Meet the psychiatrist investigating MDMA-assisted therapy for depression

Tor-Morten Kvam is a psychiatrist at the PsykForsk research team at Østfold hospital. He is also an investigator in a Phase II trial exploring the effects of MDMA-assisted therapy for major depressive disorder. Tor-Morten has also worked with MAPS and COMPASS Pathways in their respective trials with MDMA-AT and psilocybin-AT for PTSD and treatment-resistant depression (TRD).

Our founder, Floris Wolswijk, spoke with Tor-Morten Kvam to learn about his research and upcoming talk at the Nordic Psychedelic Science Conference.

What will you be speaking about at the Nordic Psychedelic Science Conference? 

At the conference, I’ll be speaking about an upcoming trial regarding psychedelics and depression. Specifically, investigating MDMA-assisted therapy for depression. The study is mainly funded by the Norwegian government. It is an investigator-initiated trial that is a collaboration between industry and academics.

MAPS is one of the key contributors to this trial and will provide MDMA for the study. While this trial is a small open-label study, we are hopeful that it will lead the way to bigger trials with more participants in order to provide us with the statistical power necessary to confirm any hypotheses we have about the effects of MDMA-AT on depression.

This is the world’s first trial with MDMA where major depressive disorder (MDD) is the target disorder, so we are hopeful that, providing the results of this pilot study are positive, we can undertake large-scale trials using MDMA-assisted therapy to treat people with MDD.

For those who don’t know, what does it mean that it’s an investigator-initiated trial? 

The trial has been conceived by the researchers who develop the protocol and serve as the sponsor-investigators who ensure that the trial is conducted appropriately. We are collaborating with MAPS’ researchers, the trial remains solely our initiative and responsibility.

Let’s take a few steps back. How did you get to be researching MDMA? Has it always been an interest or if you come here via another route? 

My interest in psychedelics started five years ago. At this stage, I had no personal experience with psychedelics. Instead, I entered the field from an academic standpoint and was fortunate enough to become part of a research group that eventually became a study site for one of the COMPASS Pathways trials. Despite receiving all the necessary training and a lengthy negotiating process over the course of 18 months we did not get the necessary regulatory approval.

Since then, we have been fortunate enough to be working with MAPS serving as a study site for their European Phase II trial investigating the effects of MDMA-AT on PTSD. Over the course of the last year, we have recruited and treated the required participants from Norway in this particular trial and although our contribution to the trial is finished, the trial is still ongoing in many countries. Now, the plan is to be a part of the Phase III trial that should start in the near future. 

As we have become very familiar with the protocol used in the MAPS Phase II trial for PTSD, the protocol for our upcoming MDMA for MDD trial is largely based on that protocol. We now have the experience and resources necessary to carry out our own study. Working with MAPS on their Phase II trial was very informative, helping us to get a better understanding of study logistics and importantly, getting experience working with the trial participants, providing them with therapy and working with the treatment overall.

You said there, there was some trouble with the regulators with being one of the sites for the COMPASS trial. What’s your experience with the regulators in Norway and has that changed over the last five years? 

I think it’s safe to say that the Norwegian regulators don’t have anything specifically against trials with psychedelics. They are concerned about the manner in which the trials will be conducted as well as the primary outcome measure in the trials. They primarily wanted us to change the primary endpoint of the trial from three to six or 12 weeks in order to better assess for any possible placebo or expectancy effects. With these kinds of psychoactive compounds, it’s fairly easy to guess what treatment you’re in. 

Unfortunately, changing this was impossible for us as COMPASS had already started the trial with their protocol which is the same protocol being used at the various test sites across the globe. We’ve moved on since then and are hopeful that we will be a test site for the COMPASS Phase III study.

You touched upon the fact that you now have more experience with recruiting participants. Can you describe this process? You wrote an article in 2021 that stated  51% of people in Norway are willing to try psilocybin within the context of a trial. Can you tell us why this may be and how do you find balance in the recruitment process?

My impression is that recruiting participants is difficult in all kinds of clinical trials. In every clinical trial, you need to be active and screen a lot of potential participants in order to get those few, that small subset of patients that could be participants in the trial. It’s very important to follow the criteria to get the right participants.

For our depression trial, we need to screen many participants in order to recruit the participants we need for the trial. We’re broadening our reach and have been contacting general practitioners, public healthcare outpatient clinics and hospitals in our neighbourhood and beyond. 

Of course, there are hopes out there that such treatments could be beneficial for a lot of people but our main interest is to have a successful trial and provide treatment in a manner that is safe and does not jeopardize the protocol or potentially harm any participants. Hopefully, we will be able to get preliminary indications about the effects in one way or the other but our priority is following the protocol and providing treatment that is safe.

In terms of all the attention psychedelics are getting in the media these days, I think it has some advantages, particularly in terms of getting people interested in the trial but again, we have to find the balance. We have to follow the current protocol and the regulations, to show regulators that our trial is safe.

This is the first trial really looking at using MDMA for MDD. What’s the rationale behind it? What can MDMA-AT do for MDD?

We know that psychotherapy works for MDD. As we have seen in the PTSD trials, MDMA-AT is drug-facilitated therapy that can result in a very deep and transformative experience.

For MDD, we don’t have the data to say that MDMA-AT can produce similar effects but we hope that we will be able to get preliminary efficacy data from our trial.

The data from the MAPS PTSD trials suggest a reduction in depressive symptoms when depression is a secondary measure. The data from the PTSD trial also indicates MDMA-AT has positive effects on a number of other measures beyond PTSD symptoms. Some of the ways MDMA-AT could help people with depression is by providing them with more insights and more self-compassion. Also, in the 70s and 80s before the ban on research on MDMA, there were some indications of MDMA having an antidepressant effect back then although no clinical trials were conducted. 

What are the big differences between this trial and other trials using MDMA-AT for PTSD? Are there big changes with regards to the protocol?

Overall, they are actually quite similar. Of course, we have a different indication (MDD) and also different outcome measures but the therapeutic intervention is more or less the same. 

We’re not preparing the participants for processing trauma in the same way that we did in the PTSD trial. I think one of the main advantages of MDMA-AT is that it’s an inner-directive approach which means we don’t have to follow a strict protocol set in manuals regarding a particular type of therapy. 

Also, we don’t need to exercise control over the participants’ processes, it’s more so the medicine and their inner healing intelligence that will bring the process forward. In this sense, the therapists are more guides or supporters of the process. We hypothesise this can lead to transformative processes across diagnoses. 

In this regard, we haven’t changed anything in the therapeutic approach between the trials. We focus on the alliance between the therapist and the patient, helping to create a trusting environment. In terms of preparation for the MDMA experience, we have followed the protocol from the PTSD trials.

It will be interesting to see what differences appear in the depression trial in comparison to PTSD trials. With the PTSD trial there are many traumatic experiences coming to the surface. I think some unexpected things may come to the surface during the depression trial and I am interested to see will they differ from those with PTSD. For example, what kinds of attachment issues or relational issues could contribute to someone’s depression. Or what kind of strategies have participants developed in order to adjust to their environment both as an adult and as a child and may be contributing to a person’s depression. 

MAPS has gotten criticism for being too open to different therapeutic methods in their approach to therapy for PTSD, and so running the risk of introducing unnecessary variables to the overall therapeutic process. For example, some therapists could be providing CBT while others are providing IFS. Is this something that you might be concerned about in the current research?

As therapists, we take our training into therapy. Each of us has received different training. I think it’s very important to be authentic and be ourselves as therapists. Maintaining authenticity is essential and part of that is helping the participants in every way we can. 

Our main focus is to build alliance and trust with the participants and help them to engage in a psychotherapeutic process. If that means occasionally diverging from the inner-directive approach and introducing specific interventions where appropriate, it can be justified. However, it is important to maintain consistency across therapists and adherence to the therapeutic approach. Our aim in our upcoming trial is to stick to the inner-directive approach as much as possible. 

What will the coming months, maybe years look like for the MDMA-AT for MDD trial?

First, we expect to start recruiting any moment now. After that, we will start the treatment and concurrently recruit more patients over the coming 12 or 18 months. By 2024 we will have the first results and be one step closer to knowing if MDMA-assisted therapy will be a suitable treatment for depression.

To learn more about Tor-Morten Kvam’s talk and see him in person, go to the Nordic Psychedelic Science Conference website.

Nordic Psychedelic Science Conference is dedicated to developing the field of psychedelic research within the Nordic countries. Participants will get the chance to be updated on the latest research, discover what opportunities might exist in the future and get to meet the experts within the field. The conference is especially relevant for academics, healthcare professionals and students.