D

ennis van der Meijden isn’t aiming to see the face of God, feel one with the cosmos, grasp the hidden reality of time and space, or embark on a sacred journey. What the Dutch graphic designer, producer, and rapper (under the professional name Terilekst) wants — and gets — from his twice-weekly “microdoses” of psilocybin is more modest.

“It sharpens all the senses, as if the frequencies of all of your atoms and energy field are raised a little bit and are being slightly more conscious,” said van der Meijden, 39, who told STAT he first microdosed psilocybin — the active ingredient in “magic mushrooms” — three years ago. It makes him energetic enough to skip coffee, “as if I’m kicked in some sort of orbit for that day.” If he becomes distracted, “I’m very much aware of that, as if seeing myself from a bird’s eye view, so I can correct myself very fast.” But van der Meijden says he’s careful not to exceed about 0.4 grams, because 0.5 made him “a bit too joyful and a bit too philosophical,” which wasn’t always appropriate.

Microdosing involves taking roughly one-tenth the “trip” dose of a psychedelic drug, an amount too little to trigger hallucinations but enough, its proponents say, to sharpen the mind. Psilocybin microdosers (including hundreds on Reddit) report that the mushrooms can increase creativity, calm anxiety, decrease the need for caffeine, and reduce depression. There is enough evidence that trip doses might have the latter effect that, on Wednesday, London-based Compass Pathways received Food and Drug Administration approval for a Phase 2B clinical trial of psilocybin (in larger-than-microdoses) for treatment-resistant depression. But research into microdosing is minimal.

In the nearly 10 years since psychologist and psychedelics researcher James Fadiman introduced the notion of microdosing and devised a widely followed protocol for it, and three years after microdosing psychedelics became the latest Silicon Valley “productivity hack,” all the evidence about its effects has been anecdotal. Psilocybin is illegal almost everywhere, so it’s been nearly impossible to study scientifically. That is changing, however, as the Netherlands and other countries effectively decriminalize it and scientists in places where it remains illegal obtain government permission to study it.

The scientific interest is driven, in part, by numerous reports over the years that psilocybin might have antidepressant or anti-anxiety effects that might guide the development of better psychiatric drugs. But it also reflects an itch to see whether there is any basis for the anecdotal accounts. Now, in the first study of its kind, scientists in the Netherlands found that psilocybin microdoses have no noticeable effect on the problem-solving, rational-thinking, and abstract-reasoning ability called fluid intelligence. But they do seem to improve two forms of thinking that underlie creativity.

“Performance was significantly higher” on tests of convergent and divergent thinking, said psychologist Bernhard Hommel of Leiden University in the Netherlands, who led the study. Convergent thinking is the ability to focus on abstract concepts to identify a single solution to a well-defined problem. Divergent thinking requires meandering mental forays and mental flexibility. Psychologists consider both to be ingredients of creativity.

Whatever the dose, psilocybin (O-phosphoryl-4-hydroxy-N, N-dimethyltryptamine) binds to receptors for the neurotransmitter serotonin. The cortex is packed with these 5-HT2A receptors, especially in areas that control reflection, imagination, and introspection, but “whether there is a minimum dose [of psilocybin that’s required to activate them] is an empirical question that we try to tackle,” Hommel said.

“It sharpens all the senses, as if the frequencies of all of your atoms and energy field are raised a little bit and are being slightly more conscious.”

Dennis van der Meijden, psilocybin microdoser

To do so, he and his colleagues zeroed in on the effects that many users report: creativity, problem-solving, and the “cognitive flexibility” deemed crucial to both. Leiden’s Luisa Prochazkova took the lead in inviting members of the Psychedelic Society of the Netherlands to participate in the study; she got 38 takers.

Before their microdose, the volunteers took three standard psychological tests, two related to creative problem-solving and one an assessment of fluid intelligence. The scientists ran chemical analyses of the mushroom samples to determine how much psilocybin they contained. Since a trip dose is about 3 grams of dried ’shrooms, a microdose is around 0.33 grams. Participants averaged 0.37 grams of the dried preparation, which can be taken with food or packed into gelcaps for easy swallowing.

About 90 minutes after the microdose, the participants took the three tests again.

In the Picture Concept Task, they saw three rows of three pictures, and had to choose three — one from each row — that were related. That requires converging on the correct solution, like noticing that a bathtub, a sink, and a hose all have something to do with water. The brain must focus, weigh alternatives, and reject wrong ones.

In the Alternate Uses Task, the microdosers had five minutes to think of ways to use a pen (tracheotomy? finger splint?) or towel. That measures divergent thinking, to move thoughts away from writing, for example, in the case of the pen.

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The microdosers also took a “progressive matrices” test: In blocks of two-by-two or three-by-three patterns, with the bottom right one missing, they had to choose which of six possibilities belonged in the blank square — a task that requires fluid intelligence.

The scientists found no post-microdose difference on the fluid intelligence test. But after microdosing, performance on the picture concept test was significantly higher (an average score of 7.6) than before (6.6). That suggested an improvement in the convergent thinking element of creativity.

The microdosers also came up with significantly more uses for pens and towels, 16.7 vs. 14.7. That suggests a microdose of psilocybin “allowed participants to create more out-of-the-box alternative solutions for a problem,” the scientists wrote. Taken together, the three findings suggest a specific effect of psilocybin microdoses on creativity but not on fluid intelligence.

For van der Meijden, a microdose of psilocybin makes his musical brainstorm sessions yield “more concepts, ideas, and solutions,” he said, partly because it lets him “better understand and visualize other people’s concepts.” In his design and illustration work, it produces a “more natural flow of line drawing” and lets him “see more possibilities in how things can be or look.” In his music, it lets him “analyze all the different instruments better” and know, for instance, whether to turn up or down the reverberation effect.

The Dutch study, which was published on a preprint site and has not undergone peer review at a journal, has several caveats. For one thing, having seen a test before might make people better at it. More problematic, the study didn’t have a control group of people who took something other than psilocybin. That leaves open the possibility that it wasn’t the compound that improved some forms of thinking, but the expectation that it would do so. Maybe people who microdose believe in its benefits enough to make those expectations reality.

On the other hand, the results fit with another new study of psilocybin. In this one, scientists led by computational neuroscientists Joana Cabral and Louis-David Lord of the University of Oxford used fMRI scans to study the brain activity of nine people who volunteered to be injected with 2 milligram (trip-inducing) doses. The chemical changed the functional connectivity of various brain regions, so that activity in one became synced with that in another. In particular, the rational, logical, well-behaved frontoparietal regions became “strongly destabilized,” the scientists reported, melding with activity in emotional and other regions to produce “unconstrained consciousness,” “mind wandering,” and a sense that everything is connected to everything else. Seeing connections that elude other people is almost the definition of creativity.

The findings in the microdosing study also fit with many anecdotal reports. One college student who is a member of the Portland, Ore., microdosing community said that although he doesn’t microdose psilocybin with the express purpose of boosting creativity or focus, he has found that “things seem to have quieted down, in terms of racing thoughts.” He can still be distracted, said Alex, 38, who asked not to be further identified because the drug is illegal in the U.S. But “if I want to go about doing something, then I have an easier time with it because I’m not being bogged down by my thoughts,” he added.

Jakobien van der Weijden takes one psilocybin microdose every three days, with bimonthly breaks, “to work more focused, more efficiently and be more creative” at his marketing job in the Netherlands, he said. (He also helps run an online community for microdosing.) “On the downside, I would often feel that the inspiration was still there at night and I would keep working on projects until late. So it was somewhat more difficult to maintain a healthy biorhythm.”

As legal strictures loosen, there will likely be more rigorous studies of microdosing psilocybin. “Scientific studies could legitimize the claimed benefits,” said Will Burns, CEO of Wenham, Mass.-based Ideasicle, which develops branding and marketing ideas. He does not microdose, Burns said, but has called for research into its purported effects, including improving productivity and creativity. “Right now, we’re swimming in a world of anecdotes and almost no one has taken this seriously,” he said. “We need scientific studies.”

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  • Another ignored problem with this study is not only that, as mentioned in the article, test subjects may have had expectations of improved performance after microdosing, but that simply taking such tests a second time may improve scores from the first test session. Knowing what kinds of questions to expect, having practiced answering the same types of questions once before, are likely explanations for the improved scores on the second round of testing. That there was no improvement on the “fluid intelligence” measure further confirms this hypothesis, since that test is less likely to get improvement in scores based on practice. One would hope for this study to be reproduced, this time with a control group whose subjects are given no psilocybin, and perhaps neither group told that they are being given something that will improve their scores, so as to distinguish between the influence of “expectations” and that of simple repetition

  • Just a layman weighing in:
    See Ayelet Waldman’s book, A Really Good Day, for a thoughtful and articulate report of how micro-dosing with LSD improved her life. More current is Michael Pollan’s book, How to Change Your Mind, which details ongoing studies at Johns Hopkins (and elsewhere) into the use of psychotropics in therapy.

  • I am very interested in this exciting research. So much better than using the current modalities of antidepressants, shown not to really be effective. Research on the subject has proven to be poor.

  • These studies and anecdotes are too preliminary to indicate much. As much as “a doctor who treats himself has a fool for a doctor and a fool for a patient”, laymen who decide to do medical experiments on themselves are no less foolhardy.

    • Higher doses of psilocybin have already shown efficacy in clinical trials for reduction of depression and anxiety symptoms (doi:10.1177/0269881116675513). Given the promise and potential of these and other tryptamine based compounds, It will be exciting to see where microdosing research takes us in terms of understanding human cognition.

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