The purpose of the psychosocial protocol in the psychedelic-assisted therapy: A scoping review

Definition and elaboration

This review defines the psychosocial protocol in the PAT as non-pharmacological components of the treatment, including interventions based on psychosocial techniques and the research context. Due to the diversity of terminology in the field, the general term psychosocial protocol was adopted to encompass any procedure beyond the neurobiological action of the substance.

Importantly, the research context is progressively acknowledged as a factor shaping both the use and interpretation of psychedelics (De La Haye et al., 2023; Golden et al., 2022), influencing treatment design, what constitutes therapeutic value, and the sociocultural standards that guide care (Bartlett et al., 2023; Langlitz and Gearin, 2024; Roseman et al., 2022). In parallel, regulatory frameworks, particularly those governing clinical research and drug approval, such as those established by the U.S. Food and Drug Administration (FDA), also play an important role in shaping psychedelic treatments (Roseman, 2025). These frameworks prioritize safety, consistency, and methodological rigor, often encouraging standardized procedures. In 2024, the FDA advisory committee declined approval for MDMA-assisted therapy, claiming insufficient evidence of efficacy (U.S. FDA, Psychopharmacologic Drugs Advisory Committee (PDAC) Meeting, 2024). Among the concerns raised was the fact that psychotherapy, a central component of the intervention, falls outside this institution’s regulatory scope.

While these requirements may cause repercussions, cultural sensitivity is an important feature of safe and effective delivery of PAT, as overly generalized procedures may overlook contextual particularities (Hadar et al., 2023; Schenberg, 2025; Williams et al., 2019). Given the sociocultural dimensions inherent to the population and mental health care (American Psychological Association, 2017), this review includes data on the geographic location of the evaluated studies, highlighting how contextual factors may jointly inform the design and deliver of psychosocial protocols.

Finally, accordingly to the literature, it is possible to elucidate that a psychosocial protocol may be developed based on the psychedelic administered, its effects, administration route and dosage (Greenway et al., 2020; Reiff et al., 2020); the sample characteristics, clinical condition and therapeutic goal (Nichols et al., 2017); and the perspective, background and training of the research team (Phelps, 2017; Tai et al., 2021). The sociocultural context impacts all these dimensions (Hartogsohn, 2017). Clarifying these variables supports the categorization of psychosocial protocols and highlights their potential purposes in PAT. The schematization of these variables is presented in Figure 1.

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Figure 1.

Identified variables considered for the psychosocial protocol elaboration.

Overview: Common procedures in PAT

In addition to approaches involving low-dose psychedelics administered within a therapeutic setting, the psychedelic model has gained prominence in recent studies (Feduccia et al., 2023). This modality focuses on administering one or a few sessions of high-dose psychedelics to induce experiences that can enhance the therapeutic process (Rodrigues, 2019; Roseman et al., 2019). Modern clinical trials typically last 1 to 3 months and involve one to three moderate or high doses of psychedelics, combined with preparatory and integrative sessions before and after the pharmacological intervention (Brennan and Belser, 2022; Timmermann et al., 2022; Watts and Luoma, 2020), as well as close monitoring and support during the acute effects of the substance (Johnson et al., 2008).

After proper screening, the preparation usually involves two to four sessions before dosing conducted by one or two professionals, most likely the same individuals who accompany the participant throughout treatment (Garcia-Romeu and Richards, 2018; Pronovost-Morgan et al., 2023). These professionals are mostly medical or mental health clinicians such as psychiatrists, psychologists, psychotherapists, nurses, and trained investigators (Seybert et al., 2025). In studies involving ayahuasca ceremonies, clinical teams may also include traditional practitioners, such as ayahuasqueros (Thomas et al., 2013; Van Oorsouw et al., 2022) or curanderos (Berlowitz et al., 2019; Giovannetti et al., 2020; O’Shaughnessy et al., 2021), reflecting the cultural context of these interventions. Although this review utilizes the term professionals, other terminologies like therapists, facilitators, guides, and sitters are commonly used (Mithoefer, 2017; Phelps, 2017).

Many protocols adopt a co-therapy model, traditionally a male-female dyad, widely adopted in MDMA studies (Mithoefer, 2017), or, alternatively, therapists matched to the participant’s gender (Horton et al., 2021; Johnson et al., 2008). These recommendations were originally intended to sustain safety and protect the therapeutic relationship, given the past ethical violations in psychotherapy with MDMA (Passie, 2018; Reiff et al., 2020). However, this approach has been reviewed since it relies on gender-based assumptions that may not reflect the diversity of participants’ gender identities and relational backgrounds (Ching and Kelmendi, 2025; Rea and Wallace, 2021; Wagner et al., 2019).

The preparation’s key functions are establishing rapport, setting boundaries and ground rules for dosing session and gathering information about the participants’ history, clinical condition, motivation, and expectations (Chisamore et al., 2024; Feduccia et al., 2023). It is also intended to set intentions, discuss participants’ concerns, provide psychoeducation (on the substance and possibly the clinical condition), explain study logistics, offer coping strategies, reassure support, foster a sense of safety, and promote participant empowerment (Gorman et al., 2021; Pilecki et al., 2021). It is often encouraged that participants have an inward focus and be open to whatever arises (Sloshower et al., 2020). Additional preparatory sessions, specific techniques for therapeutic goal and inclusion of social support may be tailored to clinical needs (Bogenschutz et al., 2015; Danforth et al., 2018; Guss et al., 2020; Johnson et al., 2014).

During acute effects, participants may be encouraged to lie down, wear eyeshades, and listen to curated music playlist to facilitate introspection (Griffiths et al., 2006, 2016; Kaelen et al., 2018). If challenging experiences ² occur, professionals may provide support accordingly agreed in preparation (i.e., therapeutic touch, acknowledgement of emotions, grounding exercises; Agrawal et al., 2024; Ching et al., 2022; Guss et al., 2020). The therapeutic stance is usually supportive and non-directive, with professionals constantly present, involving intermittent interactions and biomedical checking (Greenway et al., 2020; Thal et al., 2021). Sessions may last 6–12 hours, depending on the substance (Horton et al., 2021). The setting is often arranged to create an aesthetically pleasing and non-clinical atmosphere to enhance comfort (Cavarra et al., 2022; Reiff et al., 2020).

The post-experience integration can begin immediately after dosing session and continue in weekly or bi-weekly for 1–3 months or more (Garcia-Romeu and Richards, 2018). The purpose of this stage is mainly to support meaning-making, incorporation into daily life, and monitoring (Feduccia et al., 2023). It may also offer symptom management (Bogenschutz and Forcehimes, 2017), treatment planning (Pilecki et al., 2021), and promoting health activities and behavioral change (Greenway et al., 2020).

What lacks clarity and needs better investigation

The purpose of the psychosocial interventions is constantly announced as safety, but their depth and role vary widely, complicating the classification of PAT as a pharmacological treatment (Aday et al., 2024; Center for Drug Evaluation and Research [FDA], 2023). Besides safety, the psychosocial protocol may shape the treatment, requiring adequate assessment (Barksdale et al., 2024; Cavarra et al., 2022; Sloshower, 2018).

Current models employed are diverse and inconsistent in terminology, limiting cross-study comparisons (Jacobs et al., 2024). Recent research has primarily focused on psilocybin (Horton et al., 2021; Murphy et al., 2022; Stauffer et al., 2021), for which multiple phase 2 trials are available (Goodwin et al., 2022, 2023b; Raison et al., 2023). MDMA has also been extensively studied (Danforth et al., 2018; Mithoefer et al., 2011, 2018), including the completion of phase 3 studies (Mitchell et al., 2021, 2023). Additional investigations involve ayahuasca (Osório et al., 2015; Palhano-Fontes et al., 2019; Tupper and Labate, 2015), DMT (D’Souza et al., 2022; Falchi-Carvalho et al., 2025), and LSD (Robison et al., 2025), with the last 2 reaching phase 2 evaluation. Finally, a growing body of research is exploring other psychedelic compounds, including ibogaine (Mash, 2023; Schenberg et al., 2014), 5-MeO-DMT (Davis et al., 2019; Reckweg et al., 2023), and 4-OH-DiPT (Ludbrook et al., 2025).

These studies may apply various models such as the psychedelic-assisted psychotherapy (PAP), manualized interventions, psychological support, with individual and/or group-based approaches (Andersen et al., 2021; Anderson et al., 2020; Trope et al., 2019). Moreover, various therapeutic orientations have been incorporated to PAT, particularly during the preparation and integration phases (Brennan and Belser, 2022), such as cognitive behavioral therapy (CBT; Johnson et al., 2014; Wolff et al., 2020; Yaden et al., 2022), motivational enhancement therapy (MET; Bogenschutz and Forcehimes, 2017; Nielson et al., 2018; Walsh and Thiessen, 2018), acceptance and commitment therapy (ACT; Davis et al., 2020; Sloshower et al., 2020), “accept-connect-embody” therapy (Watts and Luoma, 2020; Watts, 2021), and conventional psychotherapeutic frameworks, including psychodynamic, humanistic-existential, transpersonal, and others (Greenway et al., 2020; Zamaria et al., 2025). Additionally, the formalization, along with the duration and scope of interventions, is rarely addressed (Hultgren et al., 2025).

Given the range of techniques applied alongside psychedelics, it is essential to clarify the purpose of these interventions to better investigate their impact. This scoping review aims to classify psychosocial protocols, especially based on their role in research, without an evaluation of efficacy. This review may provide a foundation for improved methodological rigor and the development of contextually appropriate models of care.

Psychedelic with psychological support

This category included 16 studies that briefly described the psychosocial protocols (Carhart-Harris et al., 2016, 2021; D’Souza et al., 2022; Ellis et al., 2025; Falchi-Carvalho et al., 2025; Goodwin et al., 2022, 2023b; Griffiths et al., 2016; Grob et al., 2011; McGowan et al., 2025; Moreno et al., 2006; Palhano-Fontes et al., 2019; Poulin et al., 2024; Raison et al., 2023; Robison et al., 2025; Schneier et al., 2023). Most employed one to four doses of psilocybin, with exceptions involving DMT (D’Souza et al., 2022; Falchi-Carvalho et al., 2025), LSD (Robison et al., 2025), and ayahuasca (Palhano-Fontes et al., 2019). Study designs varied from RCTs (n = 9) to open-label studies (n = 7), primarily targeting depressive disorders (n = 10). Most of the studies were conducted in North America and Europe, apart from two studies carried out in Brazil (Falchi-Carvalho et al., 2025; Palhano-Fontes et al., 2019).

One study presented a protocol for an ongoing trial (Poulin et al., 2024), while the remaining 15 reported results involving 799 participants, with a completion rate of 91.24%. Terminology was inconsistent, most often referring to psychosocial intervention as psychological support (n = 9). Three studies did not provide a formal name, but reported shortly interventions applied (Grob et al., 2011; Moreno et al., 2006; Robison et al., 2025).

The purpose found was to enhance pharmacological intervention safety by establishing favorable conditions and minimizing risks during dosing session. To create a fertile context, these protocols emphasized building a therapeutic alliance, providing psychoeducation, addressing study logistics, and exploring participants’ personal history to foster trust and prepare professionals for emergent material during dosing (Johnson et al., 2008). Additional elements included coping strategies to navigate the psychedelic experience (e.g., breathing and somatic exercises, guided imagery, agreed physical touch), intentionality setting, experience description, and expectation management, while some studies were limited to psychoeducation and logistical guidance focused solely on risk reduction (D’Souza et al., 2022; Robison et al., 2025; Schneier et al., 2023).

The format was individual preparation, support during experience, and post-treatment care, delivered through a non-directive and supportive approach. Interventions were generally minimal during dosing sessions, highlighting attentive presence and listening, without explicit therapeutic orientation. In some cases, stand-alone psychotherapy was explicitly refused or even prohibited (Goodwin et al., 2022; Robison et al., 2025), and common tools, such as music and decoration, were excluded (D’Souza et al., 2022).

Only five studies referred to formal protocols with further information about the psychosocial procedures (Carhart-Harris et al., 2016, 2021; Goodwin et al., 2022; Raison et al., 2023; Robison et al., 2025), six cited Johns Hopkins Guidelines for safety by Johnson and colleagues (2008), and five studies, all supported by Compass Pathways, referred to a specific training approach (Tai et al., 2021) or model (Kirlić et al., 2025). Notably, two studies (Carhart-Harris et al., 2016, 2021) were linked to the ACE (Accept/Connect/Embody) Model (Watts, 2021), based on ACT; however, the original studies’ data suggested limited depth, justifying inclusion in this category.

No studies formally assessed psychosocial components, reinforcing the interpretation of their secondary role to pharmacological outcomes. Reporting on duration was commonly limited, but when described, protocols ranged from one to four preparatory sessions and from a debriefing to one to four post-treatment sessions, lasting in total between 4.5 and 16 hours.

Psychological support in PAT often incorporates core psychotherapeutic principles and is frequently delivered by licensed clinicians, which can blur distinctions between support and psychotherapy. Terminological and design choices may be shaped by sociocultural, financial, ideological, and ethical factors (Aday et al., 2024). Representatively, as trials progress to later phases, regulatory pressures influence how psychosocial components are presented, with a marked tendency to downplay their therapeutic depth by reframing them as psychological support rather than psychotherapy. This pattern is particularly evident in industry-sponsored trials, which explicitly positioned psychosocial input as supportive rather than therapeutic.

For this review, categories were differentiated according to the explicit depth of therapeutic engagement offered to participants and the way psychosocial component was positioned, whether as central or as more limited element accompanying pharmacology. This category represents the leanest psychosocial protocol, oriented toward general support, monitoring, and promotion of treatment adherence (Bogenschutz and Forcehimes, 2017; Gründer et al., 2024). Delineating this category separately also serves a methodological purpose, offering options and instructions for researchers and enhancing transparency in reporting. Finally, the psychosocial procedures were less significant and rarely assessed in the results. The low level of structuredness but attempt to standardize procedures and reduce variables (Carhart-Harris et al., 2021; D’Souza et al., 2022; Raison et al., 2023) demonstrated emphasis in pharmacology.

PAP with nonspecific orientation

This category was characterized by diverse denominations, placing greater focus on individualized therapeutic processes and the clinical conditions treated. This is reflected in tailored interventions responsive to participants’ needs, including in-session insight sharing (Aaronson et al., 2023; Mithoefer, 2017; Ruse et al., 2008; Wolfson and Mithoefer, 2015), the use of creative tools (e.g., art, journaling; Ching et al., 2022; Davis et al., 2021; Rosenblat et al., 2024; Von Rotz et al., 2023), additional psychotherapeutic sessions (Davis et al., 2021; Holze et al., 2023) and adaptations to clinical or cultural contexts (Back et al., 2024; Bhagavan et al., 2024; Peck et al., 2023).

A total of 20 studies formed this category (Aaronson et al., 2023; Back et al., 2024; Bhagavan et al., 2024; Bouso et al., 2008; Ching et al., 2023; Davis et al., 2021; Gasser et al., 2014; Holze et al., 2023; Jardim et al., 2021; Mitchell et al., 2021, 2023; Mithoefer et al., 2011, 2018; Oehen et al., 2013; Ot’alora et al., 2018; Peck et al., 2023; Rosenblat et al., 2024; Von Rotz et al., 2023; Wang et al., 2021; Wolfson et al., 2020), the largest in the review, including double-blind RCTs (n = 16) and open label studies (n = 4). Substances administered were MDMA (n = 11), psilocybin (n = 7), and LSD (n = 2), delivered across one to three sessions. The main conditions treated were PTSD (n = 9), anxiety and depression related to life-threatening illness (n = 4), and depressive disorders (n = 4). Most studies were conducted in North America and Europe (n = 13), with some in Israel, Brazil, and New Zealand. Two articles presented ongoing study protocols (Bhagavan et al., 2024; Ching et al., 2023), while 18 reported results, totaling 565 participants and 508 completers (89.91%).

Studies in this category used diverse terminology, ranging from psychotherapy, and substance-assisted psychotherapy to psychological or therapeutic support, supportive therapy, psychological counselling, and substance-assisted therapy. Four studies were considered borderline to psychological support (Aaronson et al., 2023; Ching et al., 2023; Peck et al., 2023; Von Rotz et al., 2023) and were discussed until a consensus was reached, with the conclusion that all studies offered more detailed and personalized psychosocial interventions than the previous category.

Beyond safety, these studies were mainly grouped according to their objective of an individualized psychosocial care, customized to participants’ therapeutic processes and ways of relating to their clinical condition. Accordingly, these protocols were compatible with study designs that examined not only the pharmacological intervention but also the contribution of psychotherapy, or its integration with pharmacological effects. While sessions followed a structured pre- and post-treatment format, their content remained flexible to allow individualized therapeutic engagement. A predominantly non-directive and supportive approach was adopted, with some studies proposing guidance based on clinicians’ professional judgement (Mithoefer, 2017; Wolfson and Mithoefer, 2015).

Consistent with the category’s name, the therapeutic orientation was not explicitly defined. Studies referenced transtheoretical or eclectic approaches based on the professional backgrounds with non-ordinary states of consciousness, drawing from modalities such as trauma-focused therapies, bodywork, Internal Family System, Voice Dialogue, Holotropic Breathwork, Jungian, and Buddhist psychology (Bouso et al., 2008; Jardim et al., 2021; Mitchell et al., 2021, 2023; Mithoefer et al., 2011, 2018; Oehen et al., 2013; Ot’alora G et al., 2018; Wang et al., 2021; Wolfson et al., 2020). Manuals emphasized flexibility, defining professional qualifications rather than prescribing a fixed protocol (Mithoefer, 2017; Ruse et al., 2008; Wolfson and Mithoefer, 2015).

Five studies published formal protocols (Aaronson et al., 2023; Davis et al., 2021; Mitchell et al., 2021, 2023; Von Rotz et al., 2023) and 13 reported manuals, but only 11 were accessible manuals by Multidisciplinary Association of Psychedelic Studies (MAPS; Mithoefer, 2017; Wolfson and Mithoefer, 2015) and Yale University (Ching et al., 2022).

Eleven studies assessed treatment adherence (e.g., through audio recording), particularly those using the MAPS Manual for PTSD (Mithoefer, 2017), suggesting efforts to standardize and monitor non-pharmacological procedures. In addition, mostly reported (n = 14), the psychosocial protocol duration varied from 4.5 to 18 hours.

Importantly, this category had the highest proportion of MDMA studies (n = 11/15), many of which followed manuals that permitted active therapeutic engagement during dosing session, including more directive interventions when clinically indicated. These particularities may be interpreted given MDMA’s pharmacological profile, which has been associated with increased empathy, trust, and emotional openness effects (Peled-Avron et al., 2025) that can facilitate work with avoided or traumatic material, particularly in conditions such as PTSD. Furthermore, most MDMA trials have been sponsored or influenced by MAPS frameworks, which conceptualize psychotherapy as an integral component of treatment before, during, and after dosing. This psychosocial protocol reinforces the centrality of psychotherapeutic processes within MDMA-assisted treatment models.

This category occupies an intermediate position between support and fully manualized therapies, providing structured yet flexible psychotherapeutic engagement accommodated to participants’ needs, without strict adherence to a single orientation. Compared to psychological support, it allows personalized interventions beyond managing acute distress and pharmacological safety. However, its impact remains underexplored, and the importance of individualized psychosocial care is still an undergoing debate (Goodwin et al., 2023a).

PAP with specific orientation

This category aimed for individualized psychosocial care as the nonspecific PAP approach, however, aligned with defined therapeutic orientations, balancing personalization with a clear psychotherapeutic framework. Despite variable reporting, the psychosocial procedures were evaluated as central to research designs, shown by adherence ratings (Danforth et al., 2018; Wells et al., 2024), clinical and cultural adaptations from previous protocols (Lear et al., 2023; Rucker et al., 2021; Vanderijst et al., 2024; Wells et al., 2024), assessment of the therapeutic relationship (Rucker et al., 2021; Vanderijst et al., 2024) and the notion that the substance may potentiate psychotherapeutic processes (Lear et al., 2023; Ross et al., 2016; Sessa et al., 2021).

Nine studies formed this category (Danforth et al., 2018; Jensen et al., 2022; Lear et al., 2023; Ross et al., 2016; Rucker et al., 2021; Schenberg et al., 2014; Sessa et al., 2021; Vanderijst et al., 2024; Wells et al., 2024), mostly RCTs (n = 6), with psilocybin or MDMA administered in one or two sessions, alongside a few alternative dosing models (e.g., multiple ibogaine sessions (Schenberg et al., 2014) or LSD microdosing combined with psychotherapy (Wells et al., 2024)). The studies targeted substance use disorders (n = 4), social anxiety disorder (n = 2), cancer-related distress (n = 2), and depressive disorders (n = 1), and were conducted across four different continents.

Over half of the studies were protocol publications for ongoing trials (Jensen et al., 2022; Lear et al., 2023; Rucker et al., 2021; Vanderijst et al., 2024; Wells et al., 2024). Among the completed studies, 130 participants were included, with a high completion rate (92.31%). However, this estimate should be interpreted cautiously, as one study was a retrospective observational analysis based on post-treatment clinic records (Schenberg et al., 2014), which may inflate completion rates.

Terminology varied widely across studies, with several using multiple names for the psychosocial protocol such as psychological therapy or support, substance-assisted psychotherapy, brief standardized psychotherapeutic intervention, and supportive psychotherapy, while others alternated between substance-assisted therapy, and psychotherapy.

The PAP overlaps with psychological support models, such as discussing participants’ lives, psychoeducation, development of resources, and management of challenging reactions. Notably, three studies from this category were recognized as borderline to psychological support (Jensen et al., 2022; Sessa et al., 2021; Rucker et al., 2021), but all permitted deeper, participant and condition-focused therapeutic exploration, thereby potentially amplifying its role in research. The main particularity of this category was the explicit therapeutic orientation, guiding session content.

These studies paired psychedelic administration with clearly defined psychotherapeutic frameworks: DBT focused on emotion regulation, interpersonal functioning, distress tolerance, and skill development for navigating and communication during the MDMA experience (Danforth et al., 2018); CBT alongside ibogaine for substance use disorder (Schenberg et al., 2014); ACT integrated with a single psilocybin dose in alcohol detoxification, targeting psychological inflexibility ³ and cognitive processes (Vanderijst et al., 2024); and Meaning-Centered Therapy combined with psilocybin to address cancer-related distress through existential, didactic, and experiential work (Wells et al., 2024).

Remaining studies adopted eclectic psychosocial protocols, including motivational interviewing, act, guided imagery and music therapy, emotion-focused therapy, compassion-focused therapy, and cognitive-behavioral, existential, psychoanalytic, and relational approaches, allowing flexible tailoring of session content. Overall, cognitive-behavioral frameworks were the most employed orientations (n = 7).

Across studies, the format generally included individual preparation, support during dosing, and integration sessions, with adaptations to sample and clinical context. Variations involved additional sessions (Danforth et al., 2018; Jensen et al., 2022; Ross et al., 2016; Rucker et al., 2021), flexible timelines (Wells et al., 2024) and concomitant care (Vanderijst et al., 2024). Depending on the specified orientation, some studies structured sessions thematically (Vanderijst et al., 2024; Wells et al., 2024).

While experimental sessions were mostly supportive and non-directive, some studies incorporated in-session psychotherapy (Wells et al., 2024) or reduced clinician presence (Schenberg et al., 2014). Overall, despite differing levels of structure, these studies shared embedding therapeutic orientations within psychedelic treatment, emphasizing relational dynamics and psychotherapeutic depth. This reflects a more defined way to work with participants, where the specific orientation often stems from researchers’ and clinicians’ perspectives (read Langlitz and Gearin, 2024, for more information).

Although no formal protocols were published, some studies referenced adapted manuals or existing materials and guidelines (Jensen et al., 2022; Lear et al., 2023; Vanderijst et al., 2024), and several assessed adherence, fidelity, and non-pharmacological factors such as therapeutic relationships and the psychological model (Danforth et al., 2018; Rucker et al., 2021; Vanderijst et al., 2024; Wells et al., 2024). Reported psychosocial intervention duration (n = 7) ranged from 7 to 20 hours in total, indicating more extensive protocols. It typically involved one to three preparatory sessions and integration following each dosing session, lasting from 60 to 120 minutes. Exceptions were Rucker et al. (2021), who provided at least 7 hours, with a flexible number of sessions, and Wells et al. (2024), who offered seven hours simultaneously to microdosing.

Conclusively, this category reflects an emerging trend toward integrating specific therapeutic orientations into psychedelic treatment, alongside greater recognition and evaluation of non-pharmacological components, despite ongoing authors’ concerns about expectancy effects and professional influence.

Psychedelic-assisted group therapy

This category highlighted the social dimension of the psychedelic experience (Gasser, 2021; Kettner et al., 2021), positioning group processes as central therapeutic elements. Although still understudied, group formats showed potential to enhance connection, peer support, social learning, cost-effectiveness, and scalability, while also posing challenges related to group cohesion and emotional suggestibility (Cheung et al., 2024; Lewis et al., 2023a; Trope et al., 2019).

Six studies were included in this category (Agrawal et al., 2024; Anderson et al., 2020; Davis et al., 2023; Lewis et al., 2023b, 2025; Oehen and Gasser, 2022), mainly open-label trials (n = 4), viewing psychedelics as catalysts to group approaches (Oehen and Gasser, 2022). It also demonstrated strong consideration for participants’ clinical condition, applied in individuals with cancer-related distress (n = 2), trauma-related disorders (n = 3), and demoralization in long-term AIDS (n = 1), diagnoses for which shared experiences and mutual identification may offer therapeutic value.

Two studies uniquely combined different psychedelics within the same treatment and were the only ones in this category to use substances beyond psilocybin. Most studies administered a single psilocybin dose in the United States, while one analyzed a program combining consecutively a single dose of ibogaine and inhaled 5-MeO-DMT in Mexico (Davis et al., 2023), and another offered individualized MDMA and LSD dosing in Switzerland (Oehen and Gasser, 2022). Overall completion was 76.92%, with missing data mainly driven by online follow-up procedures in one study (Davis et al., 2023), whereas others reported high attendance and low attrition.

The denomination for the psychosocial protocol was heterogeneous, including terms such as substance-assisted group therapy or psychotherapy, substance-assisted therapy, and substance-enhanced group psychotherapy, with most studies utilizing multiple terms within the article.

Psychedelic-assisted group therapy distinctly had the purpose to foster trust, connection, and mutual support among participants (Lewis et al., 2023b), using group sharing and processing to reinforce experiences, validate participants, and gather feedback on the treatment format (Agrawal et al., 2024; Lewis et al., 2023a, 2025). Despite variable reporting of non-pharmacological content, the group setting was considered particularly beneficial for populations with strong communal ties, utilizing diverse techniques, such as letter exchanges, use of psychoeducational materials, participant-recorded phrases for processing, arrangement of meaningful objects in a group circle, take-home music, and participant-led integration to support engagement and meaning-making.

All studies followed a PSI model, though not all provided group-based dosing session. Anderson et al. (2020) combined individual dosing with group preparation and integration. During the dosing visit, two participants shared a breathing exercise and guided meditation, but underwent the experience separately, later narrating and reflecting together. The remaining studies implemented group dosing sessions with varying combinations of individual and group components before and after the psychedelic experience. Across studies, formats differed in group size, session structure, duration, and degree of individualization, with dosing session conducted in shared, semi-private, or individualized settings depending on clinical needs, substance characteristics, and safety considerations. Agrawal et al. (2024), alongside Lewis et al. (2023b, 2025), assigned a dedicated professional to each participant during the individual phase of the non-pharmacological sessions and the dosing. Notably, Oehen and Gasser (2022) and Davis et al. (2023) offered participant autonomy, allowing access to outdoor areas and flexibility in the integration format.

This category adopted a non-directive stance during dosing, with some extending this approach to integration by avoiding interpretative interventions. Music was used to create a shared atmosphere, occasionally including live instrumentation (Oehen and Gasser, 2022). Therapeutic orientations could be specified: three studies employed Supportive Expressive Group Therapy (SEGT; Anderson et al., 2020; Lewis et al., 2023b, 2025) and one used trauma-focused therapy (Oehen and Gasser, 2022). SEGT adaptations incorporated breathing exercises, guided meditation, psychoeducation, emotional expression, existential themes exploration, and an emphasis on mindfulness and peer support. Besides SEGT, Lewis et al. (2025) also applied Mindfulness Based Stress Reduction (MBSR), utilizing it alone as a control arm.

No specific manuals were used in this category. Two studies published a formal protocol (Agrawal et al., 2024; Lewis et al., 2025), another study referenced but adapted SEGT manuals (Anderson et al., 2020), and Lewis et al. (2023b) published separate observations on the group format (Lewis et al., 2023a). These same four articles reported the complete duration of the psychosocial intervention beyond dosing, ranging from 8 to 18.5 hours, showing less variance than other categories. Oehen and Gasser (2022) and Davis et al. (2023) partially described the extent of non-pharmacological sessions, with a high degree of flexibility in duration and format.

Assessments of non-pharmacological components varied across studies. Methods included focus group to gather qualitative feedback (Anderson et al., 2020), video recordings for safety and supervision (Agrawal et al., 2024; Lewis et al., 2023b, 2025), and audio recordings to monitor adherence, quality, and training (Agrawal et al., 2024). Some studies also assessed therapeutic alliance and patient experience using validated questionnaires such as Scale to Assess Therapeutic Relationship and HOPE Patient-Reported Experience Questionnaire (Agrawal et al., 2024; Lewis et al., 2023b, 2025).

Lastly, studies described difficulties in isolating effects, limited standardization, and potential social suggestibility. Nonetheless, this category underscored the therapeutic relevance of the group-based intervention, highlighting the importance of its comprehensive evaluation and nuanced clinical oversight.

Manualized intervention of PAP

This category was the most structured and detailed among all presented in this review, marked by an intentional balance between pharmacological and psychosocial components of the treatment, predicting personalization. The psychosocial protocol played an expanded role, with substantial practices unrelated to pharmacology and strong researchers’ investment in developing these protocols. All five studies included specific manuals and defined therapeutic orientations, either customized to the trial (Sloshower et al., 2023) or adapted from established evidence-based treatments for the targeted conditions (Bogenschutz et al., 2015, 2022; Johnson et al., 2014; Monson et al., 2020) such as Substance Use Disorder (n = 3), PTSD (n = 1), and depressive disorder (n = 1).

While it shares similarities with PAP with specific orientation, like the defined therapeutic orientation, this category is distinguished by standardized, diagnosis-focused session content aligned with explicit therapeutic goals, rather than adaptations from previous studies or non-manualized approaches. It also featured a high level of detail, with clearly systematized topics for each non-pharmacological session and, in some cases, applied psychoeducation about the treated disorder (Monson et al., 2020; Sloshower et al., 2023). Only one study lacked a detailed description of non-pharmacological sessions’ content (Bogenschutz et al., 2015), but it was included since a subsequent controlled trial (Bogenschutz et al., 2022) amplified on its format and orientation. Overall, the purpose of the psychosocial protocol was individualized psychosocial care based on a pre-established therapeutic framework and treatment goals.

Like PAP with nonspecific orientation, this category’s manuals instructed a non-directive, supportive presence during dosing sessions. However, it differed by providing a clear manualized framework that, while acknowledging personalization in session content, promoted more structured guidance.

The methodologies applied were open-label design (n = 3) and RCT (n = 2). The open-label studies administered two doses of psilocybin (Bogenschutz et al., 2015) or MDMA (Monson et al., 2020), with Johnson et al. (2014) offering an optional third dosing if the therapeutic goal was not achieved. The RCTs involved two dosing sessions comparing psilocybin with placebo or diphenhydramine, allowing dose adjustments or additional sessions after the double-blind period (Bogenschutz et al., 2022; Sloshower et al., 2023). All studies were conducted in North America and included 151 participants, with 144 completers (95.36%), representing the highest retention rate in this review. Two studies reported no dropouts, achieving full retention (Johnson et al., 2014; Monson et al., 2020).

Denomination was inconsistent across studies, with multiple labels used interchangeably. Johnson et al. (2014) outlined CBT modules and psilocybin-related topics, suggesting two parallel components within the same treatment framework. Other terms applied were psychotherapy, psychosocial intervention, substance-assisted psychotherapy, manualized psychotherapy, behavioral intervention, therapy, psychotherapeutic support, and substance-facilitated cognitive-behavioral conjoint therapy (CBCT).

Therapeutic orientations varied across studies. Bogenschutz et al. (2022) employed MET to support alcohol reduction through structured themes, personalized plans, and post-dosing motivational interviewing techniques. Johnson et al. (2014) applied CBT for smoking cessation, integrating standard CBT tools (e.g., motivational statements, scented oils for craving management, guided imagery exercises) and established tobacco dependence treatment programs. Monson et al. (2020) conducted CBCT for PTSD in couples, emphasizing psychoeducation, communication, and shared trauma processing. Sloshower et al. (2023) drew on ACT, targeting psychological inflexibility and promoting ACT-informed psychoeducation for depression to facilitate self-awareness and mindset shift.

Therapeutic orientations were predominantly CBT and its “third-wave approaches” (Walsh and Thiessen, 2018), considered by some as synergistic with psychedelic treatment (Yaden et al., 2022) and by others as potentially limiting (Mithoefer, 2017). Even when CBT was not the main framework, MET was adapted (Motivational Enhancement and Taking Action) to incorporate CBT strategies to support behavioral change (Bogenschutz et al., 2022).

This category generally offers 12–15 weeks of manualized treatment. Two studies followed a structured timeline of preparatory, between-dose, and post-treatment sessions integrating MET with psilocybin-specific procedures (Bogenschutz et al., 2015, 2022), assigning two professionals per participant to maintain role clarity, though collaboration was allowed. Other 15-week protocols delivered weekly CBT sessions tailored to specific goals, such as smoking cessation with a Target Quit Date and additional sessions for abstinence support (Johnson et al., 2014) or a three-phase manualized CBT program for PTSD with two professionals, also one for CBT and another for MDMA-related sessions (Monson et al., 2020). In contrast, Sloshower et al. (2023) implemented a shorter, semi-structured manualized format to promote consistency.

Paradoxically, only one study provided a publicly accessible manual, the Yale Manual for Psilocybin-assisted therapy of depression (Guss et al., 2020), designed to harness the synergy between ACT principles and psilocybin assisted therapy. The remaining studies referred to existing manuals (e.g., MET, CBCT, MAPS, CBT) but did not publish trial-specific manuals. Two shared study protocols (Bogenschutz et al., 2022; Monson et al., 2020), and one detailed the development of its psychotherapeutic model separately (Bogenschutz and Forcehimes, 2017). Moreover, the Johns Hopkins University Guideline (Johnson et al., 2008) was cited in two studies (Bogenschutz et al., 2022; Johnson et al., 2014).

Two studies did not assess the psychosocial protocol (Johnson et al., 2014; Sloshower et al., 2023); however, others used audio or video recordings for training and fidelity monitoring. Bogenschutz et al. (2015) analyzed MET sessions using the Motivational Interviewing Treatment Integrity (MITI 3.1) coding system (Moyers et al., 2005), and measured motivation with The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8A; Miller and Tonigan, 1996). In a later publication, Bogenschutz et al. (2022) further structured psychosocial components by incorporating COMBINE trial tools (Frances, 2007) to guide delivery, monitor adherence, and support fidelity and supervision.

The duration of psychosocial protocols ranged between 8 and 20 hours in total. The pilot study by Bogenschutz et al. (2015) just reported the number of experimental sessions. Sloshower et al. (2023) showed the greatest variability (8–16 hours), but the remaining studies had longer extensions, with at least 16 hours.

This category emphasized safety while optimizing set and setting to enhance and extend therapeutic effects, focusing on the synergy between psychosocial practices and psychedelic effects. Standardization through manuals, training, supervision, and fidelity monitoring was central, though unevenly implemented. Overall, these studies most explicitly recognized the impact of psychosocial protocols on treatment outcomes.

Practices based on tradition with western psychotherapeutic methods

This category presented a distinct perspective on PAT by integrating traditional-based healing practices with Western psychotherapeutic elements. Rooted in Indigenous knowledge, these interventions may challenge conventional evidence-based protocols and emphasize the origins of psychedelic use, which must be considered appropriately. As the field evolves, the discussion about how Western medicine investigates psychedelics, proposing different models and contexts from traditional knowledge, is a critical matter (Pilecki et al., 2021).

Central to this approach is the seek to align individual, community, ecosystem, and territory (Bouso and Sánchez-Avilés, 2020). Consequently, sociocultural and spiritual factors were significant in this category, often involving communal activities, live music, and ritual settings. Protocols were typically flexible and adapted to participant’s clinical needs, which incorporates preparation, in-session support, and integration without rigid timeline or detailed standardization of dosing, content, format, or duration.

All five studies included were observational and involved intercultural collaboration between traditional and Western practitioners. Most were conducted at The Takiwasi Center for Rehabilitation of Drug Addicts and Research on Traditional Medicine in Peru (Berlowitz et al., 2019; Giovannetti et al., 2020; O’Shaughnessy et al., 2021), while others took place in a rural First Nations community in Canada (Thomas et al., 2013) and in centers in the Netherlands (Van Oorsouw et al., 2022). Ayahuasca was the only psychedelic used, often alongside ritual tobacco and purgative plants. Treatment duration varied considerably, from a few days to several months, with weekly or biweekly ceremonies.

Treatments primarily targeted substance use disorders, apart from one study addressing depressive disorder (Van Oorsouw et al., 2022). Accordingly, this category showed a concentration of studies with ayahuasca (83.33%) and for drug abuse (66.66%). Notably, it also presented the lowest completion rate among categories, with 118 of 179 participants completing treatment (65.92%). Dropout was attributed to its lengthy duration, cultural mismatch (Berlowitz et al., 2019), and participants’ age (O’Shaughnessy et al., 2021).

Terminology was mostly consistent, primarily referring to the integration of traditional Amazonian treatments with Western psychotherapeutic methods (Berlowitz et al., 2019; Giovannetti et al., 2020; O’Shaughnessy et al., 2021). One study used the term ayahuasca-assisted therapy and group counselling (Thomas et al., 2013), while another lacked a clear terminology (Van Oorsouw et al., 2022). Although the category name was based on the most frequent designation across all reviewed articles, this review adopted the term Practices based on Tradition, acknowledging the adaptations made since the substances’ original use.

The purpose of this type of psychosocial protocol is the individualized psychosocial care while also involving communal and spiritual dimensions. Interventions combined preparatory support, group sharing, ritual elements, and culturally grounded practices (e.g., music, healing songs, diets, cleansing, ceremonies). Programs ranged from short retreats rooted in Indigenous traditions to multi-phase inpatient models integrating medicinal plants, psychotherapy (individually or in group), communal living, and reintegration activities. Overall, these approaches promoted holistic, flexible, and culturally embedded care.

This category uniquely positioned ritual, spiritual, and communal elements as integral to the therapeutic process, framing altered states within structured symbolic practices (O’Shaughnessy et al., 2021). Such components supported introspection, emotional processing, meaning-making, and integration of insights into everyday life (Giovannetti et al., 2020).

This format departed from linear, standardized models, following a progressive and personalized process guided by clinical necessities and characterized by low structuredness. A key distinction lies in the incorporation of ritual practices during ceremonies. While therapeutic orientations were often unspecified, some studies reported relapse prevention and psychodrama as frameworks for the group therapy sessions (Berlowitz et al., 2019), transpersonal and Jungian approaches (Giovannetti et al., 2020), or psychosomatic group exercises (Thomas et al., 2013).

No formal manual or study-specific protocols were provided in this category, although O’Shaughnessy et al. (2021) referenced prior publications describing Takiwasi Center treatment procedures (O’Shaughnessy, 2017). Most studies assessed non-pharmacological components, such as motivation to change and client satisfaction (Berlowitz et al., 2019; Giovannetti et al., 2020).

The duration was inconsistently reported. The Takiwasi Center studies described a long-term program ranging from 3 to 12 months, with an average of 6.5 months and multiple ayahuasca ceremonies (μ = 14), cleansing sessions (μ = 21), and psychotherapy sessions (μ = 19) determined collaboratively. Other studies specified only the number of treatment days (Thomas et al., 2013; Van Oorsouw et al., 2022).

As observational studies involving multifaceted interventions with substantial non-pharmacological components, the analysis of results may be challenging. Despite diverging from conventional scientific standards in clinical research, this category highlights the relevance of ancestral practices and the inclusion of traditional communities in the field. It points to the potential for dialogue between tradition-based and Western models, encouraging alternatives from conventional models and culturally sensitive frameworks that bridge Indigenous knowledge and contemporary clinical practice.

Qualitative methodology

This category, based on a single study (Mash et al., 2018), uniquely integrated a semi-structured qualitative elicitation interview within the treatment timeline as part of the psychosocial protocol. Conducted within 3 days after ibogaine dosing for substance use disorders, the interviews explored the participants’ subjective experiences and perceptual changes but were also considered to support reflection and meaning-making, even with no explicit research intention. Furthermore, this psychosocial technique may function as both data collection and therapeutic care, depending on when and how it is conducted.

Unlike standard post-trial qualitative follow-ups (Agin-Liebes et al., 2021; Barone et al., 2019; Beaussant et al., 2024; Belser et al., 2017; Bogenschutz et al., 2018; Breeksema et al., 2024; Gasser et al., 2015; Gukasyan et al., 2022; Johnson et al., 2017; Lewis et al., 2023a; Malone et al., 2018; Mithoefer et al., 2013; Nielson et al., 2018; Noorani et al., 2018; Roseman et al., 2018; Swift et al., 2017; Watts et al., 2017), this approach positioned narrative elicitation as a complementary intervention with potential relevance for aftercare. Through a guided questionnaire conducted by a trained interviewer, this category was formalized due to its potential impact on participants’ experiential elaboration, offering a model for integration-oriented qualitative assessment.

This 12-day inpatient study in the West Indies, United States, included a comprehensive psychosocial assessment, in-session and post-session support, motivational counselling, aftercare referrals, and post-experience elicitation interviews. Of 191 participants, 60 participated in the interviews, though selection criteria and completion rates were not reported.

No specific therapeutic orientation was defined beyond harm reduction approach following detoxification. However, the interview methodology and subsequent analysis may align with interpretative phenomenological frameworks (Brown et al., 2019; Gomes, 2021; Schenberg et al., 2017) and could represent a promising tool for post-dosing, warranting further evaluation. Manuals or protocols, and duration were not described. Interviews were recorded, transcribed, and coded for key themes, with no additional assessments.

This category emphasizes that when integrated into the treatment timeline, qualitative methods can serve as both assessment and support, utilizing participants’ narratives as a tool for integration, not solely an outcome evaluation and investigation.

All categories are summarized in their respective focuses in Figure 3.

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Figure 3.

Focuses of psychosocial protocol categories within the identified dimensions in this review.