The Science

What research tells us — and what remains to be discovered

What is Psilocybin?

Psilocybin is a naturally occurring compound found in certain mushroom species that have been used ceremonially and medicinally by indigenous cultures worldwide for centuries. Today, it is the subject of rigorous clinical investigation at major research institutions across the globe.

In the United States, psilocybin remains classified as a Schedule I controlled substance under federal law. However, Colorado has authorized therapeutic use of psilocybin-assisted therapy through the Natural Medicine Health Act (Proposition 122), creating a regulated framework for licensed practitioners to facilitate these experiences.

How It Works: Mechanisms of Action

Research is investigating how psilocybin creates its effects on consciousness and psychology. Current understanding points to several key mechanisms:

  • Serotonin 2A Receptor Agonism — Psilocybin binds to serotonin receptors in the brain, triggering cascade effects that influence mood, perception, and cognition.
  • Default Mode Network Disruption — Studies suggest psilocybin disrupts the Default Mode Network (DMN), the brain system associated with self-referential thinking. When overactive, this network correlates with rumination and rigid thought patterns. (Carhart-Harris et al., 2018)
  • Neuroplasticity Enhancement — Brain imaging studies show measurable increases in dendritic connections and neuronal flexibility, suggesting the brain becomes more "plastic" and open to new neural pathways.
  • Meaningful Experience — Research indicates that deeply meaningful or mystical experiences during psilocybin sessions often correlate with lasting psychological shifts and improvements in wellbeing. (Griffiths et al., 2016)

One concept that emerges across the research is that psilocybin acts as a non-specific amplifier — it doesn't create new feelings or thoughts so much as it amplifies what is already present within a person. This is precisely why set and setting matter so profoundly. The inner work someone brings, the safety of the environment, and the quality of facilitation all shape what gets amplified. It also means that the experience is deeply personal — no two journeys are alike.

These mechanisms are actively being studied. Early evidence suggests they may explain the potential therapeutic significance of psilocybin-assisted therapy, though much work remains.

Molecular structure visualization representing neural connectivity and the Default Mode Network

Safety Profile

Research investigating psilocybin safety in controlled settings suggests a favorable profile compared to many other substances (Griffiths et al., 2016; Ross et al., 2016):

  • Common Transient Effects — Nausea, headache, and emotional intensity are the most frequently reported effects, typically resolving as the experience concludes.
  • Serious Adverse Events — Rare in controlled settings with proper medical screening and professional supervision.
  • Dependence and Addiction — No evidence of physical dependence or addiction potential has been documented in clinical research.
  • Contraindications Are Critical — Thorough screening for personal or family history of psychosis, active suicidality, pregnancy, breastfeeding, and certain medications is essential before any engagement.
  • Set, Setting, and Facilitation — The safety and therapeutic value of psilocybin-assisted therapy depends critically on qualified facilitation, a carefully prepared environment, and proper psychological preparation.

Key Research Studies

Johns Hopkins (2016)

Studies on psilocybin for cancer-related distress found significant reductions in depression and anxiety, with effects lasting 6+ months in participants.

View published study →

NYU (2016, Follow-up 2020)

Similar investigations into cancer-related psychological distress showed that 60-80% of participants maintained clinically significant improvements at 4.5-year follow-up.

View published study →

Imperial College London

Brain imaging studies investigating Default Mode Network changes and active trials exploring potential benefits for treatment-resistant depression.

View published study →

COMPASS Pathways

Phase 3 trial (COMP005) for treatment-resistant depression achieved its primary endpoint, advancing psilocybin-assisted therapy toward potential medical pathways.

View published study →

MAPS / Usona Institute

Phase 3 trials investigating psilocybin-assisted therapy for major depressive disorder, with ongoing data collection and analysis.

View published study →

University of Colorado Anschutz

Three active clinical trials currently enrolling participants. Laurel Tropeano facilitates sessions as part of these investigational protocols.

Important Note: No psilocybin-assisted therapy has received FDA approval as of 2025. All clinical use described here is investigational, conducted under rigorous research protocols with appropriate regulatory oversight.

Colorado's Legal Framework

Colorado is at the forefront of natural medicine policy and regulation. Proposition 122, passed in 2022, established the Natural Medicine Health Act — a comprehensive regulatory framework for psilocybin-assisted therapy.

Key Features:

  • Regulated Framework — Services must be facilitated by licensed professionals at licensed healing centers under oversight by the Department of Regulatory Agencies (DORA), Office of Natural Medicine.
  • Comprehensive Safety Protocols — Every engagement includes informed consent, thorough health screening, psychological safety planning, touch boundary contracts, and transportation planning.
  • Licensed Facilitators — Facilitators must meet specific training and credential requirements and operate within a professional scope of practice.
  • Ongoing Research Integration — The framework supports clinical research while protecting participant safety and autonomy.

Current Status: Colorado and Oregon are currently the only states with operational therapeutic psilocybin frameworks, making Colorado a leader in natural medicine integration and research.

Selected References

  1. Griffiths RR, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer. Journal of Psychopharmacology. 2016;30(12):1181-1197. https://doi.org/10.1177/0269881116675513
  2. Ross S, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer. Journal of Psychopharmacology. 2016;30(12):1165-1180. https://doi.org/10.1177/0269881116675512
  3. Agin-Liebes GI, et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Journal of Psychopharmacology. 2020;34(2):155-166. https://doi.org/10.1177/0269881119897615
  4. Carhart-Harris RL, et al. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology. 2018;235(2):399-408. https://doi.org/10.1007/s00213-017-4771-x
  5. Goodwin GM, et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine. 2022;387(18):1637-1648. https://doi.org/10.1056/NEJMoa2206443
  6. Raison CL, et al. Single-Dose Psilocybin Treatment for Major Depressive Disorder. JAMA. 2023;330(9):843-853. https://doi.org/10.1001/jama.2023.14530

Questions About the Research?

Understanding the evidence is an important part of deciding whether psilocybin-assisted therapy is right for you. Let's talk.

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