Dosing and Therapeutic Conduct in Administration Sessions in Substance-Assisted Psychotherapy: A Systematized Review

Psychedelics have a long anthropological history and renewed contemporary interest across ritual, recreational, underground therapy and clinical settings. Thal and colleagues note that while several serotonergic psychedelics and entactogens (for example psilocybin, LSD, ayahuasca, MDMA) are being investigated as adjuncts to psychotherapy for conditions such as addiction, anxiety, obsessive–compulsive disorder and treatment‑resistant depression, guidance about how therapists should conduct the administration session itself remains sparse. The authors highlight that therapeutic outcomes in substance‑assisted psychotherapy (SAPT) are shaped by the pharmacology of the substance, client dispositions and subjective experiences during dosing, and by preparatory and integration work, yet practical detail about in‑session conduct is often anecdotal or under‑reported in modern trials. This systematised review aims to summarise reported practices for the administration stage of SAPT. Specifically, Thal and colleagues set out to extract information about which substances are used as adjuncts, typical dosages, the number of administration sessions across models, common client and therapist issues during dosing, the types of subjective experiences elicited, and recommended therapeutic conduct during administration sessions. The paper is positioned as the third in a series synthesising Western psychotherapeutic paradigms for SAPT developed since the 1950s, building on prior reviews of preconditions and preparation-stage practices.

Thal and colleagues conducted a systematised literature review following PRISMA 2020 guidance and focused on extracting qualitative details rather than performing quantitative meta‑analysis. They searched MEDLINE (OVID), PsycINFO (OVID) and the Cochrane Library for publications available before 1 February 2022, supplemented these searches by scanning reference lists and consulting field experts, and archived search strings on an Open Science Framework page. Retrieved records were managed in EndNote 20. Inclusion criteria were broad: studies needed to involve classic serotonergic psychedelics or MDMA as adjuncts in SAPT, incorporate a psychotherapy or therapeutic technique, describe methods or theory guiding therapist conduct, and recruit participants diagnosed with psychiatric disorders per DSM‑IV or ICD criteria. After initial screening, the team also included healthy‑participant dosing studies that explicitly investigated dose effects. Exclusions comprised in vitro or animal research, indigenous/ritualistic uses, subperceptual dosing, unavailable full text, language other than English or German, and multi‑substance combinations. The review encompassed diverse document types (clinical trials, manuals, protocols, case studies, qualitative and descriptive papers, opinion pieces, reviews and book chapters). Screening was performed by pairs of independent reviewers in two waves (initial search 1 July 2019 and a repeat search 1 February 2022). Interrater reliability for title/abstract and full‑text screening was reported as good to excellent across rounds (κ values reported as 0.72, 0.66, 0.76 and 0.90). Data extracted from eligible sources included clinical targets, study design, therapeutic framework, substances and doses administered, and number of administration sessions; the reviewers synthesised this information to describe current best‑practice approaches for administration sessions.

The combined searches yielded a large literature base. The first search produced 3,932 hits plus 45 secondary records; after duplicate removal and screening 88 sources were included from that round. The second search returned 6,619 hits; after removing 447 duplicates and screening 6,172 records, 224 full texts were assessed and, with added records and one article included after peer review, the final synthesis comprised 82 publications. The 82 included items were heterogeneous in type: 31 clinical trials, one follow‑up analysis, four treatment manuals, two study protocols, three quasi‑experiments, two case studies, three qualitative investigations, three descriptive studies, one time‑series study, 14 opinion papers, 11 reviews, and seven books or book chapters. Not every source addressed all review questions. Substances and dosing: Psilocybin doses in recent clinical trials ranged from 1.75 to 30 mg with a median of 21 mg (reported as based on an average 70 kg body weight). A post hoc analysis of 10 studies (n = 288) reported moderately high mystical and intensity scores at 20 mg/70 kg and high mystical/intensity scores at 30 mg/70 kg, with similar low–moderate challenging‑experience scores; that analysis found no advantage to bodyweight‑adjusted dosing over fixed dosing. LSD historical dosing has ranged widely (20 μg to 1,500 μg) with a recent trial using 200 μg; some sources consider 100–200 μg therapeutically optimal in healthy adults. Ayahuasca was reported in one clinical study with specified alkaloid concentrations and dosing of 0.36 mg/kg N,N‑DMT. MDMA doses in clinical work ranged from 50 to 125 mg (commonly with a booster ≈50% of the initial dose offered after 2 hr) and a median dose of 110 mg; plasma MDMA concentration (and thus subjective strength) is significantly influenced by dose per bodyweight, leading to recommendations to adjust MDMA dosing for bodyweight. The authors note that dose selection should consider substance recommendations, client intentions and prior responses. Number of sessions: Historical models included a high‑dose single‑session psychedelic model, multi‑session escalating‑dose models, and low‑dose psycholytic approaches (the latter sometimes involving many sessions, up to 80). Contemporary clinical studies generally used between one and four administration sessions with a median of two; the chosen model influenced session counts. Commencing sessions and practicalities: Day‑of protocols commonly include a brief mood/well‑being check, cancellation if illness is present, a review of intentions and practical procedures (for example bathroom, agreements on touch), and a final reassessment of dose/substance. Many protocols encourage pre‑session silence, meditation or prayer to aid surrender; clients are often invited to self‑administer the dose, lie down and adopt an inward focus. Therapists are advised to trust their judgment and decline sessions if uncertain. Music: Music is widely used through headphones and is described as shaping subjective experience and possibly therapeutic outcome. Reported effects include facilitation of peak experiences, emotional release and autobiographical processing, but music can also have unwelcome effects (misguidance, negative intensification). Empirical findings are mixed: an early LSD study (n = 49) found no music‑condition differences, whereas a small psilocybin study reported overtone‑based music increased mystical scores and marginally improved treatment response relative to Western classical music. Expert surveys and interviews have been used to compile recommended pre‑peak and peak playlists and six key criteria proposed for effective music use, but definitive evidence for curated versus personalised playlists or specific genres is lacking. Client experiences and common issues: The review summarises a typology of experiences reported across sources—sensory‑aesthetic, psychodynamic‑autobiographical, cognitive‑intellectual, symbolic‑archetypal, challenging, and mystical. Challenging experiences (anxiety, panic, dissociation, paranoia etc.) and adverse physiological reactions vary by substance and dose; clinicians are advised to validate distress, provide reassurance, use grounding techniques (breathing, guided imagery, music changes), and reserve anxiolytics or antipsychotics for severe escalation. Mystical or peak experiences (ego dissolution, unity, noetic quality) are reported as reliably occasioned by classic psychedelics in prepared settings and have been associated in some randomised trials with persisting clinical benefits; they are proposed as potential mediators of therapeutic efficacy. Therapeutic conduct: Across sources, an unobtrusive, supportive and largely nondirective stance during administration sessions is recommended, with therapists ensuring physiological and psychological safety, minimising intrusive intervention, and preserving the client's inward focus. Presence, self‑awareness and responsiveness from therapists are emphasised, although these constructs have not been systematically measured in SAPT. Use of mixed‑gender co‑therapist teams is common to reduce therapist exhaustion. Conventional psychotherapeutic techniques (for example CBT, motivational enhancement, ACT) are more often used in preparation and integration, while verbal interventions during peak effects are limited; in psilocybin protocols, structured techniques are generally withheld until the final hour. Physical contact can be supportive when pre‑agreed and non‑sexual, but the literature flags increased risk of boundary violations under suggestibility. Projection, transference and countertransference may be amplified in SAPT; authors recommend supervision and preparation to manage these phenomena, though evidence is anecdotal. Practical conclusion procedures include creative expression and encouragement of reflection; overnight observation or hospitalisation is advised if severe anxiety or suicidality persists.

Thal and colleagues conclude that while there is broad consensus in the literature for an unobtrusive, supportive therapist stance during administration sessions, the empirical foundation for specific in‑session practices is weak. Much of the available guidance derives from anecdote, early (pre‑1970) research and descriptive sources, and modern clinical trials frequently do not report detailed information about how administration sessions were conducted. Consequently, the authors argue there is a pressing need for timely, rigorous qualitative and quantitative research to evaluate how specific therapeutic conduct during dosing affects outcomes and to clarify mechanisms of action. Several specific gaps are highlighted: validation of optimal substance–dose combinations for particular disorders; investigation of ethnoracial and sex differences in metabolism, safety and efficacy (given underrepresentation of women and Black, Indigenous and People of Colour in current samples); examination of derivative compounds; empirical determination of optimal numbers of administration sessions; and better evidence about the role and ideal sequencing or personalisation of music. The authors call for studies that link the occurrence and intensity of particular experiential classes to clinical outcomes and for research into the influence of therapist characteristics such as presence, responsiveness and self‑awareness, for which measurement instruments exist but have not been applied in SAPT. The discussion also stresses the difficulty of disentangling psychopharmacological effects from psychotherapeutic components and suggests experimental comparisons—such as nondirective supportive contexts versus manualised CBT frameworks, or systematic variation of psychotherapy elements across preparation, administration and integration—would be informative. Practical clinical priorities include comparing techniques used to de‑escalate distress (for example breathing, holding hands, anxiolytics) and investigating projection/transference management. The authors further note concerns about therapeutic misconduct and boundary violations in SAPT settings due to client suggestibility, recommending regulatory scrutiny, supervision, repeated training and formalised safeguards to reduce the risk of unethical behaviour. In sum, the authors state that although SAPT clinical research is advancing, essential components of therapeutic interventions during administration sessions remain tentative and largely untested; therefore conclusive best‑practice statements are not yet possible. They propose that the comprehensive description provided can inform baseline structures for training programmes and guide future systematic investigations into how in‑session practices and client experiences influence therapeutic outcomes.