Advancing Phase 2 Clinical Trials of Psilocybin for Major Depressive Disorder

INSTITUTION: Usona Institute

PROJECT LEADERS: Robert Kargbo PhD (CMC Program Lead), Babi Wadhwani (Sr. Director, Clinical Development)

PROJECT DURATION: 2021-2023

LAB WEBSITE: Usona Institute

Usona Institute conducts and supports pre-clinical and clinical research to further the understanding of the therapeutic effects of psilocybin and other consciousness-expanding medicines. Our current focus is on alleviating depression in people for whom current medical treatments fall short in offering relief and a better quality of life.

Our work builds upon the strength of early-phase studies conducted at leading institutions, including many of our scientific collaborators. As an FDA drug “sponsor”, Usona is responsible for the initiation, management, and financing of the clinical trials towards FDA new drug approval, as well as to produce cGMP psilocybin that is tested for safety and purity under highly controlled and monitored conditions.

Usona is currently in the process of completing Phase 2 clinical studies and mobilizing for Phase 3 to move through the FDA approval process under Breakthrough Therapy designation for the treatment of Major Depressive Disorder (MDD) with psilocybin.

Funding from Tiny Blue Dot is being used to advance Usona’s psilocybin development program, including enabling the clinical studies through completion of Phase 2 trials, further development and optimization of the cGMP drug, and to prepare for early commercialization planning activities.

Broader Impact:

Depression affects over 300 million people worldwide. This is an increase of more than 18% from 2005 to 2015. Depression is a disease of epidemic proportions. Among those seeking treatment, approximately 60% still experience symptoms of depression even when receiving traditional care.

The need for better solutions is clear, and we anticipate this new approach to treatment will have a significant impact on public health, productivity, and well-being, globally.

Usona embraces the challenge of finding a better way forward. We are a non‑profit, medical research organization looking beyond the traditional treatments for depression. Our aim is to enable and move forward the research required to acquire FDA registration for psilocybin as an approved medicine (NDA) to improve mental health outcomes and provide a safe, accessible, and affordable pathway for psychedelics to reach people in greatest need.

Publications:

• The Investigator’s Brochure for Psilocybin is a detailed compendium of information on psilocybin’s pharmacology, safety, and efficacy. Consistent with our open science approach, this document is openly shared with other researchers for use in their own regulatory submissions and clinical trials, under a Creative Commons license.

• Psilocybin: Crystal Structure Solutions Enable Phase Analysis of Prior Art and Recently Patented Examples
  Sherwood, A. M. Acta Crystallographica Section C Structural Chemistry, vol. 78, no. 1, 2022.

• Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin
  Kargbo, R.B.; Sherwood, A.M.; Walker, A.; Cozzi, N.V.; Dagger, R.E.; Sable, J.; O’Hern,K.; Kaylo,K.; Patterson, T.; Tarpley, G.; Meisenheimer, P.  ACS Omega. 2020.

• An Improved, Practical, and Scalable Five-Step Synthesis of Psilocybin. Sherwood, A. M.; Meisenheimer, P.; Tarpley, G.; Kargbo, R. B. Synthesis. 2020. https://www.researchgate.net/publication/338486826_An_Improved_Practical_and_Scalable_Five-Step_Synthesis_of_Psilocybin 

• Psilocybin Therapeutic Research: The Present and Future Paradigm. Kargbo, R. B. ACS Medicinal Chemistry Letters. 2020. https://pubmed.ncbi.nlm.nih.gov/32292538 

• Preparation and Characterization of Novel Crystalline Solvates and Polymorphs of Psilocybin and Identification of Solid Forms Suitable for Clinical Development. Greenan, C.; Arlin, J.-B.; Lorimer, K.; Kaylo, K.; Kargbo, R.; Meisenheimer, P.; Tarpley, G.; Sherwood, A. (Preprint – ResearchGate). 2020. https://www.researchgate.net/publication/339238710_Preparation_and_Characterization_of_Novel_Crystalline_Solvates_and_Polymorphs_of_Psilocybin_and_Identification_of_Solid_Forms_Suitable_for_Clinical_Development 

• Psilocybin Induces Rapid and Persistent Growth of Dendritic Spines in Frontal Cortex in Vivo. Lin
  g-Xiao Shao, Clara Liao, Ian Gregg, Pasha A. Davoudian, Neil K. Savalia, Kristina Delagarza, Alex C. Kwan. Neuron, 2021. https://www.sciencedirect.com/science/article/abs/pii/S0896627321004232?dgcid=author

• Trial of Psilocybin vs. Escitalopram for Depression
  Carhart-Harris et al. N Engl J Med. 2021. 384:1402-1411. doi: 10.1056/NEJMoa2032994.

• Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial
  Davis AK, Barrett FS, May DG, et al. JAMA Psychiatry. Published online November 04, 2020. doi:10.1001/jamapsychiatry.2020.3285. https://pubmed.ncbi.nlm.nih.gov/33146667/ 

• Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial
  Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL. J Psychopharmacol. 2016 Dec;30(12):1165-1180. doi: 10.1177/0269881116675512. PMID: 27909164; PMCID: PMC5367551.

• Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up
  Gukasyan, N., Davis, A.K., Barrett, F.S., Cosimano, M.P., Sepeda, N.D., Johnson, M.W., & Griffiths, R.R. (2022). Journal of Psychopharmacology. Published Online. February 15, 2022.