A cup of coffee for depression treatment has better results than microdosing



Jim Fadiman, the veteran psychedelic researcher after whom the protocol is named, rejects MindBio’s conclusions, and trial design, out of hand. Because, Fadiman believes, patients were given the active caffeine placebo, their reported benefits may well be attributable not to a pure placebo effect, but to the actual psychoactive properties of that drug.

“Double-dummy is a remarkably apt term,” Fadiman, 86, sneers. “What I know is that if you take enough caffeine, you will not be depressed!”

Fadiman points to MindBio’s earlier, Phase 2A study, recently published in the journal Neuropharmacology, which drew markedly different conclusions. It was a non-blinded, so-called “open label” study, meaning patients knew definitely that they were being microdosed with LSD. This study found that MADRS scores decreased by 59.5 percent, with effects lasting as long as six months. It also found improvements in stress, rumination, anxiety, and patient quality of life. Fadiman says that this reportage is more consistent with his own research on microdosing. “Their prior study did wonderfully with LSD,” Fadiman says. “I have collected literally hundreds of real world reports over the years that validate those findings.”

MindBio’s Hanka stands by the science. “We are bewildered at the significant difference between the open label Phase 2A trial results and the Phase 2B trial results,” he says. “But that is the nature of good science—a properly controlled trial will get a proper result. Our Phase 2B trial was of the highest standard, a triple-blind, double-dummy, active placebo controlled trial. I haven’t seen another psychedelic trial that has gone to these lengths to control and blind a trial.”

Despite these findings, some microdosing true believers don’t seem especially shaken. In 2017, writer Ayelet Waldman (best known as the author of the Mommy-Track Mysteries series of novels that follow the adventures of stay-at-home-mom-cum-sleuth Juliet Applebaum) published A Really Good Day, a diaristic account of her own self-experiments using microdosing to treat an intractable mood disorder. She tells WIRED she’s not especially bothered by the implication that her positive shifts in mood may have merely been placebo. “In my book I took very seriously the possibility that what I was experiencing was the mother of all placebo effects,” Waldman says. “I wrote about this a number of times in various chapters and decided in the end it didn’t matter. What mattered was that I felt better.”



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