In this episode Rotem Petranker, PhD joins to discuss the current state of research on microdosing psilocybin. Dr. Petranker is the co-founder of the Psychedelic Studies Research Program at the University of Toronto and the Canadian Centre for Psychedelic Science. He recently ran the world's largest randomized controlled trial on the effectiveness of microdosing psilocybin on Major Depressive Disorder.

In this conversation, Dr. Petranker shares insights from running the world’s largest randomized controlled trial on psilocybin microdosing for major depressive disorder. He explains the origins of microdosing research, from early anecdotes and surveys to his team’s carefully designed clinical study comparing psilocybin to placebo across different environments. While participants in both groups reported significant improvements, the findings point to the powerful role of expectancy and placebo effects, alongside nuanced signals of cognitive shifts on measures like dysfunctional attitudes. Dr. Petranker emphasizes the importance of rigorous methodology, open science, and transparency in psychedelic research, while also acknowledging the stories of participants whose lives were positively impacted by study participation itself.

In this episode, you'll hear:

• What early microdosing research suggested, and its limitations in anecdotal and survey-based designs
• Why psilocybin was chosen over LSD for the study design
• What motivates people to try microdosing a psychedelic
• Key results from Dr. Petranker’s study, including reports of both positive and adverse events
• How placebo effects—and simply being part of a trial—can powerfully shape outcomes
• Reflections on how psychedelics may work by increasing connectedness

Quotes:

“There's no real rigorous definition [of microdosing]. People say, ‘oh, I'm just going to microdose some mushrooms,’ and then they often take a random amount. I think what people mean is ‘I'm going to take an amount that will not knock me out, won't cause serious hallucinations,’ but they still use an amount that they often feel. Now, this is in contrast to what people in the [academic] literature define it as, which is more like a sub-perceptual dose, a sub-hallucinogenic dose.” [2:17]

“If you microdose and go to work, just to sit under the flickering lights for eight hours in your cubicle versus, say, if you're going to microdose and then go on a walk, or do art, or do as you wish because it's the weekend, you're going to have very different impacts on your anxiety.” [15:26]

“[In our study] there were three other self-report measures of depression. There is only a significant difference on one of them, where people who were microdosing were doing better. And that was on the dysfunctional attitude scale, which measures more cognitive assumptions about life.” [26:2]

“people who microdose—regardless of why they microdose—they more or less all said that they got to what they wanted through an increased sense of meaning.” [35:05]

Links:

Psychedelic Studies Research Program at the University of Toronto

Canadian Centre for Psychedelic Science website

Canadian Centre for Psychedelic Science on X

Canadian Centre for Psychedelic Science on Instagram

Previous episode: Microdosing and the Placebo Effect with Balazs Szigeti, PhD

Previous episode: James Fadiman answers your Microdosing Questions!

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