Bernard Albat

Michel Brunel

Claude Humeau

Maurice Navarro

Yves Allieu

Bernard Canaud

Claude Jaffiol

Henri Navratil

Robert Alric

Paul-André Chaptal

Charles Janbon

Jacques Othoniel

Bernard Arnaud

Albert-Jean Ciurana

François Janbon

Michel Pages

Gérard Asencio

Jacques Clot

Daniel Jarry

Claude Peguret

Jacques Astruc

Pierre Costa

Jacques Jourdan

Jacques Pelissier

Charles Aussilloux

Françoise D'athis

Bernard Klein

Jean-Claude Artus

Paul Landais

Michel Zanca

Dominique Prat

Patrick Bastien

Dominique Larrey

Joseph Pujol

François Blanc

Alain Le Quellec

Alain Bonafe

Pierre Mares

Jean-Philippe Boulenger

Thierry Maudelonde

Gérard Bourrel

Michèle Maury

Jacques Bringer

Patrick Messner

Mireille Claustres

Bertrand Millat

Bernard Combe

Louis Monnier

Jean-Pierre Daures

Georges Mourad

Michel Dauzat

Christian Prefaut

Jean-Marc Davy

Rémy Pujol

Jean-Pierre Dedet

Jean Ribstein

Jean-Jacques Eledjam

Jean-François Schved

Robert Grolleau Raoux

Charles Sultan

Bernard Guerrier

Jacques Touchon

Bernard Guillot

Alain Uziel

Olivuer Jonquet

Michel Voisin

Emérites Professeurs

Docteurs Emerites

Pierre Alric

Eric Baccino

Jean-Paul Beregi

Hubert Blain

Pierre Boulot

François Canovas

Xavier Capdevila

Michel Chammas

Pascal Colson

Valérie Costes

Jérôme Cottalorda

Philippe Coubes

Philippe Courtet

Louis Crampette

Jean Paul Cristol

Catherine Cyteval

L A De

Jean Emmanuel Coussaye

Benoît De Wazieres

Eric Delaporte

Pascal Demoly

Jacques Domergue

Hugues Duffau

Jean Eliaou

Fabre François

Michel Jean

Samir Hamamah

Christian Herisson

Samir Jaber

Claude Jeandel

Christian Jorgensen

Michel Koenig

Pierre Kotzki

Olivier

William Camu

Guillaume Captier

Guillaume Cartron

Guillaume Cayla

Gérald Chanques

Pierre Corbeau

Bertrand Coulet

Philippe Cuvillon

Christophe Dadure

Yves Dauvilliers

Renaud De Tayrac

John De Vos

Roland Demaria

Olivier Dereure

Stéphane Droupy

Anne Ducros

Arnaud Dupeyron

Pierre Fesler

Renaud Garrel

David Genevieve

Sébastien Guillaume

Boris Guiu

Maurice Hayot

Nadine Houede

Boris Jung

Nicolas Kalfa

Kada Klouche

Pascal Kouyoumdjian

Laurence Lachaud

Thierry Lavabre-Bertrand

Jean-Philippe Lavigne

Vincent Leclercq Le Moing

Florence

Anne, Gérard et Quentin

Je remercie votre perpétuelle bienveillance et soutien à mon égard, je repense à tous ces moments précieux passés à vos côtés.

Mes parents Ling et Didier

Je suis reconnaissant pour votre affection maintes fois renouvelée, pour votre soutien moral et matériel qui m'ont permis de faire ces études. Pour ce foyer toujours ouvert dans lequel de bons petits plats m'attendent.

Josette

Je voudrais remercier tout particulièrement ma grand-mère pour toutes ces innombrables choses, petites et grandes, qui font ce que je suis aujourd'hui, pour ta confiance indéfectible dans mes choix, pour ta relecture attentive.

Nicolas

Je souhaite également exprimer ma gratitude à mon frère qui ont eu le droit et le privilège de me supporter pendant plus de vingt ans.

A mon épouse

Enfin, je ressens une profonde gratitude envers mon épouse qui m'accompagne depuis presque dix ans et avec qui je construis chaque jour une vie épanouissante.

Bien entendu, cette liste n'est pas exhaustive et je remercie tous ceux et celles que j'ai rencontré, mes collègues et mes patients avec qui j'ai eu la chance de travailler et qui m'ont fait découvrir ce métier extraordinaire.

Merci à toutes et tous

Introduction en français

Les psychédéliques connaissent un fort regain d'intérêt dans la recherche médicale actuelle avec une croissance exponentielle du nombre de publications ces vingt dernières années [START_REF] Carhart-Harris | The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future[END_REF]. L'histoire de la recherche contemporaine sur les psychédéliques a commencé dès le milieu du 20 eme siècle [START_REF] Rucker | Psychiatry & the psychedelic drugs. Past, present & future[END_REF][START_REF] Nichols | The History of Psychedelics in Psychiatry[END_REF]. Des découvertes comme la synthèse de l'acide lysergique diéthylamide (LSD) en 1938 puis la découverte de ses effets en 1943 par Albert Hofmann [START_REF]LSD[END_REF], ainsi que l'isolation de la psilocybine en 1958 [START_REF]Psilocybin[END_REF] ont La recherche scientifique sur les psychédéliques connaît un renouveau depuis maintenant la fin des années quatre-vingt dix et on assiste à la publication de résultats encourageants sur leur potentielles actions thérapeutiques [START_REF] Berkovitch | Efficacy of psychedelics in psychiatry, a systematic review of the literature[END_REF]. Les résultats de ces études démontrent des effets thérapeutiques dans le domaine des maladies psychiatriques. Des données concernant l'efficacité de la psilocybine [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF] ou de l'ayahuasca [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF] sur les troubles dépressifs s'accumulent. Ces travaux de recherche tendent à changer l'image des psychédéliques au sein des instances sanitaires. La décision de la Food and Drug Administration de qualifier la psilocybine de breakthrough therapy en 2018 dans la dépression résistante [START_REF] Compass | COMPASS Pathways receives FDA Breakthrough Therapy designation for psilocybin therapy for treatment-resistant depression[END_REF], permet une accélération de la recherche autour de la psilocybine et de ses applications thérapeutiques.

marqué
Bien que les psychédéliques présentent une toxicité physiologique basse et que leur potentiel d'abus soit faible [START_REF] Johnson | The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act[END_REF], ils peuvent conduire à des effets psychiques entraînant des comportements dangereux. Parmi les effets secondaires à court terme, on peut observer des manifestations anxieuses transitoires, des comportements agressifs, des idées suicidaires ou encore des idées délirantes [START_REF] Strassman | Adverse reactions to psychedelic drugs. A review of the literature[END_REF]. Pour les effets secondaires à long terme, les données de la littérature infirment les hypothèses concernant le risque de développer un état psychotique prolongé après la prise de psychédélique [START_REF] Goldberg | Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis[END_REF]. Il s'avère que les cas les plus graves ayant conduit à des situations dramatiques comme des comportements d'automutilation, le décès par suicide ou des actes de violences sur autrui se produisent dans des contextes de prise de psychédélique non maitrisée et/ou chez des personnes ayant des antécédents de trouble psychotique [START_REF] Strassman | Adverse reactions to psychedelic drugs. A review of the literature[END_REF]. Ces Results. The studies included always consider set and setting in their protocol but our review shows that there are major differences when going into details of each parameter. Criteria concerning the selection of participants and the care taken to create a safe environment are present in all studies. Criteria relating to the presence of monitors were the least represented.

Conclusions.

A common methodology emerges from the clinical trials, but there are differences in set and setting configuration that make comparability and reproducibility of results difficult. Harmonizing these aspects would increase the scientific validity of future studies and improve the understanding of the use of psychedelics in psychiatry.

Keywords. Ayahuasca. LSD. Psilocybin. Psychedelics. Psychotherapy. Setting.

Introduction

Psychedelics are experiencing a strong resurgence of interest in current medical research with an exponential growth in the number of publications over the last twenty years [START_REF] Carhart-Harris | The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future[END_REF]. However, the history of contemporary research on psychedelics began in the mid-20th century [START_REF] Rucker | Psychiatry & the psychedelic drugs. Past, present & future[END_REF][START_REF] Nichols | The History of Psychedelics in Psychiatry[END_REF]. Discoveries such as the synthesis of lysergic acid diethylamide (LSD) in 1938 and the discovery of its effects in 1943 by Albert Hofmann [START_REF]LSD[END_REF], as well as the isolation of psilocybin in 1958 [START_REF]Psilocybin[END_REF] marked a significant progress in the understanding of psychedelic effects. Research in this field took off in the 1950s and 1960s in the United States and spread rapidly throughout the world. The use of psychedelics, which had previously been limited to ritual use in populations that had been using these substances for centuries, and to scientific use in recent years, spread throughout society [START_REF] Michael | Voyage aux confins de l'esprit -Ce que le LSD et la psilocybine nous apprennent sur nous-mêmes, la conscience, la mort, les addictions et la dépression[END_REF]. The 1960s saw the popularisation of psychedelics, with LSD being the emblematic substance of this period. Its use worried the political authorities because, in addition to the hallucinogenic effects that potentially threatened public order, the use of psychedelic substances carried a message of social protest among certain students, artists and intellectuals of the period. This conjuncture of cultural and societal events led the political authorities to legislate against their production, sale and use. In 1968, possession of LSD was banned throughout the United States and in 1970, under President Richard Nixon, LSD was classified as a "Schedule 1" drug, making its medical use illegal [START_REF] Belouin | Psychedelics: Where we are now, why we got here, what we must do[END_REF]. This classification marked a sudden halt in the evolution of knowledge about psychedelics and their potential therapeutic application.

The term psychedelic refers in our study to serotonergic psychedelics or classical psychedelics whose main mechanism of action at the cerebral level is an agonistic effect on the serotonin 5-HT2A receptors [8,[START_REF] Johnson | Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function[END_REF]. Their chemical composition corresponds to an alkaloid structure, i.e. the psychedelic molecules have a nitrogenous base and are mostly of plant origin and sometimes of synthetic origin. There are two classes of alkaloids: i) the tryptamines, which include psilocybin, LSD, dymethyltryptamine (DMT, the psychedelic present in ayahuasca) and ibogaine, and ii)

the phenylethylamines with mescaline. The clinical effects of these substances are similar, they all cause sensory changes, alterations in the perception of time and space, mystical and spiritual experiences and ego-dissolution [START_REF] Griffiths | Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance[END_REF].

Scientific research on psychedelics has been undergoing a revival since the end of the nineties and encouraging results on their potential therapeutic actions have been published [START_REF] Berkovitch | Efficacy of psychedelics in psychiatry, a systematic review of the literature[END_REF]. The results of these studies show therapeutic effects in the field of psychiatric disorders. Data concerning the effectiveness of psilocybin [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF] or ayahuasca [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF] on depressive disorders are growing. This research is changing the perception of psychedelics within the health authorities. The Food and Drug Administration's decision to classify psilocybin as a breakthrough therapy in 2018 for resistant depression [START_REF] Compass | COMPASS Pathways receives FDA Breakthrough Therapy designation for psilocybin therapy for treatment-resistant depression[END_REF], allows the acceleration of research around psilocybin and its therapeutic applications.

Although psychedelics have low physiological toxicity and abuse potential [START_REF] Johnson | The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act[END_REF], they can lead to psychological effects resulting in dangerous behaviors. Short-term side effects may include transitory anxiety, aggressive behavior, suicidal ideation or delusions [START_REF] Strassman | Adverse reactions to psychedelic drugs. A review of the literature[END_REF]. For long-term side-effects, the literature refutes the hypotheses concerning the risk of developing a prolonged psychotic state after taking psychedelics [START_REF] Goldberg | Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis[END_REF]. The most serious cases leading to dramatic situations such as selfharm, death by suicide or violence against others have been found to occur in the context of uncontrolled psychedelic use and/or in people with a history of psychotic disorder [START_REF] Strassman | Adverse reactions to psychedelic drugs. A review of the literature[END_REF]. These data highlight the importance of the context of use and the need to pay particular attention to the selection of suitable participants for a clinical trial of psychedelics.

Environmental conditions cover two distinct aspects of the psychedelic experience, the set and the setting, which can be summarized under the generic term "context" [START_REF] Carhart-Harris | Psychedelics and the essential importance of context[END_REF]. The set corresponds to expectations, pre-existing psychological factors including psychiatric history, preparation and support of each participant before, during and after the psychedelic experience. The setting corresponds to all the environmental parameters during the administration of a psychedelic drug. Beyond the safety issue, the environmental conditions of psychedelic use also have an impact on the user's experience and on the potential therapeutic effects of these substances [START_REF] Carhart-Harris | Psychedelics and the essential importance of context[END_REF]. Several recent literature reviews have highlighted the heterogeneity in the consideration of set and setting parameters in clinical trials [START_REF] Santos | Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years[END_REF][START_REF] Wheeler | A systematic review of psychedelic-assisted psychotherapy for mental health: An evaluation of the current wave of research and suggestions for the future[END_REF]. However, there is a real interest in the identification and control of the environmental conditions under which a psychedelic drug is taken in order to optimise the clinical effects, improve the reproducibility of future studies and improve the understanding of the mechanisms of action of psychedelics.

The purpose of this systematic review is to provide a precise overview of the parameters defining the set and setting for therapeutic use of a psychedelic drug in people with a psychiatric disorder.

Methods

Data source and research strategy

Data were collected according to PRISMA recommendations [START_REF] Page | The PRISMA 2020 statement: an updated guideline for reporting systematic reviews[END_REF]. A systematic search of published studies in the literature was conducted on the PubMed database until 3 January 2022, date of the last search. All studies in the PubMed database referenced with the keywords ("Lysergic Acid Diethylamide" OR "Psilocybin" OR "Ayahuasca" OR "N,N-Dimethyltryptamine" OR "Ibogaine" OR "Mescaline") AND ("Setting" OR "Therapeutics" OR "Psychotherapy" OR "Psychiatry") were systematically screened. A search across all bibliographic references in this study was also conducted to identify potential studies not revealed by the electronic database search.

Eligibility criteria

Studies meeting the following criteria were included in this systematic review: publication in English or French, publication in a peer-reviewed journal, existence of a title and an abstract, study design corresponding to a clinical trial and existence of a diagnosis of a psychiatric disorder among the participants of the study.

The choice to include only clinical trials in the final analysis implies that metaanalyses, reviews and expert opinions were excluded. The aim of this review is to provide data corresponding to the use of psychedelics in a therapeutic context, therefore clinical trials with healthy volunteers were excluded. Clinical trials whose population was based on a previous study and whose setting was not further specified or modified by this new study were not included. Studies concerning the use of psychedelics to support withdrawal were excluded because the presence of an addiction was an exclusion criteria for most of the studies included in this review. This choice allows us to have more homogeneous results that are applicable to clinical practice because the care structures and the management of patients are often different when the main pathology is substance abuse.

Selection process

Studies that met the above criteria were first identified by reading the title and abstract. A filter by language and by the presence of an available abstract was first applied to the electronic search. The selected titles and abstracts were then subjected to a full reading of their study. Additional sources from the bibliography of the full-read studies were added at this time. After full reading, studies that did not meet the eligibility criteria were excluded. All studies remaining after this selection process were included in the final analysis. The selection process was carried out by a single author of this study (T.D) and is summarized in a flow chart (Figure 1).

Outcome definition and date extraction

A preliminary part of the results concerns the collection of data on the general characteristics of each study, i.e. which psychedelic was tested, in which indication and the number of participants. The design of each study was also identified as well as their primary outcome and information about the tolerance of the psychedelic.

The primary outcome was constructed by classifying the different criteria defining the set and setting within the studies into six domains. This way of listing these criteria was derived from the synthesis of several works on the subject [START_REF] Carhart-Harris | Psychedelics and the essential importance of context[END_REF][START_REF] Wheeler | A systematic review of psychedelic-assisted psychotherapy for mental health: An evaluation of the current wave of research and suggestions for the future[END_REF][START_REF] Byock | Taking Psychedelics Seriously[END_REF][START_REF] Andersen | Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies[END_REF],

including the most recent study establishing guidelines for the use of psychedelics in human research [START_REF] Johnson | Human hallucinogen research: guidelines for safety[END_REF]. Three domains relate specifically to the set and three to the setting.

Three domains relating to the set are :

• the methodology for selecting participants,

• the pre-session interventions designed to prepare participants for receiving a psychedelic,

• the post-session interventions dedicated to the integration of the psychedelic experience.

Three domains related to the setting are :

• the preparation of the monitors involved in the session,

• the control of the environment where the session takes place,

• the end-of-session procedure.

Data analysis

Data from the studies were compiled in tables. Data from supplementary material published as an appendix to the original study were fully read and included in the main analysis. Analysis of these data in the form of descriptive statistics serves the purpose of this review, which is to provide a clear overview of how set and setting are considered in therapeutic psychedelic research to date. Where previously defined criteria were not specified in the study, these criteria were considered as not taken into account by the study investigators.

Results

Identification and general characteristics of the studies

Thirteen studies were selected for the main analysis. Among these studies, seven assessed the therapeutic use of psilocybin [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF], five assessed ayahuasca [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF] and only one study examined the use of LSD [START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF]. The total number of participants in these studies was 296, with an average of 22.8 participants per study.

The tolerance of psychedelics was considered in all studies (except one [START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF]) and no serious adverse events were found. The indications in which the use of a psychedelic was tested were mainly unipolar depressive disorder, three studies focused on major depressive episode [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF], four studies focused on recurrent and/or treatmentresistant depressive disorder [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF], and four studies focused on depressive and/or anxiety disorders occurring in the context of a serious chronic life-threatening disease such as cancer [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF]. One study analysed the effects of psilocybin in obsessive-compulsive disorder [START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF] and one study analysed the effects of ayahuasca in social anxiety disorder [START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF]. Regarding the design of the included studies, all were clinical trials, nine were randomised trials versus placebo [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF], versus active treatment (escitalopram) [START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF], versus waiting-list [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF] or compared different doses of psychedelics [START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF]. Four studies were open-label trials without comparator [START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF]. Seven studies tested the psychedelic in a single session [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF], another five studies conducted two sessions for methodological reasons because the study design was cross-over [START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF] or the protocol included a first session with a low dose to familiarize participants with the effects of the psychedelic and then a second session with a normal dose [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF]. One study conducted four sessions with four different doses of psychedelics randomly assigned to participants in succession to identify the optimal dose [START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF]. All data concerning the general characteristics of the included studies are summarised in Table 1.

Description of the selection process for participants

The criteria for selecting participants to be eligible for the study are detailed in the methodology section of all the studies included in this review. There were several areas of focus in each study, including general medical condition, personal/family psychiatric history, addictive history including recent substance use, and consideration of drug interactions.

The medical examination to ensure the general health of the participants systematically included a physical examination with the recording of constants, an electrocardiogram, a routine blood test (blood count, liver function, kidney function, thyroid function, bHCG for women), and a urine toxicology screening was performed in eight studies [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF]. Somatic medical history restricting participation was not clearly identified in more than half of the included studies. For those studies that did provide details in this domain, chronic diseases such as diabetes [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF],

epilepsy [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF] or cardiovascular disorders [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF] were exclusion criteria. For two studies using psilocybin for depression/anxiety secondary to a cancer diagnosis, brain involvement by metastases was an exclusion criteria [START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF].

Personal psychiatric history that made patients ineligible for the study was a diagnosis of schizophrenia or other psychotic disorder [13, 14, 26-32, 34, 35], a diagnosis of bipolar disorder [13, 14, 27-32, 34, 35], a history of mania under antidepressant medication [START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF], a diagnosis of anorexia nervosa [START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF], a history of a serious suicide attempt [START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF], the presence of suicidal risk [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF], a diagnosis of borderline personality disorder [START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF]. Three studies excluded individuals with a firstdegree family history of a psychotic disorder diagnosis [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF]. Addictive history was considered in nine studies and resulted in a restriction of participation if there was a history of occasional or regular use of an 'illicit' psychoactive substance other than alcohol [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF] and a history of alcohol dependence was an exclusion criterion in four studies [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF]. It is worth mentioning that the five studies looking at the therapeutic use of ayahuasca had a single history of ayahuasca use as an exclusion criteria [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF] or a maximum of two times in a person's lifetime [START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF]. The oldest study (2006) asked participants to have already consumed and well tolerated an indole-based psychedelic alkaloid (lysergic acid diethylamide, dimethyltryptamine or psilocybin) in their lifetime in order to reduce the risk of adverse effects [START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF].

All of the included studies paid particular attention to the control of potential interactions between drugs or other substances and the psychedelic drug used.

Different methods could be observed in the studies, which were more or less common : antidepressant or other psychotropic treatments were stopped two weeks before the psychedelic session [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF], five half-lives before [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF],

four weeks before [START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF], all pharmaceutical treatments or food supplements were stopped one week before [START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF], pharmaceutical treatments were stopped without specifying a time limit [START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF], cannabis use was proscribed 24 hours before [START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF],

alcohol/tobacco/caffeine use was proscribed 24 hours before [START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF]. Also, a study using ayahuasca instructed participants to limit the consumption of tyramine-rich foods 24 hours before the session [START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF] because ayahuasca contained a mono-amine oxidase inhibitor compound in its preparation.

A detailed oral and/or written information including the effects of the psychedelics, their potential side effects and the purpose of the study was given to each participant in the studies included in this review (except for one study where this information was not mentioned [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF]). Nine studies took the time to meet each participant beforehand to establish a relationship of trust and build a therapeutic alliance. These meetings took the form of a single interview on a different day from the session [START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF] or several (two interviews [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF], three interviews of two hours each [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF]). Advice on how to behave during the session was given during these exchange times (in one study, this advice was given to the participant on the morning of the session [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF]). Participants were advised to have an open attitude to experience and to let go. Two studies took care to have the participant visit the room where the session would take place before the day of the psychedelic session [START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF].

Post-session interventions

Eight out of thirteen studies organized one or more post-session interventions.

These interventions differed in their organization and frequency. Two studies organized telephone calls either on a regular basis, once a month for six months [START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF], or on a oneoff basis the day after the session [START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF]. The main purpose of these calls was to check on the well-being of the participants and to check for any adverse effects. Four studies reported that an interview was held the day immediately following the session [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF]. These interviews were not part of a psychotherapeutic approach other than supportive, but were intended to facilitate the integration of the psychedelic experience and to discuss emotional and cognitive aspects that emerged during the session. The number of post-session interviews was one [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF] or three [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF] depending on the study.

Monitor training and presence during the session

The term monitor refers to the study staff in charge of guiding the participant through the psychedelic experience, their level of qualification, the specific preparation for this task and their number during the session differ from study to study. The training of the monitors received particular attention in three studies [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF]. One of these studies explained that the monitors were trained in a combination of psychoanalytic concepts with a transpersonal and existential psychological approach [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF], the training was not detailed in the other two studies. However, one study stated that the instructors were selected from individuals with particular interpersonal skills and had experience of meditation practice or another relaxation technique [START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF], and this same study reported that the level of academic training of the instructors varied from none to clinical psychologist. Two studies reported that at least one of the two instructors per session was an experienced psychiatrist or psychotherapist [START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF].

Slightly more than half of the studies included (53.8%) in this review reported the presence of two monitors in the same room as the participant for the entire session [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF]. Among them, one study reported that the monitors were organized to have at least one monitor present continuously throughout the 8-hour session and that they rotated between them to take a short break or go to the restroom [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF]. All of the studies mentioned earlier in this paragraph reported that the protocol included one or more prior meetings between the monitors and the participant.

The purpose of these meetings was to create a relationship of trust between the monitors and the participant. The role of the monitors during the session was above all to ensure the safety of the participant so that there was no behavior that could be dangerous to the person. The monitors were aware of potential psychological side effects such as the occurrence of anxiety and could provide support and reinsurance if necessary. Their attitude was described as the least interventionist possible, encouraging the participant to welcome the sensations without struggle and to focus on the inner experience. This approach was in line with the advice given during the presession meetings. Studies that did not provide information about the presence of monitors during the session also insisted that there should be minimal interaction between the participant and the research staff during the session [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF].

Session environment

The description of the aesthetics of the psychedelic session environment was variable. Twelve studies provided details on the composition of the environment. Four studies explained that the room was set up in a living room style [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF], four noted that the place was decorated, pleasant, peaceful [START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF] and two stated that the room was decorated with fresh flowers [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF]. Three studies described only that the lighting in the room was dim [START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF]. The main furniture for a relaxed position was either a sofa [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF], a bed [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF] or a recliner [START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF]. Particular attention was given to the control of visual and auditory distractors during the session. Five studies recommended that participants wear an eye mask throughout the session [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Grob | Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF] and one study only instructed them to close their eyes [START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF]. Nine studies chose to play a pre-defined selection of music through headphones throughout the session [12-14, 26-30, 35], the music was described as relaxing and helping to let go. One study took care to list in an appendix all the music played during the session, i.e. 7

hours and 40 minutes of music, mainly in a classical style [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF].

The safety of the place where the psychedelic is taken was a major issue for all investigators. All studies were conducted in a hospital facility, with three studies reporting that a physician was present on site in a nearby room [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF]. Only two studies specifically detailed what to do in the case of side-effects requiring medical intervention, the complete protocol for both of these studies included the management of severe anxiety resistant to simple reassurance by titration with lorazepam PO 1-2mg [START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF] or titration with diazepam PO 5-10mg [START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF] until efficacy.

End-of-session procedure

The end-of-session protocol included two distinct aspects, the presence or absence of a time dedicated to sharing the experience and the issue of a safe return home. A debriefing at the end of the session was organized in seven studies [12-14, 27, 28, 30, 35] and consisted of a brief exchange of thoughts on emotional, affective and sometimes spiritual aspects. One study asked the patient to write a short report on their experience [START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF].

A 24-hour period of in-hospital observation could be used to secure the return home, so the night following the session took the form of a short hospitalization [START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF]. For one study, a normal medical check-up at the end of the session was enough to discharge the participants [START_REF] Santos | Ayahuasca Improves Self-perception of Speech Performance in Subjects With Social Anxiety Disorder: A Pilot, Proof-of-Concept, Randomized, Placebo-Controlled Trial[END_REF]. Four studies ensured that the participant did not drive within 24 hours of the psychedelic administration by staying in hospital [START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF], ordering a taxi [START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF] or requiring a family member or close relative to pick up the participant and drive them home [START_REF] Palhano-Fontes | Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF].

Overall quality of the set and setting in the studies

All data concerning the set and setting are summarized in Table 2 environment (4 criteria) and end-of-session procedure (2 criteria) allowed each study to be rated out of 16. Seven studies scored above 13 included [START_REF] Ross | Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial[END_REF][START_REF] Davis | Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial[END_REF][START_REF] Moreno | Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder[END_REF][START_REF] Carhart-Harris | Psilocybin with psychological support for treatmentresistant depression: an open-label feasibility study[END_REF][START_REF] Griffiths | Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized doubleblind trial[END_REF][START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF][START_REF] Gasser | Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases[END_REF] and three studies scored the lowest of 6 [START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF]. Beyond this overall score, it was interesting to note which set and setting criteria were most represented among the studies and which were least represented. The criteria for the selection of participants were present in all the studies, and the same applied to the criteria for the creation of a safe environment. The criteria concerning training and the presence of monitors during the session were the least represented aspects of the setting.

Discussion

In summary, this systematic review of the literature shows that the clinical trials published in recent years, investigating the therapeutic applications of psychedelics in psychiatry, systematically considered aspects of set and setting in their study design.

However, there are variations in the quality of description and completeness of the criteria considered in these studies. Several reviews have already reported disparities in set and setting [START_REF] Santos | Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years[END_REF][START_REF] Wheeler | A systematic review of psychedelic-assisted psychotherapy for mental health: An evaluation of the current wave of research and suggestions for the future[END_REF][START_REF] Santos | Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews[END_REF]. To our knowledge, this systematic review is the first to detail all the contextual elements inherent in the use of psychedelics for therapeutic purposes. We believe that the method in which each set and setting criteria has been defined in this review allows for a comprehensive identification of the different parameters that can be controlled in a clinical trial. Our results can thus help to improve protocols for the use of psychedelics in medical research.

A major point of attention found in all the studies analyzed is the importance of ensuring the safety of participants. This safety is mainly achieved by careful selection of participants to minimize the risk of decompensating a pre-existing psychiatric or somatic disorder and by ensuring that the place where the psychedelic is taken is safe.

These safety requirements are necessary for several reasons. Firstly, the side effects of taking a psychedelic can lead to dangerous behaviors for the individual or those around them [START_REF] Strassman | Adverse reactions to psychedelic drugs. A review of the literature[END_REF]. Secondly, psychedelic sessions are long, often lasting a whole day, and require people to stay in one room for several hours without the possibility of interrupting the effects if they are not well tolerated by the person. And in the case of psychiatry, this concerns people who often have anxiety comorbidities or a suicidal risk inherent in their pathology. Thirdly, the history of research on psychedelics is marked by a long period of prohibition [START_REF] Nichols | The History of Psychedelics in Psychiatry[END_REF], notably due to concerns about the safety of the use of these substances. In order to sustain and develop research in this field, particular care is needed to reassure both participants as well as political and health authorities.

The total number of participants in the studies included in this review is relatively small and only one study compared a psychedelic with the reference treatment [START_REF] Carhart-Harris | Trial of Psilocybin versus Escitalopram for Depression[END_REF].

Future research is needed to confirm the therapeutic effects in a wider population.

Furthermore, our review confirms that psychedelic use requires significant human resources and care time. The economic considerations surrounding the feasibility of large-scale psychedelic use will need to be considered in the coming years.

The process of selecting the articles included in this review has limitations that must be pointed out. The selection and review of articles was conducted by a single author.

Our study includes only one database, which may result in a loss of information. This limitation is attenuated by the fact that the identification process included all the bibliographic references of the studies included in this review, including systematic reviews on similar themes. The examination of these references did not reveal any articles that had escaped our selection process.

Two substances that are the subject of a lot of current scientific work in the psychiatric field have voluntarily not been included in this review. These are 3,4methylenedioxy-N-methylamphetamine (MDMA) and ketamine, which do not belong to the category of classical psychedelics. It is not the purpose of this study to compare the differences in setting that may exist between different psychotropic substances.

However, we can briefly present the main reasons why the use of these two substances differs significantly from the use of classical psychedelics [START_REF] De Gregorio | Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine[END_REF].

MDMA belongs to the amphetamine class and has a psycho-stimulant effect, its action on the brain leads to the release of dopamine, noradrenaline and serotonin [START_REF] Wave | The ultimate guide to MDMA[END_REF].

The medical applications of this substance are mostly post-traumatic stress disorder 40 [START_REF] H I G B E D , A N D D . N U T T | A R e v i e w o f 3 , 4methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy[END_REF]. Protocols for MDMA trials differ from those for psychedelics in that MDMA does not induce a hallucinatory reaction to the doses administered and the therapeutic effect is achieved by the addition of a structured psychotherapeutic intervention focusing on the trauma; the number of sessions is also significantly higher [START_REF] Feduccia | Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline[END_REF]. The training of psychotherapists, the duration of therapy and safety considerations all differentiate the protocols for the use of MDMA from those of classical psychedelics.

Ketamine is a dissociative anaesthetic with an antagonistic action on NMDA receptors [START_REF] Tyler | Classics in Chemical Neuroscience: Ketamine[END_REF]. At subanesthetic doses, it is able to induce hallucinogenic effects in the individual close to those of classical psychedelics [START_REF] Wave | The ultimate guide to ketamine[END_REF]. In psychiatry, the antidepressant effect of ketamine is well established [START_REF] Fond | Ketamine administration in depressive disorders: a systematic review and meta-analysis[END_REF]. The use of ketamine in mental health does not have the same implications as for classical psychedelics.

Ketamine has been used routinely in anaesthesia since the 1970s [START_REF] Domino | Pharmacologic Effects of Ci-581, a New Dissociative Anesthetic, in Man[END_REF], and this use provides a much greater body of evidence for its safe use than for psychedelics.

Furthermore, the terms set and setting are not used for ketamine because although its use is restricted to the hospital setting, ketamine sessions are not accompanied by any specific preparation or psychotherapeutic support, simple nursing supervision is mostly in place [START_REF] Swainson | The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Reseau Canadien Pour Les Traitements De L'humeur Et De L'anxiete (Canmat) Concernant L'utilisation De La Ketamine Racemique Chez Les Adultes Souffrant De Trouble Depressif Majeur[END_REF].

The fact that a therapeutic effect was observed in studies with a set and setting reduced to the selection of participants and the securing of the place suggests that psychedelics have a therapeutic effect independently of the context. Studies on ayahuasca [START_REF] Osorio Fde | Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report[END_REF][START_REF] Sanches | Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study[END_REF][START_REF] Zeifman | Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial[END_REF] tend to have a much less developed set and setting than studies using psilocybin but still report efficacy on depressive symptoms, which may imply that there is an intrinsic antidepressant effect of the substance. This finding raises the question of the importance of the set and setting for therapeutic efficacy. To our knowledge, there are no studies comparing different settings, but recent work has attempted to isolate the role of music in the therapeutic effect of psychedelics. We can cite a study which showed that music modified the experience of the session for the participants [START_REF] Kaelen | The hidden therapist: evidence for a central role of music in psychedelic therapy[END_REF]. In this study, a positive influence of music was correlated with a greater occurrence of mystical experience. Also, another study shows that experiencing mystical manifestations during the session is positively correlated with the therapeutic response [START_REF] Haijen | Predicting Responses to Psychedelics: A Prospective Study[END_REF]. These results illustrate that a better knowledge and control of the different parameters of the set and the setting can directly influence the therapeutic effects.

Future research will gain in scientific rigor and reproducibility if investigators make an effort to systematize their protocol in this domain. Finally, studies need to confirm the scientific relevance of the different set and setting criteria, which are so far based more on empirical considerations than on data from evidence-based medicine.

Conclusion en français

  Médecine interne ; gériatrie et biologie du vieillissement, médecine générale, addictologie Gynécologie-obstétrique ; gynécologie médicale Anatomie Anesthésiologie-réanimation et médecine péri-opératoire Chirurgie orthopédique et traumatologique Anesthésiologie-réanimation et médecine péri-opératoire Anatomie et cytologie pathologiques Chirurgie infantile Neurochirurgie Psychiatrie d'adultes ; addictologie Oto-rhino-laryngologie Biochimie et biologie moléculaire Radiologie et imagerie médicale Médecine d'urgence Médecine interne ; gériatrie et biologie du vieillissement, médecine générale, addictologie Maladies infectieuses ; maladies tropicales Pneumologie ; addictologie Chirurgie viscérale et digestive Neurochirurgie Immunologie Chirurgie viscérale et digestive Biologie et Médecine du développement et de la reproduction ; gynécologie médicale Médecine physique et de réadaptation vasculaire ; médecine vasculaire (option médecine vasculaire) Endocrinologie, diabète et maladies métaboliques ; gynécologie médicale Maladies infectieuses, maladies tropicales Neurologie Médecine physique et de réadaptation Anesthésiologie-réanimation et médecine péri-opératoire Biochimie et biologie moléculaire Chirurgie viscérale et digestive Pneumologie gériatrie et biologie du vieillissement; addictologie Chirurgie plastique, reconstructrice et esthétique, brulologie Chirurgie vasculaire ; médecine vasculaire (option médecine vasculaire) Médecine interne ; gériatrie et biologie du vieillissement, médecine générale, COLINGE Jacques (Cancérologie, Signalisation cellulaire et systèmes complexes) LAOUDJ CHENIVESSE Dalila (Biochimie et biologie moléculaire) VISIER Laurent (Sociologie, démographie) 1re classe : Médecine interne ; gériatrie et biologie du vieillissement, médecine générale, VIEL Eric (Soins palliatifs et traitement de la douleur) BESSIS Didier (Dermato-vénéréologie) MEUNIER Isabelle (Ophtalmologie) MULLER Laurent (Anesthésiologie-réanimation et médecine péri-opératoire) PERRIGAULT Pierre-François (Anesthésiologie-réanimation et médecine péri-opératoire) applications des mathématiques Sciences du médicament et autres produits de santé Sciences du Médicament et autres produits de santé Sciences physico-chimiques et technologies pharmaceutiques Science biologiques, fondamentales et cliniques Sciences physico-chimiques et ingénierie appliquée à la santé Neurosciences Philosophie Physiologie Sciences du Médicament et autres produits de santé 11 / 13

  une avancée significative dans la compréhension des effets des psychédéliques. La recherche dans ce domaine a connu un fort essor dans les années cinquante et soixante aux Etats-Unis et s'est rapidement diffusée partout dans le monde. La consommation de psychédéliques, jusqu'alors limitée à un cadre rituel dans des populations consommant ces substances depuis des siècles, et à un cadre scientifique depuis quelques années, se répand dans la société [6]. Les années soixante sont le théâtre de la popularisation des psychédéliques avec le LSD comme substance emblématique de cette période. Son usage inquiète les autorités politiques, car au delà des effets hallucinogènes menaçant potentiellement l'ordre public, la consommation de substances psychédéliques véhicule un message de contestation sociale chez certains étudiants, artistes et intellectuels de cette période. Cette conjoncture d'évènements culturels et sociétaux conduit les pouvoirs politiques à légiférer contre leur production, vente et utilisation. En 1968, le LSD est interdit de possession dans tous les Etats-Unis et en 1970 sous la présidence de Richard Nixon, le LSD est classé « catégorie 1 » rendant son usage médical illicite [7]. Cette catégorisation marque un frein brutal dans l'évolution de la connaissance des psychédéliques et de leur potentielle application thérapeutique. Le terme psychédélique fait référence dans notre étude aux psychédéliques sérotoninergiques ou psychédéliques dit « classiques » dont le principal mécanisme d'action au niveau cérébral est un effet agoniste sur les récepteurs à la sérotonine 5-HT2A [8, 9]. Leur composition chimique correspond à une structure alcaloïde, c'est-àdire que les molécules psychédéliques possèdent une base azotée et sont principalement d'origine végétale et parfois d'origine synthétique. On retrouve deux classes d'alcaloïde: i) les tryptamines, avec la psilocybine, le LSD, la dyméthyltryptamine (ou DMT, psychédélique présent dans l'ayahuasca), l'ibogaïne et ii) les phényléthylamines avec notamment la mescaline. Les effets cliniques de ces substances sont similaires, elles entraînent toutes des modifications sensorielles, des altérations dans la perception du cours du temps et de l'espace, des expériences mystiques et spirituelles, des expériences de dissolution de l'ego [10].

  données attestent de l'importance du contexte d'utilisation et de l'attention particulière à accorder à la sélection des participants aptes à prendre part à un essai clinique sur les psychédéliques.Les conditions environnementales recouvrent deux aspects distincts de l'expérience psychédélique à savoir le « set » et le « setting » que l'on peut résumer sous le terme générique de « contexte »[START_REF] Carhart-Harris | Psychedelics and the essential importance of context[END_REF]. Le « set » correspond aux attentes, aux facteurs psychologiques pré-existant dont les antécédents psychiatriques, à la préparation et à l'accompagnement de chaque participant avant, pendant et après l'expérience psychédélique. Le « setting » ou cadre, correspond à l'ensemble des paramètres environnementaux pendant la prise d'un psychédélique. Au-delà de la question sécuritaire, l'ensemble des conditions environnementales de prise d'un psychédélique a également une incidence sur l'expérience de l'usager et sur les potentiels effets thérapeutiques de ces substances[START_REF] Carhart-Harris | Psychedelics and the essential importance of context[END_REF]. Plusieurs revues de la littérature récentes soulignent l'hétérogénéité dans la prise en compte des paramètres du set et du setting aux seins des essais cliniques[START_REF] Santos | Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years[END_REF][START_REF] Wheeler | A systematic review of psychedelic-assisted psychotherapy for mental health: An evaluation of the current wave of research and suggestions for the future[END_REF]. Il existe pourtant un réel intérêt à identifier et à bien maitriser les conditions environnementales de prise d'un psychédélique afin d'optimiser les effets cliniques, améliorer la compréhension des mécanismes d'action des psychédéliques et améliorer la reproductibilité des futures études.Cette revue systématique de la littérature a pour objectif de donner une vision précise de l'ensemble des paramètres définissant le set et le setting dans le cadre de l'utilisation d'un psychédélique à des fins thérapeutiques chez des personnes atteintes d'un trouble psychiatrique.SummaryBackground. The therapeutic use of psychedelics is revolutionizing current medical research in psychiatry. Scientific data are accumulating, particularly on the safety and efficacy of their use. However, the preparation of the participants (set) and the environmental conditions of taking a psychedelic (setting) have never been systematically reviewed.Methods. We conducted a systematic review of set and setting parameters in studies investigating the therapeutic use of psychedelics in subjects with a psychiatric diagnosis. Clinical trials published in the PubMed database up to 3 January 2022 were examined. The different parameters were classified into six domains: participant selection, pre-session and post-session interventions, monitor presence, environmental management, end-of-session procedure.

  . Participant selection (3 criteria), pre-session interventions (3 criteria), post-session interventions (1 criteria), instructor training and attendance during the session (3 criteria), session

Figure 1 -

 1 Figure 1.

Monsieur le Professeur Jorge Lopez Castroman

		Praticiens Hospitaliers Universitaires PH chargés d'enseignements
	CAZAUBON Yoann ABOUKRAT Patrick Les études en médecine sont longues et exigeantes, le travail de thèse n'y déroge pas. BRINGER-DEUTSCH Sophie DJANIKIAN Flora LE MOINE DONY Marie-Christine RIDOLFO Jérôme
	DAGNEAUX Louis AGUILHON Sylvain A travers ces mois captivants de recherche et d'écriture, de nombreuses rencontres BRINGUIER BRANCHEREAU Sophie DONNADIEU-RIGOLE Hélène LETERTRE Simon RIPART Sylvie
	DUFLOS Claire AKKARI Mohamed ont contribué de près ou de loin à cette réflexion, j'aimerais ici, leur rendre hommage. BRISOT Dominique FAIDHERBE Jacques LOPEZ Régis RONGIERES Michel
	GOULABCHAND Radjiv ALRIC Jérôme	BRONER Jonathan	FATTON Brigitte	LUQUIENS Amandine	ROULET Agnès
	MIOT Stéphanie AMEDRO Pascal	CADE Stéphane	FAUCHERRE Vincent	MANZANERA Cyril	RUBENOVITCH Josh
	ROCH Benoît AMOUROUX Cyril	Pneumologie, addictologie CAIMMI Davide Paolo	FAURE Elsa	MARGUERITTE Emmanuel	SANTONI Fannie
	SARRABAY Guillaume ANTOINE Valéry	Génétique CARR Julie	FILLERON Anne	MARTIN Lucille	SASSO Milène
	SOUCHE François-Régis ARQUIZAN Caroline	Chirurgie viscérale et digestive CARTIER César FILLOLS Mélanie	MATTATIA Laurent	SCHULDINER Sophie
	ATTALIN Vincent Au président du jury, CASPER Thierry	FITENI Frédéric	MEROUEH Fadi	SEGURET Fabienne
	AYRIGNAC Xavier	CASSINOTTO Christophe FOURNIER Philippe	MEYER Pierre	SENESSE Pierre
	BADR Maliha	CATHALA Philippe	GAILLARD Nicolas	MICHEL Moïse	SERRE Jean-Emmanuel
	BAIS Céline Professeur des Universités -Praticien Hospitalier (Psychiatrie) du CHU de Nîmes CAZABAN Michel GALMICHE Sophie MILESI Christophe SKALLI El Medhi
	BARBAR Saber Davide	CHARBIT Jonathan	GENY Christian	MORAU Estelle	SOLA Christelle
	Je tiens à vous exprimer toute ma gratitude pour l'honneur que vous m'avez témoigné
	BASSET Didier	CHEVALLIER Thierry	GERONIMI Laetitia	MORQUIN David	SOULLIER Camille
	BATIFOL Dominique en acceptant la direction de mes travaux. Je vous suis reconnaissant de m'avoir fait CHEVALLIER-MICHAUD Josyane GINIES Patrick MOSER Camille SOUKSI MEDIONI Isabelle
	BATTISTELLA Pascal bénéficier de votre intérêt, de votre compétence, de votre rigueur scientifique et de COLIN Olivier GRECO Frédéric MOUSTY Eve STOEBNER DELBARRE Anne
	BAUCHET Luc votre soutien. De plus, votre relecture finale méticuleuse m'a sans aucun doute permis CONEJERO Ismael GUEDJ Anne Marie MOUTERDE Gaël TEOT Luc
	BELL Ariane de préciser mon propos. CONSEIL Mathieu	GROSSIN Delphine	PANSARD Nicole	THIRION Marina
	BENEZECH Jean-Pierre	CORBEAU Catherine	GUYON Gaël	PERNIN Vincent	TUNEZ Virginie
	BENNYS Karim	COROIAN Flavia-Oana	HEDON Christophe	PERRIGAULT Pierre François VACHIERY-LAHAYE Florence
	BERNARD Nathalie	COUDRAY Sarah	HENRY Vincent	PEYRON Pierre-Antoine	VERNES Eric
	Aux membres du jury,
	BERTCHANSKY Ivan	CRANSAC Fréderic	JAMMET Patrick	PICARD Eric	VIALA Maurice
	BIBOULET Philippe	CUNTZ Danielle	JEDRYKA François	PICOT Marie Christine	VINCENT Laure
	BIRON-ANDREANI Christine DARDALHON Brigitte	JREIGE Riad	PIERONI Laurence	WAGNER Laurent
	BLANC Brigitte	DAVID Aurore	KINNE Mélanie	POQUET Hélène	WALTHER LOUVIER Ulrike
	BLANCHARD Sylvie	DE BOUTRAY Marie	LABARIAS Coralie	PUJOL Sarah-Lise	ZERKOWSKI Laetitia
	BLANCHET Catherine	DE LA TRIBONNIÈRE Xavier LABORDE Caroline	PUPIER Florence
	BLATIERE Véronique	DEBIEN Blaise	LACAMBRE Mathieu	QUANTIN Xavier
	BOBBIA Xavier	DELPONT Marion	LANG Philippe	RAFFARD Laurence
	BOGE Gudrun	DENIS Hélène	LAZERGES Cyril	RAPIDO Francesca
	BOURRAIN Jean Luc	DEVILLE de PERIERE Gilles LE GUILLOU Cédric	RIBRAULT Alice
	BOUYABRINE Hassan	DI CASTRI Alberto	LEGLISE Marie Suzanne	RICHAUD-MOREL Brigitte
					16

Pharmacologie fondamentale ; pharmacologie clinique ; addictologie Chirurgie orthopédique et traumatologique Biostatistiques, informatique médicale et technologies de la communication Médecine interne ; gériatrie et biologie du vieillissement ; addictologie Médecine interne ; gériatrie et biologie du vieillissement ; addictologie

Madame la Docteur Clémentine Estric

	Cheffe de clinique (Psychiatrie) du CHU de Nîmes
	Tous mes remerciements et ma gratitude pour ta grande disponibilité, ta patience, tes
	partages d'expérience et tes nombreux conseils et remarques constructives qui m'ont
	permis d'améliorer la qualité ma thèse. Je t'exprime ma reconnaissance de m'avoir fait
	confiance et de m'avoir accompagné tout au long de cette recherche.

Madame la Docteur Géraldine Audemard

	Praticienne Hospitalière (Psychiatrie) du CHU de Nîmes
	Toute ma reconnaissance pour m'avoir accueilli si chaleureusement au sein de ton
	équipe du CMP. Je tiens à te remercier pour le temps passé, le dynamisme, la patience
	et ta confiance tout au long de ces stages enrichissants sur le plan clinique et humain.
	Ces stages auprès de toi m'auront permis sans aucun doute de gagner en autonomie
	dans ma pratique. Soit assurée de ma profonde gratitude. Aussi, je tiens à t'exprimer
	mes remerciements pour l'honneur que tu témoignes en participant à ce jury.
	Monsieur le Docteur Ismaël Conejero
	Praticien Hospitalier (Psychiatrie) du CHU de Nîmes
	Je vous exprime mes sincères remerciements pour avoir pris part à mon jury et pour
	l'intérêt que vous avez porté au sujet. Merci également pour votre investissement dans
	les enseignements que vous aviez dispensé pendant mon externat et dont je conserve
	un excellent souvenir.
	A toutes les personnes ayant participé de près ou de loin à l'élaboration de cette thèse,

Monsieur le Docteur Mocrane Abbar Je voudrais vous remercier tout particulièrement pour l'intérêt que vos avez portez au sujet et que vous m'avez transmis à travers des lectures et des témoignages. Aux médecins qui m'ont encadré au cours des différents stages de mon internat, les Drs Lionelle Schenk et Blandine Deffinis, les Drs Aurore Larue et Thomas Gibon, le Dr Jean-Yves Galan

	Je tiens à témoigner ma reconnaissance aux médecins qui m'ont encadré au cours des
	différents stages de mon internat.

A mes co-internes Emmanuel Diaz, Raphaël Chancel, Charlène Mapou, Emmanuel Levain

	A l'
	Pour leur aide, leur soutien et leur gentillesse.

équipe de la documentation de la BU Médecine de Nîmes Je

  ne souhaite pas oublier le personnel professionnel et étudiant de la BU sans qui ce travail n'aurait pu être mené à bien. Leur accueil m'ont permis de travailler nuit et jour depuis le début de mes études de médecine dans de bonnes conditions.

L'hospitalité St Jean Paul II du Gard

	Merci de l'accueil chaleureux que vous m'avez réservé et de m'avoir permis de
	comprendre de nouvelle perspective sur mon métier.

Maël-Amauri Barale-Penanguer, Claire Colombet, Chloé Delecourt, Mathilde Garrel et Mathieu Colloca, Samantha et Kevin Pijoan, Thibaut Roux et Stella Bertrand, Lionel Zeganadin et Elise Pétron

	Leurs attentions et encouragements m'ont accompagné tout au long de ces années.
	Nos rencontres, nos discussions et soirées jeux de société dont j'ai profité à leur côté
	m'ont permis de souffler dans l'écriture et ont fait naître de réels liens d'amitiés qui a
	mes yeux n'ont pas de prix. Qu'ils soient tous assurés de ma plus profonde gratitude
	et estime.

Table des matières

 des

	Introduction en français	22
	Summary	26
	Methods	29
	Data source and research strategy	29
	Eligibility criteria	30
	Selection process	30
	Outcome definition and date extraction	31
	Data analysis	31
	Results	32
	Identification and general characteristics of the studies	32
	Description of the selection process for participants	33
	Pre-session interventions	35
	Post-session interventions	35
	Monitor training and presence during the session	36
	Session environment	37
	End-of-session procedure	38
	Overall quality of the set and setting in the studies	38
	Discussion	39
	Conclusion en français	42
	Références	44
	Annexes	49
	Serment d'Hippocrate	56
	Résumé	57

anxiety

Remerciements

Open label

S E T

Participant selection

Ensure that the participant is in good general health

Consideration of pharmacological interactions

Exclusion criteria taking into account psychiatric/ addictive history

Pre-session

Information on psychedelic effects

Meeting dedicated to the therapeutic alliance

Advice on the attitude to adopt during the session

Post-session

Post-session meeting 0

Meeting between monitors and participant before the psychedelic session

End-ofsession procedure

Debriefing at the end of the session 0

Ensuring a safe home return L'harmonisation de ces aspects augmenterait la validité scientifique des études futures et améliorerait la compréhension de l'usage des psychédéliques en psychiatrie.

Mots-clés: Ayahuasca. LSD. Psilocybine. Psychédéliques. Psychiatrie.

Psychothérapie. Revue systématique. Setting.