Many people do not inspect what is reported before forming an opinion or accepting someone else’s opinion. The actual results are certainly worth a look.

But I think we need to consider whether the authors even were asking the right clinical question.

By narrowly construing the trial as a test of the efficacy of MDMA for PTSD, the authors may have missed some limitations. The trial is NOT primarily being a drug trial, but more properly, a trial of a drug always being delivered in conjunction with a poorly specified and unproven psychotherapy.

I have some relevant background and expertise for forming an opinion about this.

I was involved in various stages of writing and reviewing grant proposals, applications for use of human subjects, and justifications for the burden that studies place on medical patients. I was a co-principal investigator on a center grant with the responsibility of developing and implementing psychosocial interventions combined with drugs. I served on the committee monitoring the progress of a major clinical multisite trial of treatment of depression to prevent heart attacks for safety and data quality. I was an external scientific advisor conducting process evaluations that might reveal what happened in trials for anomalous results.

I have never encountered anything at all like the psychotherapy manual for the Nature Medicine trial of MDMA for PTSD.

If you like, you can wade through the actual manual here, but it is very vague and demands of your time to get to crucial details. Or you can see how promoters describe the treatment in promotional material on their websites, including graphic videos.

I am a clinical health psychologist concerned with delivering the best treatment within the limits of scarce funding. That makes me a mental health services researcher. I am deeply concerned with the lack of assurance that the same psychotherapy was delivered across settings in the trial reported in Nature Medicine.

I could imagine making a bit of a fuss if I were on a committee to evaluate ahead of time whether a major clinical trial of MDMA, a drug that was illegal and otherwise unpatentable could depend on the validity of this treatment and whether it was faithfully delivered.

Basically, investors are asking for a monopoly because they will ensure the safety and efficacy of MDMA by embedding it in a package with their psychotherapy. They claim to be so convinced by a lack of evidence that MDMA is safe or effective outside of such a package. So much so that they will not bother to gather new evidence against the null hypothesis of MDMA being unsafe and ineffective for PTSD.

In the loose, informal atmosphere that occasionally develops in closed meetings, I could imagine my younger self reading juicy sections from the manual, and insisting on playing promotional videos to the committee from the 15 sites that were available to prospective participants during recruitment.

With some degree of mock seriousness, I might have asked whether different music might have elicited a different response from patients, whether the flowers and fake artifacts were necessary.

What if a patient did not welcome what was intended to be the soothing touch of a same or different gender person while under the influence of a disorienting drug and while possibly being stimulated to sexual arousal?

I could expect blowback and protests if I raised the last point. I would come prepared with documentation that sex with a patient had occurred in at least one MAPS trial and that the unlicensed counselor had pleaded, of course, that the sex was consensual.

This claim is outrageous without substantiation. I invite you to find it here. Psychedelic therapy has a sexual abuse problem

I doubt anyone involved in reviewing the data from the trial for the US Food and Drug Administration has ever seen such psychotherapy being proposed to accompany all marketing of a drug. I would love to hear the discussion the review will generate.

Claims that findings are groundbreaking, breakthrough, or otherwise extraordinary deserve more scrutiny and maybe even skeptics thinking longer and harder about what was going on in a study.

Many on social media assume that claims that have made it into a world-class medical journal no longer need to be vetted. They believe that they can take what is said about the psychotherapy in an article in an impressive journal with their critical tools to appraise the study being left in their toolbox.

I am not one of those people. I am hoping to convince some readers that they do not want to be that kind of person either. That is generally my goal in teaching and writing about clinical trials, but I think that the Nature Medicine article is a particularly good teachable moment. The authors and their backers are screaming so loudly and incessantly that there has never before been such a study.

I am getting some pushback to my skepticism about the trial, only some of which will be disclosed here. There has been an effort to stop the publication of my critiques and remove what I have published so far. If what I have written were patently stupid, I think that would be discovered soon or later and what I have published could be left published to embarrass me.

The threshold should be high for making an article disappear, rather than simply flagging with a statement of concern or retracting it.

I first probed a fawning New York Times article about the trial with improbable claims, obviously written with the collaboration of the Nature Medicine authors. I complained that the journalist should have protected readers by getting her own experts and by providing an independent critical appraisal.

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…medium.com

Next, I limited myself to a single sentence in the abstract of the Nature Medicine article. I wondered aloud why so few “experts” were speaking out about a reporting of this study that was so wrong in so many ways.

The MDMA-Assisted Therapy for PTSD Study: What You’ll Get Wrong
Seldom have so many experts had such strong opinions about an open-access drug trial they did not read carefully…medium.com

In the last installment, I focused on only the list of authors, the contributions that justified their getting authorship, and the authors’ affiliations. I concluded that there was good reason to treat the study not as strictly as a pharmacological trial but as a trial of psychotherapy in combination with either a drug or an inert pill-placebo. I proposed:

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.

Surprises in the Authorship of a Paper About MDMA to Treat PTSD
Some of the 39 authors practice alternative medicine and unvalidated psychotherapies, with little research experience

I am pleased that my intuitions have generally been confirmed that there is something wrong going on with the way the study is being sold. Yet, I wince at some of the things I have written and mistakes that may have been made. Even if I have been wrong in some respects, I could be on to something. We could reach a consensus that the study is flawed, at least enough to temper the authors’ claim made in the abstract and echoed all over the world:

“We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.”

The authors and their sponsors are pushing for expedited review and approval by the US Food and Drug Administration. This was hastily done with intravenous infusion of ketamine, which — as I covered here — did not go so well.

One reader,Julian Willet, MD is unconvinced enough by what I have been writing to post a comment:

Nature Medicine is a well-respected journal and generally decently trusted (though naturally, some papers can get through the cracks). Perhaps that occurred, but I cannot say. I skimmed the paper and the results are significant/impactful, which would make it an attractive paper to publish even if there could be potential controversy.

I asked the opinion of an expert statistician who has consulted on trials of psychedelics and he replied:

*I have read the results section a few times since published (and compared) to protocol. I would say that generally it looks sound and I would guess they have a professional statistician in the team or use a consultant. That’s from what I can deduce from the paper.

His comment left me self-doubting and defensive. I went back to the Acknowledgment section of the article. I counted the number of therapists listed. I replied to him, “What if there are 40 therapists?”

Suffice to say, that reply changed his mind and got him doubting too.

Only as I sat down to write this article, did I realize the implications of what I had written to him.

The Nature Medicine article portrayed the clinical trial as evaluating whether MDMA was superior to an inert pill-placebo under tightly controlled conditions. It would be reassuring to know if the results did not vary across the clinics and providers, but we probably should not expect any surprises.

It is simple enough to standardize the providing of a pill and not expect much variation across sites and providers. Not so with psychotherapy that is so incompletely specified. I expect lots of variation in how the psychotherapy is implemented with which patient, with which therapist, in which setting.

The trial is initially blinded so that neither the clinician nor the patient knows whether the patient is assigned to get the MDMA or an inert substance in an identical capsule. The trial quickly becomes unblinded in the first half-hour of the first eight-hour session. There are three such sessions. I would be especially concerned with the improvisation that would occur once the patient and therapist knew whether the patient was getting the MDMA.

I do not have to prove my skepticism is correct. The burden is on the authors of the Nature Medicine article to prove me wrong. They are facing an evaluation by the FDA with a lot at stake.

Stay tuned and we will probe the Results section, aided by the lens I have developed in this article.

The post Before Looking at the Results of the Paper on MDMA to Treat PTSD… appeared first on Medika Life.

Newspapers are a key venue for the promoters to make their case to convert laypersons into consumers in what is projected to be a multibillion-dollar industry.

Should newspapers take on this function to signal that their brand is more avante garde than their stodgy competitors? Or is it newspapers’ job to filter the information they are given and take a critical stance in order to protect their readers?

Arecent article is one of a number in the New York Times covering what is claimed to a breakthrough in the acceptance and use of previously illegal drugs.

Click on this link to the article, preferably on a desktop computer to get the full effect.

A Psychedelic Drug Passes a Big Test for PTSD Treatment. A new study shows that MDMA, known as Ecstasy or Molly, can bring relief when paired with talk therapy to those with…www.nytimes.com

You will see the opening of the article displayed as a bold split-screen ribbon that takes over your entire screen display. One blackened side with white font announces the psychedelic drug MDMA has passed a “big test” as a treatment for PTSD.

The other side is a slick photo that has been shot at an upward angle that might be used for the trailer of a Netflix movie being released next week. A caption indicates that the buff traditional male was a patient in the PTSD clinical trial, not a paid actor.

He is quoted as describing the effects of the drug: “Literally I’m a different person.”

Many readers will relax and be entertained by the article. The article is from the Health section of the NY Times. It might fit better in the Leisure or Entertainment sections.

Some readers might be seeking something other than entertainment and might feel cheated.

Once upon a time, I recommended the NY Times as a trustworthy, authoritative go-to place for intelligent laypersons without the skills, time, or resources to evaluate scientific and medical claims for themselves that might impinge on their well-being or wallet. I stopped when I repeatedly saw prominent journalists publishing fawning reports of the products being offered by positive psychology TED talkers and other wellness wannabe advice gurus.

The NY Times journalists were acting like publicists and were not appropriately critical interpreters of what the gurus were trying to sell us.

Let’s analyze this article and see if we should similarly be skeptical about the promotion of psychedelic drugs in the NY Times, but let’s keep the task simple.

We will give a lot of attention to four large, high-quality staged photos.

These photos represent four of the seven named sources who are quoted. I will comment on how the seven are quoted. I will briefly bring in my other reactions.

I am encouraging readers to be skeptical about what is conveyed in the article if they are making any decisions about their health and wellbeing or for what readers should tell others, as on social media.

Scroll below the banner introducing the and you find it the article is about a peer-reviewed report in one of the most prestigious scientific journals, Nature. However, no link is provided to the paper because it is not yet published. We will have to rely on what the journalist tells us about what is in the paper, assisted by the sources she brings into the article.

Some readers might cry foul at this point. They believe that newspaper articles should provide a link to important papers being discussed so that motivated, sophisticated readers can check what is being said in the newspaper.

Savvy readers might even note that scientific journals often protect their own reputation and the lay public from misleading statements in newspapers by placing an embargo on newspaper accounts until the scientific article is published.

Let’s proceed anyway, and decide whether it is a good idea to rely on the NYT article by itself.

The NYT article introduces its Source #1, a neuroscientist at Johns Hopkins University. He gushes that he is “excited as he gets” about a clinical trial and that this trial is like no other.

The journalist assures the readers that Source #1 is credible because he was not an author of the forthcoming Nature report of the trial.

It does not take much of a Google search to find that Johns Hopkins University is the recipient of millions of dollars from foundations like the one that funded the study. You can also search and find an article where I marveled at the capability of Johns Hopkins University to mount a publicity campaign for papers reporting research on psychedelics.

After some more praise of the research, the NYT journalist brings in the first author of the study as Source #2. Describes as a neuroscientist, she informs us of her delight that now is the first time in 50 years that people are willing to consider psychedelics as medical treatments.

This statement is followed by a large photo of Source #2 that is attributed to the NYT, again dominating an entire desktop display of the article. She is dressed in black and wears a floral kerchief that matches a jungle-like backdrop of lots of probably artificial flowers. The photo is striking, but ambiguous in its message. Certainly, the NYT and the author are opting out of portraying the author as a whitecoat investigator of medications.

Next, readers are introduced to Source #3 who is described as an emeritus professor and the former chair of psychiatry at a prestigious medical school. He complains that:

“All new treatments in medicine have always had a temporary halo effect by being new and by promising more than they can deliver.”

That is the signature statement that this particular expert offers all the time in social media. He is known to be critical of overdiagnosis and overmedication of mental health problems. We cannot be sure how this quote came about. There is no indication that the journalist provided him with a copy of the embargoed article by or invited him to make further comment, as would be customary.

The NYT article has at least provided its obligatory dissenting voice before returning to comments of Source #1the first author of the study. She explains that the study was not an evaluation of a drug but a treatment package in which the drug is combined with psychotherapy. She theorizes that the combination allows “the brain to process painful memories and heal itself.”

This explanation is elaborated and amplified by Source #4, the senior (last) author of the paper. He hints the therapy is intensive and demanding and indicates that the patient must be motivated to work on their traumatic experiences to benefit.

The therapy starts before the patient is given the medication or the placebo to prepare the patient for the experience if they are provided the medication, rather than the placebo, Patients are told to expect from the medication, they will quickly know which condition they have been assigned.

Source #4 acknowledges that participants and clinicians should be blinded to the condition the patient is assigned throughout the trial and the final assessment of outcome. This is so the results can be considered unbiased and valid in the Food and Drug Administration approval process. Source #4 dismisses objections that patients quickly becoming unblinded in this study, by simply saying that this is not a problem.

Newspaper accounts routinely quote senior authors about the purpose and results of the clinical trial that they have overseen. Experienced journalists expect senior authors to be boastful and self-congratulatory and may protect readers by challenging the senior author directly or introducing a dissenting expert. However, Source #4 is also the founder of the funding source for the trial and he has raised over $100 million in two years to promote acceptance of the use of psychedelics as medical treatments and in spa treatments.

Normally, representatives of funding sources are not included as authors on papers reporting clinical trials. Instead, the articles acknowledge who funded the trial, but declare that the funding source had no say in the analysis and interpretation of data.

This is not a typical clinical trial and the NYT including commentary from a funding source is not normal.

It is not reassuring that the funding source is a nonprofit corporation, any more than it is reassuring that other sources who are cited are described as not involved in the conduct of the study when their institutions also receive substantial money from similar foundations.

Source #5 is identified as the patient in the study who was introduced in the first banner display that opened the NYT article. He describes the vivid nightmares that dominated his life before the study and how nothing he tried could free him from them. His life was in ruins.

Then, Source #5 described the treatment sessions he received in the trial:

During his first of three sessions in early 2019, lying on a couch with eyeshades, and in a lucid dreamlike state, Mr. Ostrom encountered a spinning, oily black ball. Like an onion, the ball had many layers, each one a memory. At the center, Mr. Ostrom relived the moment in Iraq, he said, that “I became the person I needed to be to survive that combat deployment.” Over the next two sessions, Mr. Ostrom engaged with “the bully,” as he calls his PTSD alter ego, and asked permission for Scott to return.

Source #5 describes how he is now gainfully employed and owns a house, that he shares with a girlfriend and a service dog named Tim.

Readers do not have a basis for disputing Source #5’s personal account of his lived experience of suffering and miraculous cure. Many readers will find it an inspiring story, maybe even suitable for re-telling in a Netflix film.

But skeptics can point out that such vivid, retrospective subjective experiences are not retrieved from their storage as accurate accounts of what happened. Memories are shaped by retelling and suggestions from the later environment. Source #5’s subjective experiences are not generalizable facts, in the sense that we can expect to hear from other persons who suffer from PTSD. Unless we cast aside all skepticism, we cannot accept his accounts as validating the theoretical accounts that proponents of psychedelic treatment want us to believe. After all, the therapists in the study prepared patients to expect certain experiences and coached their interpretations of their experience while under the influence of the drug.

This account is immediately followed by a full-screen photo of the earlier Source #4, the enterprising senior author and creator of the foundation that raised millions for this ambitious initiative.

Let’s put that aside and focus on what the photo conveys.

I see what could be a rented attic apartment. It must be a cheap place, because the wall is stained, perhaps by a serious leak in the roof. There is an air conditioner that is crammed into the window and an inexpensive ventilation fan. The room is quite messy and could use a good cleaning. The man is sitting cross-legged on the floor and vaguely smiling. He is either entertained by what is watching on a vintage TV or oblivious because of his altered state of consciousness.

I do not know what to make of this, except that is a sharp contrast to the portrayal of the first author in her junglelike background and this man as the head of a flourishing nonprofit foundation.

Some seemingly factual information about the history of MDMA follows, interrupted by a cockamamie theoretical orientation of how MDMA-assisted therapy works that cites a mouse study as evidence:

Its primary therapeutic effect may come from its seeming ability to reopen what neuroscientists refer to as a “critical period,” the window during childhood when the brain has the superior ability to make new memories and store them.

Maybe, but who can know? My skepticism is getting the best of me. Anyway, we may be reaching a saturation point in not being able to learn anything new from further exploration of the photos and sources selected for the article.

I should leave readers on their own to form judgments on their own about Source #6, except that I will point out that he is a junior qualitative researcher at Hopkins, of course not an author of the study. I don’t know how he has the expertise to declare that

The findings ‘make a clear case for medical approval,” something that “represents a sea change that could revolutionize health care.’”

I can’t help commenting on Source #7, a patient who says the MDMA-assisted therapy allowed him:

To revisit his traumatic memory through the eyes of his 4-year-old self, unclouded by stigmas, adult interpretations, or heavy emotion.

“This allowed me to accept myself and recognize who I am,” he said.

The final of the four photos depicts Source #7 in a magical forest of tall trees and no underbrush, looking skyward. Perhaps he has found his Own Private Idaho.

“My Own Private Idaho” is an imaginary place where one is locked in the arms of love — that is, both protected and free. It is the promise of America, chronically out of joint with reality, especially for its most vulnerable inhabitants.

The NY Times invested a lot in producing this article so slickly. I am sure the promoters of psychedelics were pleased with what their collaboration and granting of access to patients accomplished. Maybe readers were entertained, but what did they learn?

The post Is the New York Times a Shill for Promoters of Psychedelics? appeared first on Medika Life.