What the Evidence Tells Us About Microdosing Psilocybin (And Where My Physician Skepticism Meets My N-of-1)

I have been thinking about what psilocybin gave me, underneath all the mechanisms, data, and the careful clinical reasoning I am about to walk you through.

What psilocybin gave me was a dropped glass.

I was about three weeks into my first Fadiman protocol when it happened. Kitchen, early morning, glass hit the tile, bounced, didn’t break. And instead of the clench that usually follows a minor accident in a woman who has been running on cortisol for years, something different happened. I watched it bounce. I leaned down, picked it up, went back to making coffee.

The lurch of overreaction wasn’t there.

I stood in my kitchen and took that in. My inbox hadn’t changed. My schedule hadn’t changed. My deadlines, all the same. What had changed was the space between the stimulus and my response to it. There was a pause in there, new and unmistakable, where my nervous system used to be immediately airborne.

I want to be honest about what I am describing, because it was not a revelation and it was not bliss. It was gritty and quiet and slightly disorienting, the way any real homecoming is. Decades of having learned to live above my body, for all the right reasons, and here was the evidence that the address might be changing. A dropped glass. A borrowed moment of something close to ordinary ease.

I had been a physician long enough that I could describe functional dissociation to a patient with genuine compassion and clinical precision. I knew the neuroscience. I had done the somatic work, the therapy, the breath practices. I could draw the diagram of exactly why a woman who has learned that her body is a site of risk will eventually move upstairs into cognition and stay there. I had done enough of my own therapeutic work to know that story was mine too.

Knowing it had not been enough to undo it. Something in those three weeks had apparently been silently and skillfully renegotiating the terms.

That is what I mean when I say psilocybin may be the most useful thing I have tried in midlife. It reached something the talking and the breathing and the understanding had not quite reached. (Certainly, the parts of the brain involved in understanding what happened to you are different than the parts that store the memory.)

All to say, I owe you more than a literature review in Part 2. (Read Part 1 here.)

Here is what this essay covers:

The rigorous evidence, including the controlled trials that came back negative and why they don’t close the question

The mitochondrial hypothesis: where the preclinical biology is real and where the human data has not been gathered

Why the studied population is not you, and what that means for a midlife woman making this decision

What my own HRV and cortisol data show across a Fadiman protocol

The sex-data gap: what the research has not studied about women, and why it is the central problem

I am running this experiment on myself. I have been tracking my own data and my patients’ for a decade. I will tell you what I see.

The research on midlife women and psilocybin has not been done. Women are making this decision anyway. What follows is the most rigorous map I can draw of the territory.