Some psychedelic medicine developers want to ditch the therapy aspect. What could go wrong?

Back in 2016, Rosalind Watts volunteered to work on one of Imperial College London’s early trials investigating psilocybin for depression. She had previously spent several years as a clinical psychologist with the UK’s National Health Service and quickly saw the incredible potential for psychedelics to help people with mental health problems. By the following year, Watts had abandoned her conventional healthcare work, joining the Imperial team and evangelizing the benefits of these miraculous medicines.

Psilocybin is one of several psychedelic drugs currently being explored as treatments for a variety of mental health issues. These drugs, which also include LSD, DMT and adjacent compounds like MDMA and ketamine, can give users profound shifts in perception, both during a dose session and in the weeks or months following. This particular consciousness-altering aspect to the drugs means patients can require more therapeutic support than they would if they were receiving conventional psychiatric medications.

As time passed, Watts grew concerned that these drugs were not being administered with enough broad support for patients. She was finding many clinical trial participants, months later, struggling with the return of their previous sense of disconnectedness and depression, alongside big questions that had been raised in the psychedelic session, with no one to talk to about them. Even with bespoke and careful therapeutic containers created for the trial, the support ended very quickly afterwards.

So Watts and a colleague set up the UK's first community-based psychedelic integration group to provide a safety net to catch any participants in their next trial who might find they needed help afterwards.

“We went and sat in a community center,” Watts recalls in an interview with Salon. “We gave our time for free, month after month, because many people were having psychedelic experiences without enough support, after trials and retreats, and most months we witnessed people really struggling to cope alone with the aftermath of intense and confusing experiences."

Disillusioned with corporate impacts on the psychedelic space, Watts changed path to develop a long term community integration framework for building connectedness to self, community and nature after a psychedelic experience. This was designed to catch people who might struggle to integrate experiences with the drugs after consuming the psychedelic renaissance hype.

In a frank Medium post published two years ago, Watts expressed remorse at contributing to a “simplistic and dangerous” narrative around psychedelic medicine. She still believes psychedelics are incredible agents for catalyzing healing but is also concerned there’s a growing narrative suggesting we need to just take the drug and everything will be fine.

Watts wrote, “the greatest threat to a healthy psychedelic future is the fetishizing of just the drug alone,” adding, “Whether plant, or synthesized compound of one, there is a narrative that all you need to do to change your mind is eat something. I unknowingly contributed to that narrative.”

Don’t call it therapy

For the past 70 years, most Western medical uses of psychedelics have centered on the way these drugs can serve as an adjunct to psychological therapy, or psychotherapy. From treating alcoholism to alleviating depression and anxiety, the general idea has been that psychedelics can amplify suggestibility, increase neuroplasticity and accelerate the clinical process of psychotherapy.

In fact, for much of the current so-called “psychedelic renaissance,” the treatment has been explicitly referred to as psychedelic-assisted psychotherapy. While there may be more and more research illustrating exactly what psychedelics do pharmacologically to our brain, for the most part it was never particularly controversial to suggest the drugs should always be delivered in tandem with a broad program of psychological preparation and integration.

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It’s pretty unusual in psychiatry for a drug’s efficacy to be fundamentally influenced by counseling or psychotherapy. Certainly medicines such as antidepressants or drugs like buprenorphine for opioid use disorder are known to be more effective when accompanied by clinical support — but they are often administered solely as pharmacological treatments.  

Psychedelics, on the other hand, are considered to be so life-altering, emotional and sometimes distressing that having a licensed practitioner nearby to walk one through the experience has been one approach to reducing harm or side effects.

Over the last few years, however, the word “therapy” has been appearing less and less in psychedelic clinical trials as the research moves closer to real-world applications and approval by agencies like the U.S. Food and Drug Administration (FDA). Setting aside the somewhat atypical example of MDMA-assisted therapy for PTSD — a treatment modality that intrinsically intertwines psychological interventions into its process — recent clinical research with classical psychedelics (psilocybin, LSD and DMT) has quietly dropped the psychotherapy and replaced it with a variety of more ambiguous terms such as psychosocial support.

Compass Pathways has led the way in this semantic shift. Currently deep in Phase 3 trials testing psilocybin for depression, the company has been forceful in its reframing of psychedelic medicine away from the classic psychedelic psychotherapy model. Compass studiously avoids any reference to psychotherapy in its trial work, instead calling its research “psilocybin treatment with psychological support”.

A provocative 2022 commentary published in the American Journal of Psychiatry and co-authored by Guy Goodwin (Compass’ Chief Medical Officer) and Ekaterina Malievskaia (Compass’ co-founder) made the case for psilocybin treatment being a drug therapy first and foremost. They argued support to ensure psychological and physical safety was of course necessary with psilocybin treatment, but their dose-response data purportedly indicated efficacy was primarily a pharmacological effect and more expansive psychotherapy programs were not necessary.  In other words, the drug does most of the work.

Part of this subtle shift in nomenclature has been informed by the FDA’s first guidance for psychedelic clinical studies, released in mid-2023. The guidance established an assortment of clinical issues the drug regulator will be considering when looking at applications to bring psychedelic medicines to market.

One crucial question the FDA raised in the document was what it saw as a problematic conflation of drug effect and psychotherapy when exploring the therapeutic efficacy of psychedelics. It suggested clinical research should attempt to separately quantify the contribution of psychotherapy from the drug’s effects when evaluating a patient’s response to the treatment.

Essentially the question being asked was are these drugs still safe and effective in the absence of psychotherapy?

A recent advisory committee to the FDA was particularly focused on this question when trying to evaluate the safety and efficacy of MDMA for PTSD. This problem with psychotherapy ultimately played a part in the committee’s near unanimous recommendation against the approval of MDMA therapy, which could dampen hopes that the drug will be legally prescribed in the near future.

The drug does all the work?

In early March of this year, psychedelic startup MindMed made a pair of striking announcements. It revealed the FDA had granted breakthrough status designation to its investigational drug MM120, a patented formulation of LSD. It also revealed data from its Phase 2b study testing MM120 for generalized anxiety disorder. According to the company, a single dose of the psychedelic drug led to significant and sustained clinical improvements for up to 12 weeks.

Less prominent in MindMed’s announcement, but perhaps most significant, were details surrounding the treatment protocol being tested. MindMed was claiming to have completely eliminated all traces of psychotherapy from its treatment model.

In an investor presentation the company proudly declared its MM120 trial contained no “preparation,” no “integration,” and no “ongoing therapeutic engagement.” This was psychedelic medicine pared back to the absolute minimum. Spend a day taking the drug in a safe clinical environment and then go back to your life.

Speaking to Salon, MindMed’s chief medical officer Dan Karlin said the primary goal of the trial was to home in on the sole pharmacological effect of the drug, as suggested by the FDA. Every step of the trial design looked to remove conventional traces of psychotherapy while maintaining basic levels of support necessary for patient safety.

“There are elements of the history of these drugs, like the need for psychotherapy, that we were doing our best to try and test if that is a real need,” Karlin explained to Salon. “Not because we don't think people would benefit from it, because psychotherapy helps. But because we wanted to see if the drug worked without it.”

So instead of a series of preparatory therapy or support sessions before a drug dose, MindMed simply engaged with the patient in an expanded informed consent process. According to Karlin, informed consent for psychedelics looks a lot like it would for any other psychotropic medication except it is maybe, “a little more robust.”

“The conversation there is about what people may or may not experience, from a perceptual standpoint, from a cognitive standpoint, from a physical sensation standpoint, and from an emotional standpoint. Then there's a putative conversation about mechanism,” Karlin said, describing MindMed’s informed consent process.

In the room for a dosing session there are two “monitors.” One of those monitors is either a medical doctor or a nurse practitioner, while the other need only have a bachelor’s degree with some working experience in anything “adjacent to psychiatry.” Some of the session monitors used in the MindMed trials did have experience with psychotherapy. However, that was not a requirement when selecting personnel. In fact, Karlin explains some of those monitors in the trial were even medical doctors from non-psychiatric fields such as oncologists and gastroenterologists.

“In the room, these folks are instructed explicitly not to provide psychotherapy,” Karlin notes. “What they do provide is monitoring obviously for safety, though that has not really been much of an issue. They do things like vital signs, checks and then they assist the participant if they need anything.”

Of course, sitting in a room with someone going through a high dose psychedelic experience is rarely a completely passive experience. Karlin admits there were moments where participants were in distress or looked for some kind of engagement with the monitors. In those instances, the monitors were instructed to reorient the participants to what’s happening in the room and remind them the drug’s effects will pass.

“In essence, it’s supervising, not therapy,” he stresses. “Most patients on very high doses are not looking for dyadic engagement. They're not looking to be psychotherapized. Occasionally, someone would say something or ask a question that might be sort of leading towards something that could be a more therapeutic intervention. And then the instruction that the DSM [dose session monitor] had been given was to redirect back to the patient, they have to do their thing while they're here.”

Once the dose day was over the participants went home and were followed for several months to track the effectiveness of the treatment. Two in-person assessments were conducted in the week after the dose. Here, the participant met up with one of the monitors present during their dose. Karlin stresses no “systematic psychotherapy” took place at these follow-up appointments. The participants simply completed assessments to measure their symptoms and occasionally asked the monitors about events that may or may not have occurred during their dose session.

So, has MindMed demonstrated a psychedelic drug can be clinically effective in the absence of psychotherapy or a broad psychological support protocol when treating certain psychiatric conditions? Does this mean the future of psychedelic medicine is a clinic where patients drop in, spend a day experiencing a drug while under supervision, and then simply leave with no follow-up support or management necessary? Maybe.

But what if this therapy versus drug binary is the wrong way to think about the impact of psychedelics? Is this dynamic a red herring that could be diverting our attention away from other, more deeply metaphysical issues that can emerge with psychedelic use? If researchers are only measuring a drug’s efficacy using anxiety or depression scales and tracking adverse effects from the perspective of things like suicidality could they be missing other kinds of long-term adverse impacts?

Ontological shock

“My sense of self was gone. It was like it had been obliterated into a million pieces,” Theo said. “And I couldn't really work out who I was. I just had this, like, routine of going to work. And I just stuck to that as a means of like, keeping some sense of inner structure by having some outer structure. And, like, if I'm honest, if I'd sat and thought about that for a while, for the first few weeks, I think I would have just cried because like, it didn't seem very clear who I was anymore.”

Theo participated in an ayahuasca ceremony in his mid-20s. His experiences in the weeks and months following the psychedelic brew led him to profoundly question his identity. Theo is one of 26 people interviewed in a new preprint study exploring the varieties of existential distress that can follow a psychedelic experience.

There’s Adriene, a woman in her 30s who, after a magic mushroom experience alone in her apartment during the pandemic, changed her life path from being an atheist dominatrix to taking vows and becoming a Buddhist nun. There’s Cal, whose experience with DMT and cannabis at a party moved them away from a journey to become a rabbi and into a world of Wicca and paganism.

Western science has a name for these radical transformations, coined in the early 1970s by philosopher Paul Tillich:ontological shock. Tillich’s work was focused on how we as humans conceive of God and what happens to us if we are confronted with God’s non-existence. One of his definitive works concluded with the iconic line, “The courage to be is rooted in the God who appears when God has disappeared in the anxiety of doubt.”

Tillich suggested certain experiences in life can trigger a kind of spiritual destabilization where people are confronted with existential realizations. This ontological shock is precipitated by challenges to one’s worldview or beliefs. For Tillich, an ontological shock was primarily contained within a theistic frame. So something like a near-death experience, for example, could bring a person face-to-face with a feeling of there being no God in the universe. This profound break in a person’s belief system can be frightening for many, leaving one feeling unmoored, disconnected and groundless.

Over the last few decades, the term ontological shock has been more broadly used to describe experiences where someone’s fundamental metaphysical beliefs are deeply challenged beyond theism. Members of alien abduction communities, for example, often speak of the ontological shock they experience after an abduction encounter.

Psychedelic experiences are also deep mediators of ontological shock. From a clinical perspective these kinds of psychedelic-induced ontological shocks are not merely a bothersome side effect of the drug, but instead could be crucial to the kinds of healing being seen in medical contexts.

“The therapeutic benefits of psychedelics are theorized to be driven by increases in entropy — a measure of uncertainty — that shift individuals' reliance on their prior beliefs,” the researchers write in the study. “This destabilizing mechanism allows for a recalibration of cognitive structures, enabling the re-evaluation of previously rigid mental models. However, when individuals lack adequate psychological or social resources, this increase in uncertainty can lead to distress manifesting as confusion and difficulty accommodating the ungrounding of established worldviews.”

Psychedelics in a disconnected world

Most of the work Ros Watts does nowadays is in establishing systems of support for people after psychedelic experiences. She co-runs an online integration community called ACER Integration that offers peer support and a 12 step process for building connectedness. The big problem, from Watts’ perspective, is that 21st century Western culture is disconnected and isolating, lacking any kind of context or container to help people safely integrate psychedelic experiences.

“If you put psychedelics into a disconnected culture, then people go back to disconnectedness, and they're left with these big huge questions with no one to talk to,” Watts says.

A reigning aphorism of the psychedelic renaissance is that these drugs have been safely used by innumerable Indigenous cultures for thousands of years. And while that may be true, Watts is keen to stress a big difference between every psychedelic-using community in the past and people in the world today.

“Indigenous groups have [used psychedelics] as part of a community,” Watts explains. “You have loads of support, you're doing it in a group of people, you have your shaman, you have your community care. There's no 'psychedelic integration', because you're living in a community of people who are integrating all the time. After a psychedelic session people need a community of ongoing support from people who understand. Not just to mitigate risks, but to maintain benefits. We can't extract the medicine from its context of doing it that way.”

From MindMed’s perspective, Karlin doesn’t deny some people can have challenging experiences with psychedelics, but he stresses drug developers do not control the practice of medicine. And neither does the FDA, he adds. By establishing a potential baseline of safety and efficacy in their clinical trials, Karlin argues MindMed is helping broaden access to these medicines if they were to be eventually approved.

“The goal is that in the real world this is just another tool in the toolbox … to bring this toward regulatory approval in such a way that a label and REMS [Risk Evaluation and Mitigation Strategy], if one is required, are as much as is needed for true safety, but broad enough that this can be incorporated into a lot of different types of practice patterns.”

Karlin agrees psychedelic drugs can lead to patients making large life changes due to the nature of the experience. But he doesn’t see this as something wholly novel to psychedelics. He argues patients undergoing psychotherapy, for example, can often come to similar major life-changing realizations.

“People getting good psychotherapy sometimes leave their families,” he says. “That's the nature of exploring one's own mind. These drugs can accelerate that process in many cases, but they don't change someone. They just open people to the idea that maybe they're not on the path that's right for them now.”

Watts is a little more concerned about the shockwaves likely to ripple through communities if these drugs are simply slotted into a Western medical model without broader support systems in place. Her experiences with people who have been deeply unsettled by psychedelic trips led her to believe small, grassroots organizations are going to have to pick up the pieces when big pharmaceutical companies start rolling these medicines out. And she feels pharmaceutical companies making profits off these drugs have a larger responsibility to at the very least offer financial support to these organizations.

“The list of deep, powerful experiences where you need a hand to hold and need someone to work with you afterwards is very long,” Watts says. “So what [these companies] could do if they had compassion is support people through those processes. And not gaslight them by saying, ‘yeah, this [single drug dose] is going to fix you.’ What they would also do is they would provide a proportion of their profits, to support grassroots organizations who have been set up to catch the people who are damaged by psychedelic therapy.”