Microdosing Benefits Might Be Largely Placebo, Experimental Study Suggests

The sometimes hyped benefits of microdosing—regularly using small amounts of psychedelic drugs like lysergic acid diethylamide (LSD)—might be overstated, new research this week suggests. The study found that people who microdosed did experience psychological benefits, including greater sense of well-being, but that these benefits weren’t substantially different from how others felt when they took a placebo instead. The experimental study’s findings indicate that at least some of the positives of microdosing can be attributed to the placebo effect, but the study does have its own caveats.

Psychedelic drug treatment has emerged as a promising approach to improving people’s mental health in recent years. Some studies have suggested that drugs like LSD and psilocybin—the main ingredient in magic mushrooms—can help treat anxiety and depression, particularly when combined with therapy. Other research has found evidence of positive changes in the brain cells of animals or people when exposed to psychedelics, further bolstering the case for a real biological benefit. One method of using these drugs is microdosing, which is when people take much smaller doses than used recreationally, on a regular schedule.

Much of the evidence for the benefits of microdosing has been based on real world observations or anecdotal experiences, though, which comes with its limitations. Some people’s self-reported symptoms while taking a drug will improve, for instance, even if the drug hasn’t treated the underlying condition causing those symptoms. One clear way to overcome the limitations of anecdotal evidence is through a placebo-controlled study, but these studies are generally expensive and take a lot of time and resources to pull off. That’s especially true for microdosing studies, since these drugs are still illegal in many countries and scientists have to jump through hurdles to use them for research.

The authors behind this new study, published in eLife Tuesday, decided to take a unique approach to carrying out their placebo-controlled study. They enlisted the aid of people already microdosing regularly, then helped them essentially conduct the experiment on their own.

These citizen-scientists were given instructions on how to make the experiment placebo-controlled, so that they wouldn’t know whether they were taking a placebo or the real drug (mostly LSD, but some also took psilocybin). This included putting the drug, which was in powder form, inside opaque gel capsules, then putting these capsules and placebo capsules inside envelopes that contained a week’s supply of four doses. Some envelopes would contain nothing but placebo, others contained a mix of both placebo and the drug.

All of the envelopes had a QR code attached that would allow the researchers to know the contents of each envelope and the specific order of pills taken that week, but not the volunteers. Some of the subjects of the study were randomly assigned to microdose two of the four weeks and received placebo during the other two weeks, and some were receiving the placebo the entire time. During the study, all the volunteers regularly filled out surveys about their ongoing psychological state.

All in all, 191 people completed the experiment, making this the largest placebo-controlled study of its kind, according to the authors. Microdosing volunteers reported psychological improvements from their baseline, including reduced anxiety and greater sense of well-being, but so did people taking placebo, and overall, there weren’t any significant differences between all three groups.

“The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect,” the authors wrote.

There are some important caveats to these findings. For one, the study did find a small but statistically significant difference on certain outcomes when comparing the placebo group to the microdose group; these included improvements in mood, energy, and creativity. But the researchers argue there’s a mundane explanation for that as well. About 72% of the time, better than chance, the volunteers were able to accurately guess whether they were taking a placebo or drug. So it’s possible their expectations of feeling better rose when they correctly suspected they had taken the drug as opposed to placebo, meaning that their blinding wasn’t entirely foolproof.

The study also couldn’t control variables like the purity or actual dosage of the microdosing, since it relied on the typical drugs that the volunteers were using already (on average, users reported taking 13 micrograms of LSD per dose, but the authors couldn’t test how much of the active ingredient people were taking). And though they did try to make sure people stuck to the instructions they were given, the very nature of the study meant they had less control over whether everything was followed correctly. As for the ethics of this research, the authors said they only reached out to self-identified microdosers and that they didn’t collect any other identifiable personal information from them besides their email (the study was cleared by an outside committee).

It’s also worth highlighting that psychedelic drugs are being studied and taken for mental health in different ways, and microdosing is only one approach. Some researchers have argued that it’s the intensive experience of taking psychedelics (either in relatively high microdoses or macrodoses), along with guided therapy, that really provides the clearest benefits to people, for instance. In 2019, the drug ketamine was adapted into a FDA-approved treatment for depression. This is taken in smaller doses than when taken recreationally and under medical supervision, but it may also be a higher dosage than what people would take on their own while microdosing.

Importantly, the authors also note that the volunteers of the study were generally healthy, with only 7% having a current mental health diagnosis. So they don’t discount the possibility that microdosing could still be useful for people experiencing mental illness.

Of course, no single study should be seen as the final word on any topic, especially when it’s relying on an experimental approach. Still, the authors hope that their unique study design can be used in the future for other tricky areas of research where it’s hard to include a placebo control. One immediate benefit could be cost, since this study only required around 1% of the funding typically used to run a clinical trial. Other possible applications for this approach include studying CBD, nootropics, and nutrition, they wrote.