There is also a surprise key person among the authors of the Nature Medicine article — a mastermind, if you would like — behind the design, interpreting, and reporting of the psychotherapy aspects of the trial whom I would not have expected.
This author has built a reputation on his disdain for evidence-based psychotherapies. His books and workshops promote questionable psychotherapies with dubious mechanisms of mind-body interactions, backed up by dramatic anecdotes, not evidence.
Who could that be?
This revelation only encourages me to examine the trial more closely as an evaluation of psychotherapy combined with medication — not as primarily as a drug trial, as most everyone else has been doing.
This reframing involves a very different set of criteria that could expose a different set of inadequacies in the trial of MDMA as a treatment for PTSD — such as the lack of standardization of the therapy across settings and therapists.
Nature Medicine is among the most prestigious medical journals in the world. It seldom publishes clinical trials and never before has published a trial of a medication combined with psychotherapy.
I have already been discussing my concerns about this clinical trial in two Medium articles.
Is the New York Times a Shill for Promoters of Psychedelics? Evidence that the newspaper is not sufficiently detached from promoters to provide an open-minded but skeptical.
The Nature Medicine article is available open access, meaning you can view it for free.
Mitchell, Jennifer M., et al. “MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study.” Nature Medicine (2021): 1–9
Clicking on the link takes you to the article on the website, where you can also download a free PDF. However, if you just read the article on the website, the authors are listed like this:
Click on the […] at the website and it expands to the full list of 39 authors.
That number of authors in itself is mindboggling, especially when you consider that 39 is the number of patients assigned to pill placebo who completed the trial. That ratio of authors to patients in a clinical trial is extraordinary.
Check out the list of authors’ affiliations and their specific contributor statements available in the article that justified awarding authorship. You will find some real surprises.
I will touch on some of these details before ending with a bombshell revelation that changed my thinking about this study, raised my already high level of skepticism about it, and pointed me in some new directions in probing the study.
The 39 authors list 25 different affiliations, of which seven are academic medical settings with research capacity. Authors’ academic degrees are not listed in the article, but a Google search reveals few MDs and fewer psychiatrists. Only a few of the MDs list university medical affiliations.
Four authors list the same academic setting as their affiliation. One is the Ph.D. neuroscientist who is the first author. The other authors in that setting are the Ph.D. regulatory affairs coordinator and an internist and an assistant professor MD Ph.D. who is in residence at a nearby Veterans Administration Hospital.
Beyond the other six academic medical settings that are each listed by one author, there are some interesting affiliations.
The largest number of authors (12) are with the MAPS Public Benefit Corporation, San Jose, California. The for-profit corporation will manage sales for prescription MDMA when it is approved by the Food and Drug and Administration. For now, the corporation provides training for therapists as well as:
A team of wonderful night attendants who stay with study participants at the clinic during the required overnight stay following MDMA sessions. The night attendants continue the care and support of participants by delivering or preparing dinner and breakfast, setting up their sleeping arrangements, and remaining available throughout the night should participants need anything at all. During this time, the therapy team and study physician remain on call should there be any problems or concerns.
Most affiliations are for only one or two authors and seem to be private practice settings awaiting approval of psychedelics by the FDA. Their names are suggestive of particular kinds of mystical spa experiences: Zen Therapeutic Solutions, Fluence (defined as a mysterious, magical, or hypnotic power), Nautilus Sanctuary, Wholeness Center, and the San Francisco Insight and Integration Center.
Some of these settings currently — or will in the future — offer spa experiences for people without requiring a diagnosis of a psychiatric disorder. At Aguazul-Bluewater, Inc, one of the authors of the Nature Medicine article offers Rolfing Structural Integration sessions.
In the relaxed biographic sketches provided at their affiliations, a number of authors express the intention to use prescription MDMA not as a formal mental health treatment, but for wellness treatments administered in spa settings specializing in alternative medicine.
Some of the authors of the Nature Medicine articleespouse the use of psychedelics as a transformative experience conceived as an integration of mysticism and neuroscience that is decidedly outside the range of testable and disprovable scientific explanation.
Many of the authors are clinical psychologists who are not quantitative research scientists, but who instead dabble in impressionistic qualitative or mixed-method research related to psychedelics.
I did not see or endorsements of conventional, evidence-based therapies in any of the authors’ personal statements. I found abundant references to the view of personal change as a mystical or spiritual experience somehow involving neuroscience and the brain, but not really spelled out in conventional scientific terms.
It is safe to say that these clinical psychologists do not confine the psychotherapy they offer for PTSD to the manualized treatments with the strongest scientific support, exposure, and cognitive reprocessing therapy. That would be just too stifling and downright boring, especially given the exciting transformative experience that psychotherapy is supposed to provide.
What does it mean to be listed as an author on an article in a highly selective, prestigious medical journal like Nature Medicine?
It is generally understood that authorship on scientific papers requires an intellectual contribution to the conduct of research. In addition, an author must take responsibility for the final version of the paper that will appear in the journal.
I am “only” a clinical psychologist, and I do not have an M.D. Critics might say I am hypocritically pretending to be more scientific than these authors in calling for a more rigorous, i.e., medical approach to this treatment.
The Nature Medicine article presents the case that MDMA is an amazingly effective treatment for PTSD, yet also that it is potentially so dangerous and subject to abuse that it must remain a prescription-only drug delivered under the supervision of a physician.
MDMA has been around for a while and cannot be patented. The Nature Medicine clinical trial tests a packaged delivery system in which the drug augments or facilitates psychotherapy that is said to dramatically reduce the suffering and burden of PTSD.
No one is claiming that taking MDMA by itself is effective in treating PTSD. There is ample evidence to the contrary. So, what is the nature of the psychotherapy that is presumed to allow MDMA to achieve its therapeutic effect?
The psychotherapy offered in this trial is not presumed to be effective in treating PTSD by itself, without MDMA. There is no prior evidence that the particular psychotherapy administered as part of this trial as effective for any clinical problem in any situation.
Although it has been given little attention in the enormous press coverage that has been given to the trial reported in the Nature Medicine paper, a lot depends on the credibility of the psychotherapy provided in the trial. At stake are hundreds of millions of dollars already invested in what is expected to be the multibillion-dollar business of marketing prescription psychedelics plus psychotherapy in a package ensuring their safety and effectiveness as mental health treatment and pleasurable spa experiences.
If MDMA is not patentable, why not patent the package of the drug plus less expensive psychotherapy with greater evidence of efficacy as a mental health treatment, like a modified version of exposure therapy?
Enter the mastermind behind the psychotherapy being offered in this trial
The intellectual responsibility for this parrticular psychotherapy as it is described in the Nature Medicine article largely depends on the nineteenth author, psychiatrist Bessel van der Kolk.
According to the author-contribution statement, Bessel can de Kolk (KvdK) has unrivaled contributions to the article.
BvdK was among the four authors having full access to all of the data in the study and taking responsibility for the integrity of the data and the accuracy of the data analysis. Other contributions attributed to him include the basic design of the study. He was among the authors who collected the data and carried out sponsor oversight of data collection. He was part of the group that carried out statistical analysis and interpretation of data.
He was among the four authors who drafted the original paper. He was a member of the larger group critically revising the paper for important intellectual content.
The two contributions not listed for BvdK are obtaining funding and carrying out supervision and training.
Outside of this trial, BvdK has an enormous following among credentialed and non-credentialed therapists and counselors, as well as a substantial proportion of laypersons who believe their lives have been impacted in a profound way by adversity and trauma. He has sold millions of copies of popular books worldwide, his workshops draw large crowds, and his videos get huge traffic on YouTube.
Yet, many research-oriented mental health professionals consider BvdK a popularizer, not a research-oriented clinician-scientist. Many of us experience enormous frustration with his talks and writing. He promises too much from unproven psychotherapies. Lasting change does not necessarily come with such theatrics as he suggests.
BvdK denigrates scientific evidence and well-established evidence-based therapies. At the same time, he presents unproven somatic therapies and discredited therapies such as tapping and emotional freedom techniques in vivid anecdotes in which miraculous results never fail to be achieved in dramatic, sudden moments of therapist intervention.
BvdK’s best-selling books, like The Body Has its Reasons, present discredited theories like Polyvagal Theory and Mirror Neuron Theory in simplistic terms. Rebuttal and refutation by experts would require long technical explanations that would bore lay audiences to tears and put them to sleep.
Not everyone would agree with me, and certainly not even all evidence-based clinician-researchers. Yet, I think I could muster a considerable consensus that BvdK’s depictions are not to be trusted of the research status of psychotherapies and the scientific status of their presumed basic mechanisms of change.
Such skepticism is just a useful starting point. We might have to revise our opinion with a closer look at the Nature Medicine article, its supplementary materials, and the enormous publicity its authors have so skillfully orchestrated.
Regardless, there are big questions:
How can a drug which is ineffective when simply taken by itself be combined with a psychotherapy without evidence of effectiveness as a standalone treatment to yield results in the treatment of PTSD that have never before been seen?
What if the FDA approval of the marketing of the previously illegal street drug Ecstasy as a treatment for PTSD is restricted excuslively to the drug being delivered with a psychotherapy that was developed under the supervision of Bessel van der Kolk?
That would be very strange, but there is a lot of startup funding betting on that possibility. The Franchising of specialty clinics has already begun.
We will have to see how FDA grapples with whether to tie the marketing of a drug to a specific psychotherapy — or is open to continued experimentation with other packages, breaking the monoply of MAPS.