in bees, mental health psychopathologies, and used as a biodefense layer from which the entire global economy could benefit. He’s also really into old growth forests of the pacific northwest.

Stamets, who commonly wears a velvety textured hat made from a mushroom, gave a presentation to a packed crowd in a small hotel in Central Austin. As a child, this would have been impossible for Stamets, who had a stutter so bad functioning in day to day life was nearly impossible. The cure, for him at least, was psychedelics. His talk centred around his findings on the cognitive effects of a combination of molecules, which he called the Stamets Stack that were used in a large, naturalistic, observationally designed experiment that followed psilocybin microdosers (n = 953) and a control group (n = 180). These findings were subsequently published in Nature, more or less the gold standard for Academic Publication journals. The compounds in the study where a trio of psilocybin, niacin (B3 Vitamin), and lion’s-maine mushroom (Hericium erinaceus), and the cognitive assessment used was a a finger tapping test (a common cognitive assessment), whereby the participants tap their fingers on the phones screen as a way of measuring the cognitive performance of all of the neuronal connections that run up and down our bodies.

It’s common for people to think of the brain as a single large organ, stored up in the head, and when we think of things that modify brain function, many can be led to believe that all those modifications happen in the skull. But our central nervous system (of which the brain is just one component) runs neurons all throughout our bodies (via the peripheral nervous system) and so, neurological compounds that alter the performance of our neurons can indeed, improve things like motor responses — so long as they work of course.

The results showed, very simply, improvements in mood and mental health (small to medium sized improvements) and psychomotor performance improvements, specifically in older adults. This, I suppose, was expected. But one curiosity they discovered was that combining psilocybin with lion’s -maine and B3 didn’t seem to improve mood or mental health, but in the older participants, this combination did improve motor functioning when compared to groups who only used psilocybin alone. One could speculate, I suppose, that lionsmaine, often thought to improve neurological functioning and stimulate neurogenesis, could be responsible for this, but honestly, this is outside the scope of today’s sermon.

One practical benefit, according to Stamets, of combining the three compounds together, other than the pharmacological interactions that justified their mixture, was it justifies the combination to be patentable, putting it, at least partially, under the direction of Satmets himself. This move is very on brand for Stamets, whose world views often hark back to the 1960’s visions of free access, non-corporate control, and transparency towards compounds that could provide vast amounts of utility. Through patenting, he believes it would prevent the pharmaceutical industry from muscling in on the mushroom’s genetics and commercialising it, much as companies like Monsanto have done with other beneficial botanicals.

The Stamets Stack explained

Finding the exact instructions and dosage online to microdose in the same way that was used in the study is an easy feat, but for completeness, this is how I approached it when I gave it a whirl myself.

• I took 150mg Psilocybin Mushroom powder in capsule form,
• with roughly 100mg of Lions-mane powder, also in capsule form,
• followed by a 200mg Niacin supplement readily available from any chemist.

I took these three compounds on the following schedule;

• Took it for 4 days, (tue,wed,thur,fri)
• Then took three days off (sat,sun,mon),
• and did that for 4 weeks,
• After that, I took 2 weeks off entirely

And I found that doing this, unlike the LSD method I had used years back, the effects sustained themselves for as long as I used the protocol. The effects also stayed fairly consistent. There seemed to be no tolerance buildup, at least subjectively, for me.

My experiences

People who do it frequently say positive things about microdosing, myself included, but I really wanted to know if it was making any kind of objective difference? I didn’t want to use something like this if I was just tricking myself all over again that it was helpful. There is plenty of this going around and frankly, I figured it was time to put my money where my mouth was and be open to the idea that maybe this was all just placebo. To do this, I would have to think a bit more scientifically. Could I measure some degree of cognitive functioning that was more related to my life? I could obviously imagine doing a finger tapping test and inferring this had cognitive benefits, but my life does not orbit around tasks in which finger tapping is wildly helpful. I wanted to know if I was more creative, was I cognitively more flexible (a common claim with microdosing) or could I produce ideas that were profound?

I landed on doing a bit of a cognitive experiment on myself — the worst kind, with a focus on measuring how much creative flexibility it was giving me. Methodologically speaking, there are plenty of things wrong with how I did this, so I’m not suggesting these results should be taken for empirical evidence or anything, but I’m more so just sharing my experiences, with a few numbers.

Measuring Creative Flexibility

I looked around for some cognitive assessments that would measure aspects of creativity that were a bit more “prefrontal cortex” centred. I landed on using the Wisconsin card sorting test. Typically, this test is used to measure executive functions and particularly flexibility in problem-solving, and the ability to shift strategies. The test is simple enough, and works like this.

A series of four cards are presented as follows. There are colours, shapes and also, a total number of elements on each card. (as shown below).

The participants’ job is to try and work out what the rules of the game are. In the above example, are you supposed to match the two blue stars to the four blue circles because the rules are (match for colour?) or, are you supposed to match it to the shape, in which case, do the two blue stars match to the two green stars (matching for shape). You can also match for the total number of elements. What makes the game tricky is that sometimes, as in the above example, if you were to match the two blue stars to the two green stars, you don’t know (if the game says you were successful) if the rules were the total number of stars, or if it was the shape. So to play the game requires you to pay attention, remember what you just did, a lot, and speculate on rules which may or may not turn out to be true. It’s quite difficult and taxing on the mind. It is also timed, you have to move quickly and make decisions without missing a beat. The only feedback you get is whether your choice was correct.

I decided to do some baseline tests to measure my cognitive errors roughly 1 week apart — I expected some practice effects here but I wanted to see if they showed up. I did 6 in total, and recorded the three error types on the Wisconsin card sorting test that are available. Then, I did three separate tests on the Stamets stack and compared my results. The results can be seen in the figure below with the black being when I was not on the treatment, and the lighter grey being on it. You can see, quite clearly, that I made fewer cognitive errors while on the protocol.

I’ve also put the actual scores and the % to changes in the table just for transparency. The averages of the trials are on the right and the overall % improvement is in green on the right hand side of the table. Essentially, on average…

• My overall error count reduced 6.67% on the Stamets stack
• My perseveration error count reduced by 4.34% on the sack
• As did my non-perseveration error count, which dropped by 3.70%.

How does it feel?

Firstly, my mood and the effects of micro dosing using the stack, was better than using LSD. Not only did my mood stay elevated over a much longer period (I did this over months), I saw no deterioration of the effects. I think the reason for this may however be the regimented spacing and having time off from the protocol, perhaps making the whole application more of a long term possibility. Also, there were no headaches using the mushrooms, compared to LSD, which I found was a bit of a drawback. My verdict on this, from my experiences, is that this was vastly superior to trying to microdose LSD.

More poignantly, why might my Wisconsin card sorting errors be lower on the stack? This could be for all kinds of reasons. First, expectancy and research biases. As I did this I was keen for the results to work, so I probably tried harder on the tests, even subconsciously. Maybe this is true, maybe it’s not, when I did the baselines I did try really, really hard and I had so many trials that it seems difficult to put this down to anything else. And when I was on the stack, I’m not exactly sure I was even trying equally as hard. But it’s hard to know how much of an influence this has. There is only one way to tell obviously, more people, blind trials, better run experiments, none of which i’m planning on doing.

Thirdly, the factor I wonder about is that I might have gotten better at card sorting as time went on, but you don’t really see this in the numbers. Technically I could do more statistical analysis on this stuff I supposed but with a small sample size it hardly seems worth it. In an ideal world, I’d have a chance to randomise which treatment I did first and then second, or do one of those ABAB tests, but with an (n = 1) this is not really feasible — besides, I have vastly too much shit to focus on right now to make this a project beyond what it already was.

Fourth, it was just me, but having such a low sample for this cognitive test, it’s hard to draw anything meaningful. Full disclosure though, someone else I know played along and did the experiment too and saw similar results (I only refrain from including them because she didn’t do the same number of baselines or tests on the protocol). The only difference in her results was that her baseline scores were better than mine to start, but she too showed an improvement when using the stack.

But then again, it might actually work. At a guess, this would be my assumption about what’s going on.

• Psilocybin’s role in enhancing neuroplasticity and cognitive flexibility should improve participants’ ability to shift strategies during the WCST.
• Lion’s Mane’s neuroprotective and neurogenic effects might lead to better memory retention of the sorting rules?
• Niacin’s role in improving blood flow could enhance the overall effectiveness of the other compounds, contributing to sustained attention and focus during the task.
• Placebos are good, and they work too.

I’m publishing this because frankly, because I did the work and would hate for it to just sit in a drawer. Maybe someone might read this and go yeah — we should probably do a real study or put actual effort into this beyond just some guy waxing on about it on medium. Which of course, people have done (Dinkelacker & Pop, 2023; Wießner et al., 2022; Basedow et al., 2021)

So yeah. That’s my story. Don’t do drugs.

References

Dinkelacker, J., & Pop, I. (2023). Microdosing psychedelics has no impact on cognitive function in naturalistic settings. J Psychol Clin Psychiatry, 14(4), 111–117.

Wießner, I., Olivieri, R., Falchi, M., Palhano-Fontes, F., Lucas Oliveira Maia, Feilding, A., Draulio B. Araujo, Ribeiro, S., & Luís Fernando Tófoli. (2022). LSD, afterglow and hangover: Increased episodic memory and verbal fluency, decreased cognitive flexibility. European Neuropsychopharmacology, 58, 7–19. https://doi.org/10.1016/j.euroneuro.2022.01.114

Basedow, L. A., Riemer, T. G., Reiche, S., Kreutz, R., & Tomislav Majić. (2021). Neuropsychological Functioning in Users of Serotonergic Psychedelics — A Systematic Review and Meta-Analysis. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.739966

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