What it is
Guided psychedelic sessions in research share a rough shape. Participants meet the research team beforehand, the session takes place with trained staff in the room, and there are meetings afterwards [1]. In trial language these are preparation, the administration session and integration [2]. This discipline studies those human and environmental parts of the experience: who is present, what is said and done, what the room is like and what the person expects.
The vocabulary is slippery. Set is the mind a person brings and setting is the surroundings, and the two are hard to separate, as experts in a 2025 consensus exercise reported, including how far in time the setting extends [2]. The person who stays with a participant is called a monitor, guide, sitter or facilitator. A review found a wide range of practices under the word integration, with ten well-developed models, all published since 2017 [3].
A Johns Hopkins paper published online in December 2025 proposes that psychological support is interaction aimed only at keeping the participant safe, while psychotherapy is aimed at safety and at treatment benefit [4]. A trial cannot say what human contact added unless it reports what happened in the room. In healthy adults nobody is being treated, so the useful question is whether context alters what a person experiences and what lasts afterwards.
Metanoia keeps this discipline among its six because context cannot be subtracted from any study of natural psychedelics in healthy adults. A result from a quiet laboratory room with two trained monitors may not carry over to a retreat or a ceremony, and the size of any gap is not known. The discipline is research on support frameworks, and providing one is a different job that is not Metanoia's.
What is known
The short version. Context shapes the experience, and the evidence for that is consistent but mostly observational. How far it shapes lasting outcomes in healthy adults is largely untested. In pooled laboratory data the identity of the facilitator explained under one percent of the variation in the acute experience of healthy volunteers. Trials in patients describe their human support poorly. Integration has many definitions and almost no outcome data. In one Oregon cohort, facilitators recorded only one of four serious reactions that participants later described themselves.
Set and setting: what the label covers
A 2016 review sets two ideas side by side. Placebo theory describes how expectation, belief and context change responses to any treatment, and set-and-setting theory was built for psychedelics to instruct therapists and users in shaping effects [5]. A later paper names four contextual "common factors" found across healing traditions and argues they blur the idea of a clean placebo [6]. Neither adds data.
One analysis pooled 23 controlled laboratory studies of psilocybin, covering 409 administrations to 261 healthy volunteers. The amount of drug was the strongest predictor of the response, and several non-drug factors still contributed. Absorption, a cheerful state before the session and few recent psychological problems went with pleasant and mystical-type experiences, emotional excitability went with both mystical-type experience and anxiety, and a brain-scanner setting was the strongest predictor of anxiety, while sex, education and neuroticism did not predict a negative response. Expectation was not measured, setting was represented only by the scanner contrast, the volunteers were young, highly educated and screened, and the design cannot show cause [7].
A prospective online study, which follows people forward in time, followed people planning to take a psychedelic on their own. Survey completion fell from 654 people to 212, about a third reported an earlier psychiatric diagnosis, 74 percent were men and 90 percent had used psychedelics before. Feeling well prepared predicted fewer challenging experiences, and comfort in the setting showed only a trend. Being in a "therapeutic environment", a category that included retreats, predicted neither the experience nor well-being, though the authors note they did not define it [8]. A 2018 opinion paper from the same group proposed a test design [9].
Imperial College London built a nine-item readiness scale. In 28 healthy volunteers, who completed a shortened version, set and rapport together explained 40 percent of the variation in mystical-type experience, though neither was significant alone (p = 0.088 and p = 0.074), and set alone explained 16 percent of the variation in challenging experience. In two large observational datasets the scale explained only about 2 to 7 percent, and the authors write that it may be too early to use it as a safeguard [10].
Expectation
If people expect a psychedelic effect, some of them report one. In a study of 33 students told they were taking a drug like psilocybin, in a party-like room with confederates acting out effects, everyone received a placebo. About 61 percent said they felt some effect, and a few scored at levels typical of active psilocybin in other studies [11].
Two studies of microdosing outside clinics, a different practice from guided sessions, point the same way. In a self-blinded study, 1,630 people registered and 191 completed. Outcomes improved in the microdose group and in the placebo groups with no significant difference between groups, and in 21 of 22 comparisons outcomes were better when participants guessed they had taken the active capsule. The authors say the study may have lacked statistical power [12]. In a prospective survey with no control group, 316 people enrolled and 81 reached the four-week endpoint, and nearly half reported an earlier psychiatric diagnosis [13].
In patients the picture is mixed and less settled than it first looks. An exploratory analysis of a trial in 55 adults with depression, not preregistered and using an unvalidated two-item measure of expectation, found that expectation for the antidepressant predicted response while expectation for psilocybin did not, and suggestibility predicted response only in the psilocybin arm. The equivalence tests were not significant, so the authors can neither rule out nor confirm an expectancy effect in the psilocybin arm. After adjusting for expectation, the difference between the two arms in the original trial was no longer there, which the authors read mainly as a nocebo-type effect in the antidepressant arm [14].
The trial model: preparation, session, integration
The 2008 safety guideline from Johns Hopkins, remains a field reference. It is an expert guideline and not a comparative study, so it records what one group adopts as procedure and does not show that the safeguards prevent harm. Its safeguards include exclusion of volunteers with a personal or family history of psychotic or other severe psychiatric disorder, careful preparation, at least two monitors and follow-up contact. At the time of writing, none of the 54 volunteers who had received a high dose of psilocybin at that centre had shown evidence of persisting psychosis or psychological problems related to their sessions [1].
The ReSPCT guidelines came from four survey rounds among 89 experts in 17 countries, and about 30 percent of the panel dropped out by round four. Free-text responses were merged into 49 items and four rounds left 30, with agreement set at 70 percent and two items kept after subgroup discussion. The authors state limits: the work was survey-based, restricted to clinical trials and drew mostly on Western experts, about 80 percent of the final-round panel was white, and expert opinion is not proof [2].
What happens in the room is still thinly reported. Hopkins authors applied their support-versus-psychotherapy criteria to 11 published classic psychedelic trials. Ten of the 11 were more or less consistent with one label or the other, but clear distinctions were possible in only 4 [4]. A May 2026 correction to the paper could not be retrieved [16]. A phase 2 trial in treatment-resistant depression that enrolled 233 adults gave psychological support in every arm, so by design it cannot separate the support from the drug. The support was manualised, time-limited and not a stand-alone psychotherapy, with at least three preparation sessions, two monitors and two integration sessions [17]. The trial was industry-funded, and its comparison was between amounts of the drug given with the same support.
A 2025 technical report shows how a support framework can be written down. It describes a group retreat model for people with metastatic cancer and anxiety or depression, in a single-arm, open-label study with licensed lead facilitators. The outcome data sit in a companion paper that was not read [39].
Who sits in the room
One path analysis used the psilocybin arm (30 patients) of a trial that compared psilocybin therapy with an antidepressant in major depressive disorder. A stronger therapeutic alliance predicted better pre-session rapport, emotional breakthrough and mystical-type experience, and lower depression scores at six weeks, though after correction for two comparisons the mystical-type pathway fell to p = 0.06. A weaker alliance before the second session predicted higher end depression scores, with standardized coefficients of -0.33 and -0.31 in the two models of the results. The abstract reports -0.49 for this link, but in the results that value belongs to a different link. The sample was screened for rapport, with 44 of 103 candidates excluded for concern about it. In the escitalopram arm the alliance predicted neither the acute experience nor the outcome, according to the paper's discussion, since the supplementary material was not read. [18].
Another analysis pooled nine psilocybin studies with 60 facilitators. After controlling for study and participant differences, facilitators accounted for 0.8 percent of the variation in acute subjective effects among healthy volunteers and 13.6 percent in clinical samples. The authors suggest facilitators may play a clinically meaningful role in patient populations [19]. It concerns the acute experience, not what facilitators add to safety or to lasting outcomes.
Support outside the clinic, in non-patient groups
An online study followed 886 people enrolled before a psychedelic ceremony or retreat. Only 399 reached the four-week endpoint, and the path model rests on the 213 who had every time point. Communitas, a felt sense of togetherness and shared humanity, reported for the retreat as a whole predicted higher well-being (0.16) and social connectedness (0.19) four weeks later. Female gender predicted lower communitas (-0.17). There was no control group, and the sample was self-selected, mean age 44, 91 percent white and highly educated, and not restricted to healthy adults. The authors warn that in ritual settings heightened suggestibility and blurred boundaries can lead to instability, and they refer to reports of sexual abuse [20].
A registered feasibility trial from University College London will randomise 40 non-treatment-seeking adults without a diagnosis to a 21-day digital preparation course or to background music alone. The trial is partly funded by the psilocybin manufacturer, and the protocol separates its support model from therapeutic intervention [21]. The ClinicalTrials.gov record (NCT06815653) was last updated on 26 November 2025 and showed no results on 4 October 2026. It listed the trial as recruiting with an estimated primary completion date of March 2026, while the protocol puts recruitment as running to June 2026 and the last follow-up in September 2027, so the registry dates do not match the protocol [22] [21].
Integration: widely used, barely tested
A Brazilian online survey of 1,379 people validated an integration scale whose scores correlated with mystical experience (r = 0.636), and open-ended answers named reflection, professional support, practice, nature and social support, and also difficulties in integration. The survey was cross-sectional [23].
Searches of PubMed and Europe PMC on 2 October 2026 found no randomised trial of an integration programme against no programme in healthy adults. A search is not proof of absence, but the literature offers definitions, models, qualitative studies and cross-sectional scales instead.
Safety and ethics
The safety data come mostly from patients. A meta-analysis of 214 classic psychedelic studies, with analysable adverse event data for 3,504 participants, found no serious adverse events in any healthy participant and late serious events in about 4 percent of psilocybin outpatients with preexisting neuropsychiatric disorders, including events the authors did not link to the drug, such as a death from worsening cancer, a miscarriage and a planned surgery. Healthy participants did report non-serious events that needed medical or psychiatric attention, at low rates: a psychotic reaction in 0.4 percent of LSD participants and 0.2 percent of psilocybin participants in the early phase. Only 16 of 68 studies since 2005 described systematic adverse-event assessment, and the authors flag underdetection and say the findings cannot be generalised to unsupervised use [24]. A 2026 narrative chapter on complications notes the lack of consistent prevalence data [25].
Oregon's public dashboard for 2025 recorded 5,935 clients and 5,375 sessions, with behavioural adverse events at 2.42 and medical ones at 2.79 per 1,000 sessions. The same client may be counted more than once, and 32.6 percent of clients came from outside Oregon. The dashboard holds no validated outcome measures and only acute events, and low counts may reflect incomplete reporting by staff who are not required to be clinicians. The paper's table of serious behavioural reactions does not add up to the annual total it prints, so that count is not used here [26].
In a separate cohort followed forward in time, 346 Oregon clients were tracked for three months. Four (1.2 percent) had serious behavioural reactions that needed medical attention, all first-time psilocybin users who had sought it to treat mental health symptoms and had preexisting conditions. The authors report that facilitators recorded only one of the four. The other three surfaced in participants' own follow-up reports, which described worsening anxiety or depression and, in two of the four cases, new thoughts of death, suicide or self-harm. The authors report that three of the four described the experience as highly meaningful, though the case table is less uniform: one called it among the five most meaningful experiences of their life, two likened it to meaningful experiences that come about every five years, and one called it no more than routine. The cohort reported no unwanted touch or sexual contact by facilitators, and lasting perceptual changes of the kind called HPPD in the preceding 30 days from 10.0 percent of participants at one month and 8.7 percent at three months, with one person describing significant distress. It is not a healthy-adult sample. The design was observational with no comparison group [27].
Ethics sits beside safety. A 2024 consensus statement from a 27-person meeting reached 20 points across five issues, including informed consent, professional boundaries and physical touch [28]. A 2023 JAMA Psychiatry viewpoint is titled "Studying Harms Is Key to Improving Psychedelic-Assisted Therapy", and since it has no abstract and its full text was not accessible, only the title was read and its content is not described here [29]. A narrative analysis of one smoking-cessation pilot argued that the treatment manual itself can reshape a person's sense of identity [30].
Training, licensing and rules
Each legal statement below gives its jurisdiction, its source and the date it was checked, or says that it is not verified.
Oregon (state law). The sources are Oregon Health Authority (OHA) documents [31] [32] [33] and ten rules from the state's administrative rules, OAR 333-333 [40], all read on 4 October 2026. The state requires what it calls a non-directive approach, and licensed facilitators must be present for preparation, administration and integration sessions. Applicants must be 21 or older, complete an approved training programme and pass a state exam [32], with a pass mark of 75 percent, unlimited attempts and four hours of continuing education a year [40]. For training programmes applying or renewing from 1 January 2025, the rules require at least 128 hours of core teaching in nine modules [33] [40], and a practicum of at least 40 hours that from 1 January 2026 must take place at a licensed service centre [40]. According to the fact sheet dated December 2024, a client needs no prescription or referral, may come for any reason, and must attend at least one preparation session first [32].
That fact sheet has been overtaken on other professional licences. It says licensed facilitators may not practise on another professional licence in preparation, administration or integration sessions, which OAR 333-333-5130, in force from 1 January 2026, keeps as the default, with an exception. A facilitator who has notified the OHA of an eligible professional licence, may provide health care or mental health services in preparation and integration sessions if the client has been told. The exception does not cover the administration session, and in the sessions it covers the facilitator is exempt from the non-directive requirement. Facilitators otherwise neither diagnose nor treat physical or mental health conditions [40]. The exception bears directly on the line between support and therapy that this discipline studies. Ten rules of the division were read, and the rest of it was not.
Colorado (state law). A 2023 law (SB23-290) put facilitator licensing under the state's Division of Professions and Occupations, according to the legislature's bill summary [34]. The Division's licensure rules (4 CCR 755-1), in the emergency version in force from 5 December 2025, create two licence types, Facilitator and Clinical Facilitator [35]. Applicants for either must be 21 or older and complete an approved training programme of at least 150 teaching hours across 14 content areas, plus at least 40 hours of supervised practicum and 40 hours of consultation. A Facilitator does not independently practise medicine or psychotherapy, and only the Clinical Facilitator licence requires an existing Colorado clinical licence. A facilitator who holds an active secondary licence may provide health care or mental health services within that licence alongside natural medicine services. A person without a licence may hold a sincere religious, traditional cultural or spiritual ceremony if every participant is told so and it is not tied to commercial activity [35]. The rules were read on 4 October 2026 in 13 of their sections only, and an emergency rule can change. The statute itself (C.R.S. 12-170) was not read at an official source, so this page makes no statement that rests on it.
The wider field. Interviews with 13 of the 20 US training organisations the authors contacted, chosen by snowball and purposive sampling, reported no universally accepted accreditation or licence in the US. It was a quality-improvement exercise and not a representative survey, and the counts of how often an item was mentioned are not adoption rates. One programme warned that trainees may leave believing they learned psychotherapy, when the programme does not teach it. The authors write that Colorado licence recipients must hold a clinical licence, which by the rules above is true only of the Clinical Facilitator tier [36] [35]. A competency framework from one Canadian programme is practice-based, not externally validated and not a consensus standard, and it grew out of a programme with 219 students whose authors take part in it [37].
The federal framework
In July 2026 the US Food and Drug Administration issued a final guidance, "Psychedelic Drugs: Considerations for Clinical Investigations", finalising a June 2023 draft. The whole 13-page guidance was read on 4 October 2026. It is nonbinding and addressed to sponsors developing psychedelic drugs for medical conditions. On the human side it says the contribution of the psychotherapy component to any observed efficacy "has not been characterized", that consent forms should describe the increased vulnerability and suggestibility during the session, that developers consider measuring expectation and ask participants and raters to guess who received the drug, and that safety monitoring is expected to include two monitors for the whole session, the lead a licensed provider with graduate-level training and clinical experience in psychotherapy, the assistant with a baseline degree or nursing training and at least a year in a licensed mental health setting, and a physician available within 15 minutes if the lead is not one [15]. The guidance does not mention healthy adults, state programmes, facilitators or integration. It notes that many psychedelic drugs are Schedule I controlled substances under federal law (21 CFR 1308.11) [15]. The state programmes above license services under state law, and they do not change that federal classification.
Null results, failures to replicate and weak methods
Most of the findings above come from designs that cannot separate cause from correlation: one setting contrast, a healthy readiness-scale group of 28, an alliance analysis of 30 patients, a retreat study that lost more than half its sample, and two uncontrolled Oregon datasets [7] [10] [18] [20] [26] [27].
Several results are null, or fail to line up. Being in a therapeutic environment predicted neither the experience nor well-being in the prospective online study [8]. In the depression trial, the link between alliance and outcome found in the psilocybin arm was not found in the escitalopram arm [18]. The expectation effect appeared for the antidepressant and not for psilocybin, but the equivalence tests were not significant, so the psilocybin result is not a confirmed absence [14]. The medium-strength arm of the phase 2 trial did not separate from control, and a failure in its testing hierarchy leaves its secondary outcomes without a significant conclusion [17]. No integration trial was found, and the one registered preparation trial has no results [22].
What is not known
Does preparation change lasting outcomes in healthy adults, and which of its parts do so, as opposed to habit or ritual? The only registered randomised test found for this page is a feasibility trial without results [21].
Can support be described precisely enough in trial reports to tell it from psychotherapy and to compare studies? A leading attempt reached a clear answer in 4 of 11 trials [4].
What does support contribute to safety in people without a diagnosis, as distinct from the quality of the experience? The facilitator-variance paper cannot answer this [19], and the Oregon cohort suggests that whether a difficulty is noticed depends on who is asking and when [27].
Does integration help, harm or do nothing? The definitions are many, the outcome literature is thin, and difficulties in integration are a reported theme in their own right [23].
What must be recorded about context so that results from a laboratory, a retreat and a regulated service can be pooled? ReSPCT is the best answer so far, and it was built from expert opinion for clinical trials [2].
What Metanoia asks
It has three questions. Which parts of preparation and integration change long-term outcomes in healthy adults, and which are habit or ritual? Can support be described precisely enough in trial reports to tell support from psychotherapy and to compare studies? What must be recorded about context so that results from different settings can be pooled?
Metanoia's long-term goal is a comprehensive research center: an institution that keeps monitoring and reporting the field's evidence, convenes researchers, registries and regulators around shared reporting standards, and also conducts its own research, beginning with a validated measure of flourishing and a naturalistic observational cohort studied under those standards, and growing toward laboratory work in cultivation, chemistry and genetics under full legal authorization. The center is planned, not built, and its location has not been decided. Metanoia does not hold or supply any material, and any study involving a controlled substance would take place only under the legal authorization the law requires.
Therapeutic practice cannot say whether a person grew. It can say how the human side of an experience was arranged and recorded, which makes other measures interpretable without replacing them. Nature Connectedness and Social Connection appear among the integration strategies people report, and Self-Awareness and Emotional Resilience are the dimensions closest to what reflection afterwards is usually said to address. No study read for this page tested, against a comparison condition, whether any preparation or integration practice raises any of the twelve dimensions in healthy adults.
History in brief
Studerus and colleagues trace the definitions of set and setting to Leary and colleagues in 1963 [7]. Hopkins researchers reviewing the history in 2008 wrote that the earliest academic work was designed without regard to set and setting, and that later studies with more preparation and interpersonal support reported fewer panic reactions and paranoid episodes, though the studies they cite date from the 1950s and 1960s and were not controlled [1]. Interviews with 16 Peruvian healers describe a retreat-like diet in which benefits are credited to the plant, the conditions and the healer's skill [38]. Tradition validates neither a safety claim nor a benefit claim, and none of it is evidence about healthy adults.
Sources
Reliability levels follow Metanoia's scale. Level 1 is a primary source or any peer-reviewed publication, reviews included, and it also covers official regulator, statute and registry records. Level 2 is a reliable secondary source that is not peer reviewed. Level 3 is grey literature, community material or a preprint. Level 4 is a traditional or ethnographic source. Levels 3 and 4 describe the type of source and say nothing about quality. Each entry says how much was read.
- Johnson M, Richards W, Griffiths R. J Psychopharmacol 2008, 22(6):603-620. DOI 10.1177/0269881108093587 Grade 1. Peer-reviewed expert guideline from Johns Hopkins, not a comparative study. Read in full (author manuscript). Reference list not counted. Note: the guideline's safeguards also include a safe physical environment and follow-up contact that checks for lasting perceptual changes. It named overwhelming distress during the session as the most likely risk and prolonged psychosis as rarer.
- Pronovost-Morgan C et al. Nat Med 2025, 31(7):2186-2195. DOI 10.1038/s41591-025-03685-9 Grade 1. Delphi consensus statement, 89 experts. Read in full. Supplementary tables not read. Note: the Delphi method has experts rate statements over repeated rounds. The 770 free-text responses were merged into 49 items. The variables cover the physical environment, session procedure, the therapeutic framework (guiding approach, preparation and integration protocols, follow-up, staff qualifications) and subjective experience, including the alliance with the facilitator.
- Bathje GJ, Majeski E, Kudowor M. Front Psychol 2022, 13:824077. DOI 10.3389/fpsyg.2022.824077 Grade 1. Concept analysis and review. Read in full. Note: the concept analysis defines integration as an active process of revisiting and making sense of the experience with intention and support, and its sources mixed peer-reviewed articles, books and blog-style writing.
- Schettino JR, Cheung K, Nayak SM, Weiss BM, Yaden DB. Gen Hosp Psychiatry 2026, 99:30-40 (online 29 December 2025). DOI 10.1016/j.genhosppsych.2025.12.021 Grade 1. Conceptual paper with criteria applied to 11 published trials. Abstract only. Full text not accessible.
- Hartogsohn I. J Psychopharmacol 2016, 30(12):1259-1267. DOI 10.1177/0269881116677852 Grade 1. Review. Abstract only. Full text not accessible.
- Gukasyan N, Nayak SM. Transcult Psychiatry 2021, 59(5):652-664. DOI 10.1177/1363461520983684 Grade 1. Conceptual review. Abstract only. Full text not accessible. Note: the four common factors are the relationship, the healing setting, a rationale and a ritual.
- Studerus E, Gamma A, Kometer M, Vollenweider FX. PLoS One 2012, 7(2):e30800. DOI 10.1371/journal.pone.0030800 Grade 1. Pooled analysis of 23 controlled studies, 261 healthy volunteers, 409 administrations. Read in full. Supplement not read. Note: absorption is a trait of becoming deeply caught up in experiences, mystical-type experience is a questionnaire-scored state of felt unity and sacredness, and emotional excitability is a tendency to strong feeling. The favourable state was an active and cheerful state just before the session, and the other factor was few psychological problems in the preceding weeks.
- Haijen ECHM, Kaelen M, Roseman L, et al. Front Pharmacol 2018, 9:897. DOI 10.3389/fphar.2018.00897 Grade 1. Prospective online observational study, 654 people at the first time point and 212 at the last. Read in full. Note: mystical-type experience predicted a rise in well-being two weeks later.
- Carhart-Harris RL, Roseman L, Haijen E, et al. J Psychopharmacol 2018, 32(7):725-731. DOI 10.1177/0269881118754710 Grade 1. Opinion article with new findings. Abstract only. Full text not accessible. The abstract does not mention expectation. Note: the paper argued that classic psychedelics may be unusually sensitive to context.
- Angyus M, Osborn S, Haijen E, et al. Psychol Med 2024, 54(12):3539-3547. DOI 10.1017/S0033291724002204 Grade 1. Scale validation in four datasets, including 28 healthy volunteers and a depression trial. Read in full. Supplementary correlation tables not read. Note: the nine-item scale splits into set, rapport and intention.
- Olson JA, Suissa-Rocheleau L, Lifshitz M, Raz A, Veissiere SPL. Psychopharmacology 2020, 237(5):1371-1382. DOI 10.1007/s00213-020-05464-5 Grade 1. Single-arm placebo study, 33 students. Abstract only. Full text not accessible. Note: many participants reported no change.
- Szigeti B, Kartner L, Blemings A, et al. eLife 2021, 10:e62878. DOI 10.7554/eLife.62878 Grade 1. Self-blinded, placebo-controlled citizen-science study of microdosing, 1,630 registered and 191 completers. Read in full. Supplementary files not read. Note: volunteers arranged their own placebo capsules so that they did not know which they took. In the placebo groups mindfulness and paranoia improved too, while well-being and life satisfaction did not.
- Kaertner LS, Steinborn MB, Kettner H, et al. Sci Rep 2021, 11:1941. DOI 10.1038/s41598-021-81446-7 Grade 1. Prospective online survey of microdosing without a control group, 316 enrolled and 81 at the primary endpoint. Read in full. Supplement not read. Note: positive expectation at baseline predicted well-being gains.
- Szigeti B, Weiss B, Rosas FE, et al. Psychol Med 2024, 54(8):1717-1724. DOI 10.1017/S0033291723003653 Grade 1. Exploratory analysis, not preregistered, within a randomised trial in major depression, n = 55 (clinical population). Read in full (open-access PDF). Supplementary tables not read.
- US Food and Drug Administration, Center for Drug Evaluation and Research. Psychedelic Drugs: Considerations for Clinical Investigations. Guidance for Industry, final, July 2026, docket FDA-2023-D-1987. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/psychedelic-drugs-considerations-clinical-investigations (page content current as of 13 July 2026, checked 4 October 2026) and PDF https://www.fda.gov/media/169694/download. Grade 1. Official nonbinding regulatory guidance. Read in full, all 13 pages. Note: the guidance says a factorial design that varies drug and psychotherapy separately may help, and that the in-session monitor can usually work out the treatment from the participant's behaviour, which may bias later therapy. Intense perceptual effects can make blinding fail.
- Schettino JR et al. Erratum. Gen Hosp Psychiatry 2026, 100:318. DOI 10.1016/j.genhosppsych.2026.05.005 Grade 1. Published erratum. PubMed record only: no abstract, and what it corrected could not be retrieved. Full text not accessible.
- Goodwin GM, Aaronson ST, Alvarez O, et al. N Engl J Med 2022, 387(18):1637-1648. DOI 10.1056/NEJMoa2206443 Grade 1. Phase 2 randomised trial in treatment-resistant depression, 233 participants (clinical population). Read in full from the open publisher page. Tables and supplementary appendix not read.
- Murphy R, Kettner H, Zeifman R, et al. Front Pharmacol 2022, 12:788155. DOI 10.3389/fphar.2021.788155 Grade 1. Path analysis within a randomised trial, psilocybin arm n = 30 (clinical population, major depression). Read in full. Supplementary material, including the escitalopram arm, not read. Note: in the results the -0.49 value belongs to the link in which depression in the middle of treatment predicted a weaker alliance and rapport. The authors stress the small sample and the depressed population, and caution against extrapolating. Emotional breakthrough is a self-rated sense of emotional release, and a path analysis is a statistical method that traces how one measure predicts another.
- Goldy SP, Sepeda ND, Hilbert SN, et al. Psychiatry Res 2026, 359:117010. DOI 10.1016/j.psychres.2026.117010 Grade 1. Pooled multilevel analysis of 9 studies, 298 participants, 670 sessions, 60 facilitators. Abstract only. Full text not accessible. Note: the authors compare the clinical figure with the therapist effect in traditional psychotherapy, about 8 percent.
- Kettner H, Rosas FE, Timmermann C, Kartner L, Carhart-Harris RL, Roseman L. Front Pharmacol 2021, 12:623985. DOI 10.3389/fphar.2021.623985 Grade 1. Prospective online observational study, 886 enrolled, 399 at the four-week endpoint, 213 in the path model. Read in full. Supplement not read. Note: the sample was mostly psilocybin mushrooms or truffles (80 percent) and ayahuasca (16 percent). Well-being rose from baseline with Cohen's d = 0.62 and connectedness with d = 0.46. Rapport hours before the ceremony predicted ceremony communitas directly (0.19) and through felt emotional support.
- McAlpine R, Jaglinska M, Jedlovszky K, et al. BMJ Open 2026, 16(3):e107512. DOI 10.1136/bmjopen-2025-107512 Grade 1. Randomised feasibility trial protocol, 40 non-treatment-seeking adults planned. No results. Read in full. Supplement not read. Note: the course is built around meditation. It measures feasibility first, and later well-being and the quality of the experience over nine months.
- ClinicalTrials.gov. NCT06815653, Digital Intervention for Psychedelic Preparation (DIPP): Comparing Meditation and Music-Based Programs. https://clinicaltrials.gov/study/NCT06815653. Grade 1. Official registry record, read in full through the registry's data service on 4 October 2026: status Recruiting, last update posted 26 November 2025, estimated primary completion March 2026, estimated study completion December 2026, no results posted.
- Garcia ACM, Maia LO, Meireles E, Barco JAV, Tofoli LF. J Psychoactive Drugs 2026 (online 19 May 2026). DOI 10.1080/02791072.2026.2673842 Grade 1. Cross-sectional online survey, n = 1,379. Abstract only. Full text not accessible. Note: the open-ended answers were coded with AI assistance reviewed by researchers, and named spiritual and meditative practice, time in nature, social support and personal change as integration strategies.
- Hinkle JT, Graziosi M, Nayak SM, Yaden DB. JAMA Psychiatry 2024, 81(12):1225-1235. DOI 10.1001/jamapsychiatry.2024.2546 Grade 1. Systematic review and meta-analysis, 214 studies, clinical and healthy samples. Read in full (author manuscript). Supplement not read. Note: 114 of the studies had analysable adverse event data, and only 20 of the 68 since 2005 reported all adverse events.
- Majic T, Gouzoulis-Mayfrank E, Evens R. Curr Top Behav Neurosci 2026, 77:127-151 (online 25 February 2026). DOI 10.1007/7854_2026_614 Grade 2. Narrative review chapter in an edited series, peer-review status not confirmed. Read in full from the open PDF. Note: the chapter classifies complications by time course (acute, subacute, long term).
- Yu F, Tafur J, Moreno F, Dahmer S. Front Psychiatry 2026, 17:1777387. DOI 10.3389/fpsyt.2026.1777387 Grade 1. Descriptive analysis of Oregon's public aggregate dashboard for 2025. Read in full. Supplementary tables not read. Note: the most common reasons given were general health and wellness (30.6 percent) and change of perspective (27.7 percent), alongside anxiety (23.8 percent) and depression (22.0 percent). The 2025 counts were 13 behavioural and 15 medical events.
- Korthuis PT, Cook RR, et al. JAMA Netw Open 2026, 9(8):e2630608. DOI 10.1001/jamanetworkopen.2026.30608 Grade 1. Prospective observational cohort (OPEN) in Oregon's regulated service, n = 346. Read in full. Supplement not read. Note: retention was 90.2 percent, and the reactions were reported at one month and three months. Six of seven participants whose facilitators had recorded nausea or vomiting described no difficulty at any follow-up. Average age was 49.5, 76.6 percent had finished college, and 64.5 percent gave treating mental health symptoms as a reason for attending. The authors conclude that state rules limited to events within three days of a service probably underestimate reactions.
- McGuire AL, Cohen IG, Sisti D, et al. JAMA Netw Open 2024, 7(6):e2414650. DOI 10.1001/jamanetworkopen.2024.14650 Grade 1. Consensus statement from a 27-person meeting. Abstract only. Full text not accessible (the publisher page blocked automated access).
- McNamee S, Devenot N, Buisson M. JAMA Psychiatry 2023, 80(5):411-412. DOI 10.1001/jamapsychiatry.2023.0099 Grade 1. Viewpoint. Title only: PubMed has no abstract and the full text was not accessible.
- Devenot N, Seale-Feldman A, Smith E, Noorani T, Garcia-Romeu A, et al. Kennedy Inst Ethics J 2022, 32(4):359-399. DOI 10.1353/ken.2022.0022 Grade 1. Narrative analysis of one pilot trial's manual and session reports (clinical population: smoking cessation). Abstract only. Full text not accessible.
- Oregon Health Authority. Oregon Psilocybin Services overview. https://www.oregon.gov/oha/ph/preventionwellness/pages/oregon-psilocybin-services.aspx. Grade 1. Official state page, read in full on 4 October 2026. Note: after Ballot Measure 109 (2020), the OHA began taking licence applications on 2 January 2023 and service centres opened in summer 2023.
- Oregon Health Authority. How to become a licensed psilocybin facilitator in Oregon, fact sheet updated December 2024. https://www.oregon.gov/oha/PH/PREVENTIONWELLNESS/Documents/Facilitator-License-Fact-Sheet.pdf. Grade 1. Official state document, read in full on 4 October 2026. Out of date on one point: its statement on other professional licences is overtaken by OAR 333-333-5130 [40]. Note: applicants must also hold a high school diploma or equivalent and pass a background check.
- Oregon Health Authority. Facilitator Training Program Core Curriculum Worksheet, version marked 8.7.26 (the date format is ambiguous), citing OAR 333-333-3060. https://www.oregon.gov/oha/PH/PREVENTIONWELLNESS/Documents/TP-Curriculum-Worksheet.pdf. Grade 1. Official state document, read in full on 4 October 2026. Note: the curriculum worksheet, in a version marked 8.7.26, lists the nine modules and an observed practicum, and its ethics module covers touch and consent, sexual boundaries and abuse of power. The practicum is at least 30 hours of direct practice and 10 of consultation.
- Colorado General Assembly. SB23-290 Natural Medicine Regulation and Legalization, bill summary. https://leg.colorado.gov/bills/sb23-290. Grade 1. Official legislature page, summary read in full on 4 October 2026. The text of the bill was not read. Note: the Natural Medicine Health Act of 2022 was followed by the 2023 law.
- Colorado Department of Regulatory Agencies, Division of Professions and Occupations, Office of Natural Medicine Licensure. Natural Medicine Licensure Rules and Regulations, 4 CCR 755-1, emergency rule adopted 5 December 2025, eDocket 2025-00594. https://www.sos.state.co.us/CCR/DisplayRule.do?action=ruleinfo&ruleId=3453. Grade 1. Official state rules. Read in part on 4 October 2026: rules 2.1, 2.2, 2.4, 2.5, 3.1, 3.2, 4.1(F), 6.6, 6.13, 6.16 (beginning), 6.19, 6.21 and 8.3 of a 65-page document. Not read in full.
- Palitsky R et al. PLoS One 2026, 21(5):e0350037. DOI 10.1371/journal.pone.0350037 Grade 1. Quality-improvement interviews with 13 of 20 US training organisations contacted, not a representative survey. Read in full. Supplement not read.
- Dames S et al. J Eval Clin Pract 2026, 32(5):e70556. DOI 10.1111/jep.70556 Grade 1. Practice-embedded quality-improvement framework from one programme, 219 students. Read in full. Appendices not read.
- Berlowitz I, O'Shaughnessy DM, Heinrich M, Wolf U, Maake C, Martin-Soelch C. J Ethnopharmacol 2022, 286:114910 (online December 2021). DOI 10.1016/j.jep.2021.114910 Grade 1. Peer-reviewed interview study, 16 healers. The practices it records are traditional testimony. Abstract only. Full text not accessible (open-access copies sit behind bot checks). Note: the retreat-like diet has social, behavioural and food restrictions, with attention to safety measures and to healer training. The tradition is described by its practitioners and recorded in a peer-reviewed interview study.
- Back AL, McGregor BA, Billingsley L, et al. Psychedelic Medicine 2025, 4(3):222-230 (online 9 December 2025). DOI 10.1177/28314425251404460 Grade 1. Technical report describing a group retreat facilitation model, single-arm open-label study NCT05847696, clinical population (metastatic cancer with anxiety or depression). Read in full from the open publisher page. Reference list and appendices not read. Note: the model borrows from rites of passage, with a preparation phase, the session and a phase of reincorporation, over three days, and all four lead facilitators were clinically licensed. The report is a description of practice with facilitator quotations, in a clinical group.
- Oregon Secretary of State. Oregon Administrative Rules, Chapter 333, Division 333: OAR 333-333-3050, 3060, 3070, 3080, 3090, 3200, 3300, 5000, 5120 and 5130, current versions with amendment histories. https://secure.sos.state.or.us/oard/. Grade 1. Official state rules. The ten rules named were read in full on 4 October 2026. The rest of the division was not read. Note: eligible professional licences under OAR 333-333-5130 include psychologist, social worker, counsellor, nurse and physician.
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