The Acceleration of Psychedelic-Based Treatments: In Conversation With Daniel R. Karlin, MD, MA

CLINICAL CONVERSATIONS

Following a recent executive order directed at the US Department of Health and Human Services, the US Food and Drug Administration (FDA) has announced a series of regulatory actions aimed at accelerating development of psychedelic-based treatments for serious mental illness.^1-3 Federal support of investigational therapies for psychiatric disorders where current pharmacological options are lacking could be transformative for disorders like depression, posttraumatic stress disorder (PTSD), and alcohol use disorder.

Daniel R. Karlin, MD, MA, the chief medical officer of Definium Therapeutics, while excited by this news, says his company is staying the course for their novel candidate, lysergide tartrate (DT120 ODT), remaining committed to rigorous research and development. However, the accelerated attention is welcome.

DT120 ODT—an ergoline derivative belonging to the group of classic serotonergic psychedelics, which acts as a partial agonist at serotonin-2A receptors—is now under study for major depressive disorder (MDD) and generalized anxiety disorder (GAD). Last week, Definium also announced an expansion of the DT120 ODT program with the planned initiation of the phase 3 Haven study in PTSD.⁴ In a phase 2b trial, DT120, formerly known as MM120, demonstrated positive results for the treatment of GAD, in which a single dose of 100 µg produced a 7.7-point improvement on the Hamilton Anxiety Rating Scale (HAM-A) compared with placebo at week 4.Furthermore, 50% of participants achieved clinical remission after 4 weeks.⁵

Read our conversation with Dr Karlin on the FDA news and the progression of DT120 ODT here.

Psychiatric Times: President Trump recently signed an executive order titled, “Accelerating Medical Treatments for Serious Mental Illness.”¹ This order directs the FDA to issue National Priority Vouchers for Breakthrough Therapy-designated psychedelics. How could this impact access and research on psychedelics, in your opinion?

Daniel R. Karlin, MD, MA: We are just absolutely thrilled for the positive regard and attention that this sort of a thing generates. The interactions that we have had with the FDA to date have been extraordinarily productive and have led us to a great deal of alignment with the agency on the development program that we are undertaking, and ultimately the studies that will lead to, if they are successful, an NDA submission. This attention from the president is completely consistent with what we have been doing anyway, and consistent with the engagement we have had with the agency in concern to their agreeableness and thoughtfulness, their attention, and their timely responses to us.

For us, the main focus continues to be that we do good science that demonstrates the conditions for safe and efficacious use of these drugs across the conditions we are interested in, including MDD and GAD. From a material standpoint, it is not clear what—if any—change this would lead to in terms of our process toward a potential approval.

But again, positive attention is always welcome, as is the broad recognition, both for our drug and for the category to which it belongs. It continues to ratify what we demonstrated in phase 2, which is a remarkable degree of efficacy and durable efficacy after a single dose of drug, and what we intend to show in phase 3.

PT: Talk to us about the research. Is there a specific data point that sticks out to you? How does DT120 differ from other psychedelics in the pipeline?

Karlin: In a phase 2 dose response study of DT120, which is our pharmaceutical LSD, we were able to demonstrate that a single dose of 100 micrograms or 200 micrograms (though the dose we have brought forward into phase 3 is 100 micrograms), given without any adjuvant or any other intervention including psychotherapy, produced a rapid response that was observable as soon as 1 day after treatment. It was quite a robust change, and that change persisted for the full 12 weeks that we watched patients after a single dose. Participants started with at least moderate to severe anxiety, and 48% of those participants on the 100-microgram dose were in remission 12 weeks later. That is the sort of change that we are able to see with our drug. Now, others in the category have done differently designed studies, and some have been looking at multiple doses of drug given with adjuvant psychotherapy. At this point, there is no real grounds for head-to-head comparison. We are confident that the properties that DT120 has demonstrated thus far in research, and obviously we hope it will continue to demonstrate, put it in a top tier category.

PT: Recently, we have seen a real turning of the tide with psychedelics. Everyone seems more excited now than perhaps they were a few years ago. For the clinicians who are still on the side of hesitancy, what would you say to convince them that this is something that we need in the psychiatric landscape?

Karlin: We engage with folks who come at this from all sorts of prior beliefs. Some people are incredibly enthusiastic, some people are neutral, and obviously there are some who are hesitant or even negative. I can only say so much, right? We have a drug in development. When people express hesitancy to us and say, “Well, you know, the evidence isn't yet adequate to convince them,” that is okay. You cannot prescribe these drugs yet. They are not approved, and we have not finished phase 3. It is incumbent on us to have design studies that are methodologically robust, as we believe we have, such that when we are able to read out data from these studies, even folks who come at this from a hesitant position can be confident that the measured effects that we are able to demonstrate represent real drug effects.

In no way do I take the position that folks who are hesitant or have doubts are wrong. It is the job of prescribers, whether they are physicians or advanced practice nurses, to bring evidence-based therapies to their patients. Skepticism when the data are not fully released is a very reasonable position. We just hope that they evaluate the evidence that we generate with an open mind, even if it is a skeptical open mind. People can certainly ask questions.

Again, we design our studies to be as robust as possible, so that the data that they generate are reliable and of high integrity. I would not ask anyone to believe anything that exceeds the data.

PT: With DT120, is there anything you wish prescribers and psychiatric clinicians knew? Is there something you think that is misunderstood about DT120 specifically?

Karlin: That is an excellent question. DT120 is pharmaceutically optimized LSD, and it is obviously made to pharmaceutical manufacturing standards, but at the end of the day, it is LSD. LSD does have the history that it has.

Now, one thing to keep in mind about LSD’s history is that it may not be as it seems. There was a lot of effort made to vilify LSD when it was made a controlled substance, and it was associated with some cultural phenomena that were polarizing at the time. In many people's minds, it is still quite polarizing. But the sense some people have that the LSD experience is somehow dramatic or incredibly anxiety inducing, or that people frequently have so-called bad trips—that has not been our experience. The actual patient experience is generally a very gentle one, and people do not needing much intervention at all from the dosing session monitors who are in the room with them to be able to have a safe and comfortable experience on dosing day.

The effects of the drug are what you expect with a psychedelic drug. People have perceptual changes, they have some emotional changes. They certainly have some changes in the way that they are thinking during the course of the day, but all of that is tolerated quite well by participants through that dosing day. I think that is probably the biggest misconception that we run into, particularly with DT120 vs other psychedelics: that there is this expectation about the experience of the drug, that it is more challenging than what we are seeing it to be in our trials.

PT: We have heard some hesitancy on the part of clinicians following this fast track order from the President. They want psychedelics to be accessible, but they want it through the regular, rigorous approval process. How is Definium remaining committed to research and data in the wake of this news?

Karlin: From the Definium perspective, we are not slowing or stopping any of our scientific enterprise. This news, while welcome, does not materially shift our plans. We have provided study designs and timelines, and number of enrollments we expect in these studies. We think that we have planned the best possible studies that we could to demonstrate the safety and efficacy of the drug, and we will continue to efficiently get great data to run those studies. Any efficiencies that can be generated in the review process, anything that the agency can do more effectively, would be certainly welcome. But our scientific agenda and the need to demonstrate that safety and efficacy not just to regulatory bodies, but ultimately to the health care providers who will prescribe the drug and will monitor sessions, has not changed. We need patients to have confidence that the drug that we bring forward, if approved, is being brought to them because of rigorous science and because the evidence supports it.

PT: Is there anything else to conclude that you would like to share?

Karlin: We are incredibly excited coming off of our Analyst Day, where we shared some information about blinded sample size, as well as the estimations and enrollment statuses of these studies. We have great confidence that these data will continue to show that DT120 could have a tremendous impact on the well-being of people and on psychiatry as a field.

Dr Karlin is the chief medical officer of Definium Therapeutics.

References

1. Accelerating medical treatments for serious mental illness. The White House. April 18, 2026. Accessed April 24, 2026. https://www.whitehouse.gov/presidential-actions/2026/04/accelerating-medical-treatments-for-serious-mental-illness/

2. U.S. Food and Drug Administration. FDA Accelerates Action on Treatments for Serious Mental Illness Following Executive Order. April 24, 2026. Accessed April 24, 2026. https://www.fda.gov/news-events/press-announcements/fda-accelerates-action-treatments-serious-mental-illness-following-executive-order

3. Duerr HA. FDA fast-tracks psychedelic therapies for depression, PTSD, and alcohol use disorder. Psychiatric Times. April 24, 2026. https://www.psychiatrictimes.com/view/fda-fast-tracks-psychedelic-therapies-for-depression-ptsd-and-alcohol-use-disorder

4. Definium Therapeutics highlights DT120 ODT (lysergide tartrate) clinical advancements and commercial strategy at Investor and Analyst Day. News release. April 22, 2026. Accessed April 24, 2026. https://ir.definiumtx.com/news-events/press-releases/detail/223/definium-therapeutics-highlights-dt120-odt-lysergide-tartrate-clinical-advancements-and-commercial-strategy-at-investor-and-analyst-day

5. Robison R, Barrow R, Conant C, et al. Single treatment with MM120 (lysergide) in generalized anxiety disorder: a randomized clinical trial. JAMA. 2025;334(15):1358-1372.