Beyond the psychotherapy debate: the participant support model as a safety-centred framework within clinical trials of psychedelics

Introduction

Non-pharmacological support in clinical trials of psychedelic medications remains debated and can be conflated with psychotherapy, creating scientific ambiguity and regulatory uncertainty. Historically, academic and clinical perspectives have led the field, emphasising safety and therapeutic optimisation. Sponsors, however, must evaluate efficacy in placebo-controlled conditions, where standardised clinical environments are critical to interpretable results; loosely defined and inconsistently implemented environments, by contrast, increase variability and limit interpretability.

Study Aims

To develop a research informed participant support framework aligned with sponsor responsibilities for evaluating drug safety and efficacy.

Methods

We conducted a systematic review of published literature that distinguished psychological support from psychotherapy and reviewed Phase 2 trial experiences, including participant interviews. We then developed a PS framework, aligned with protocol demands, regulatory expectations, and Good Clinical Practice to be implemented in Phase 3.

Results

We defined PS as non-directive, protocol-aligned interactions focused on participant safety, psychoeducation, and study engagement – distinguished from psychotherapy, which applies structured psychotherapeutic frameworks to support safety while also facilitating symptom treatment and/or enhancing efficacy. Hence, PS defines the boundaries of safe and consistent trial conduct rather than delivers or enhances therapeutic effects.

To ensure consistent global clinical trial delivery, we present the “Participant Support Framework,” a multi-component system that provides Facilitator training, consistent PS delivery, and quality oversight (Table). Facilitators are trained to deliver standardised, non-psychotherapeutic support that emphasises safety, orientation, and supportive presence. We complement this approach with participant-facing learning materials to support informed consent and expectation setting; site staff training to promote a consistent participant experience and environment; structured mentorship to address performance gaps; and adherence monitoring to evaluate fidelity across sites. Taken together, these components reduce variability in non-pharmacological conditions while maintaining sensitivity to participant experience and supporting more consistent and interpretable drug safety and efficacy outcomes.

Table: Participant Support Framework Components

Component	Description	Primary Function
Facilitator Support	Non-directive preparation and support during dosing and the post-dose period	Safety, psychoeducation, participant monitoring, ethical conduct
Facilitator Training	Translation of the PS manual into standardised, protocol-aligned facilitator behaviours and procedures	Consistency, safety, and protocol adherence in PS delivery
Participant Facing Materials	Educational and preparatory resources	Informed consent, expectation setting, autonomy
Staff Training	Participant-facing staff training	Consistency of participant experience, safety coordination
Mentorship	Proactive and remediation support for facilitators	Quality maintenance and addressing non-adherence
Adherence Monitoring	Systematic evaluation of PS fidelity	Standardisation, data integrity, regulatory compliance

Conclusions

This PS model replaced the loosely defined concept of “psychological support,” explicitly distinguishing it from psychotherapy in line with prior published literature, and guided the design of a multidisciplinary implementation framework aligned with scientific and regulatory requirements. By embedding it within the RCT design, we enhance transparency, reproducibility, and interpretability of trial outcomes. These distinctions support rigorous evaluation of investigational products while maintaining high standards of participant safety.

References

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