Psilocybin therapy in the HSE: Pathways, opportunities, and challenges

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Reference: January 2026 | Issue 1 | Vol 12 | Page 58

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Classical serotonergic psychedelics, such as psilocybin, show growing evidence of therapeutic potential, with emerging indications of transdiagnostic efficacy across several mental health disorders, including depression, anxiety, and substance use disorders. While early-phase studies yielded encouraging results, recent larger-scale phase 3 trials, such as those evaluating psilocybin for treatment-resistant depression (TRD), have shown more modest effects, and further findings from ongoing trials are eagerly awaited.

The long-term trajectory and real-world impact of these therapies within Irish psychiatry remain uncertain. However, in anticipation of potential approval, Ireland has an opportunity to proactively plan for and implement the integration of psychedelic therapies. Here, we briefly outline the clinical, ethical, and practical challenges and opportunities associated with potential pathways for incorporating psychedelic therapies into the Irish public mental health system.

Psychedelic therapy

Classical serotonergic psychedelics, including psilocybin, LSD, and the short-acting compound 5-MeO-DMT, primarily activate serotonin 5-HT2A receptors, and to a lesser extent 5-HT1A receptors. These compounds stimulate synaptogenesis and neural plasticity, and produce transient alterations in functional brain connectivity.

These neurobiological effects are thought to create a period of heightened psychological flexibility or an altered experiential state (“therapeutic window”), during which individuals may be better able to address entrenched or maladaptive patterns
of thought and behaviour.

Psychedelics are typically administered alongside manualised psychological support. The model generally comprises preparatory sessions centred on establishing trust, ongoing passive support during the dosing session, in which participants are encouraged to focus inward, often lying comfortably with eyeshades and listening to music, and non-directive integration sessions following dosing.

Evidence thus far

The past two decades have marked a modern era of renewed psychedelic research, during which studies have rapidly expanded across multiple clinical conditions, including depression/TRD, anxiety conditions (generalised anxiety disorder, PTSD, OCD), substance use disorders, end of life distress, and eating disorders.¹

Psilocybin for depression, especially TRD, is probably the furthest along the pathway toward regulatory approval as a licensed therapy. In the phase 2 (COMPASS) trial, each person with TRD received a once-off dose of either 1mg, 10mg, or 25mg of psilocybin with psychological support before, during and after psilocybin administration.²

Among those receiving the highest dose, approximately 40 per cent responded, meaning their depression scores improved by 50 per cent or more.² Emerging data suggest that individuals may continue SSRIs during psilocybin therapy.³

With only one phase 3 psilocybin trial demonstrating modest symptom improvement (-3.6 MADRS points), the evidence remains preliminary, and results from the other ongoing COMPASS trial are eagerly awaited, as they will play a major role in the FDA’s decision to approve psilocybin therapy for TRD. Although timelines for approval are not yet clear, ongoing high-quality research internationally suggests that regulatory authorisation in some capacity is a realistic future possibility.

Furthermore, a recent phase 2 trial of 5-MeO-DMT suggested a potential therapeutic role in TRD, and future comparative studies of short- versus long-acting psychedelics would be of interest.⁴

TCD Psychedelic Research Group

Psychedelic therapy trials have been conducted in Ireland for several years, and a dedicated research group has been established. This multidisciplinary team, which collectively established the Psychedelic Research Group at Trinity College Dublin (TCD) – Ireland’s first academic group dedicated to psychedelic science – brings together leading expertise in clinical trial design and methodology, addiction psychiatry, psychedelic therapy, pharmacology, neuroscience, and health economics, and includes individuals with lived and living experience. This collaborative approach ensures that psychedelic therapies are explored from multiple perspectives.

The group conducts both industry-sponsored and independently-funded clinical trials, alongside mechanistic research, further strengthening TCD’s position as a national hub for cutting-edge psychedelic research and developing infrastructure, specialist expertise, and training capacity.

The HRB-funded and TCD-sponsored POSITRON trial (PsilOcybin with pSychologIcal supporT foR cOcaiNe), a randomised controlled pilot feasibility study of psilocybin therapy for cocaine use disorder, is due to commence in 2026. In parallel, the Immuno-Psych project aims to advance understanding of the immune-modulatory mechanisms of psychedelics.⁵

The group is cultivating national and international collaborative networks to strengthen Ireland’s global profile in psychedelic science, expand opportunities for competitive funding and strategic partnerships, and ultimately accelerate the translation of research into meaningful clinical benefits for patients in the public health system in Ireland.

Expanding towards a national psychedelic research programme would generate real-world evidence, support precision stratification and augmentation strategies, enable integration of digital tools, and track biopsychosocial-environmental outcomes to optimise therapeutic outcomes.⁶

National Drug Science Centre?

A promising potential direction for the future of psychedelic therapies in Ireland could involve establishing a national drug science centre that embeds psychedelic research within a broader interdisciplinary and translational science framework. A pathway toward such a centre could begin modestly, by expanding the existing TCD group to develop a national psychedelic research programme consortium encompassing preclinical laboratories, clinical trial units, and HSE-linked service pilots.

Over time, this could evolve into a permanent drug science centre, with psychedelics embedded alongside other novel compounds. This staged approach would allow Ireland to scale research capacity, attract international funding, and ensure translational pipelines directly inform clinical policy and practice.

Several international research centres, such as the Centre for Psychedelic Research at Imperial College London and the Centre for Psychedelic & Consciousness Research at Johns Hopkins University, could serve as models for embedding psychedelic research within broader interdisciplinary and translational science frameworks in Ireland.

By combining foundational neuroscience with controlled clinical trials and implementation research, the centre would aim to generate high-quality evidence on safety, efficacy, and mechanisms of action, while developing scalable and sustainable treatment models that can be embedded within existing health service structures.

Specialised psychedelic medicine pilot clinic

Amid uncertainties regarding regulatory approvals and optimal delivery models, given the distinctive structural and organisational features of Ireland’s public health system, the establishment of a dedicated HSE pilot specialist clinic within the public mental health system merits consideration.

A HSE-supported pilot programme could facilitate the gathering of real-world outcomes, including cost-effectiveness assessments, a national outcomes registry, and assessing evidence-based integration into the Irish public mental health system. These efforts would prioritise ethical integrity, rigorous safety standards, equitable access beyond private care, standardised approaches, consistent adverse event monitoring, and robust informed consent procedures.

Public participation

As public support for psychedelic therapies continues to grow, there is an opportunity to ensure that any future HSE-delivered model is shaped by the perspectives of service users, carers, and communities. Facilitating this will require the formation of a diverse coalition, including clinicians – such as members of Irish Doctors for Psychedelic-Assisted Therapy (IDPAT) – researchers funders, policymakers, and members of the public, to collaboratively develop an ethical, evidence-informed, and sustainable model for psychedelic therapy in Ireland.

Importantly, a meaningful co-created approach and collective discourse around psychedelic therapies can help foster greater transparency and trust. This process aligns expectations with the evolving evidence-base, particularly in managing over-optimism around therapeutic potential and clarifying eligibility criteria, and help to define outcomes that are most relevant to service users and their families.

This highlights the necessity of standardised, evidence-based care pathways that prioritise clinical effectiveness, patient-centred practice, ethical integrity, and continuity of care, all of which are essential for a future public psychedelic service.

Challenges

Although psychedelic therapies demonstrate promising therapeutic benefits, several challenges must be addressed to evaluate the viability of psychedelic therapy within the Irish healthcare system. Methodologically, the potentially strong subjective effects of psychedelics can compromise blinding, allowing expectancy effects to influence outcomes beyond the drug’s pharmacological action. Although strategies exist to mitigate blinding issues, it may b e necessary to acknowledge that complete blinding is likely unattainable in practical terms.

Another key issue is the marked variability in response to psychedelic therapy, both across participants and within the same dose, as well as uncertainty regarding the durability of therapeutic effects.⁷ Additionally, self-selection bias, associated with expectancy, may constrain generalisation. Together with challenges in maintaining blinding and managing expectancy effects, these factors underscore the importance of careful trial design, rigorous monitoring, and cautious interpretation of results when evaluating the real-world clinical viability of psychedelic therapies.

Furthermore in Ireland, psilocybin is listed as a Schedule 1 controlled substance under the Misuse of Drugs Act 1977 (as amended, via the 2006 Declaration Order).

Despite the absence of regulatory approvals from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), a small but increasing number of countries have permitted the use of psychedelic therapies in regulated clinical settings. In 2023, Australia’s Therapeutic Goods Administration became the first national regulator in the world to reclassify psilocybin and MDMA, permitting their use in specific medical contexts.

Germany, New Zealand, Canada, and Switzerland have established special access programmes for psychedelic therapies. The Czech Republic, through national legislative reform, is poised to become the first EU Member State to authorise psilocybin therapy at a national level without prior approval from the EMA, potentially setting a precedent for Ireland and other countries.

Divergent international approaches highlight the ongoing uncertainty surrounding the integration of psychedelic therapies into routine clinical practice. In Ireland, while HPRA oversight remains appropriately cautious, both the HPRA and HSE have an opportunity to draw on pragmatic models from other jurisdictions.

While formal regulatory approval remains the most robust pathway, a flexible, phased approach, such as the proposed HSE pilot clinic, combined with a coordinated research programme, offers a practical means to explore the incorporation of these therapies into existing community mental health services.

Beyond regulatory authorisation, implementing psychedelic therapies in Ireland will require National Centre for Pharmacoeconomics (NCPE) evaluation, reimbursement decisions from the HSE Corporate Pharmaceutical Unit, and hospital-level approval, with each hospital following its own processes and timelines.

This complexity suggests that Ireland could benefit from piloting a dedicated psychedelic therapy pathway that aligns regulatory authorisation with NCPE assessment and reimbursement planning to ensure meaningful access.

The cost-effectiveness of psychedelic therapies is likely to play a central role in their integration and long-term sustainability within public health systems. Projecting costs is complex due to multiple factors, including the price of proprietary drug formulations, the duration and frequency of preparatory and integrative therapy sessions, and the need for specialised personnel/nurse time.

Furthermore, the durability of therapeutic effects and potential need for multiple dosing sessions will need to be assessed. Cost-effectiveness within the Irish public health system may be enhanced by utilising existing community infrastructure, personnel, and established governance structures.

Non-medical use

Classical psychedelics are not considered physiologically addictive and do not produce dependence or withdrawal syndromes. This contrasts with substances like ketamine, which carry a risk of physiological tolerance and dependence, and MDMA, which may produce psychological dependence and tolerance with repeated use.

The landscape remains complex, and safeguarding public health requires a clear distinction between medical integration and recreational or commercial liberalisation. Efforts to incorporate psychedelic therapies into clinical practice coexist alongside movements advocating for recreational use and the expansion of commercial markets.

Conflating these agendas risks complicating policy development, weakening ethical safeguards, and undermining the scientific credibility of psychedelic research.

Conclusion

Over the coming years, the responsible development of psychedelic therapies in Ireland will require coordinated action across clinical, regulatory, and research domains. Future efforts should prioritise independent research, robust national infrastructure, and evidence-based regulatory frameworks.

At the clinical level, a HSE-supported pilot programme, delivered through a phased hub-and-spoke model, could evaluate feasibility, acceptability, cost-effectiveness, and referral pathways within existing community mental health services. Such pilots would provide essential insights into how psychedelic therapies might be integrated safely and equitably into routine care.

At the research level, a national psychedelic research programme could generate real-world data, support precision stratification and augmentation strategies, integrate digital monitoring tools, and track bio-psycho-socio-environmental outcomes, ensuring that Irish evidence informs Irish policy.

Alongside this, national governance structures, clinical registries, and accredited training pathways would embed psychedelic treatments within established professional and ethical frameworks.

Ireland must develop integration pathways that combine regulatory approval, reimbursement, training, and outcome monitoring. This coordinated approach, rather than isolated approvals, will determine whether psychedelic therapy can become sustainably integrated and equitably accessible.

Sustainable implementation will also require participatory governance involving service users, community mental health teams, GPs, and other stakeholders, ensuring that enthusiasm is balanced with realism, and that emerging therapies remain aligned with public health priorities.

Ultimately, the real-world value of psychedelic therapies will depend not only on their clinical effects, but on how effectively they are embedded within a cohesive, equitable, and sustainable public health system. By committing early to pragmatic pilots, coordinated research, and inclusive governance, Ireland can establish trusted, evidence-led pathways and ensure the responsible stewardship of psychedelic therapy.

For more information on the work of The Psychedelic Research Group, please go to https://www.tcd.ie/medicine/psychiatry/research/psychedelic-research-group.