Getting The Ducks in a Row in Europe – The EMA Workshop on Psychedelics – Day 1

On April 16th, 2024, exactly 81 years after Albert Hofmann‘s accidental discovery of LSD‘s psychedelic properties, the European Medicines Agency (EMA) convened a landmark meeting: the Multi-stakeholder Workshop on Psychedelics – Towards an EU Regulatory Framework.

This event brought together key players in the psychedelic ecosystem, including regulators, researchers, industry representatives, and patient advocates, to discuss the future of psychedelic medicine in Europe. The discussions aimed to explore the therapeutic potential of psychedelics, address regulatory challenges, and chart a path for safe and effective implementation of these promising treatments within the existing EU framework.

This post documents my notes from the first day of the meeting. A fuller exploration of the implications and key findings will be reported at a later date. This page will be updated with a link to the recording once it becomes available.

Opening Remarks and Objectives

The meeting commenced with opening remarks from EMA Head of Office for Therapies for Neurological and Psychiatric Disorders, Pavel Balabanov, who acknowledged the significant mental health challenges facing Europe, with 1 in 6 individuals affected. He emphasized the need for a robust, evidence-based approach to psychedelic medicine, considering the unique challenges of patient access and treatment administration.

Balabanov stressed the importance of integrating psychotherapy for safe use, ensuring controlled access, and utilizing health technology assessment (HTA) for reimbursement considerations. The EMA’s commitment to supporting the development of safe, effective, and high-quality psychedelic medicines was underscored.

He then outlined the day’s objectives, emphasizing the workshop’s aim to gather diverse perspectives on the therapeutic potential of psychedelics, clarify their safe and effective use, and identify regulatory challenges and opportunities within the current EU framework.

Session 1: From Development to Patient Use: Opportunities & Challenges

European Regulatory Perspective

Marion Haberkamp from the German Federal Institute for Drugs and Medical Devices (BfArM; also speaking on behalf of the EMA) provided a European regulatory perspective on psychedelic drugs in psychiatry. She highlighted the growing body of research on psychedelics (the number of trials in Europe has doubled in the last 12 months) for conditions like treatment-resistant depression (TRD) and post-traumatic stress disorder (PTSD), and acknowledged the scientific and regulatory challenges.

The Landscape of Psychedelic Research:

Haberkamp began by highlighting the significant burden of mental health disorders, particularly major depressive disorder (MDD), which stands as a leading cause of disability worldwide. She then traced the evolving landscape of psychedelic research, from the early discoveries of Albert Hofmann to the resurgence of interest in recent years, fueled by promising clinical studies and substantial funding initiatives like the Horizon Europe program (which provided €6.5 million for psychedelic research into existential distress (EOL anxiety)). This shift signifies a transition “from stigmatization to expectation” surrounding psychedelic medicine.

Recent Regulatory Activities:

Haberkamp outlined recent activities undertaken by EU regulators to address the growing interest in psychedelics. These include publications in prestigious journals like The Lancet, participation in conferences like the ECNP New Frontiers meeting, and updates to the EMA draft depression guideline to include sections on esketamine (Spravato) and psychedelics. Additionally, she mentioned the potential impact on guidelines for other mental health conditions like anxiety disorders, PTSD, and substance use disorders.

Scientific and Regulatory Challenges:

The presentation delved into the multifaceted challenges associated with the development and implementation of psychedelic medicines in the EU. These challenges encompass scientific, legal, and practical obstacles:

• Clinical Trial Design:
  • Placebo and Blinding: The subjective effects of psychedelics pose significant challenges to maintaining double-blind conditions in clinical trials. Strategies like low-dose active placebos or alternative control conditions need careful consideration.
  • Dose Finding: Determining the optimal therapeutic dose for different psychedelics and indications requires further research.
  • Maintenance of Effect: Ensuring the long-term efficacy of psychedelic treatment and addressing the potential need for recurrent dosing remain key questions.
• Psychotherapy Integration:
  • Role of Psychotherapy: The presentation questioned whether psychotherapy is essential for both safety and efficacy in PAT. The need to differentiate between psychological support and formal psychotherapy was highlighted.
  • Standardization: Standardizing the therapeutic approach, including setting, training of therapists, and the specific type of psychotherapy employed, is crucial for ensuring consistent and reliable outcomes.
• Safety Considerations:
  • Adverse Effects: Managing potential adverse effects like anxiety, derealization, negative experiences (“bad trips”), addiction, and cardiovascular effects requires careful monitoring and risk mitigation strategies.

Regulatory Pathways and Tools:

Haberkamp emphasized that psychedelics must adhere to the general standards for drug approval, ensuring a positive benefit-risk balance. Regulatory tools like Summary of Product Characteristics (SmPCs), Risk Management Plans (RMPs), and Post-Authorization Safety Studies (PASS) can be employed to ensure safe and effective use. Additionally, controlled access programs and educational materials can further minimize risks.

Collaboration and Future Directions:

The presentation concluded by highlighting the EMA’s commitment to supporting the development of psychedelic medicines through early involvement in the Innovation Task Force (ITF) and Scientific Advice Working Party (SAWP; among other frameworks that could be utilized). Collaboration with HTA bodies was also emphasized to ensure a smooth transition from clinical trials to real-world implementation.

Open Questions and the Path Forward:

Haberkamp expressed particular interest in understanding the role of non-hallucinogenic psychedelics (5HT2a agonists) and the specific contributions of psychotherapy in PAT. The presentation underscored the need for continued research and open dialogue between regulators, researchers, and clinicians to navigate the evolving landscape of psychedelic medicine and address the unmet needs of patients with mental health disorders.

Australian Regulatory Perspective

Robyn Langham, Chief Medical Advisor at the Therapeutic Goods Administration (TGA) in Australia, presented a detailed overview of Australia’s groundbreaking approach to regulating psychedelics. The TGA’s decision to down-schedule MDMA and psilocybin for specific therapeutic uses marked a significant shift in the global landscape of psychedelic medicine.

Down-Scheduling and Access:

Langham began by summarizing the TGA’s landmark decision to down-schedule MDMA and psilocybin as of July 1st, 2023. This allows for the prescription of these substances by authorized psychiatrists for the treatment of PTSD (MDMA) and treatment-resistant depression (psilocybin), respectively. However, access is subject to several restrictions and controlled through the Authorized Prescriber (AP) scheme.

Navigating the Scheduling Framework:

Langham explained Australia’s drug scheduling system, which categorizes substances based on their therapeutic value and potential risks. Schedule 9, where most psychedelics reside, is reserved for substances with no currently established therapeutic use. The down-scheduling of MDMA and psilocybin to Schedule 8 acknowledges their potential therapeutic benefits while recognizing the need for controlled access and ongoing research (though Schedule 8 still presumes addiction risks which most would say are limited with psychedelics).

The Authorized Prescriber Scheme:

The AP scheme serves as a key mechanism for controlled access to MDMA and psilocybin. Under this scheme, the TGA grants authority to qualified medical practitioners to prescribe these substances for specific indications and patient populations. To become an AP, a psychiatrist must:

• Be a registered psychiatrist in Australia with relevant experience.
• Obtain approval from a Human Research Ethics Committee (HREC) for a specific treatment protocol, including informed consent procedures.
• Demonstrate a therapeutic relationship with the patient, ensuring personalized care and avoiding mass prescription.
• Comply with state/territory regulations regarding possession and supply of these substances.

Controls and Responsibilities:

The AP scheme incorporates several controls to ensure patient safety and responsible use:

• Limited Settings: Treatment must occur in controlled environments, ranging from day hospitals to specialized clinics, with no take-home prescriptions allowed.
• Reporting Requirements: APs must report the number of patients treated and any adverse events to the TGA twice per year.
• Continued Research: Clinical trials remain crucial for expanding access to other indications and generating further evidence on safety and efficacy.

Clinical Guidance and Advertising Controls:

The Royal Australian and New Zealand College of Psychiatrists (RANZCP) provides clinical guidance for psychiatrists through a Clinical Memorandum. Additionally, advertising of MDMA and psilocybin to the public is strictly prohibited, and consultations must be conducted on a one-on-one basis.

Current Status and Future Directions:

As of April 16th, 2024, nine psychiatrists have been authorized to prescribe MDMA and/or psilocybin. While the number of patients treated remains relatively low due to the stringent requirements and associated costs, the AP scheme represents a significant step towards integrating psychedelic-assisted therapies into mainstream mental health care. The TGA emphasizes the importance of continued research and collaboration with stakeholders to ensure safe and effective access to these promising treatments.

American Regulatory Perspective

Marta Sokolowska, Deputy Center Director for Substance Use and Behavior Health at the U.S. Food and Drug Administration (FDA), presented a detailed overview of the FDA’s perspective on psychedelic drug development. Her presentation highlighted the agency’s recognition of the growing interest in psychedelics and its commitment to facilitating research while ensuring patient safety and drug efficacy.

The Growing Interest in Psychedelics:

Sokolowska began by underscoring the significant mental health challenges in the United States, with 57.2 million doctor visits annually attributed to mental health concerns. She then presented several indicators of the burgeoning interest in psychedelics as potential therapeutic agents:

• Legislative Action: Both federal and state-level initiatives are exploring the therapeutic potential of psychedelics. Notably, the National Defense Authorization Act for FY 2024 mandates the Department of Defense to study psychedelic-assisted therapies for conditions like PTSD and traumatic brain injury in active-duty service members.
• Increased IND Applications: The FDA has observed a substantial rise in Investigational New Drug (IND) applications for psychedelic research, with such applications now constituting a significant portion of their workload.
• Breakthrough Therapy Designations: Several psychedelic therapies have received Breakthrough Therapy designation, indicating preliminary clinical evidence of substantial improvement over existing treatments. Examples include MDMA for PTSD, psilocybin for treatment-resistant depression and major depressive disorder, and LSD for generalized anxiety disorder.

Recent FDA Activities and Guidance:

Sokolowska highlighted the FDA’s recent efforts to provide guidance and support for psychedelic drug development:

• Draft Guidance for Industry: In June 2023, the FDA issued its first draft guidance specifically addressing psychedelic drug development. This document, titled “Psychedelic Drugs: Considerations for Clinical Investigations,” outlines general considerations for sponsors conducting clinical trials with psychedelics.
• Focus on Clinical Trial Design: The guidance acknowledges the unique challenges associated with psychedelic research and emphasizes the need for well-designed clinical trials that address factors like blinding, placebo control, dose-finding, and long-term efficacy.
• Public Workshop: The FDA, in collaboration with the Reagan-Udall Foundation, convened a public workshop titled “Advancing Psychedelic Clinical Study Design” to further explore and address key issues in psychedelic research.

Clinical Considerations and Challenges:

Sokolowska elaborated on specific clinical considerations and challenges highlighted in the FDA’s guidance:

• Efficacy Assessment: Factors such as the subjective effects of psychedelics, expectancy bias, and the potential influence of the therapeutic setting can complicate efficacy assessments.
• Study Design: The need for adequate and well-controlled studies with appropriate comparators and blinding strategies is emphasized.
• Real-World Use: Challenges associated with real-world implementation, such as therapist training, patient monitoring, and long-term safety, need to be addressed.

Limits of FDA Authority:

Sokolowska clarified the boundaries of the FDA’s regulatory authority, emphasizing that the agency focuses on regulating human drugs, including product labelling, monitoring clinical trials, and implementing Risk Evaluation and Mitigation Strategies (REMS). The FDA does not regulate the practice of psychotherapy, the practice of medicine, or post-market monitoring of psychedelic use outside of clinical trials.

The Path Forward:

The FDA’s presentation underscored the agency’s commitment to supporting responsible and scientifically rigorous research into the therapeutic potential of psychedelics. Collaboration with researchers, industry sponsors, and other stakeholders remains crucial for navigating the evolving landscape of psychedelic medicine and ensuring the development of safe and effective treatments for patients with mental health disorders.

Legal Status and Impact on Research

Tadeusz Hawrot, representing the Psychedelic Access And Research European Alliance (PAREA), delivered a compelling presentation on the legal challenges hindering psychedelic research and development. He highlighted the historical context of psychedelic scheduling and its detrimental impact on scientific progress, advocating for policy reforms to unlock the therapeutic potential of these substances.

Psychedelics: An Enduring Part of Human History:

Hawrot began by reminding the audience that psychedelics have been an integral part of human history, with evidence of their use in indigenous cultures and spiritual practices dating back centuries. However, the scientific exploration of these substances was abruptly halted by international drug control conventions.

The Impact of Scheduling:

Hawrot discussed the Single Convention on Narcotic Drugs (1961) and the UN Convention on Psychotropic Substances (1971), which placed most psychedelics in Schedule I, a category reserved for substances with a high potential for abuse and no recognized medical use. He argued that this scheduling decision was not based on scientific evidence but rather on political and cultural factors.

Consequences of Restricted Research:

Hawrot highlighted the detrimental consequences of scheduling psychedelic research:

• Stifled Research: The stringent regulations and stigma associated with Schedule I substances have significantly hampered research efforts, leading to a dearth of scientific knowledge about the therapeutic potential of psychedelics.
• Limited Clinical Trials: The difficulty in obtaining research permits and the associated costs have restricted the number and scope of clinical trials, hindering the development of evidence-based treatments.
• Barriers to Collaboration: Scheduling has created barriers to scientific collaboration, limiting the exchange of knowledge and expertise between researchers across borders.
• Financial Constraints: The stigma surrounding Schedule I substances has made it difficult to secure funding for research, both from public and private sources.
• Patent Issues: The dominance of pharmaceutical companies in large-scale trials has led to patent restrictions, limiting access for researchers and indigenous communities.

EU Policy Recommendations:

Hawrot proposed several policy recommendations to address the current legal barriers and foster psychedelic research in the EU:

• Rescheduling: Initiating discussions with the Commission on Narcotic Drugs (CND) to explore the possibility of rescheduling psychedelics based on current scientific evidence.
• Incentives for Innovation: Implementing policies that encourage and support research and development in mental health, such as regulatory protection and enhanced EMA support programs like PRIME (Priority Medicines).
• Accelerated Assessment Pathways: Utilizing mechanisms like accelerated assessment, conditional marketing authorization (CMA), and adaptive pathways to expedite the development and approval of promising psychedelic therapies.
• Predictable Reimbursement Environment: Establishing clear and predictable reimbursement pathways to ensure patient access to psychedelic treatments after approval.

A Pan-European Approach:

Hawrot advocated for a pan-European, multidisciplinary advisory body or commission dedicated to novel mental health therapies. This body would provide guidance and support for integrating psychedelic treatments into national healthcare systems, ensuring equitable access and consistent standards of care across the EU.

Conclusion:

Hawrot’s presentation effectively highlighted the urgent need for policy reforms to address the legal barriers hindering psychedelic research and development. By promoting evidence-based scheduling decisions, fostering collaboration, and providing incentives for innovation, the EU can unlock the therapeutic potential of psychedelics and address the growing mental health crisis.

Challenges with Health Technology Assessment

Carlos Martín Saborido, a health economist specializing in Health Technology Assessment (HTA) in Spain, presented a critical analysis of the challenges associated with evaluating the value of psychedelics within the existing HTA framework. He drew upon the experience of esketamine (Spravato) for treatment-resistant depression (TRD) to illustrate the complexities of assessing cost-effectiveness and determining reimbursement for psychedelic-assisted therapies (PAT).

The Case of Esketamine:

Saborido began by discussing the case of Spravato, a nasal spray formulation of esketamine approved for TRD and reimbursed in Spain since November 2022. While the clinical benefits of Spravato are recognized, HTA bodies face challenges in determining its cost-effectiveness due to several factors:

Challenges in HTA for Psychedelics:

Saborido outlined the specific challenges encountered in applying the traditional HTA framework to psychedelic therapies:

• Defining the Target Population:
  • Extrapolating from Clinical Trials: Identifying the appropriate target population for PAT outside of the controlled setting of clinical trials can be difficult, especially considering the presence of comorbidities and the heterogeneity of patient profiles.
• Intervention and Administration:
  • Supervision Requirements: The need for supervision during and after psychedelic experiences raises questions about resource allocation and cost implications. The level of supervision required (e.g., inpatient vs. outpatient) and the associated costs need to be carefully considered.
  • Setting and Infrastructure: Determining the appropriate setting for PAT administration (e.g., specialized clinics, hospitals) and the associated infrastructure costs presents a challenge.
• Choosing Comparators:
  • Defining Treatment Failure: Establishing clear definitions of treatment failure for previous therapies is crucial for selecting appropriate comparators in cost-effectiveness analyses.
  • Alternative Therapies: The role of alternative treatment options like electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and psychological therapies needs to be considered when evaluating the comparative effectiveness of PAT.
• Measuring Outcomes:
  • Clinical Significance: Defining clinically meaningful outcomes and establishing thresholds for determining the superiority of PAT over existing treatments require careful consideration.
  • Long-Term Follow-Up: The need for long-term follow-up data to assess the durability of treatment response and potential for relapse presents a challenge, especially given the limited real-world evidence currently available.

The Need for a New Framework:

Saborido concluded by emphasizing the limitations of the traditional HTA framework in evaluating the value of psychedelics. He argued for the development of a new framework that takes into account the unique characteristics of PAT, including the importance of the therapeutic setting, the role of psychotherapy, and the potential for long-term benefits that extend beyond symptom reduction. This new framework should consider broader societal impacts and incorporate qualitative data to capture the full value proposition of psychedelic therapies.

Czech National Experience with Medical Use

Jiří Horáček, representing the National Institute of Mental Health in Prague and the Czech Psychedelic Research Foundation (PSYRES), shared the Czech Republic‘s extensive experience with ketamine-assisted psychotherapy (KAP) for treatment-resistant depression (TRD). His presentation highlighted the country’s pioneering role in psychedelic research and the successful implementation of KAP within the existing healthcare system. He presented data from the PSYON clinic, demonstrating the efficacy and safety of KAP with long-term follow-up.

A Rich History of Psychedelic Research:

Horáček began by outlining the Czech Republic’s long-standing involvement in psychedelic research, dating back to the 1950s with Stanislav Grof‘s groundbreaking LSD studies. This research continued in the 1990s with animal and human studies exploring the therapeutic potential of psychedelics for various mental health conditions.

Current Research Initiatives:

Horáček highlighted several ongoing research projects in the Czech Republic:

• Head-to-Head Comparison: A study comparing the efficacy of psilocybin and ketamine, with midazolam as a control, in patients with TRD and depression associated with cancer.
• RAFAEL Study: Investigating the potential of psychedelic experiences to induce regression of atherosclerosis, a condition characterized by plaque buildup in arteries.
• KAP for PTSD: Exploring the use of KAP for treating PTSD in military personnel and civilians affected by the conflict in Ukraine.
• PsyPal Project: A comprehensive initiative focusing on psychedelic research and therapy (the Horizon-funded study that has recently started).

PSYON: A Model for Psychedelic Clinics:

Horáček presented the PSYON clinic, a private psychedelic clinic established in 2019, as a successful model for integrating KAP into mainstream mental health care. Key aspects of the PSYON model include:

• Insurance Coverage: PSYON has established contractual relationships with most insurance companies in the Czech Republic, allowing for reimbursement of KAP treatment for a majority of patients.
• Treatment Protocol: The clinic utilizes a standardized KAP protocol, including informed consent, medical examinations, operationalized psychotherapy, and a curated music playlist. Ketamine is administered in various forms (oral, intramuscular, or intravenous) depending on individual needs.
• Clinical Evaluation: Treatment outcomes are rigorously assessed using standardized psychometric measures like the PHQ-9 for depression, GAD-7 for anxiety, and PHQ-15 for somatic symptoms. Follow-up assessments are conducted at 30, 90, and 180 days post-treatment.
• Treatment Models: PSYON offers various KAP models tailored to individual needs, including single ketamine administration with preparatory and integration sessions (KAP1), repeated ketamine sessions (KAP2 and KAP3), and ketamine treatment alongside antidepressants (AD ket).

Clinical Experience and Outcomes:

Horáček shared data from PSYON, demonstrating the efficacy and safety of KAP for TRD:

• Significant Improvement: Patients treated with KAP showed significant reductions in depression and anxiety symptoms, with sustained effects observed at 6-month follow-up.
• Individualized Approach: The clinic’s individualized approach, tailoring treatment protocols to each patient’s needs and preferences, has contributed to positive outcomes.
• Safety Profile: KAP treatment at PSYON has demonstrated a favorable safety profile, with minimal side effects reported.

Conclusions and Implications:

Horáček’s presentation showcased the Czech Republic’s leadership in psychedelic research and the successful implementation of KAP as a reimbursed treatment option for TRD. The PSYON model offers valuable insights for other countries seeking to integrate psychedelic therapies into their healthcare systems. The data presented underscores the potential of KAP as a safe and effective treatment option for patients with TRD, offering hope for improved mental health outcomes.

Q&A

Following the presentations, a dynamic Q&A session ensued, featuring engaging discussions and diverse perspectives from regulators, researchers, industry representatives, and audience members. The session delved into critical issues surrounding psychedelic research, regulation, and clinical implementation.

Psychotherapy and Regulation:

• EMA’s Stance: The EMA representative emphasized that while they can regulate the drug component of PAT, psychotherapy falls outside their purview. Factorial designs in clinical trials could help disentangle the contributions of drug and therapy, but clear guidance from clinicians and researchers is needed.
• FDA’s Perspective: The FDA acknowledged the challenges of regulating psychotherapy and highlighted the role of state medical boards in overseeing clinical practice. It also mentioned collaboration with institutions like the Veterans Affairs (VA) on KAP implementation.
• Australian Collaboration: The TGA representative emphasized collaboration with the college of psychiatrists and the medical board to ensure appropriate oversight and regulation of practitioners involved in psychedelic-assisted therapy.

Blinding and Placebo Control:

• Challenges and Alternatives: Several participants, including David Nutt and the CMO of Cybin, questioned the overemphasis on blinding in psychedelic trials, citing challenges and potential biases. Alternative approaches like low-dose active placebos or focusing on long-term outcomes were suggested.
• EMA’s Tools: The EMA representative acknowledged the difficulties of blinding but highlighted existing tools and strategies, such as those employed in Spravato trials, to assess and mitigate potential bias.

Patient Populations and Treatment Focus:

• TRD vs. MDD: The rationale behind focusing on treatment-resistant depression (TRD) as the initial target population was questioned. Some participants advocated for exploring the potential of psychedelics for earlier-stage MDD or other mental health conditions.
• Benefit-Risk Assessment: Regulators emphasized the importance of a thorough benefit-risk assessment for different patient populations, acknowledging that the balance may shift for those with less treatment resistance.

Real-World Evidence and Implementation:

• Value of Real-World Data: Participants discussed the potential of real-world evidence to complement clinical trial data and inform regulatory decisions. Regulators expressed interest in exploring frameworks for incorporating real-world data into the evaluation process.
• Challenges of Implementation: The need for standardized protocols, therapist training, and infrastructure development to support the safe and effective implementation of PAT was highlighted.

Rescheduling and Legal Barriers:

• Advocating for Change: David Nutt and other participants advocated for rescheduling psychedelics based on current scientific evidence, arguing that the current Schedule I classification hinders research and limits access to potentially life-saving treatments.
• EU Policy Reform: The need for EU-level policy reforms to facilitate research, incentivize innovation, and streamline regulatory pathways for psychedelic medicines was emphasized.

Additional Points of Discussion:

• The Role of Psychological Support: Participants debated the distinction between psychotherapy and psychological support, and the minimum level of support necessary for safe and effective PAT.
• Individualized Treatment: The importance of tailoring treatment protocols to individual patient needs and preferences was highlighted.
• Learning from the Underground: Several participants advocated for incorporating knowledge and experience from the underground psychedelic community into research and clinical practice.

Overall, the Q&A session fostered a rich exchange of ideas and perspectives, highlighting the complexities and opportunities surrounding psychedelic medicine. The discussions underscored the need for continued research, collaboration, and policy reform to unlock the full potential of psychedelics and address the unmet needs of patients with mental health disorders.

Panel Discussion – Perspectives from Multi-Stakeholders

The panel discussion, facilitated by Pavel Balabanov from the EMA, brought together a diverse group of stakeholders to share their perspectives on the future of psychedelic medicine in Europe. The discussion highlighted the importance of a collaborative approach, integrating insights from patients, clinicians, researchers, industry representatives, and regulators.

Patient Advocacy and the Participant Experience:

• Ian Roullier (PsyPAN): Representing Psychedelic Participant Advocacy Network (PsyPAN), Roullier emphasized the importance of centering the participant experience in discussions about psychedelic medicine. He highlighted the need for additional therapy and integration support to maximize the benefits and minimize the risks of psychedelic experiences. Roullier advocated for a balanced approach that acknowledges the limitations of psychedelics as “therapeutic catalysts” rather than one-time cures. He stressed the need for affordability and safety, calling for a coordinated EU-wide strategy and the formation of a multidisciplinary advisory body.

Psychiatric Perspectives and Clinical Implementation:

• Geert Dom (EPA): Representing the European Psychiatric Association (EPA), Dom acknowledged the significant unmet need in mental healthcare and the potential of PAT to address this gap. He emphasized the importance of developing clear guidelines and protocols for psychedelic therapies, while also recognizing the limitations of existing treatment approaches in psychiatry. Dom raised concerns about the growing trend of patients seeking psychedelic treatments in unregulated settings and stressed the need to consider the diversity and complexity of real-world patient populations.

Industry Perspectives and Drug Development:

• Nanco Hefting and Guy Goodwin (EFPIA): Representing the European Federation of Pharmaceutical Industries and Associations (EFPIA), Hefting and Goodwin presented the industry perspective on psychedelic drug development. They highlighted three key challenges:
  • Defining Acceptable Comparators: The difficulty of blinding in psychedelic trials necessitates exploring alternative comparators and study designs.
  • Minimal Support for Safety: Standardizing the level of psychological support required for the safe administration of psychedelics while avoiding the potential bias of formal psychotherapy is crucial.
  • Collection of Adverse Events: Developing a consensus on how to record and report adverse events, including distinguishing between typical psychedelic effects and true adverse events, is necessary.

Insights from Illicit Drug Monitoring:

• Liesbeth Vandam (EMCDDA): Representing the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Vandam provided insights into the landscape of illicit psychedelic use in Europe. She highlighted concerns about the increasing availability and diversity of substances, the potential for adulteration, and the vulnerability of individuals seeking psychedelic experiences outside of medical settings. Vandam emphasized the need for clear communication to differentiate between medical and non-medical use of psychedelics and to address potential risks associated with unregulated use.

The Role of Brain Research and Advocacy:

• Suzanne Dickson (EBC): Representing the European Brain Council (EBC), Dickson emphasized the growing burden of brain disorders and the urgent need for innovation in mental healthcare. She highlighted the limitations of traditional research methods for studying psychedelics and called for adaptations to the regulatory process to accelerate the development of effective treatments. Dickson expressed support for incorporating patient perspectives and engaging healthcare professionals in the implementation of psychedelic therapies.

Canadian Approach and Special Access Programs:

• Kathy Soltys (Health Canada): Representing Health Canada, Soltys shared insights into Canada’s approach to regulating psychedelic research and facilitating access through clinical trials and the Special Access Program (SAP). She highlighted the importance of rigorous safety standards and ethical considerations in clinical trials and emphasized the role of the SAP in providing access to unauthorized treatments for patients with unmet medical needs.

The panel discussion showcased the diverse perspectives and collaborative spirit necessary to advance psychedelic medicine in Europe. The insights shared by stakeholders emphasized the need for a balanced approach that prioritizes patient safety, scientific rigor, and ethical considerations while acknowledging the unique challenges and opportunities presented by these promising therapies.

Interventions (Questions) from the Audience

The final segment of the workshop featured interventions from the audience, further enriching the discussion with diverse perspectives and raising critical questions about the future of psychedelic medicine in Europe.

Treatment Approach and Patient Populations:

• Phased Approach vs. Early Intervention: Balabanov initiated a discussion on whether a two-step approach, starting with the most treatment-resistant patients, is the optimal strategy for psychedelic drug development. While regulators emphasized the need for robust evidence before expanding access, some participants advocated for exploring the potential of psychedelics for earlier-stage patients to prevent the progression of mental health conditions.
• Benefit-Risk Assessment: The importance of a thorough benefit-risk assessment for different patient populations was reiterated, acknowledging that the balance may shift for those with less treatment resistance or different conditions.

Rescheduling and Regulatory Reform:

• Challenges and Opportunities: David Nutt and other participants continued to advocate for rescheduling psychedelics based on current scientific evidence, highlighting the barriers imposed by the current Schedule I classification.
• EU Policy Considerations: The need for EU-level policy reforms to facilitate research, incentivize innovation, and streamline regulatory pathways for psychedelic medicines was further emphasized. Suggestions included temporary research scheduling, similar to Schedule II, to enable more research within the EU.

Psychotherapy and Standardization:

• Distinguishing Support from Therapy: The discussion revisited the distinction between psychological support and formal psychotherapy in PAT. Regulators expressed concerns about the variability and complexity of psychotherapy, while acknowledging the importance of standardized support measures for ensuring safety and efficacy.
• Minimum Standards: Participants explored the possibility of defining minimum standards for psychological support or integration therapy, recognizing that these standards may vary depending on the specific psychedelic compound and indication.

Real-World Evidence and Integration:

• Value of Real-World Data: The potential of real-world evidence to complement clinical trial data and inform regulatory decisions was further discussed. Regulators expressed interest in exploring frameworks for incorporating real-world data into the evaluation process, particularly for assessing long-term safety and effectiveness.
• Learning from Unregulated Settings: Several participants highlighted the wealth of knowledge and experience accumulated in the underground psychedelic community and advocated for incorporating these insights into research and clinical practice.

Additional Points and Considerations:

• Mechanistic Studies: The importance of mechanistic studies to elucidate the biological and psychological mechanisms of action of psychedelics was raised.
• Standardization of Setting: Participants discussed the need for standardization of the therapeutic setting, including considerations for the physical environment and the role of music or other sensory stimuli.
• Indigenous Use and Cultural Considerations: The impact of regulations on indigenous cultures and traditional uses of psychedelics was acknowledged, highlighting the need for respectful and inclusive approaches to psychedelic medicine.

The audience interventions further enriched the workshop, highlighting the diverse perspectives and ongoing dialogue surrounding psychedelic medicine. The discussions underscored the need for a collaborative approach that integrates scientific rigour, patient-centred care, and ethical considerations to ensure the responsible and effective development of psychedelic therapies for mental health disorders.