Best of The Neuroethics Blog: The Army’s on Ecstasy: Marching Toward an Ethical Drug Policy

Over the past year, The Neuroethics Blog has been highlighting the most impactful, exciting, and popular posts from our nearly ten-year history.

Today's post is an update by Dr. Jordan Kohn on his piece The Army’s on Ecstasy: Marching Toward an Ethical Drug Policy, which was originally published on October 3, 2012.

Image Courtesy of Pixabay

It’s hard to believe that over seven years have passed since authoring the Neuroethics Blog post, The Army’s on Ecstasy: Marching Toward an Ethical Drug Policy. At the time, initial results from the first Phase II randomized controlled trial (RCT) using MDMA-assisted psychotherapy for treatment-resistant post-traumatic stress disorder (TR-PTSD) had just been published (Mithofer 2011). More broadly, psychedelics research, which includes the use of classical hallucinogens (e.g., psilocybin, LSD) to treat opioid addiction, major depressive disorder, and end-of-life anxiety, was slowly metamorphosing from a larval stage into mainstream, biomedical maturity. In that article, I’d discussed the psychotherapeutic mechanisms by which MDMA was believed to mitigate PTSD, had provided a brief history of MDMA-related drug policy, and examined how the federal government had, wittingly or not, stifled scientists’ attempts to explore the therapeutic effects of psychedelics for individuals suffering from psychiatric illness.

Since late-2012, there have been massive developments in this space, and I’ve had the good fortune and opportunity to remain connected to it. Here are three questions that deserve attention: (1) what do the data show? (2) how and where is the field progressing? and equally important, (3) how has broader society responded? In this post, I’ll address each of these questions in turn, and provide my own perspective based on observations and interactions I’ve had with members of the ‘psychedelic neuropsychiatry’ community over the preceding years. 

Background: As discussed in my previous post, the imperative for exploring alternative treatments for PTSD was based in part upon alarming rates of military veteran suicides, which are approximately 50% higher than non-veteran US adults, but have not worsened through 2019 (however, population-wide ‘deaths of despair’ – often suicides – have dramatically increased). Given the high lifetime prevalence of PTSD in the general adult population (estimated at 6-9%), which can emerge following sexual assault or social conflict, as well as the frequent failures of conventional t

reatments, and PTSD-associated health complications, such as increased cardiovascular disease risk, the need for novel, effective treatments persists. Enter MDMA.

Methods: Most inquiries by US-based researchers into the biomedical literature begin on PubMed. A cursory search of peer-reviewed journal articles over the last five years using the terms “MDMA PTSD” yielded over fifty publications on the topic as of February 2020, which include results from randomized controlled trials (RCT), case studies, meta-analyses, and reviews in high-impact journals, including Journal of the American Medical Association (JAMA) and Biological Psychiatry. Furthermore, at least eleven MDMA-specific clinical trials are currently recruiting subjects across North America. An even broader PubMed query of “psychedelics psychiatry” returned over 650 results since 2015, with the same terms on ClinicalTrials.gov indicating fifty actively recruiting trials in the US. Clearly, the field has been, and remains, very active. 

Image Courtesy of Pixabay

Results: Academic literature aside for now (see below), I was able to gain first-hand insights into recent developments in this space through my attendance at the American College of Neuropsychopharmacology annual meeting in December 2019. This particular meeting is more clinically-focused than others I attend, with many neurologists and psychiatrists in attendance, and to my surprise, the proceedings included two, 2.5 hour-long panel discussions on the topic of psychedelics to treat neuropsychiatric conditions. From what I recall of the aforementioned Dr. Mithoeffer’s presentation, six Phase II clinical trials of MDMA-assisted psychotherapy for TR-PTSD have been completed over the last 12 years or so, totaling over 1,400 MDMA administrations, with durable (>12 month) Clinician-Administered PTSD Scale (CAPS) score improvements far exceeding therapy-only comparator groups, and no adverse serious events (ASE) reported. Evidence for improvements in secondary mental health measures, such as depressive symptomatology and sleep quality, is also compelling.

While the field has a number of champions and advocates justifiably ringing the bells of a ‘renaissance,’ others remain cautious, particularly given preclinical studies in mice suggesting that MDMA, in high doses, could be neurotoxic, and case studies in humans that report psychological complications, such as psychosis, panic, or amnesia following single-use (discussed in Schenk and Newcombe, 2018). It is important to point out, however, that the developing guidelines for administering MDMA would mitigate most, and likely all, of these complications, as the compound would only be consumed within clinical settings under the close supervision of healthcare providers, following extensive pre- and post-session psychotherapeutic preparation. In other words, patients are visiting their psychotherapist or psychiatrist or psychologist, not their local pharmacist, for treatment. 

Future Directions: Back to the Phase II data. So impressive were they, in fact, that the Food and Drug Administration recently awarded Breakthrough Therapy Designation, an expedited drug development pathway, for MDMA-assisted psychotherapy due to its demonstration of substantial improvement over available pharmacotherapies (Feduccia et al., 2019). Furthermore, in mid-January 2020, the FDA approved an Expanded Access program for ten treatment sites conducting MDMA trials, allowing trained providers and their patients who are unable to participate formally in the Phase III trials to utilize the therapy. The Multidisciplinary Association for Psychedelic Studies (MAPS), led by Rick Doblin, anticipates that continued success and completion of Phase III trials will lead to FDA approval as early as 2022, potentially a full year ahead of his expected timeline from our conversation for the Blog in 2012. 

As public and private funding for psychedelic research expands, academic institutions have strengthened their commitments as well. For instance, Johns Hopkins University has recently launched the Center for Psychedelic & Consciousness Research, with a “focus on how psychedelics affect behavior, mood, cognition, brain function, and biological markers of health.” As of November 2019, two private research groups (Usona Institute and Compass Pathways) had also been awarded Breakthrough Therapy Designations for their psilocybin medications in Phase IIb trials of treatment-resistant depression. If the results of these trials are as promising as those of the Phase II work in MDMA, it’s likely that psilocybin will also be awarded FDA approval in the coming years. 

Image Courtesy of Pixabay

Society and Ethics: Both the media and the public have been aware of these promising clinical findings. Major media outlets, from Time Magazine to The New York Times, have written articles on the topic, as have prominent authors (see Michael Pollan’s search for transcendence through psychedelic experimentation in “How to Change Your Mind,” and Ayelet Waldman’s attempt to modulate her emotional landscape using micro-dosed LSD in “A Really Good Day: How Microdosing Made a Mega Difference in My Mood, My Marriage, and My Life.”) Ceremonial use of ‘plant medicines’ is also growing. Throughout major metropolitan areas, one can now find “psychedelic integration” or “medicinal mindfulness” groups, where people gather discuss their experiences and support each other’s responsible use, as well as psychedelic psychotherapists. These facilitators, and their clientele, approach psychedelic sessions with distinctly different intentions from recreational users, which has important implications for harm reduction. My own informal conversations with non-scientist friends and acquaintances have revealed enthusiastic self-experimentation by many to address their psychiatric and neurological ailments, from depression to cluster headaches. Beyond clinical purposes, others have incorporated psychedelics as an adjuvant to their own spiritual or religious practices. In fact, an ongoing, open-label pilot study seeks to determine the effects and possible utility of psilocybin-facilitated experiences for professional religious leaders. This is a particularly interesting and underexplored area of research, and could be translated into the treatment of risk factors for clinical comorbidities, such as loneliness in older adults or physician burnout.

For now, most researchers are keeping their ‘eyes on the prize’ and constraining their focus to mitigating severe mental and physical illnesses through the use of psychedelic-assisted psychotherapy. However, interesting topics beyond psychiatric disorders have begun to emerge, particularly in the field of disorders of consciousness (DoC). These disorders, which include devastating forms of impairment, such as a persistent vegetative state (PVS) or minimally conscious state (MCS), that follow acute brain injury and are extremely difficult to treat. One group has recently proposed administering psychedelics to these patients (Scott and Carhart-Harris, 2019), which presents ethical issues related to consent and the inability to communicate adverse psychological events (see Peterson et al., 2019). As psychedelics research continues to develop, other issues that are common to biomedical ethics, such as equity (see Michaels et al., 2018 for review of inclusion of under-represented minority groups in clinical studies of psychedelics), will need to be addressed. In summary, it is an exciting time for the field of psychedelics research, and MDMA-assisted treatment for PTSD, specifically. At the moment, it appears that academics, regulatory agencies, and the public have adopted a more clear-eyed perspective of risk-benefit tradeoffs in the psychedelic medicine space, and have opted to proceed with exploring their clinical utility to mitigate the social and economic burden of hard-to-treat neuropsychiatric illnesses.

______________

Dr. Kohn is a Postdoctoral Fellow in the Department of Psychiatry at the University of California, San Diego. His primary research interests lie within psychoneuroimmunology, particularly understanding disease-modifying biobehavioral mechanisms in the contexts of aging, metabolic dysfunction, psychosocial stress, and psychiatric illness. His work focuses on further understanding the mechanisms by which behavioral interventions, such as Tai Chi, exercise, and compassion meditation training, influence disease outcomes and in utilizing those insights to optimize treatment strategies. Dr. Kohn is currently involved in projects evaluating empathy and loneliness in improving psychological and physical health outcomes.

Want to cite this post?

Kohn, J. (2020). Best of The Neuroethics Blog: The Army’s on Ecstasy: Marching Toward an Ethical Drug Policy. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2020/04/best-of-neuroethics-blog-armys-on.html