A Shorter Trip to Healing? The Promise of a New Psychedelic Compound

This article answers the question: What did a recent Phase 1 human trial reveal about the psychedelic compound 4-OH-DiPT? 

A recent Phase 1 clinical trial has provided the first formal evaluation of 4-OH-DiPT, a synthetic psychedelic similar to psilocybin. The study found that 4-OH-DiPT produces a psychoactive experience with a favorable safety profile, but with a significantly shorter duration of 3 to 4 hours. This article explores the findings of this study and four other key papers, examining the potential of this short-acting psychedelic for therapeutic use, particularly in conditions like postpartum depression and PTSD. 

The world of psychedelic therapy is buzzing with excitement about the potential of new and novel compounds to treat a wide range of mental health conditions. While psilocybin, the active ingredient in magic mushrooms, has been the star of the show so far, researchers are now exploring a new generation of psychedelic compounds that could offer unique advantages. One such compound is 4-OH-DiPT, a synthetic psychedelic that is structurally similar to psilocybin but with a much shorter duration of action. This could be a game-changer for psychedelic therapy, as it could make the experience more manageable and accessible for a wider range of patients.

This article will delve into the first-ever human trial of 4-OH-DiPT, exploring what the science says about its safety, tolerability, and potential therapeutic effects. We will also look at other recent research that is shedding light on the unique properties of this promising new compound, including its potential to treat postpartum depression and PTSD. By the end of this article, you will have a better understanding of what makes 4-OH-DiPT so exciting and what it could mean for the future of mental health treatment.

The First Human Trial of 4-OH-DiPT

A landmark 2025 study published in the Journal of Clinical Psychopharmacology marks the first time that 4-OH-DiPT has been formally evaluated in humans (Ludbrook et al., 2025). The Phase 1, double-blind, randomized, single-ascending-dose, placebo-controlled study was designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the compound. The results were promising, suggesting that 4-OH-DiPT has a favorable safety profile and produces a psychoactive experience that is similar to psilocybin, but with a much shorter duration of 3 to 4 hours.

This is a significant finding, as the long duration of a psilocybin experience (which can last up to 8 hours) can be a major barrier for some patients. A shorter-acting psychedelic could make the therapy more manageable and less intimidating, which could open the door to treatment for a wider range of people. The study also found that the psychoactive effects of 4-OH-DiPT were dose-dependent, with higher doses producing more intense mystical experiences. This suggests that the therapeutic effects of the compound could be tailored to the individual needs of the patient. 

This study is a crucial first step in the development of 4-OH-DiPT as a potential therapeutic agent. It provides a solid foundation of evidence for the safety and tolerability of the compound, and it opens the door to further research into its potential therapeutic applications. The next section will explore one of the most promising of these applications: the treatment of postpartum depression.

A New Hope for Postpartum Depression

Building on the promising results of the Phase 1 trial, a 2025 article in Clinical Trials Arena reports on the success of a Phase 2 trial of RE104, a prodrug of 4-OH-DiPT, for the treatment of postpartum depression (PPD) (Clinical Trials Arena, 2025). PPD is a debilitating condition that affects many new mothers, and there is a pressing need for new and more effective treatments. The results of the Phase 2 trial suggest that RE104 could be a major breakthrough in the treatment of this condition.

The trial found that a single dose of RE104 produced a rapid and sustained reduction in the symptoms of PPD. This is a remarkable finding, as current treatments for PPD can take weeks or even months to take effect. The short duration of the RE104 experience is also a major advantage in this patient population, as it would allow new mothers to receive treatment without having to be away from their babies for an extended period of time. The success of this Phase 2 trial has paved the way for a larger, late-stage trial, which is expected to begin next year. 

This is a very exciting development in the field of psychedelic therapy. It suggests that 4-OH-DiPT could be a safe and effective treatment for a condition that has a major impact on the lives of many women and their families. The next section will explore another potential application of 4-OH-DiPT: the treatment of PTSD.

Extinguishing Fear and Enhancing Resilience

In addition to its potential for treating PPD, 4-OH-DiPT is also being explored as a potential treatment for post-traumatic stress disorder (PTSD). A 2023 study in Neuropsychopharmacology found that 4-OH-DiPT enhanced fear extinction in mice, a key process in the treatment of PTSD (Kaplan et al., 2023). Fear extinction is the process by which we learn to no longer be afraid of something that was previously frightening. This is a crucial mechanism for overcoming the debilitating fear and anxiety that are the hallmarks of PTSD.

The study found that mice that were given 4-OH-DiPT were better able to extinguish their fear of a specific cue that had been previously associated with an aversive stimulus. The researchers also found that 4-OH-DiPT enhanced the activity of GABAergic neurons in the basolateral amygdala, a brain region that is critical for processing fear and anxiety. This suggests that 4-OH-DiPT may work by enhancing the brain's natural ability to regulate fear and anxiety. 

This study provides a strong rationale for further research into the use of 4-OH-DiPT for the treatment of PTSD. It suggests that this compound could be a powerful tool for helping people to overcome the debilitating effects of trauma. The next section will explore the chemistry behind 4-OH-DiPT and its prodrug, RE104.

The Chemistry of a Shorter Trip

To understand how 4-OH-DiPT can have such a profound effect on the brain, it is important to understand a little bit about its chemistry. A 2024 study in ACS Chemical Neuroscience provides a detailed look at the synthesis and activity of RE104, the prodrug of 4-OH-DiPT that was used in the PPD trial (Cameron et al., 2024). A prodrug is an inactive compound that is converted into an active drug in the body. In this case, RE104 is converted into 4-OH-DiPT, which is the active psychedelic compound.

The researchers who developed RE104 designed it to be rapidly cleaved in the body, which is why it has such a short duration of action. They achieved this by attaching a glutarate moiety to the 4-OH-DiPT molecule. This moiety is quickly removed by enzymes in the body, releasing the active 4-OH-DiPT. This clever bit of chemistry is what makes RE104 so promising as a therapeutic agent. It allows for a controlled and predictable psychedelic experience that is both safe and effective. 

This study provides a fascinating glimpse into the science behind the development of new psychedelic compounds. It shows how a deep understanding of chemistry can be used to create drugs that are tailored to the specific needs of patients. The development of RE104 is a major step forward in the field of psychedelic medicine, and it is likely to pave the way for the development of other novel psychedelic compounds in the years to come.

Conclusion: A New Tool in the Psychedelic Toolkit

The emergence of 4-OH-DiPT as a promising new psychedelic compound is a testament to the incredible pace of innovation in the field of psychedelic medicine. With its shorter duration of action and favorable safety profile, 4-OH-DiPT offers a new and exciting tool in the psychedelic toolkit. The promising results of the Phase 1 and Phase 2 trials suggest that this compound could have a major impact on the treatment of a wide range of mental health conditions, from postpartum depression to PTSD. As research into this fascinating compound continues, we may be on the verge of a new era of psychedelic therapy, one in which we have a wider range of tools to help people heal and grow.

References

Cameron, L. P., Bryson, N., & Alexander, R. (2024). RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-N,N-diisopropyltryptamine. ACS Chemical Neuroscience, 15(10), 2045–2054. https://doi.org/10.1021/acschemneuro.4c00058

Clinical Trials Arena. (2025, August 18). Reunion’s psychedelic therapy to advance after Phase II PPD success. https://www.clinicaltrialsarena.com/news/reunions-psychedelic-therapy-to-advance-after-phase-ii-ppd-success/

Kaplan, K. M., Starr, H. L., & Fantegrossi, W. E. (2023). Psilocybin analog 4-OH-DiPT enhances fear extinction and GABAergic inhibition of principal neurons in the basolateral amygdala. Neuropsychopharmacology, 48(13), 2023–2032. https://doi.org/10.1038/s41386-023-01744-8

Ludbrook, G., Bryson, N., Taylor, B., Hocevar-Trnka, J., Johnson, M. W., Hirman, J., Morrish, G., Alexander, R., & Pollack, M. (2025). Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous RE104: A Double-Blind, Randomized, Single Ascending Dose Placebo-Controlled Study. Journal of Clinical Psychopharmacology, 45(5), 441–453. https://doi.org/10.1097/JCP.0000000000002047

Disclaimer: Psychedelic Assisted Psychotherapy has not been approved by any regulatory agencies in the United States, and the safety and efficacy are still not formally established at the time of this writing.