Systematized Review of Psychotherapeutic Components of Psilocybin-Assisted Psychotherapy

Research on mental illness treatment has expanded to include renewed clinical interest in psychedelic-assisted approaches that combine pharmacology with psychotherapeutic processes. Horton and colleagues frame psilocybin-assisted psychotherapy (PAP) as an intervention in which both the drug and the psychological context — commonly discussed as "set and setting" — are considered central mechanisms of therapeutic change. Although multiple trials over the past 25 years have reported promising clinical outcomes for conditions such as depression, anxiety, substance use and demoralisation, the authors note a gap in the literature regarding the detailed structure, content, and role of psychotherapy within PAP protocols. This systematized review therefore aims to characterise how psychotherapy has been integrated into modern PAP trials. Specifically, Horton and colleagues sought to answer: what roles do therapists play in PAP, what is the typical structure of PAP sessions, and which psychotherapeutic modalities and techniques have been used alongside psilocybin? Treatment outcomes from eligible trials were also summarised to provide context for how psychotherapeutic components relate to clinical results. The intent is to inform future work that seeks to refine PAP procedures and identify which psychotherapeutic adjuncts are most appropriate for different clinical indications.

The investigators performed a systematized review of peer-reviewed human clinical trials of psilocybin published between 31 December 1994 and 23 January 2021. They followed many elements of systematic review methodology, including a PRISMA-informed search protocol developed by the first author (Horton) and reviewed by a co-author, but the review differed from a full systematic review because it did not include a formal risk-of-bias assessment nor a second independent reviewer for screening. Eligibility required that studies administer psilocybin in a clinical setting with psychological support and evaluate PAP either for a specified psychiatric condition or to interrogate PAP structure/content. Both Phase I and later-phase trials were eligible. PubMed and PsycInfo were searched using the single term "psilocybin" to maximise capture of relevant trials; reference lists and, where necessary, direct contact with study authors were used to clarify missing information. Screening occurred in two stages: level 1 title-and-abstract screening followed by level 2 full-text screening using the stated eligibility criteria. Extracted variables included authorship and year, blinding status, sample size and population, therapeutic constructs measured and primary outcomes, therapists' credentials, numbers and content of meetings at each stage (pretreatment, treatment, posttreatment), and dosing. Data were collated into tables and figures in Microsoft Excel. The authors note that some data were incomplete and that attempts to obtain missing details from trial authors were sometimes unsuccessful.

From 1,058 records identified in the two databases, 912 records were excluded at title-and-abstract screening and 146 full-text articles were assessed. After accounting for duplicates and applying eligibility criteria, 11 clinical trials were included in the review. Several trials produced multiple publications that provided complementary information. Role and qualifications of therapists: All 11 trials reported session therapists whose core responsibilities were preparatory work, providing psychological support during psilocybin administration, and facilitating postsession integration. A dyadic model with two therapists present during dosing was standard across studies; all but one trial reported at least two therapists during treatment sessions. Three studies intentionally paired one male and one female therapist. Training in psychedelic psychotherapy and in recognising and managing psychedelic experiences was reported in all trials and was prioritised over formal academic credentials. Reported therapist titles and credentials varied: psychologists and psychiatrists were the most commonly listed titles (each reported as N=19 across the dataset), many therapists held master's-level qualifications (N=15, often in social work, N=8), eight held bachelor's degrees, and other roles included chaplain, nurse, shiatsu therapist and life coach. Several studies distinguished primary and assistant therapist roles. Structure of PAP: Every trial followed a three-stage structure: pretreatment, treatment, and posttreatment. Pretreatment sessions occurred in all 11 studies and aimed to build therapeutic rapport, set intentions, and prepare participants for the psilocybin experience; the number of preparatory sessions averaged about 3.3 (SD 1.44) though some details on total preparatory hours were not clearly reported for all trials. Treatment sessions were the only stage in which psilocybin was administered (11/11). These sessions typically lasted long periods (mean session length reported as approximately 7.46 hours, SD 0.78), commonly involved the participant lying down with eyeshades and listening to a standardised music playlist, and were conducted in a nondirective, supportive manner. A decorated, comfortable room resembling a living room was reported in 10 of the studies (91%). Interaction with therapists generally increased toward the end of the dosing session. Posttreatment or integration sessions were reported in 10 of the trials (one trial did not clearly indicate posttreatment sessions). Where reported, the number and duration of integration sessions varied across studies (mean number reported as about 6.1, SD 4.61, N=10, but several studies lacked complete data despite attempts to contact authors). Integration discussions typically occurred between doses when multiple dosing sessions were used. Psychotherapeutic modalities and techniques: Music therapy was used in every trial (11/11); all used a standardised playlist during dosing, typically comprising neoclassical, classical or ambient selections with minimal lyrics, and in some trials playlists were standardised to improve comparability. Several conventional psychotherapies were adapted and explicitly cited in individual studies: motivational enhancement therapy (MET) was incorporated in Bogenschutz et al.'s alcohol study with reported inclusion of seven MET sessions within a 12-session psychosocial package; Johnson et al. used cognitive behavioural therapy (CBT) components across four pretreatment sessions for tobacco cessation; Anderson et al. modified supportive-expressive group therapy (SEGT) for palliative care populations. Other trials described eclectic or person-centred approaches drawing on supportive, existential, Rogerian, psychodynamic, or logotherapeutic elements. Specific psychotherapeutic techniques reported across studies included emphasis on building the therapeutic relationship (reported as a primary goal in eight studies, 73%), body-scanning mindfulness exercises, journaling/open-ended narrative writing followed by integration discussion, guided imagery or meditation practices, supportive touch and reality orientation during challenging moments, and structured integration work postdosing. Eight studies explicitly described integration work in posttreatment sessions. Outcomes and adverse events: No trial reported serious adverse events attributable to psilocybin, and no participant required the planned 'rescue' medication during dosing sessions. Common transient adverse events included increased blood pressure, headaches and anxiety. Quantitatively, all but one trial reported statistically significant improvements in targeted outcomes (depression, anxiety, substance use measures, attitudes/mood), and seven studies reported large effect sizes for clinically relevant constructs. Johnson et al.'s tobacco cessation trial reported 7-day point-prevalence abstinence of 80% at the 6-month follow-up and 53% abstinence maintained at 12 months. Among depression/anxiety studies, four of five demonstrated clinically significant reductions; Grob et al. achieved significance by 6 months. Qualitative analyses from selected trials highlighted processes such as participants shifting from disconnection to connection and from emotional avoidance to acceptance, and participants frequently reported music as a central facilitating element. Griffiths et al. was the only trial among those reviewed to include psychotherapeutic support as an independent variable; their analyses suggested that greater psychotherapeutic support correlated with larger short- and long-term improvements in domains such as daily life experiences, gratitude and meaning.

Horton and colleagues interpret the reviewed literature as demonstrating consistent procedural structure across contemporary PAP trials, with pretreatment, dosing, and posttreatment stages forming the backbone of protocols. They emphasise that therapists fulfil three core roles — preparation, in-session supportive presence, and integration facilitation — and that modern PAP predominantly uses a nondirective supportive therapeutic stance during dosing accompanied by standardised music playlists. The authors position these findings relative to earlier mid-20th-century distinctions between psycholytic and psychedelic therapy, noting that recent trials have not commonly implemented in-session, directive psychotherapy during low-dose sessions the way psycholytic paradigms did. Instead, conventional psychotherapies tend to be applied outside dosing sessions (in pretreatment and integration) or minimally during the final hour of dosing. Music emerged in the authors' synthesis as a potentially central, active component in facilitating emotional processing and guiding the psilocybin experience, supported by qualitative reports from several trials. Key limitations acknowledged by the study team include the review's own methodological constraints: as a systematized review it did not include a formal risk-of-bias assessment and lacked a second independent reviewer. In addition, several trials lacked complete reporting of details such as hours of preparatory or integration work despite attempts to contact authors, which constrains comprehensive cross-study comparison. The heterogeneous designs and variable reporting across trials limit capacity to ascribe specific effects to psychotherapeutic components versus the pharmacological action of psilocybin. Looking forward, Horton and colleagues recommend empirical research to disentangle the therapeutic contribution of psychotherapy within PAP. Suggested approaches include trials that vary the intensity or modality of psychotherapeutic support (for example, minimal nondirective supportive care versus an evidence-based psychotherapy such as CBT) while controlling for nonpharmacological factors, use of low-dose psilocybin or placebo controls to isolate drug effects, blinded outcome assessment, and strategies to mitigate therapist allegiance bias (for instance, employing experts aligned with each adjunctive modality). The authors also highlight the need to adapt PAP procedures to be culturally and structurally inclusive and sensitive to diverse patient populations, and they note that practicing therapists — often non-psychiatrists in the reviewed trials — will likely play a central role in delivering PAP if it becomes a licensed treatment, making targeted PAP training for clinicians important.

The review consolidates contemporary PAP practice as a three-stage intervention in which therapists provide preparatory, in-session supportive, and integration services, and where music and nondirective support are near-universal components. Horton and colleagues conclude that isolating psilocybin's independent effects requires better-controlled trials that account for psychotherapeutic variables, and they suggest that the influence of psychotherapy on outcomes may be larger than current literature indicates. Finally, the authors observe that counsellors and therapists are well positioned to contribute to PAP delivery and can engage through specialist training, participation in trials, or continued professional attention to PAP's development.