Development and Evaluation of a Therapist Training Program for Psilocybin Therapy for Treatment-Resistant Depression in Clinical Research

Clinical psychological support is mandated by regulators as an integral component of psilocybin therapy to protect participants' physical and psychological safety. Interest in psychedelics for a range of mental health conditions has grown, and early clinical research with psilocybin has shown signals of rapid and sometimes durable improvements in depression and anxiety. Regulators expect not only standardised drug manufacturing and clinical data but also consistent delivery of the psychological support that accompanies psychedelic-assisted interventions; this creates a need for a clearly defined, scalable therapist training pathway. Lai and colleagues describe the development and practical implementation of a manualised therapist training programme designed for a Phase IIb international, multicentre, randomised controlled trial of psilocybin therapy for treatment-resistant depression (clinical trial NCT03775200). The clinical trial randomises 216 participants to low (1 mg), medium (10 mg) or high (25 mg) doses of COMP360, a GMP-produced psilocybin formulation, each administered alongside structured psychological support delivered by specially trained therapists. The paper focusses on the rationale, the multi-component training curriculum, fidelity procedures, lessons learned from early implementation, and implications for scaling to Phase III and post-approval practice.

The paper reports on the design and roll-out of a multi-component therapist training programme developed for the COMP360 Phase IIb TRD trial. Training was created collaboratively with mental health researchers, clinicians and experts, and its content and therapist selection criteria were agreed with the FDA and incorporated into the Investigational New Drug programme. Training comprises four mandatory components: a self-paced online learning platform, an interactive 5-day in-person course, supervised clinical training in research sessions, and ongoing mentoring plus participation in monthly webinars for continuing professional development. Therapist eligibility required a professional mental health licence in good standing and demonstrated clinical experience appropriate to psychotherapy or mental health counselling. For United States sites the FDA required therapists to hold at least a master’s level qualification and that two trained therapists be present at each psilocybin session. A psychiatrist must be available on-site to respond to emergencies and receives separate training. Sites selected therapists according to local regulatory and institutional requirements and interviewed candidates to assess motivation, presence, openness and familiarity with Good Clinical Practice (GCP). The online component, called the Shared Knowledge Platform, contains over 20 hours of video modules and materials on psilocybin neuroscience, psychopharmacology, safety, ethics, the therapeutic manual, re-enacted clinical scenarios and adherence rating tools. In-person training (groups of 10–15) emphasised role-plays, peer feedback and trainer assessment of interpersonal and clinical skills. Clinical training required therapists, in agreement with the FDA, to participate in at least four psilocybin research sessions as supporting clinicians before leading sessions independently; prior relevant experience from other psychedelic trials could partly or fully waive this requirement. Ongoing mentoring follows a structured format similar to clinical supervision but without formal managerial authority; mentors meet monthly and produce written action points. Webinars are held monthly and therapists are required to attend at least 50% to present cases and share learning. The team developed fidelity measures to quantify adherence to the therapeutic approach. The fidelity instrument comprises items for preparation (25 items), session (18 items) and integration (12 items); items are rated on a three-point scale ("Yes", "Yes, but below the desired level", "No"). Fidelity assessment uses video-recorded sessions, self-ratings by therapists and external raters, with non-therapist raters required to complete online modules and group training. For evaluation of the training programme, the researchers collected anonymous post-training surveys from therapists and conducted semi-structured 90-minute interviews with a subset of therapists after 35% of participants had received psilocybin therapy. The qualitative data from surveys and interviews were not subjected to formal qualitative analysis.

At the time of reporting, more than 65 therapists and assisting therapists had completed the full training to work across COMPASS Pathways' psilocybin studies in North America and Europe. The therapist cohort included psychologists, psychiatrists, master’s-level clinicians, nurses, CBT diploma therapists and PhD mental health specialists. Reported years since qualification averaged 25.9 years (SD 8.8) with a range of 2–32 years. Training was implemented across 21 sites in 10 countries. Thirty-seven therapists completed the anonymous post-training survey. On questions about the amount and usefulness of feedback during training, 18 rated trainer feedback as "sufficient" and 19 as "more than enough"; for usefulness of feedback 2 rated it "somewhat useful" and 34 "very useful". Although the paper does not provide a full distribution of the 1–5 overall training quality ratings, survey and interview responses converged: therapists described the training as comprehensive and well structured. They reported the Shared Knowledge Platform to be a valuable resource before and during clinical activity. The 5-day in-person course was universally regarded as sufficient, provided trainees had completed the online preparatory material first. Clinical training—the supervised participation in actual psilocybin research sessions—was consistently cited as the most beneficial and the most challenging component of training. Therapists offered specific requests for additional online material, including modules addressing psychiatric and medical comorbidities, suicidality, medication washout, expanded cultural competency content and resources for therapist self-care. The fidelity scale is being validated and refined, and across the study therapists self-rate every session while external raters also assess recorded sessions. The authors note limitations of the feedback data: the programme was at an early stage and most therapists had supported only a small number of participants, and thus the dataset does not permit analysis of any relationship between therapist training experience and participant-level safety or efficacy outcomes.

Lai and colleagues interpret their experience as indicating that structured, multi-component clinical training is essential to deliver consistent, high-quality psilocybin therapy within regulated clinical trials. They note a paucity of formal research on training for psychedelic-assisted therapies and distinguish their programme from other existing postgraduate or sponsor-run trainings by its direct alignment with the COMPASS protocol and regulatory requirements. Clinical, supervised experience is emphasised as central and not easily outsourced, leading the researchers to recommend concentrating clinical training at selected academic sites with sufficient enrolment and experienced trainers to support a sustainable certification pathway. The authors discuss contested issues in the field, including whether therapists should have personal experience of psychedelic drugs. They report that the current programme does not include mandatory personal drug experience but allows discussion of such experiences, recognising both potential benefits and barriers to inclusion. Fidelity assessment is presented as fundamental for internal validity, regulatory compliance and future reimbursement decisions; the authors advocate introducing fidelity measures early in training and plan a dedicated fidelity manual for Phase III. They also acknowledge logistical challenges in delivering ongoing mentoring and professional development across wide geographic and time-zone differences and propose solutions such as regional training centres, a "train the trainer" model and greater use of technology. Exploration of machine learning and artificial intelligence to support fidelity measurement and feedback is described as an area under investigation. Key limitations acknowledged by the investigators include the early stage of the programme, limited therapist exposure to participants at the time of reporting, and the absence of formal analysis linking training metrics to participant safety or clinical outcomes. They indicate future work will focus on validation of fidelity instruments, expansion of online modules (including cultural competency), and scalable mechanisms for clinical training and quality assurance.

The authors conclude that rigorous therapist training is critical to ensure consistent and high-quality psilocybin therapy in clinical trials and for potential post-approval delivery. They stress that early, active and ongoing collaboration among mental health experts is necessary to develop a training methodology that is rigorous, effective and scalable. To meet the demands of Phase III studies and wider clinical deployment, the researchers advocate adopting enhanced online learning technologies and establishing clear pathways for clinical training, which will require close public, academic and industry collaboration.