Essentials: Psychedelics for Treating Mental Disorders | Dr. Matthew Johnson

Johnson describes the preparation phase as critical not just for screening but for the therapeutic mechanism: 'the experience itself is very much shaped by that container, by the environment and the degree to which one allows it to happen.' The preparatory relationship with guides becomes the template for trust that allows the patient to surrender during the session. The session itself is largely non-directive — 'any emotional response is welcome — you could be crying like a baby hysterically' — because the goal is to follow the experience wherever it leads rather than direct it. Integration (post-session therapy to consolidate insights) is standard in research protocols and is considered essential for lasting change.

Johnson distinguishes between the population-level psychiatric risk (screening for psychosis) and the near-universal challenge of bad trips — the latter is not a disorder, it can happen to the psychologically healthiest person given a high enough dose in an imperfect setting. The screening process is therefore not sufficient to prevent difficult experiences; it is the necessary condition for safety in the most serious risk categories. The preparation phase that follows screening is what addresses the bad-trip risk for the general population.

The clinical importance of surrender extends beyond the session. Johnson draws the analogy to trust-building in psychotherapy: 'one of the common themes of good psychoanalysis or psychotherapy of any kind is that there's a trust built between the patient and the analyst and that relationship becomes a template for trust more generally and trust in oneself.' The psychedelic accelerates this by making the experience of letting go viscerally real rather than intellectually understood. Patients who surrender during the session often report not just therapeutic benefit but a lasting change in their relationship to anxiety — having learned at a somatic level that they can survive reality shattering.

Johnson describes a specific participant who said 'I feel like my heart is going to rip through my chest' and was visibly experiencing tachycardia/high BP from her perception. The subject was not in objective cardiac danger, but the felt experience was terrifying. The nitro protocol addressed the physiological component without sedating the participant or ending the session — the therapeutic experience continued. This illustrates a broader design principle of psychedelic trials: keep the pharmacological 'safety net' interventions as minimal as possible to avoid disrupting the therapeutic arc.

Johnson positions MDMA as potentially better than classic psychedelics specifically for trauma because 'the chances of having an extremely challenging experience — the bad trip — is much lower.' With classic psychedelics, a patient processing severe trauma may hit the reality-shattering threshold in a way that overwhelms the therapeutic container. MDMA's combination of elevated dopamine and serotonin produces empathy, emotional openness, and reduced fear without the full model-dissolution of psilocybin or LSD. The reconsolidation mechanism Johnson alludes to is consistent with basic memory research: when a traumatic memory is retrieved in a low-fear, high-trust state, the re-encoding changes the emotional valence of the memory. 'Someone could really reprocess their trauma in a way that has lasting effects — and clearly there's probably something in reconsolidation of those memories.'

The neuroplasticity hypothesis comes from a specific research lineage: labs including David Olson's (UC Davis) and Brian Roth's have shown psychedelics promote structural neural changes in rodent brain. Johnson notes 'those effects may be at play in the improved psychiatric treatments we're dealing with — we don't know that, but it seems like a decent guess.' The specific population (retired combat athletes with both depression and TBI history) is chosen because it creates a naturalistic setting where both endpoints are clinically relevant and the TBI exposure is documented and quantifiable by career length and sport type.

Johnson describes humans as 'prediction machines' whose experience is 'large part top-down.' Psychedelics disrupt this by forcing dis-habituation — the phenomenon where a normally automatic, invisible perception suddenly appears miraculous or foreign. The most common effect is a widening of what he calls 'the perceptual bubble': a narrow percept (a hand, a sound, an emotion) is suddenly experienced with extraordinary vividness and weight. In the therapeutic context, the percept being expanded is typically an emotion, a memory, or a self-concept. The smoker who has told himself 'I can't quit' a thousand times suddenly feels the gravity of agency — 'I can just decide' — not as an intellectual proposition but as a lived, somatic certainty. That felt certainty persists.

Johnson says: 'I think those are both speculating but you have to pass through this sort of reality shattering including your sense of self and one can handle that in one of two ways — you can either completely surrender to it or you can try to hang on and if you try to hang on it's going to be more like a bad trip.' He notes that the same person can pass from terror to beauty within minutes once surrender occurs, which is why guides are trained to coach the patient through difficult passages rather than terminate the experience. The mystical experience — a felt sense of unity with all things, dissolution of self-other boundary — is the outcome that the Hopkins data specifically correlates with long-term therapeutic improvement.

Johnson recounts a participant who, mid-session, said: 'My god, it's like I can really just decide — like flicking off a bike — I can decide not to smoke.' The participant held onto this realization after the session. Johnson generalizes this to cancer patients: 'I'm causing most of my own suffering. I can follow my appointments, I can do everything, but I'm not getting outside, I'm not playing with my grandkids — I'm choosing to do that.' The shared structure is a felt experience of agency that breaks the model 'I am powerless over this.' He calls these 'duh experiences' because the content itself isn't novel — patients have been told these things before — but the felt certainty is completely different.

Johnson notes that the handful of credible studies range from 'finding no effect whatsoever to just a little bit of impairment — like impairing someone's ability to do time estimation and production tasks.' He points out that impaired time estimation is a safety hazard for people using microdoses in functional settings (work, driving), which is exactly the use case being promoted. He assigns the highest probability to a modest anti-depressant effect via chronic low-level serotonin-2A stimulation — analogous to the mechanism of SSRIs — while being dismissive of the creativity and cognitive enhancement claims.

Johnson describes the proposed design as targeting retired MMA athletes who are 'exposed to repetitive head impacts like a lot of sports' and 'are retired from the sport and are suffering from depression.' The primary aim is depression treatment (where the psilocybin literature is strong); the secondary exploratory aim is to use MRI gray matter volumetrics over time to look for structural changes. He is explicit about the epistemic status: 'we've got some rodent data, we've got some human anecdotes' — this is hypothesis generation, not established therapy. The primary justification for the MRI aim is that if psychedelics improve psychiatric outcomes partly via neuroplasticity, that neuroplasticity should be detectable structurally.