About a decade in the past, many media outlets—incl WIRED—zero in on a strange trend at the intersection of mental health, drug science, and biohacking in Silicon Valley: microdosingor the habit of taking small amounts of psychedelic drugs that seek not full-blown hallucinations but milder, stronger effects. Usually using psilocybin mushrooms or LSD, the archetypal microdoser looks for less melting walls and open-eyed kaleidoscopic visuals than improving mood and energy, like a gentle spring breeze blowing through the mind.

Anecdotal reports place microdosing as a kind of psychedelic Swiss Army knife, providing everything from more focus on a spiked libido and (perhaps the most promising) has been reported level of depression. This is a miracle for many. Others remain cautious. Can it really be 5 percent of a dose of acid all that? A recent, extensive study by an Australian biopharma company suggests that the benefits of microdosing may be overstated – at least when it comes to addressing clinical depression symptoms.

A Phase 2B trial of 89 adult patients conducted by Melbourne-based MindBio Therapeutics, which examined the effects of microdosing LSD in the treatment of major depressive disorder, found that the psychedelic actually above performance by a placebo. Over an eight-week period, symptoms were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), a widely recognized tool for the clinical evaluation of depression.

The study has not yet been published. But MindBio CEO Justin Hanka recently released the top-line results of his LinkedInwants to show that his company is “ahead of the curve in microdosing research.” He called it “the most powerful controlled placebo trial ever done on microdosing.” It was found that patients dosed with a small amount of LSD (from 4 to 20μg, or micrograms, well below the threshold of a mind-blowing hallucinogenic dose) showed observation uptick in feelings of well-being, but worse MADRS scores, compared to patients given a placebo in the form of a caffeine pill. (Because patients in psychedelic trials usually expect some kind of mind-altering effect, studies are often blinded using so-called “active placebos,” such as caffeine or methylphenidate, which have their own apparent psychoactive properties.)

This means, in essence, that a medium-strength cup of coffee may be more beneficial in treating major depressive disorder than a small dose of acid. Good news for regular caffeine users, perhaps, but not so much for researchers (and biopharma startups) who are counting on the efficacy of psychedelic microdosing.

“This may be a nail in the coffin for using microdosing to treat clinical depression,” Hanka said. “It probably improves how people with depression feel – not enough to be clinically significant or statistically significant.”

Despite the pessimism, these results are consistent with the suspicions of others skeptical researcherswho have long believed that the benefits of microdosing are less the result of a small amount of psychedelic catalyst, and more due to the so-called “placebo effect.”

In 2020, Jay A. Olson, who is a PhD candidate in the Department of Psychiatry at McGill University in Montreal, Canada, conducted an experiment. He gave 33 participants a placebo, telling them it was a dose of a psilocybin-like drug. They were led to believe that there was no placebo group. Some researchers who are in the small movement of the effects of the drug, in a room treated with trippy lighting and other visual stimulants, in an attempt to curate the “optimized expectation” of a psychedelic experience.

The result ROLEtitled “Tripping on Nothing,” found that most participants reported feeling the effects of the drug—even without the actual drug. “The main conclusion we have is that the placebo effect may be stronger than expected in psychedelic studies,” Olson, now a postdoctoral fellow at the University of Toronto, told WIRED. “Placebo effects are stronger than what you get from microdosing.”