‘Microdoses’ of LSD work no better than dummy pills, study suggests

People who microdose, or take tiny doses of psychedelic drugs, swear that the practice boosts their mood, focus and productivity without causing a “trip.” But a new study finds that these perceived benefits may be due to the placebo effect.

The study, which involved nearly 200 participants, is one of the largest “placebo-controlled” studies on psychedelics ever conducted, in which people take either a real microdose of psychedelics or a placebo — i.e. a “dummy pill.” The study had a unique design in which participants were “self-blinded,” meaning they followed instructions at home to mix up their microdose pills with placebo pills, so they didn’t know which they were taking.

The researchers found that participants who microdosed — usually with LSD — for about a month did indeed experience psychological benefits, including boosts in well-being and life satisfaction. However, those in the placebo group experienced similar improvements, and there was no statistically meaningful difference between the two groups, the researchers said.

The findings “suggest that these improvements are not due to the pharmacological action of microdosing, but are rather explained by the placebo effect,” or the expectation that a particular drug or treatment will work, the authors wrote in their study, published Tuesday (March 2) in the journal eLife.

The results don’t mean that people who microdose aren’t getting any benefits. “Our results are mixed: On the one hand, we observed microdosing’s benefits in a wide range of psychological measures; on the other hand, equal benefits were seen among participants taking placebos,” study lead author Balázs Szigeti, a research associate at Imperial College London in the United Kingdom, said in a statement. “Many participants who reported that they experienced positive effects while taking the placebo were shocked to learn after the study that they hadn’t been taking the real drug.”

The authors caution that their self-blinded study wasn’t as rigorous as a true randomized controlled clinical trial. For one, participants were eligible for the study only if they were already microdosing, and they sourced their own drugs from the black market; so the researchers could not verify the purity or the dosage of the LSD participants were using.

But the authors say their study design more accurately reflects how microdosing is done in “real-world” settings, compared with studies conducted in a laboratory.

Real and dummy pills 

Microdosing became trendy in Silicon Valley about five years ago, and soon became more popular around the world. But much of the support for the benefits of microdosing comes from anecdotal reports, and there are few rigorous scientific studies of the practice — most of the studies that have been conducted lack a control group, or group of people who don’t take microdoses.

In the new study, the researchers recruited 191 microdosers for their online study. About three-quarters of the participants reported microdosing with LSD or a similar (analog) drug; and about 25% reported microdosing with psilocybin, the psychoactive ingredient in “magic mushrooms.”

Participants then underwent the self-blinding process: They placed their real microdoses into pill capsules, and also made a set of placebos, which were just pill capsules with nothing inside. Then, they placed capsules into envelopes with QR codes for tracking by the researchers, and shuffled the envelopes. By the end of the process, the participants didn’t know which pills they were taking.

One-third of participants took only placebo capsules for four weeks; one-third took only real microdoses; and one-third took “half and half,” meaning they took placebo pills for a total of two weeks and real microdoses for a total of two weeks (alternating between a week of placebo pills and a week of microdoses). The participants also completed online surveys to assess their mental health and cognition. 

Soon after taking the real microdoses, participants reported improvements in mood, creativity and anxiety. But participants who took a placebo — but thought they were taking a microdose — also reported similar benefits, meaning that the actual content of the capsules didn’t matter for their effects; rather, participants’ beliefs did, the authors said.

What’s more, neither the microdose nor the placebo group saw improvements in the results of their cognitive tests during the study.

It’s important to note that many of the participants correctly guessed whether they were taking a microdose or a placebo, largely because they were familiar with subtle sensations from the drugs such as muscle tingling and stomach stress; but the study researchers did take these guesses into account in their analysis.

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Remaining questions 

“It certainly appears so far that at least a significant portion of the claimed benefits of microdosing are the result of placebo effects,” Matthew Johnson, a professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine, who was not involved in the study, told Live Science in an email. “This should be no surprise, because the placebo effect is nearly always at play in the real world use of a medication.”

Still, Johnson added that “the big remaining question for me is whether all of the claimed benefits are the result of a placebo effect,” or whether there are some direct beneficial effects from the drug microdoses in addition to the placebo effect. “My best guess is that there is indeed some direct efficacy for at least some measures and in some circumstances and some individuals, but we need more research to further tease out placebo from any direct efficacy,” Johnson said.

The authors note that the study participants were generally healthy, and it’s unclear if the finding would differ in a population that had been recently diagnosed with a mental health condition.

Originally published on Live Science.  

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