Microdosing for Depression Appears to Work About as Well as Drinking Coffee

About a decade ago, many media outlets—including WIRED—zeroed in on a weird trend at the intersection of mental health, drug science, and Silicon Valley biohacking: microdosing, or the practice of taking a small amount of a psychedelic drug seeking not full-blown hallucinatory revels but gentler, more stable effects. Typically using psilocybin mushrooms or LSD, the archetypal microdoser sought less melting walls and open-eye kaleidoscopic visuals than boosts in mood and energy, like a gentle spring breeze blowing through the mind.

Anecdotal reports pitched microdosing as a kind of psychedelic Swiss Army knife, providing everything from increased focus to a spiked libido and (perhaps most promisingly) lowered reported levels of depression. It was a miracle for many. Others remained wary. Could 5 percent of a dose of acid really do all that? A new, wide-ranging study by an Australian biopharma company suggests that microdosing’s benefits may indeed be drastically overstated—at least when it comes to addressing symptoms of clinical depression.

A Phase 2B trial of 89 adult patients conducted by Melbourne-based MindBio Therapeutics, investigating the effects of microdosing LSD in the treatment of major depressive disorder, found that the psychedelic was actually outperformed by a placebo. Across an eight-week period, symptoms were gauged 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’s CEO Justin Hanka recently released the top-line results on his LinkedIn, eager to show that his company was “in front of the curve in microdosing research.” He called it “the most vigorous placebo controlled trial ever performed in microdosing.” It found that patients dosed with a small amount of LSD (ranging from 4 to 20μg, or micrograms, well below the threshold of a mind-blowing hallucinogenic dose) showed observable upticks 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 typically expect some kind of mind-altering effect, studies are often blinded using so-called “active placebos,” like caffeine or methylphenidate, which have their own observable psychoactive properties.)

This means, essentially, that a medium-strength cup of coffee may prove more beneficial in treating major depressive disorder than a tiny dose of acid. Good news for habitual caffeine users, perhaps, but less so for researchers (and biopharma startups) counting on the efficacy of psychedelic microdosing.

“It’s probably a nail in the coffin of using microdosing to treat clinical depression,” Hanka says. “It probably improves the way depressed people feel—just not enough to be clinically significant or statistically meaningful.”

However despairing, these results conform with the suspicions of some more skeptical researchers, who have long believed that the benefits of microdosing are less the result of a teeny-tiny psychedelic catalyst, and more attributable to the so-called “placebo effect.”

In 2020, Jay A. Olson, then 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 actually a dose of a psilocybin-like drug. They were led to believe there was no placebo group. Other researchers who were in on the bit acted out 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 resulting paper, titled “Tripping on Nothing,” found that a majority of participants had reported feeling the effects of the drug—despite there being no real drug whatsoever. “The main conclusion we had is that the placebo effect can be stronger than expected in psychedelic studies,” Olson, now a postdoctoral fellow at the University of Toronto, tells WIRED. “Placebo effects were stronger than what you would get from microdosing.”