Funding MDMA-Assisted Therapy Research for Veterans
MDMA-Assisted Therapy (MDMA-AT) research goes back decades and there have been exciting developments recently
Through large clinical trials sponsored by Multidisciplinary Association for Psychedelic Studies (MAPS), promising results in the reductions of PTSD and its devastating side effects have recently come to light. Although methodological challenges still exist, Healing Breakthrough’s goal is to fund research and advocate for clinical trials in the VA. We support research that evaluates whether all Veterans with PTSD can benefit from this new treatment.
Supporting evidence from MDMA-AT research
Phase II Studies
A Phase II trial tests the safety and feasibility of a new treatment. From 2004 to 2017, six Phase II MDMA-Assisted psychotherapy trials were conducted for PTSD treatment. All six studies demonstrated acceptable safety and promising initial efficacy results. The FDA, after reviewing all available data in 2016, granted Breakthrough Therapy Designation to MDMA-AT in 2017 and approved the designs of two Phase III trials that started in 2018.
Phase III Studies
A Phase III clinical trial tests how well a new treatment works compared with a standard treatment. In the first Phase 3 randomized, double-blind, placebo-controlled study of MDMA-assisted therapy, participants with severe PTSD were randomized to receive either manualized therapy with MDMA or with a placebo at one of 15 study sites.
At the primary endpoint, 67% of participants in the MDMA group no longer met diagnostic criteria for PTSD, compared with 32% of participants in the placebo group.
The results of this first Phase III trial of MDMA-assisted therapy in people with severe PTSD indicate that three sessions of MDMA-assisted therapy significantly reduced PTSD symptoms and functional impairment, compared to placebo.
Why do we need to fund rigorous MDMA-AT research in the VA?
With the significant and positive results of the Phase III studies and FDA approval on the horizon, it seems the next step would be for the VA to roll out treatment nationally. However, past efforts to scale PTSD psychotherapies within the VA have shown the need for larger clinical studies with Veteran participants.
Veterans experience more mental health and medical conditions simultaneously than the general public—which can make traditional PTSD treatments less effective in the Veteran population.
Veterans experience higher rates of PTSD, suicide, unemployment, homelessness, and incarceration than may be typical for research participants. As a unique demographic, Veterans need research prioritizing their needs – and we're here to fund that research.
Funding Veteran-focused research helps remove barriers in the VA
Funding Veteran-focused research in the VA means furthering the ability to identify systemic and practical barriers that may prevent widespread adoption. Currently, clinicians must see 30 veterans weekly and typically have 50-minute therapy appointments. It will take procedural and policy changes to move to six-hour sessions with two therapists for MDMA-AT sessions—which can only be identified through VA research.
MDMA-AT requires the correct physical facilities with the appropriate setting for treatment to work. These areas may be difficult to find in typical VA hospitals.
Focusing on Veteran participants for research studies provides VA clinicians with the confidence needed to believe these research findings apply to their patients and their needs.
What are some of the methodological challenges of doing MDMA treatment research?
MDMA-AT clinical trials are very difficult to conduct. Researchers have to contend with several unique sources of potential bias that may influence their results. Some sources of bias include:*
1. Hype
Positive media coverage of MDMA to treat PTSD e.g. these stories ABC News, CBS, Forbes, New York Times, Wall Street Journal, and Fox News have the potential to increase positive expectations in research subjects compared to other types of PTSD treatment.
2. Blinding
Blinding, or masking, means that the researchers do things to make sure that participants (and sometimes the therapists as well in double-blinding) don’t know whether they got MDMA or a placebo.
The problem is that the subjective effects of high-dose MDMA are often so pronounced that it is difficult to mask participants to their treatment conditions. To put it simply, participants usually know whether or not they received the drug, and that can bias the results. With all the hype around the medication, patients who know they are receiving MDMA will have greater positive outcome expectancy, which is associated with better treatment results.
Although it may look like the bias doesn’t matter as long as the patient receives MDMA, not having properly blinded studies affects our interpretation of how well MDMA-AT is for PTSD and for what populations it is appropriate.
3. Potential Comparators/Placebos
Given the difficulty of blinding subjects to experimental conditions, what makes for a good placebo in MDMA research? Ideally, we would have an intervention that patients have trouble differentiating from MDMA-AT, but without the active ingredient that provides therapeutic benefit.
Inactive placebos such as lactose have been used before, but the majority of participants (95%) and all of the therapists correctly guessed the condition assignment. Active placebo comparators have been used in clinical trials in which the control condition closely resembles the side effects of the experimental treatment without providing therapeutic effects. Therapy protocols and all of the procedures being the same have been done before, but it’s hard to find something that mimics the effects of MDMA without providing therapeutic benefits.
4. Lack of Attention to Implementation Context
In MDMA-AT research, two therapists are required to be present throughout the six-hour medication sessions. This may prove unrealistic in typical VA clinical practice. Studies also need to investigate the barriers and facilitators to successful adoption and inform efforts to scale MDMA-AT throughout the VA System.
How do we overcome these challenges to evaluate MDMA-AT in VA?
Methodologically rigorous studies of MDMA-AT in the VA will be necessary to establish whether MDMA-AT works for VA patients.
This means recruiting a large sample of Veterans with PTSD who do not have previous experience with MDMA, randomizing participants to condition, using an active control condition such as low-dose MDMA, and paying attention to the implementation context - i.e. how this innovative treatment can fit into existing processes of PTSD treatment.
Healing Breakthrough is currently focused on securing both public and private funding to support this important work.
*Aday JS, Heifets BD, Pratscher SD, Bradley E, Rosen R, Woolley JD. Great Expectations: recommendations for improving the methodological rigor of psychedelic clinical trials. Psychopharmacology (Berl). 2022 Jun;239(6):1989-2010. doi: 10.1007/s00213-022-06123-7. Epub 2022 Apr 1. PMID: 35359159