New Hope for Treatment-Resistant Depression: Inside PSI’s Clinical Trials

For many people living with treatment-resistant depression (TRD), standard antidepressants and traditional psychotherapy aren’t enough. When symptoms persist after multiple medications or interventions, hope can feel out of reach.

At Psychedelic Science Institute (PSI), we’re helping change that story through a new generation of clinical trials  examining the potential of evidence-based psychedelic-assisted therapies for mental and neurological health.

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Why Treatment-Resistant Depression Needs New Options

Treatment-resistant depression affects roughly one-third of adults diagnosed with major depressive disorder (MDD). That means millions continue to experience debilitating symptoms despite trying two or more antidepressant medications.

Traditional options often take weeks to work and many come with unwanted side effects. Others, like electroconvulsive therapy or transcranial magnetic stimulation , can be effective but aren’t accessible or appropriate for everyone.

That’s why PSI’s research team, born from the union of the Pacific Neuroscience Institute’s TRIP Center and the California Center for Psychedelic Therapy, is pioneering new approaches to depression care. Our TRIP Clinics in Santa Monica and Hollywood are designed to safely study and deliver innovative psychedelic-assisted treatments for people living with TRD.

Related reading: Psychedelic Therapy for Depression | Find Relief at PSI

Advancing Research Through Clinical Trials

PSI is one of the few research organizations in the U.S. actively conducting multiple clinical trials in psychedelic-assisted therapy, including studies sponsored by AtaiBeckley, MindMed, Cybin, and the Usona Institute.

Each trial follows FDA and DEA guidelines, with randomized, double-blind, placebo-controlled designs considered the gold standard in clinical research. PSI’s current studies focus on psilocybin, LSD, psilocin and DMT, four psychedelic compounds that have shown potential to positively impact mood, cognition, and emotional processing.

At PSI, our Elumina VLS-01-203 DMT clinical trial, conducted in partnership with AtaiBeckley, is designed to evaluate the safety and efficacy of short-acting DMT in adults with treatment-resistant depression. The study aims to assess whether a single, carefully monitored psychedelic experience can produce rapid and lasting improvements in mood and cognitive flexibility.

All studies are  reviewed by independent ethics boards focused on the rights and safety of all participants. Additionally, PSI’s research teams are uniquely experienced in the development and implementation of psychedelic treatments for mental health.  We know how vulnerable it can be to participate in our trials and keep participant safety and data integrity at the center of all our work.

What Participation Looks Like

Participating in a clinical trial at PSI starts with an open conversation focused on your safety, comfort, and personal healing goals. Every participant’s journey starts with a screening and evaluation, where our medical and mental health teams carefully review your history to confirm eligibility and ensure that participation is right for you.

If you qualify, your experience typically follows three key phases designed to balance scientific rigor with compassionate care:

1. Preparation and intake – Treatment starts with one of PSI’s multidisciplinary teams, including a physician or advanced practice prescribing clinician and a licensed psychotherapist, for a full intake. This includes a detailed medical and mental health history, baseline assessments, and plenty of time to get questions answered to ensure participation is right for you.
   
   
2. Study sessions – During dosing visits, participants receive either the investigational medicine or placebo in a comfortable, supervised environment. A licensed clinician and trained study staff remain present throughout to ensure your physical and emotional well-being. For most studies, if you are assigned placebo, you may be given an opportunity to receive investigational medicine in a later study session.
   
   
3. Integration and follow-up – After each dosing session, you’ll meet with an experienced psychotherapist to reflect on your experience and explore how to apply insights in daily life. These integration sessions are central to PSI’s approach, helping participants translate research experiences into lasting personal growth.
   
   

All studies take place at PSI’s TRIP Clinics in Santa Monica and Hollywood, which combine state-of-the-art medical oversight with a calm, therapeutic environment. 

Learn more about participation: Becoming a Research Volunteer at PSI

Early Insights from Psychedelic Research

While PSI’s current TRD studies are ongoing, earlier research from institutions such as Johns Hopkins University, Compass Pathways, and the Usona Institute has demonstrated that psychedelic-assisted therapy can produce rapid and sustained reductions in depressive symptoms, even among individuals who have not responded to traditional antidepressants.

These therapies appear to work by promoting neuroplasticity, which is the brain’s ability to form new connections, and by temporarily disrupting activity in the default mode network (DMN), a neural network linked to repetitive thinking and self-image.

At PSI, our work builds on this growing evidence base through rigorous, controlled trials that measure both immediate symptom improvement and longer-term emotional flexibility. By combining cutting-edge neuroscience with psychotherapeutic integration, we’re helping define what the future of depression treatment could look like.

Beyond Trials: Accessing Care at PSI

Not everyone who applies for a clinical trial will meet eligibility criteria, but care doesn’t end there. For those seeking support now, PSI offers Ketamine-Assisted Psychotherapy (KAP) through our TRIP Clinics in Santa Monica and Hollywood. 

KAP combines medical supervision with psychotherapy to help patients process their experiences and support lasting progress. Many participants who do not qualify for research studies find that KAP offers a safe, evidence-informed alternative grounded in the same principles of neuroplasticity and emotional insight.

How to Get Involved

If you or someone you love is living with treatment-resistant depression, participating in a clinical trial may be an opportunity to contribute to breakthrough research and find new hope.

Getting started is simple:

• Learn more online – Visit our Clinical Trials page for details on active and upcoming studies.
  
  
• Connect with our team – Reach out through our contact form or call one of our TRIP Clinic locations. Our coordinators will walk you through eligibility, screening, and what to expect.
  
  
• Share with loved ones – If you know someone struggling with depression, sharing information about PSI’s research could make a meaningful difference.
  
  

Together, we can help advance safe, effective, and inclusive therapies that redefine what’s possible in mental health care.

Frequently Asked Questions

What makes PSI’s clinical trials unique?
PSI combines world-class research protocols with a person-centered therapeutic model, ensuring participants receive compassionate, individualized attention throughout the process.

Which medications are being studied?
Current trials include psilocybin, LSD, psilocin, and DMT. These psychedelic compounds are being evaluated for their antidepressant effects.

Is participation free?
Yes. All study medications, clinical visits, and professional supervision are provided at no cost to participants, funded by research sponsors.

What if I don’t qualify?
Our clinicians can discuss alternative care options like Ketamine-Assisted Psychotherapy (KAP), available year-round at our TRIP Clinics in Los Angeles.

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