By John Clifton, M.D., VETS Director of Research

When most people hear about psychedelic clinical trials, they envision a single, transformative session, maybe two, resulting in rapid, life-changing outcomes. But the reality is more complex.

Clinical trials to date have largely focused on a limited dosing regimen, typically one to three sessions spaced over several months. These tightly controlled protocols are necessary to generate consistent data and meet regulatory standards. But they don’t necessarily reflect how psychedelic therapy is applied in the real world, especially for veterans and others living with complex, treatment-resistant conditions.

This disconnect is particularly relevant for veterans navigating chronic PTSD, TBI, or moral injury—conditions that often don’t resolve in one or two sessions.

What We’ve Learned from Clinical Trial Dosing

These trials have taught us a lot. For instance, dose ranges of psilocybin in clinical settings have helped researchers understand general thresholds:

  • 10mg/70kg or less: Often mild or even sub-perceptual for many individuals
  • 20mg/70kg: Moderate to strong for some; milder for others
  • 30mg/70kg+: Typically considered a high dose with intense effects, but not for everyone

Even within these standardized ranges, individual responses vary wildly. Some participants may report no effect at 30mg/70kg, while others experience a deep or meaningful experience at half that. Human neurobiology, trauma history, and context matter, and we don’t fully understand why yet.

Real-World Practice Looks Different

Once a drug moves from trial to clinic, treatment often strays from the protocol. This isn’t unique to psychedelics. For example, psychiatric medications (i.e., SSRIs, SNRIs, etc.) are prescribed in widely varied doses depending on the setting and the patient’s needs. What starts as a carefully controlled dose in research often expands or adapts in practice. Though personalized treatment may benefit many patients, there are downsides to not having research to fall back on, especially with psychedelics.

For example, in legal psychedelic retreats abroad it’s common for participants to experience multiple psilocybin ceremonies in a week with doses that often exceed those used in clinical trials. Ayahuasca is also taken more frequently in traditional settings. These retreats may also combine two different substances, like ibogaine and 5-MeO-DMT, over the course of the retreat. That doesn’t always mean these approaches are always better—or safe for everyone—but they highlight a growing disconnect between the lab and how treatment protocols are actually being administered.

What If One or Two Doses Isn’t Enough?

Let’s take a closer look at a hypothetical example:

  • Person A finds lasting relief from depression after just one or two psilocybin sessions.
  • Person B, however, doesn’t. Under a typical trial protocol, they might be labeled a “non-responder” or even a “treatment failure” But what if Person B simply needs a different protocol?
  • Four psilocybin sessions across a year instead of two?
  • More smaller doses instead of just a few larger doses?
  • A longer period of therapy and trust-building before the first dose?
  • A personalized integration process spanning several months?
  • A combination of different substances, administered thoughtfully and with clinical oversight?

The truth is, we don’t know. We haven’t studied them because clinical trials are typically less about tailoring treatment to each person’s needs and more about testing general hypotheses that conform to existing regulatory and clinical standards.

The Cost of Narrow Design: Rethinking Research Design

To be clear: we’re not advocating for more substances across the board, nor are we suggesting that higher doses are appropriate for every patient. More is not always better, and sometimes less is actually better. Some individuals may never respond to psychedelic therapy, regardless of dose or protocol.

But we won’t find the best answers if we limit our thinking.

If we only study one, two or three dose protocols in research for the next several decades, we risk setting false expectations for the broader public and missing opportunities to discover more effective treatment protocols than what we currently know. Headlines often highlight rapid results after a single session, while real-world healing journeys are often messier, longer, and more individualized.

Psychedelic therapy is in a strange position because it is one of the few cases where treatment has occurred legally in other areas of the world for decades while being illegal in the United States. This tends to not happen in the development of new medications, where it is only after the medication is approved that we have some idea of what treatment looks like outside of the trials.

Therefore, what’s needed is more creative study designs that mirror what’s already happening in compassionate, real-world care, especially for complex cases like those seen in the veteran community.

It takes 4-7 years or more and sometimes millions of dollars to bring a psychedelic clinical trial from inception to publication. That’s a long time to wait for answers, especially for people struggling now.

If we want to know what truly helps those with chronic, treatment-resistant conditions, we must invest in broader, more adaptive research strategies.

That means exploring different dosing frequencies, timelines, combinations, and contexts. And it means funding more diverse studies, not just those aiming to find the minimum effective dose to get through regulatory hurdles.

Final Thoughts

Psychedelics represent a new category of medicine that don’t fit nicely into the existing boxes we’ve created for pharmaceutical drugs and medications. And while fixed-dose, fixed-frequency protocols may help get them approved, they’re unlikely to reflect the full healing potential these substances offer in clinical practice.

At VETS, we advocate for monitored, clinical use of psychedelic-assisted therapies—not decriminalized or broad legalization—and we believe research should reflect the real-world challenges veterans face.

It’s time for research to catch up with reality, and for science to investigate the diversity of healing journeys, not just the simplicity of headlines.

Editor’s Note: This article is for educational purposes only and does not constitute medical advice or imply treatment recommendations. Psychedelic-assisted therapy remains under research and is not approved for widespread clinical use in the U.S. outside of regulated trials or expanded access programs.

About John Clifton, M.D., VETS Director of Research

John M. Clifton, M.D. holds a B.A. in neuroscience from Vanderbilt University and earned his M.D. from The University of Maryland School of Medicine. He developed his early research and clinical skills at the Johns Hopkins Center for Psychedelics and Consciousness Research where he supported and co-authored several clinical trials and epidemiological studies. He then went on to complete medical school where he conducted additional original psychedelic research. From psychedelic experiences to mind-body approaches for chronic pain recovery, John continues to support a wide variety of individuals in their healing processes using evidence based coaching techniques. He currently resides in Baltimore, MD.