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!

Psychedelic Medicine Association

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In this episode of the Psychedelic Medicine Podcast, Rick Strassman, MD joins to discuss the topic of endogenous DMT. Dr. Strassman is adjunct associate professor of psychiatry at the University of New Mexico in Albuquerque and author of DMT: The Spirit Molecule and The Psychedelic Handbook. His DMT and psilocybin studies in the early 1990s initiated the renewal of human research with psychedelics in the U.S.

In this conversation, Dr. Strassman discusses the finer details of DMT, from endogenous production in humans and animals, to visionary experiences and theological implications. Dr. Strassman also covers the research that's been done regarding endogenous DMT, clarifying what we do and don’t know about the role of the pineal gland and how this might relate to what is reported during near-death experiences. He also discusses the personal and relational quality of psychedelic experiences induced by DMT, mentioning that unitive mystical experiences were actually rare in the trials he conducted, with more experiences having a personal quality, drawing upon the life experiences and interests of the participants. In closing, Dr. Strassman shares his thoughts on the origins of the visions that many report during DMT use.

In this episode you'll hear:

• The overlap between psychedelic experiences and meditation techniques
• The relationship between fear, self-awareness, and difficult DMT experiences
• The placebo effect and psychedelic research
• Dr. Strassman’s thoughts on non-hallucinogenic psychedelics
• DMT as a possible treatment for strokes to prevent damage and speed recovery
• Effects of microdosing in animals and humans

Quotes:

“I think the best term for these compounds is psychedelic, which means mind manifesting or mind disclosing, because only one of our fifty-five or so normal volunteers had what one might call a mystical unitive state. … Everybody basically had an experience that was totally dependent on them. It was not inherent in the drug.” [9:45]

“You could still speculate that to the extent that non-drug states resemble those brought on by giving DMT… that DMT plays a role in the production of those states. But the data aren't there yet. That's why we need more people doing this research.” [24:16]

“If psychedelics are super placebos and if we have a psychedelic drug in our brain, it's attempting to speculate that normally the placebo effect could be mediated by endogenous DMT.” [27:42]

“If you starve neurons of oxygen they start dying, but if you add DMT they survive much longer. So there seems to be some neuroprotective effect of DMT on ischemic damage to neurons, at least in the test tube.” [32:27]

Links:

Dr. Strassman’s website

The Psychedelic Handbook by Dr. Strassman

DMT: The Spirit Molecule by Dr. Strassman

DMT and the Soul of Prophecy: A New Science of Spiritual Revelation in the Hebrew Bible by Dr. Strassman

Dr. Strassman on Facebook
Previous episode: Exploring DMT Entities with Matthew Johnson, PhD

Psychedelic Medicine Association

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In this episode Steven Zeiler, MD, PhD joins to discuss the promise of psychedelics for stroke healing. Dr. Zeiler is an associate professor and physician at Johns Hopkins School of Medicine specializing in cerebrovascular disease, including acute stroke therapy, prevention, and recovery. He is a lead investigator for a Rose Hill Life Sciences research trial, conducted in partnership with Johns Hopkins University, exploring the use of psilocybin-assisted therapy to enhance motor function in patients with neurological injuries.

In this conversation, Dr. Zeiler explains that after a stroke, there is a natural but time-limited critical period during which the brain is highly plastic and capable of repairing motor function. His research, inspired by work on psychedelics reopening critical learning windows, shows in animal models that a single high dose of psychedelics combined with intensive rehabilitation can restore lost motor abilities even after recovery has plateaued. Throughout, Dr. Zeiler emphasizes that psilocybin itself doesn’t heal the brain directly but creates a window of heightened neuroplasticity that, when paired with targeted therapy, may dramatically improve recovery outcomes for stroke survivors.

In this episode, you'll hear:

• What happens to patients during a stroke
• The critical period of stroke recovery and how psychedelics may reopen this opportunity
• Why conducting a safety and tolerability study of psilocybin for stroke patients is crucial
• What forms of deficits and recoveries Dr. Zeiler’s study will measure
• Dr. Zeiler’s speculations on what integrating psychedelic treatments into stroke medicine could look like
• The importance of specialized interventions that take advantage of the critical recovery period

Quotes:

“What has been a little forgotten about in a lot of stroke management situations is helping the person get over the deficits with which the stroke has left them. And if you can't move an arm, you can't move a leg, that's a big deal. And we are not quite as good at addressing some of those problems.” [5:11]

“[The potential of psychedelics for stroke recovery] is probably less about addressing the injury itself and more about helping the remaining parts of the brain turn on to address what's lost.” [7:36]

“We're not suggesting that the psychedelic itself has some sort of magical property that would just repair the brain, but it primes the situation to allow that input that we then provide over the next many days, many weeks, to affect a recovery.” [13:31]

“Imagine something as complicated as the brain going through a repair mechanism: could you imagine one molecule acting on one receptor being able to affect a recovery? I couldn't imagine that—it's too complicated a thing. And so having something like a mechanism of action that is acting through multiple pathways, I think has to be the case if we're going to affect something as complicated as brain repair.” [17:30]

Links:

Dr. Zeiler on LinkedIn

Super Room for Enriched Neurological Repair at Green Spring (SENRG)

PHATHOM (Psychedelic Healing: Adjunct Therapy Harnessing Opened Malleability)-Stroke Project

Psychedelic Medicine Association

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