People who take tiny amounts of LSD, “magic mushrooms,” and related drugs report a range of benefits, from more creativity to improved psychological well-being. But do these microdoses—typically less than 10% of the amount that causes a true psychedelic experience—actually benefit the mind?
That’s been a hard question to answer. Placebo-controlled trials are tricky to pull off, because psychedelics are so tightly regulated. Now, researchers have come up with a creative workaround: They’ve enlisted microdosing enthusiasts to hide their drugs in gel capsules and mix them up with empty capsules.
The upshot of this “self-blinding” study: Microdosing did lead to improvements in psychological well-being—but so did the placebo capsules. “The benefits are real,” says lead author Balázs Szigeti, a neuroscientist at Imperial College London. “But they are not caused by the pharmacological effects of microdosing.”
The findings, however, are “the least interesting thing about this study,” says Noah Haber, a study design specialist at Stanford University. The “very, very clever” method of self-blinding pushes the boundaries of what can be investigated using randomized placebo controls, he says.
Getting the new study off the ground wasn’t easy. Obtaining ethical approval to enroll psychedelic-taking volunteers was a “long and difficult process,” Szigeti says. And then he had to go out and find those volunteers, which he did by reaching out to microdosing communities, giving talks at psychedelic societies, and holding an “ask me anything” discussion on Reddit. Szigeti eventually garnered more than 1600 sign-ups, but once potential participants realized they’d have to procure their own psychedelics, interest ebbed, and only 246 ended up in the experiment.
There were also hiccups in the self-blinding procedure. The unusual approach required participants to lay out sets of weekly doses of both psychedelics and placebo capsules, group them into blank envelopes tagged with QR codes printed from the study website, then shuffle the envelopes to disguise the contents; the volunteers scanned the codes to get instructions on which envelopes to choose each week.
To ensure that the pills felt the same, study participants who used psilocybin mushrooms weighted their placebo capsules with substances like sugar, for example. Still, Szigeti says “mushroomy” burps made it easy for the participants to guess when they’d taken actual mushrooms. After having to discard some data, he and his colleagues asked the volunteers to make placebo capsules with a nonpsychedelic mushroom instead.
Even after all of this, study participants—especially those taking higher doses—were still sometimes able to guess whether they had taken a placebo. The scientists could track this because the volunteers reported their guess after every dose. (Some reported sensations like digestive issues, muscle tingling, and seeing colors differently as reasons for their guesses.)
Although that meant the self-blinding was not bulletproof, the reporting had the advantage of giving the researchers another check on whether the supposed benefits of microdosing tracked with people’s expectations.
Overall, Szigeti and his colleagues found that people who thought they had taken psychedelics felt greater well-being and lower anxiety than those who thought they had taken placebo, regardless of what they actually took, they conclude this week in eLife.
The results echo the findings of the handful of very small placebo-controlled studies, says Johns Hopkins University psychedelics researcher Albert Garcia-Romeu, who was not involved with the work. But the new study was much larger and had more long-term observations, he says. Still, he thinks the results are likely to be contentious, because microdosing enthusiasts may not be convinced by findings that go against their own experiences.
Haber also says the new study comes with caveats. Participants were free to set their own microdose regime, he notes, meaning the doses and substances varied. Volunteers also may not have perfectly followed the rules, he says, and results from a self-selected group of microdosing advocates may not generalize to other groups of people.
Szigeti and his colleagues are planning another, improved self-blinding trial on psychedelic microdosing that will give people even more flexibility on their dose schedule, but ask them about their experiences more frequently throughout the day. They also hope to take the method further, by studying other trends like cannabidiol oil use and teaming up with nutrition researchers to study the true value of supplements.
This first study is like a half-time score of two-to-zero at a soccer game, Szigeti says: It’s not impossible that psychedelic microdosing might come back against the odds and show an effect, but “from what we have, it just does not look good.”