Dr. Matthew Johnson — A leading psychedelics researcher who ran clinical trials at Johns Hopkins on psilocybin and related compounds for depression, anxiety, smoking cessation, and trauma. One of the scientists bringing psychedelic therapy inside the walls of academic medicine with peer-reviewed work.
The gist
Andrew Huberman and Dr. Matthew Johnson unpack what actually defines a psychedelic, walking through the pharmacological classes from the serotonin 2A agonists (LSD, psilocybin, DMT, mescaline) to NMDA antagonists (ketamine, PCP, dextromethorphan) and the entactogen MDMA. Johnson frames psychedelics as tools that dissolve the brain's top-down models of reality, especially the model of the self, which he argues is the common denominator behind their lasting therapeutic effects. He details the clinical protocol used at Hopkins, from psychiatric screening and preparation through the guided session, and describes how patients can have 'duh' moments of agency that help them quit smoking, reprocess trauma, or escape depression. He is candidly skeptical of microdosing, noting no credible peer-reviewed evidence of benefit, while reserving his greatest enthusiasm for heroic doses. The conversation closes on early-stage hopes for using psychedelics to repair brain injury in retired athletes.
Big reveals
- Johnson confirms credible (though very rare) cases of people on psychedelics believing they could fly, and a research volunteer who tried to dive through a painting on the wall.
- Even with ideal preparation at a ~30 mg psilocybin dose, about a third of people report a 'bad trip' at some point in the session.
- Johnson states there is no credible peer-reviewed evidence that microdosing works; studies range from no effect to slight cognitive impairment.
- He argues the reality-shattering 'bad trip' and the transcendental mystical experience are two sides of the same gateway, depending on whether you surrender or hang on.
- He claims the common denominator across wildly different psychedelic experiences is a persisting change in self-representation.
- Reveals plans to study psilocybin in retired UFC/MMA athletes with repetitive head-impact history, hoping for both depression relief and measurable brain repair.
Things worth remembering
- Psilocybin occurs naturally in over 200 known species of mushrooms, and DMT is found in dozens of plants.
- All classic psychedelics act as agonists or partial agonists at the serotonin 2A receptor.
- Dextromethorphan, the active ingredient in 'robo-tripping' cough syrup, produces effects overlapping with classic psychedelics as an NMDA antagonist.
- MDMA is classed by itself as an 'entactogen' (touching within) and 'empathogen,' distinct from the classic psychedelics.
- When blood pressure spikes too high in a session, the protocol is a physician administering nitroglycerin under the tongue, which doesn't affect the experience.
- Therapeutic psilocybin sessions typically use a 20 to 30 mg dose of pure psilocybin, not eaten mushrooms.
- One or two or three high-dose sessions can produce improvements in depression months later and in addiction over a year later.
- Research shows people get a less meaningful psychedelic experience when inside an fMRI or doing cognitive tasks.