Incumbent Paradigm · Psychiatry · Phase 3: Stressed

The Chemical Imbalance Myth

The serotonin hypothesis is crumbling. The 2022 umbrella review found no consistent evidence linking depression to serotonin levels.

M31 Capital · February 2026
Phase 3
Status: Stressed
3/5
Forces Stressed
280M
Affected Globally
2026
Phase 3 Data

For decades, patients were told depression was a "chemical imbalance." In 2022, a comprehensive umbrella review in Molecular Psychiatry found no consistent evidence that depression is caused by low serotonin. The narrative that justified billions in SSRI prescriptions was not supported by the evidence.

The Replacement Thesis

Psychedelic medicine is the direct replacement. Single-dose psilocybin protocols demonstrate durable remission in treatment-resistant depression through neuroplasticity induction and default mode network disruption — not chronic symptom suppression.

Five Forces Assessment
Scientific ValidityStressed — serotonin hypothesis debunked
Economic ViabilityStressed — massive market but outcomes poor
Cultural LegitimacyStressed — patients increasingly skeptical
Institutional IntegrityHolding — psychiatric establishment defending
Regulatory CaptureHolding — SSRI infrastructure deeply embedded
Replacement
Psychedelic Therapy
Direct replacement for SSRIs in TRD, PTSD, anxiety.
Catalyst
2026 Phase 3 Calendar
MindMed GAD, Compass TRD, Helus MDD — all reporting this year.
Signal
Patient Migration
Ketamine clinics, meditation, functional psychiatry growing.
Risk
Institutional Defense
Psychiatric establishment will resist psychedelic adoption.
M31 Assessment

The Foundation Is Gone

The SSRI model is at Phase 3. Scientific foundation removed; institutional forces maintain status quo. The 2026 psychedelic data is the catalyst. Position before the data drops.