EMA Embarks on Psychedelic Trip

May 7, 2024, LinkedIn Live — It’s the Age of Aquarius. Representatives from the European Medicines Agency (EMA) held a virtual meeting for researchers, journalists, and other interested parties, where it announced plans to revisit the therapeutic potential of psychedelic compounds for mental health conditions such as treatment-resistant depression, addictive disorders, posttraumatic stress disorder, and end-of-life psychological distress. These compounds include mescaline, N,N-dimethyltryptamine, lysergic acid diethylamide (LSD), and psilocybin.

The virtual briefing, which was held on the social media platform LinkedIn, fell on the heels of a 2-day, 16-17 April, multistakeholder workshop, during which robust discussions were held among patients, healthcare professionals, academics, regulators, and industry to forge a path forward for research and development. In Tuesday’s virtual briefing, EMA’s chief medical officer, Steffen Thirstrup, underscored the current challenges with regard to mental health treatment. Not only has there been a surge in mental disorders, one that has been exacerbated by the COVID-19 pandemic, but innovations in mental health treatments have been lacking.

“As you look back over the past decade, we haven’t really seen any therapeutic advances for disorders,” said Thirstrup. “I believe psychedelics deserve a second chance.”

Taking a Page From US Regulators

A rationale underlying the EMA’s decision to explore psychedelics is the ‘breakthrough therapy’ designation granted by the US Food & Drug Administration this past March to lysergide (LSD) d-tartrate (MM120, Mind Medicine) for the treatment of generalized anxiety disorder. This designation provides expedited regulatory review in conditions where therapeutic needs are not met by current drugs.

“I was a bit concerned, both from a patient’s perspective and a public health perspective, that all of the development was being done in the US and focusing on the US way of treating these disorders,” said Thirstrup, pointing to the European market requirements, especially in terms of post-authorization pricing.

Similar to the United States, the current scheduling of these drugs presents challenges in terms of regulation and distribution. In Europe, psychedelics are classified as Schedule I substances of little therapeutic value and fall under the 1971 United Nations Convention on Psychotropic Substances Act. This is further exacerbated by a variety of different restrictions that are placed on access to these compounds for research purposes across member states. Consequently, rescheduling might ultimately need to be changed on a global scale, according to Thirstrup.

This is a critical point, considering the dearth of research. Thirstrup said that although the findings of published studies are positive, most of the research harkens back to more than 50 years and does not represent the current scientific standards needed to obtain EMA marketing authorization. Moving forward, he emphasized that the EMA has “the right tools” to help developers, also noting that, in addition to pharmaceutical partners, there are “opportunities for engagement from small- to medium-sized enterprises, especially academia.”

Unanswered Questions

As the EMA encourages partners and stakeholders to enter the psychedelic landscape, there are many unanswered questions.

One of the most important is what Thirstup referred to as “set and setting.” This means that study designs should not only consider the mindset of the patient going into psychedelic therapy but also the setting where the therapy occurs.

For now, the EMA appears to be focused on psychedelic-assisted therapy, meaning that these compounds are intended to be used adjunctively to modify or improve baseline psychotherapy. However, psychedelics have also been used in a supervisory setting, a strategy that requires a professional to monitor a patient’s “trip” and intervene or provide guidance accordingly. Thirstrup noted that either approach would need to be mimicked within a clinical trial setting and meet current requirements for review, including establishing safety and efficacy, all of which would ultimately affect authorization and labeling.

The question of inactive placebo was also raised. “We know that, for many mental disorders, the placebo response seen with traditional antidepressants and antipsychotics is huge,” said Thirstrup. “The challenge, of course, is to find a placebo that does not break the blinding; it’s definitely an experience where people are not unaware that something is happening. There’s no good answer here.”

For now, Thirstrup advised that developers consider their choice of comparative placebo (eg, low-dose alternatives with the same effects on the central nervous system as psychedelic compounds), design studies that account for potential biases, and address them in the analysis.

Additional considerations of relevance for the clinical community include optimum dosing, safety, and pharmacological properties, as well as the development of a risk management plan, given that these products are currently scheduled.

Closing, Thirstrup reiterated that the opportunities are wide open. “We are very keen on engaging with developers in the broadest thinkable sense,” he said.

Liz Scherer is a US-based independent health and science journalist.

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