No difference between psilocybin microdosing and placebo, trial finds

With psychedelics well and truly hitting the mainstream, scientists are finally subjecting many anecdotal claims to the rigors of clinical research. The phenomenon of microdosing is one of those well-known psychedelic practices that many advocates ardently suggest leads to numerous improvements in well-being.

Despite its prevalence in popular culture, the idea of microdosing is relatively new. Characterized in detail little more than a decade ago by James Fadiman, the practice suggests tiny sub-perceptual doses of psychedelic drugs can lead to enhancements in productivity, creativity, mental well-being and energy.

The key to microdosing is repeated small doses, usually once every three days for a few weeks, and psilocybin or LSD are the most common psychedelic drugs microdosed. Doses are usually no more than 10 percent of a standard psychedelic dose, and it is important users garner no acute perceptual hallucinogenic effects from a given microdose. Basically, if you feel like you are tripping then you have taken too much.

Despite the popularity of microdosing, it is still unclear whether the practice actually works or is just a glorified placebo. Very little clinical research has so far tested the phenomenon, and the few studies that have been published to date seem to indicate microdosing may not be doing much at all.

This new study is among the first to use a double-blind, placebo-controlled design to test microdosing. The European study looked at whether psilocybin microdosing led to improvements in emotion processing and reductions in symptoms of anxiety and depression.

Over 50 subjects participated in the cross-over trial, completing a pair of three-week testing blocks. For one block the participants took five to seven psilocybin microdoses, and in the other block they were given placebo capsules. On two occasions during each three-week block the participants came into the lab to perform a variety tests exploring creativity, emotion perception and aesthetic feelings.

The researchers utilized capsules containing 0.7 grams of psilocybin truffles. They estimate this to equal a microdose of around 1.5 milligrams of psilocybin. Active full doses of pure psilocybin used in clinical research are often between 20 and 30 milligrams.

Corresponding author on the study, Michiel van Elk tells New Atlas his team found no tangible differences in participants comparing the periods they were psilocybin microdosing and the periods they were given placebo. In fact, van Elk says the biggest surprise was how many participants guessed when they were taking active microdoses and when they were taking a placebo.

“Indeed it turned out that there was no effect of psilocybin on most of the different measures that we included in our study,” van Elk says in an email to New Atlas. “What surprised us most was that many participants broke blind: they figured out what condition they were assigned to (placebo or microdosing). This might well be related to the fact that many participants also had prior experience with microdosing and psychedelic drug use.”

Interestingly, the study reports depression scores improved from baseline to block one regardless of whether a participant was randomized to placebo or psilocybin in that first block. And in block two, when participants mostly broke blind and correctly guessed which block was active and which was placebo, they still registered little difference on all measures studied, regardless of what they had been taking.

One of the few objective measures van Elk says seemed to be directly influenced by psilocybin microdosing was a dilation of time perception, but not in the direction the research team expected. Instead of psilocybin potentially slowing a person’s sense of time it seemed to do the opposite.

“… we found that psilocybin microdosing resulted in an underestimation of time, whereas we would have expected that it would dilate time perception,” explains van Elk. “We found this by using a so-called temporal reproduction task, in which participants were instructed to reproduce short temporal intervals. This task is difficult to fake and thus we are quite confident that these findings are not driven by participants breaking blind, but reflect some low-level effect of the psilocybin microdose on temporal perception.”

Unlike some prior clinical studies looking at the effect of a single microdose, this trial explored the effect of microdosing for up to three weeks. While there is a suggestion that the benefits of microdosing require a cumulative effect of engaging in the practice for weeks, or even months, van Elk is skeptical his study simply missed certain improvements that would have ultimately appeared if the trial was conducted for a longer period of time.

“I would be surprised if the long-term effects outweigh the short-term effects of microdosing,” van Elk says. “Psilocybin appears to exert a very direct acute effect on the neurotransmitters in the brain, which should be picked up by sufficiently sensitive measures. So far most studies have not provided convincing evidence for the effects of microdosing, but I am sure that with more sensitive measures, it should be possible to detect an effect. If there are longer-term effects at all, I guess these should be mediated by the downstream effects that psilocybin has on our brain and body, such as increases in glutamate, BDNF, anti-inflammatory properties and increased neuroplasticity. But we are only beginning to understand these complex effects.”

A recent observational study from researchers Vince Polito and Richard Stevenson at Australia's Macquarie University did find signals that psychedelic microdoses may be generating some kind of effect. But most significantly, Polito and Stevenson’s research found the measured effects of microdosing were not exactly what the users subjectively assumed.

Ultimately, van Elk believes his data points to the popular benefits of psilocybin microdosing being mostly a manifestation of the placebo effect. However, he doesn’t rule out there being some tangible effects from the practice. It just may not be doing what people think it's doing.

“Most of the evidence so far points out that it is likely a placebo-effect,” van Elk says of microdosing. “At the same time, I remain open to the possibility that there might be more to it – as the findings with the temporal reproduction task demonstrate. I strongly believe in the power of placebo and many important findings can likely be accounted for by placebo. But at the same time, there are also boundary conditions on what a placebo can achieve.”

Exploring the placebo effect further, van Elk says he and colleagues have conducted a study on placebo microdosing, in which all groups in a cohort received placebo doses. The results are yet to be published but van Elk does indicate many subjects taking a placebo microdose reported subjective effects.

“We pick up some subjective effects, as it seems that some participants indeed believed they were affected by the placebo,” notes van Elk. “But also there, we could not find any effect on the different dependent measures that we included.”

Moving forward, the next focus of investigation for van Elk will be to look at the effects of what he refers to as mini-doses of psilocybin. These are doses of psilocybin where mild subjective hallucinogenic effects can be detected, but they are still much lower than what many would regard as a full psychedelic dose of the drug.

Ultimately, van Elk still thinks there may be some effects from psilocybin microdosing but he is cautious to point out that the effects of the popular practice may not necessarily be all positive.

“Psilocybin microdosing might still play a role – but it is good to remain cautious on using it in practice, as it might also have unwanted side effects,” van Elk tells New Atlas. “If anything, most studies show that psychedelics hamper rather than facilitate performance, so I don’t expect microdosing to actually have a beneficial effect on many objective measures of cognitive performance. Microdosing might also result in dangerous interactions, when consumed together with other substances, so it is important to remain careful.”

The new study was published in the Journal of Psychopharmacology.