Autumn reflections

Thursday, September 19, 2024

Kevin Balktick

Founder + Director

Horizons: Perspectives on Psychedelics

“I have made this longer than usual because I have not had time to make it shorter.”

Blaise Pascal, “Lettres Provinciales” (1657)

A long journey

This is a long letter, and quite unlike anything I have published before.

In general, I have been more comfortable allowing our conference’s overall program and individual speakers to define the story.

However, this has been a season of reflection for me, and I felt that this was the right moment to distill and share the view from my desk.

The FDA advisory committee’s public hearing and vote in June followed by the FDA’s decision in August to not approve the application for MDMA have been greatly disappointing for advocates of psychedelic medicine.

These events, combined with the ensuing media cycles and their downstream effects, have cast a cloud over this entire field. For many individuals and projects, the consequences have been significant, and difficult.

While I have read quite a few reactions from the perspective of drug development and regulation, I wanted to add a longer-term and more personal viewpoint.

First, a disclosure: I have been honored with a leadership role at the Psychedelic Science 2025 conference. This is separate from my work with Horizons. Like all MAPS board members and staff, I have no financial relationship with Lykos or material interest in the approval of MDMA. Nor do I serve as a spokesperson for MAPS. The views expressed below are my own.

So, what follows is a little long and sometimes wanders a bit far afield, but some things deserve more than bullet points or “posts.”

Gratitude

I want to start by expressing my love for autumn in New York.

The freshness of the back-to-school season that follows Labor Day has always felt more like the new year than January 1. The city is alive with cultural events of every stripe, and very soon, the Catskills and Adirondacks will turn into a kaleidoscope of leaves for a few glorious weeks.

Next, I want to again share my gratitude for everyone who has gone on the journey with Horizons through its many chapters of growth and transition. Thank you to everyone who remained loyal and joined us in New York in May following our stumble in October, and to all of the new friends in the Pacific Northwest who have warmly welcomed us to Portland over the last few years.

Updates about our 2025 conferences and the future of Horizons will emerge at some point this winter.

Bittersweetness

Since 2007, we have held sixteen Horizons conferences in New York City and two in Portland, Oregon. Save our most recent event in May, all of them have been held in the fall.

This autumn, I feel a little sad to not look forward to the rustle of seats filling in the morning, the applause and release at days’ end, and the glow of long evenings full of dinners and parties.

But, there is also some relief. Large event projects are a heavy burden to carry. It is stressful to balance the quality to which we aspire with the limited budgets available, particularly while navigating the politics of a very passionate community.

So, while the absence of the autumn conference tradition is disappointing, it has also been a joy to fill the season’s evenings and weekends with people, rather than the glow of the screen.

Multiplicity and singularity

At Horizons, I have endeavored to illuminate many views of the psychedelic ecosystem, including its multiple present realities, the shifting views of its past, and its numerous possible futures.

There are many worthwhile lenses to see through beyond the narrow (if noble) spectacles of science and medicine. And of course, as Americans need periodic reminding– the U.S. is not the only country in the world.

So, before going any further, I would like to pay sincere respects to the world’s many nations and cultures; the federally protected use of sacraments by Native Americans; religious freedoms established by UDV vs. USA; the statewide regulatory systems of Oregon and Colorado; the nebulous questions of ketamine; and of course, the 30-ish million living Americans who have used psychedelics.

Having said that, in the below, I am addressing the model of FDA-regulated medicine in the U.S. that holds sway over the current discussion of psychedelics among our conference’s audience.

Bitterness

As you no doubt had already heard before opening this letter:

In August, the FDA declined to approve the application by Lykos Therapeutics for MDMA-assisted therapy for PTSD based on the presented evidence to date, and instead recommended that Lykos complete an additional study.

MAPS formally filed with the FDA to begin this research in 2001. More than two decades of research culminated in two Phase 3 studies (1, 2) published in Nature Medicine.

In its New Drug Application, Lykos presented the FDA with evidence that the treatment met the requisite efficacy and safety outcome measures established in the trial’s Special Protocol Assessment, which was approved by the FDA in 2017 following years of preliminary studies.

So, in August, many of us hoped that in light of these findings and the path seemingly set by the FDA, MDMA might finally step through the gate and into the garden of regulated medicine.

Instead, MDMA is being asked to wander in the desert for another set of years, and only approach the altar once again after it has performed the ritual of a third Phase 3 study.

While we do not know the FDA’s official rationale for their response, and thus cannot truly assess or debate whether their decision is well or poorly justified, from a larger, less administrative viewpoint– the present situation certainly seems unjust.

MDMA has been known since the 1960s and in widespread circulation for nearly three decades. Its properties and risk profile are well-known and documented. The body of scientific evidence for its utility as an adjunct to therapy is substantial, in addition to extensive study of its naturalistic use. Millions of Americans use MDMA each and every year. Its popularity has not led to a public health crisis.

The Dutch Ministry of Health, Welfare, and Support recently arrived at similar conclusions in an official report published in May.

Accepted medicines and treatments are not expected to work universally or uniformly, or to be without risk or complexity, or even for their mechanisms to be fully understood.

While further study would (and hopefully will) further explore these themes, on the basis of evidence at hand, it seems reasonable to grant MDMA entrance to the pantheon of FDA-regulated medications available for use under the direct supervision of a clinician.

The blessing of the FDA approval graces amphetamines, cocaine, fentanyl, morphine, ketamine, and numerous other drugs that– despite sometimes checkered histories and known risks– doctors are permitted to use at their discretion and accountability in service of their patients’ health.

In time, we may learn more about the FDA’s decision if Lykos elects to share the details of the Complete Response Letter. The scientific community would surely benefit from this knowledge, and it would enable a more fulfilling discussion of the decision. For now, we are all, myself included, simply speculating.

Regardless of the quality of the FDA’s response— the disappointment that many patients, care providers, advocates, and community members are feeling is very real. The aftermath has been a bitter season. Many who work in this field have experienced days filled with brutal headlines, hard conversations, tough decisions, ruined plans, and the inevitable emotional toll.

We took the risk of daring to hope, and are now reeling from an adverse reaction.

Outside looking in

We can’t say we weren’t warned. The spectacle of the FDA advisory committee’s public hearing in June was a reminder of the world outside the psychedelic echo chamber.

The external advisory committee was convened at the end of the public hearing. The advisors were primarily without conflicts of interest in the field of psychedelics. They also seemed to be without much knowledge of it at all. This is an area of study whose scholarship goes back a century, and includes decades of peer-reviewed studies and commentary.

The day’s carefully prepared information packet– with its intended focus and boundaries, criteria for approval evaluation, specific prompts for discussion, references to protocols, data and measures, Lykos’ briefing and presentation, as well as the FDA’s own draft of guidance for psychedelic trials– was unceremoniously cast aside in favor of ad hoc criticism.

In my viewing, it seemed that both Lykos and the FDA itself were expecting a more erudite discussion and were genuinely surprised by what unfolded.

While I might have begrudgingly respected a sincere and well-informed skeptical discussion about trial design for drugs that are susceptible for functional unblinding, or the unique challenges of a new treatment model that combines both a drug and psychotherapy, it seemed to me that many of the advisors were not eager to engage with the studies and data in any meaningful way.

There are others who have written commentary on the various issues raised by the advisors, which I will not walk through in detail. I hope everyone takes the time to read deeply, think critically, and form your own opinions.

The day concluded with a nearly unanimous vote recommending against interpreting the studies as demonstrating either efficacy or safety.

(Due to the one-way nature of the public hearing format, the assembled panel was not asked what the institutions of psychiatry have done for patients suffering with PTSD for the last 24 years, during which no new pharmaceutical treatments have been approved.)

In the ubiquitous media coverage that followed, deep reportage from science journalists and editors familiar with clinical trials and the study of psychedelics was rarely found. Instead of elevating the public’s understanding of the web of factors and issues at play, the day’s most acerbic pullquotes were sent on parade.

How much did the FDA administrators truly weigh the vote of the advisory committee and the subsequent national media frenzy in their decision? This is unlikely to appear in any official memo to be unearthed years later. We can only speculate, and will probably never know.

Of course, Horizons has been hosting speakers from MAPS (and later MAPS PBC, now known as Lykos Therapeutics) to present on these studies since our first conference in 2007.

I am proud of the role that Horizons has played in helping peer-reviewed research about psychedelics reach a larger audience.

However, I am also taking a moment to reflect on the unbridled optimism for approval projected from our stage in recent years.

While I still stand behind the science that we’ve put on our stage, I am also recognizing the value in listening to those who are outside looking in.

The waiting room

While I feel compassion for the scientists, therapists, and activists impacted by the FDA’s response, my deepest sympathies are for the patient community.

Those in suffering are being asked to sit for quite a bit longer in the waiting room, unsure if they will ever receive the doctor’s appointment they were hoping to schedule.

Like many people who work in this field, I regularly receive appeals from individuals and families who are truly suffering and have exhausted all available treatment options. These deeply sincere letters, text messages, and voice memos wash ashore each week and are often painful to receive. Many of them likely would have been eligible for MDMA-assisted therapy.

It is sad and unfair that these people and their children, siblings, parents, relatives, friends, and colleagues will have to wait another set of years for an option within the system of medicine to become available.

Dark corners and daylight

While the advisory committee raised many different issues, and the FDA’s official rationale is not publicly known, it seems a cruel irony that one theme frequently discussed as a justification for non-approval of MDMA is concern about patient safety and ethical boundary violations by therapists.

Prolonging the dark ages harms patients twice. First, by withholding a viable treatment, particularly for those whom existing options have failed. And second, by sending many of those patients into an underworld of unregulated care providers.

The practice of medicine (in general) will, unfortunately, always contain misconduct and ethical transgressions. The questions are what can be done to decrease their prevalence and how to create accountability when these episodes do occur.

While ethical misconduct occurs within all forms of psychotherapy, I have yet to hear a call for ending the licensing and regulation of psychologists, or a claim that misconduct is inherent to talk therapy itself, rather than a dark reflection of larger unhealthy cultural norms.

Approval of MDMA for use under the supervision of clinicians would create safety and accountability. It builds a system of professionals and patients who never have to seek or provide care under the shadow of criminality. It creates an environment where patients have safe routes of reporting and recourse, and where misconduct leads to consequences.

The importance of ethics and accountability have been a topic of great conversation in the psychedelic community for many years now, gracing every conference stage, stacks of journal articles, the curricula of training programs, and the feeds of innumerable media projects.

This remains an important theme that the psychedelic community is genuinely engaged with, and is eager to bring into practice. But we are still waiting for daylight.

The arrow of time

These special molecules have been on a very long journey.

According to physicists, time itself may be somewhat of an illusion– simply an artifact of our all-too-human tendency to perceive our personal vantage point as being singularly authoritative, rather than one-of-many potential observatories in a multidimensional garden of forking paths.

During hard times, it is easy to mistake one’s own viewpoint at a given moment for a definitive and eternal state of being.

Astronomers date the birth of the sun to approximately 4.5 billion years ago.

Recent research dates collections of dried peyote buttons in the Lower Pecos desert to about 6,000 thousand years ago– long before Albert Hofmann’s bicycle ride in April 1943.

In an alternative timeline that might have been, all of the psychedelic therapeutic trials currently underway might have been completed decades ago with the benefit of federal grants, making the drama of public hearings and high-stakes decisions a distant memory by now.

However, in a more nearby cluster of the spacetime continuum, the Controlled Substances Act passed in 1971, the Spring Grove research center closed in 1976, and MDMA was scheduled in 1985.

Despite those setbacks, MAPS began its first steps with the FDA in 2001, Roland R. Griffiths and his team at Johns Hopkins published their first paper in 2006, and the first Horizons conference was held in the autumn of 2007 at Judson Memorial Church.

A decade later, the FDA granted Breakthrough Therapy designation for MDMA-assisted therapy for the treatment of PTSD in 2017, and then to two psilocybin programs for the treatment of depressive disorders (1, 2) in 2018 and 2019. That year also marked the release of How To Change Your Mind, transforming psychedelics into a palatable dinner party conversation topic across the country. By the end of 2021, the world was much richer in psychedelic science than it had been in 2017.

Much more recently, federal grantmakers have begun to fund clinical trials using psychedelics. In March of this year, the FDA granted Breakthrough Therapy to LSD for the treatment of Generalized Anxiety Disorder. In May, Horizons had the honor of hosting a Presidential appointee, the Undersecretary for Health of the VA, on our stage. He was eager to discuss MDMA.

From the vantage point of 2007, let alone 1971, the probabilities of reaching any of these milestones might have seemed near-zero. And yet, here we are.

Despite the setbacks of this summer, in just a few short years, the FDA will likely be asked to consider New Drug Applications for psilocybin, and perhaps once again, MDMA.

Science and hope

When Horizons began, it was unclear if there ever would be Phase 3 trials to debate the merits of.

There was no validation from the media or the institutions of medicine. There was almost zero funding available. People asked to register for the conference in cash, out of fear that using a credit card might result in attention from law enforcement. There were very few active studies, and pursuing this avenue of research was seen as “career limiting.”

These were not the conditions under which science could easily flourish.

And yet, this community persevered and built a new canon of peer-reviewed publications in top journals and a global network of research centers.

The world now teems with psychedelic science across oceans and across disciplines. Much, if apparently not all, of the unwarranted skepticism and cynicism of the previous era has been greatly eroded by this generation’s waves of research. While the water mark of public acceptance may rise and recede over time, I do not foresee a future where the waters run dry.

Science is not a fixed state and has no terminus. It is a process whose product improves with iteration, scale, and engagement. The best response to challenges to today’s research is to practice more and better research.

Ultimately– I do have faith that psychedelic-assisted therapies will become regulated medical treatments in the near future on the basis of their scientific merit.

I invite you to join me in pairing the process of science with this act of faith.

Autumn, winter, spring, summer, autumn

I look forward to seeing all of you in June at Psychedelic Science 2025 in Denver, and the following autumn at the next Horizons conferences.

In the meantime, I hope you will continue your own work in service of the collective good, and that these gatherings might serve as meaningful chapters in your story.

Especially in seasons where outside validation is sparse, getting to do the work itself can be its own reward.

Thank you for listening.

Sincerely,