Nadav Liam Modlin,1 Michael Creed,1,2 Maria Sarang,1 Carolina Maggio,1 James J Rucker,1,2 Victoria Williamson3,4

1The Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, SE5 8AF, UK; 2South London and Maudsley NHS Foundation Trust, Maudsley Hospital, Denmark Hill, London, SE5 8AZ, UK; 3King’s Centre for Military Health Research, King’s College London, London, SE5 9RJ, UK; 4Department of Experimental Psychology, Anna Watts Building, University of Oxford, Oxford, OX2 6 GG, UK

Correspondence: Nadav Liam Modlin, The Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 16 De Crespigny Park, London, SE5 8AF, UK, Email [email protected]

Introduction: Post-traumatic stress disorder (PTSD) is associated with significant patient burden. While pharmacotherapies and evidence-based psychotherapy interventions (EBPI) are effective, studies consistently highlight inadequate outcomes and high treatment dropout. Psychedelic therapy (PT) has shown preliminary promise across difficult-to-treat conditions, including MDMA-assisted therapy for PTSD, however trials of classical psychedelics in PTSD are lacking. Understanding patients’ experiences of EBPI could help promote safety in PT.
Aim: To systematically review qualitative research on patients’ subjective experience of EBPI for PTSD, and of PT, and examine areas of overlap and divergence between them.
Methods: Systematic literature searches for studies published between 2010 and 2023 were conducted on OVID, PubMed, Web of Science, and PsycInfo. Included were original studies in English that presented qualitative data of patient experiences of EBPI in PTSD, or PT for any indication. Extracted data from included studies were analysed using thematic synthesis. Syntheses were completed separately for EBPI and PT, before similarities and differences between the therapies were identified.
Results: 40 research articles were included for review: 26 studies on EBPI for PTSD, and 14 studies on PT. EBPI studied were CBT, EMDR, CPT and PE. Psychedelic compounds studied were psilocybin, ibogaine, LSD, MDMA and ketamine, for treatment of substance use disorders, anxiety relating to physical illness, depression, and PTSD. Core themes from patient experiences of EBPI: 1) patient burden in PTSD treatment; 2) readiness; 3) key mechanisms of change; 4) psychological safety and trust. Themes identified in the review of PT: 1) indirect trauma processing; 2) reorganisation of self-narratives via processes of relatedness and identification; 3) key treatment characteristics.
Conclusion: This study suggests overlap between patients’ experience of EBPI and PT in terms of key mechanisms of change, the importance of psychological safety and readiness to engage in treatment. Trauma-informed care paradigms and practices may improve safety and acceptability of PT research.

Introduction

Trauma exposure is associated with an increased risk for psychopathology1–3 including post-traumatic stress disorder (PTSD), major depressive disorder (MDD) and dissociative disorders. PTSD, characterised by debilitating comorbid symptomatology and psychosocial dysfunction, is associated with significant individual and societal burden.4,5 Pharmacotherapies (eg, paroxetine and sertraline) and evidence-based psychotherapy interventions (EBPI) for PTSD, such as prolonged exposure (PE) or trauma-focused cognitive behavioural therapy (TF-CBT), are considered effective.6–8 Despite EBPIs effectiveness, studies consistently highlight difficulties, including inadequate treatment outcomes9,10 and poor patient retention.11 Psychological treatment of PTSD may be challenging and complex,12 potentially due to the significant symptomatic and psychosocial burden patients endure (eg, perceived negative experiences related to the treatment across different domains, including emotional, relational, physical, systemic, and practical aspects).13 Further, patients who find treatment ineffective and seek additional care are also at increased risk of re-traumatisation due to the need to repeatedly recount their traumatic experiences to providers.14

In response to the unmet clinical need in PTSD15, and difficult-to-treat mental-health conditions16, studies investigating psychedelic forms of therapy have shown promise in so-called “treatment-resistant” patients.17–21 Psychedelic therapy (PT) is an umbrella term for interventions administering serotonergic hallucinogens such as 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin) and lysergic acid diethylamide (LSD) or entactogens such as 3,4-Methyl enedioxy methamphetamine (MDMA) alongside manualised psychological interventions.22–25 Despite PT’s favourable safety profile in research settings and advances in understanding of its neurobiological, psychological, and behavioural effects,26–29 significant gaps of knowledge remain. Clinically, it is not well understood how PT supports positive outcomes across conditions and compounds.30 Positive results are often associated with patient reports of increased insightfulness,31 emotional breakthrough32 and mystical-type experiences,33 however, experimental studies are needed to establish causality. Importantly, qualitative research has highlighted the significance of the intervention’s non-pharmacological factors,34,35 including interpersonal rapport and music listening to positive outcomes.36,37

In PTSD, MDMA-assisted therapy appears highly efficacious in clinical trials, reducing symptoms and improving quality-of-life in patients with chronic PTSD.20,38 However, completed trials of classical psychedelics in PTSD are lacking, with several early phase studies recruiting as of October 2023. Correspondingly, there is an absence of trauma-focused clinical practice guidelines in PT. Despite considerable advances in treatments for PTSD in recent years,9 there remain significant challenges associated with standard PTSD treatment, including disruptions to the patient’s linguistic capacities and biological stress dysregulation.39 Therefore, considering patients’ experience of EBPI may help personalise care and promote safety outcomes for traumatised participants in PT trials. Further, as the number of psychedelic trials grow40 and with Australia approving the therapeutic use of MDMA and psilocybin in mental-health,41,42 it is vital that regulators, healthcare systems and clinicians have access to a repository of in-depth knowledge of patient experiences to inform operational, clinical, and training protocols that support patient safety. As most PT trial participants must be unsuccessfully treated by first-line interventions, understanding the positive and negative experiences of EBPI patients could help optimise PT protocols.

Qualitative research is well-placed to provide an in-depth understanding of patients’ subjective experience of trauma and treatment.43–45 Therefore, this research aims to review qualitative studies in EBPI for PTSD and PT, examining areas of intersectionality and divergence to promote a multidisciplinary dialogue. A synthesis of the themes in the selected studies will be conducted to provide a broad understanding of patients’ experience of the treatments. Based on the data, areas of clinical interest will be discussed to promote patient outcomes and safety in PT.

Methods Search Strategy

A systematic literature search was conducted to identify papers studying patients’ qualitative experiences of either EBPI in PTSD, or PT. Given the paucity of existing qualitative literature on PT for PTSD, an expanded second search was conducted to include studies on PT for any clinical indication, including but not limited to depression, substance use disorders, and anxiety associated with life-threatening illness. The search was conducted between January and March 2023. Search terms related to PTSD, psychotherapy, psychedelics, qualitative methods, and patient experience were defined (Table S1) and entered in major research databases (OVID, PubMed, Web of Science, and PsycInfo). Reference lists of included studies on PT and specific relevant journals specialising in psychedelic science and traumatology were manually searched to ensure suitable articles were not missed. Transparent Reporting of Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.46 The systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO).

Eligibility Criteria

Papers deemed eligible for inclusion were original, peer-reviewed studies presenting qualitative data with an identifiable qualitative research methodology (eg, grounded theory, interpretative phenomenological analysis, etc.), focused on patient experiences of either EBPI in PTSD, or PT for any indication. Papers must have been published between January 2010 and March 2023. This date range was chosen as modern psychedelic research began to emerge after 2010, and such a date range would allow comparison with contemporaneous EBPI literature.

Papers were excluded if they did not present new research (eg, systematic reviews), were not peer-reviewed, not published in English, studied others’ experiences (eg, clinicians, family members) or indications other than PTSD (unless studying psychedelics, where any clinical indication was included as previously outlined). Studies were also excluded if they were not specifically studying the experience of EBPI, or if they were studying internet- or phone-based therapy only. Mixed-methods studies were included if qualitative data of patient experiences was clearly presented. PRISMA diagrams for both literature searches are presented in Figures 1 and 2.

Figure 1 PRISMA flow diagram of evidence-based psychotherapy interventions (EBPI) literature search.

Figure 2 PRISMA flow diagram for psychedelic therapy (PT) literature search.

Selected papers were assessed for quality using the Critical Appraisal Skills Programme (CASP) criteria.47 This involves assessing the paper across ten domains, and assigning a score of 0–10, 10 representing a paper of high quality. The overall quality of the included studies was high, with an average rating of 8.2 (range: 5–10) (see Tables 1 and 2).

Table 1 Overview of EBPI Study Methodologies, Settings, Sample Characteristics and CASP Quality Ratings

Table 2 Overview of PT Study Methodologies, Settings, Sample Sizes and CASP Quality Ratings

Data Extraction

Data from the included studies were extracted and included: author/year; study design; qualitative methodology; psychological intervention; setting; sample size; demographics; key themes identified; and data relating to patients’ reported experiences. Authors NLM and MC systematically reviewed papers and extracted the data, cross-checking data for concordance.

Data Analysis

Extracted data from the studies was analysed using thematic synthesis.79 Author NLM read and re-read the data before assigning open-coded descriptive themes to the results. Once all themes were assigned, these were then distilled into core themes, with sub-themes to supplement and expand on the core themes. These themes were then reviewed by VW and MC and agreed upon by all authors.

A thematic synthesis was completed separately for the studies of EBPI and studies of PT. After completing these thematic syntheses, similarities and differences between the therapies were identified. Our findings from the EBPI synthesis are presented first, followed by the key themes found across PT studies. Excerpts from included studies are presented to illustrate key findings with additional excerpts in Table S2.

Results EBPI in PTSD

The initial search returned 1286 papers. After screening and assessing papers for eligibility, the final number included was 26 (see Figure 1 for screening details).

Of the included studies, the majority were conducted in the USA (n=12) and the UK (n=6), with one study each in Denmark, the Netherlands, South Africa, Norway, and Sweden. Psychotherapies studied were TF-CBT (n=6), PE (n=5), eye-movement desensitisation and reprocessing (EMDR, n=3), cognitive processing therapy (CPT, n=2), with a number of studies (n=9) on various or combined therapies. Study designs varied between standalone qualitative studies (n=11), qualitative analyses within clinical trials (n=7), treatment acceptability studies (n=4), and mixed methods (n=3). See Table 1 for further details.

Psychedelic Therapy

128 papers were initially found on PT. After screening and eligibility assessment, 14 papers were included in the review (see Figure 2 for screening details).

Studies were primarily conducted in the USA (n=8), with others in the UK (n=2), Brazil (n=2), Mexico (n=1) and Switzerland (n=1). Psilocybin (n=8) was the substance most studied, with other studies investigating ibogaine (n=3), LSD, MDMA and ketamine (all n=1). Indications for treatment included substance use disorders (n=7), anxiety relating to physical illness (n=5), depression and PTSD (both n=1). See Table 2 for further details.

EBPI in PTSD Patient Burden in PTSD Treatment

All EBPI studies (n=26) highlighted patient-reported burdens associated with PTSD treatment. For some patients, tolerating these challenges appeared to increase feelings of agency. However, in many cases, this experience caused distress and destabilisation, at times, impacting patient retention.

This synthesis found 4 prominent sub-themes associated with patient-reported burden:

Real-World Barriers Tolerating Treatment Emergent Adverse Events Misaligned Treatment Rationale and Expectancy Interpersonal difficulties with staff and peersReal-World Barriers

Related to engaging in treatment, patients across studies reported practical concerns regarding scheduling and travel difficulties and competing practical, financial and/or relational demands.88,91 This was compounded by the psychological burden associated with the treatment (eg, symptom exacerbation) and pre-existing psychosocial stressors. Patients expressed concerns about the potential adverse impact of the treatment on their psychosocial functioning during and after treatment.52,80,81,92 Patients discussed feeling conflicted about complying with the treatment as this often competed with their on-going “real-world” responsibilities.

I felt very overwhelmed, and I felt very lost and very frantic in what I had to do [for therapy]. Especially having the homework to do, but then knowing I could not do it. Because I knew my reaction was going to upset my daughters. So, then trying to find time later at night, but then writing about all of that would disturb my sleep - what little I get. And the disturbed sleep would mean I was up all night. so it just kind of snowballed.80

Some patients reported concerns about the insufficient time allocated for treatment.81–83 These patients expressed their perception that the structure of weekly psychotherapy did not support the full achievement of therapeutic gains.

With weekly sessions, you never truly get over the trauma.81

For some patients, concerns regarding premature endings were also reported.83 This may be due to the short-term nature of the outpatient treatment, the treatment failing to address integral aspects of patients’ difficulties, and/or attachment-related anxieties known to contribute to PTSD psychopathology.49

The therapy has really helped, but I need more because I am just open, you know when you get that blast and you see that mushroom cloud, I am like the mushroom cloud it has not dissipated yet.83

This was contrasted with findings from residential or intensive treatment programs which seemed to mitigate patients’ avoidance of challenging feelings/symptoms, with some patients reporting that this type of care allowed them to get more out of the treatment.

Tolerating Treatment Emergent Adverse Events

All studies reported patients’ experience of intense and difficult to tolerate responses to treatment. Frequently reported internal states associated with exposure to traumatic material included fears about the pain associated with reliving due to the need to openly talk about and/or vividly imagine certain aspects of patients’ index-trauma. Correspondingly, trauma-related “maladaptive defenses”,84 such as experiential avoidance, were reported across most studies.

When you come, you have to really like talk about it and how you’re feeling and that brings it like to the surface and it’s really raw and that’s really hard and sometimes, you know, you don’t feel like doing that ‘cause it’s painful.85

Misaligned Treatment Rationale and Expectancy

Several studies50,80,86,87 highlighted the importance of providing psychoeducation regarding PTSD symptoms, the treatment’s rationale, and its expected effects to positive outcomes.

I really do not understand CPT. Like what it’s supposed to do? I would not really know.80

Studies also reported the significance of managing patient’s pre-treatment expectations and considering the degree of alignment between the treatment’s rationale, procedures, and patient’s needs.80,82,88–90

They [the clinicians] just want to go into the past, but we need or what I need is how to cope with what I have right now, and then everyday civilian life, instead of just regressing and getting to the roots.88

Interpersonal Difficulties with Staff and Peers

Studies highlighted patients’ interpersonal difficulties with clinical staff and, in group-based interventions with their peers, as factors influencing engagement in treatment and outcomes.70,82,91–93 At times these gave rise to patient feelings of disconnection and invalidation.80

I was pissed off that people were trying to desensitize me to something horrible that happened because it almost seems like, ‘Oh you’re overreacting just think about, just be around it enough and you won’t feel that way anymore.91

In group settings, studies reported the impact of negative perceptions of other group members on patient retention and outcomes.

I was overwhelmed with knowing that I would soon have to tell my story. The fear of exposure was almost too much.93

Demonstrating the clinical relevance of strong social support systems outside of the clinic on recovery, patients appeared to use relationships to adhere to the treatment protocol.

Studies70,88,91,92 also discussed how psychosocial stressors such as isolation adversely impacted participants’ experience of the treatment.

I did not really have anyone in-person to talk to. I did not really have a lot of support in terms of like family or friends, or relationships around me that were good.70

Readiness

Studies highlighted the contribution of intrapersonal factors (eg, patient traits, beliefs, and internal resources) to the overall experience of treatment.50–52,81,82,84,85,89–95 Most studies referred to the significant psychological burden PTSD treatment entails (eg, fear of re-traumatisation, worsening of symptoms and functional destabilization). Correspondingly, in this synthesis, we found that intrapersonal factors reportedly influenced patients’ perception of their experience of treatment, and conversely, their willingness to engage in often-challenging therapeutic processes. The umbrella term “readiness” was chosen by authors to reflect various sub-themes identified.96

Patients described processes of coming to terms with the severity of their PTSD symptoms and psychosocial difficulties. This form of tentative acceptance seemed important in overcoming ambivalence about seeking treatment and then, tolerating challenging aspects of the therapeutic process.

Some patients referred to deeply held personal desires and values that encouraged engagement in treatment.

I’m really scared to go into [dialectical behavioral therapy (DBT) prolonged exposure (PE). But. you get your DBT skills first [and] I think that’s what’s going to help me the most. I don’t want to live like this anymore. I deserve to be happy.91

Once in treatment, some patients reported intentional behaviors aimed at making the most out of their treatment, cultivating a willingness to face fears associated with reliving their index-trauma.50–52,81,82,84,85,89–95 In contrast, in the context of possessing a willingness to confront pain, some participants reported feeling incapable of engaging fully in imaginal exposure to traumatic events. This may be due to use of defenses, such as avoidance, and hesitancy about engaging in treatment due to psychosocial instability.53,97

Because I avoided talking about things, I probably didn’t get the full help I could have gotten.82

Key Mechanisms of Change

Reviewed studies suggested a variety of key mechanisms of change associated with positive outcomes. EBPI in PTSD usually entails revisiting traumatic memories to gradually reduce hyper- and hypo-arousal states, characterised by nervous system dysregulation, depersonalisation or dissociation.98 Aspects related to the previous theme (eg, “readiness”) appeared to support patients make use of the treatment process. Mechanisms of change identified in this synthesis include attainment of insight, behavioral activation, corrective emotional experiences, and changes in trauma narratives during and after treatment.

Patients who responded to treatment described attaining insight into their persistent responses to internal states associated with their index-trauma.50–52,81,87–90,95,99–101 Conversely, this may have also supported patients to feel validated and achieve a sense of mastery over their symptoms. Studies discussed the importance of cultivating self-awareness and possessing the capacity to notice “signals”94 surrounding the need for self-regulation.

If I was being triggered. usually it would come out in anger or fear. Before I did not really know why I was doing that and then throughout my therapy I realized it was the fear of their vulnerability.100

In addition to consolidating learning pertaining to individual responses to traumatic stimuli, some treatment responders discussed achieving greater recall of the event, which appeared to play a significant part in the therapeutic process.95

That went a little deeper with every session. And with every trauma, actually. At some point, I could recall things that I had never. That I had never thought about again, that never crossed my mind.95

Beyond attaining insight into emotional and behavioral responses to trauma, some patients described how greater insight facilitated corrective emotional experiences and shifts in their trauma narratives, accompanied by greater compassion towards self.51,87,93,101 Further, referring to the support and encouragement of the therapist, patients detailed how behavioral activation was facilitated by empowering therapists who promoted patients’ sense of agency and autonomy.

[The clinician] left a lot of decisions up to me. I felt like he was taking my experience into consideration and not just his diagnosis [of me]. I felt like he allowed me to take part in what I felt was going to work for me.92

In group-based interventions, fears of exposure and difficult relational dynamics could make it hard to engage in group-based interventions. However, for patients who responded well to the group setting, insights and corrective emotional experiences were facilitated by processes of identification with others, leading to feelings of validation and belonging.51,54

Psychological Safety and Trust

All studies highlighted the importance of psychological safety and trust in patient experience and PTSD treatment outcomes. This core theme distinguishes between psychological safety (PS) and trust. PS in healthcare settings refers to a myriad of systemic and interpersonal attributes leading to a shared belief that the treatment setting is safe to engage in interpersonal risk-taking.102 In the context of mental-health care, PS enhances patient security and feelings of empowerment through promoting an organisational culture imbued with openness and mutual respect.103 Conversely, trust refers to the interpersonal dynamic established between the provider and patient.104 Trust is considered a fundamental component in trauma-informed models of care due to high rates of betrayal and harmful relational power dynamics reported in trauma survivors.105,106

This synthesis identified 3 sub-themes, which taken together, were found to contribute towards and determine the quality of PS and trust perceived by the patient.

These include:

4a. Experience of Therapist

4b. Experience of Group and Wider Psychosocial Setting

4c. Experience of Self

Experience of Therapist

Across all studies, patients reported positive and negative reactions to their therapists which impacted their engagement in treatment. Possessing trust in the therapists’ attunement and competency was associated with patient feelings of safety and validation. This appeared to enhance patients’ ability to engage in the often-challenging treatment processes by supporting openness and affective regulation. On the other hand, some studies70,80,82,92 reported patients felt misunderstood or interpersonally hurt following interactions with their therapists. These occurrences appeared to hinder treatment engagement, highlighting the centrality of interpersonal trust in trauma-focused psychotherapy.

The trust in her [the clinician] and the fact that she understands me and can keep up with me and actually get to know me. This is very, very important.94

Experience of Group and Wider Psychosocial Setting

Patients reported both positive and negative reactions to the impact and clinical utility of group-based interventions. Positive perceptions of the group were characterised by increased feelings of belonging, confidence, and openness. Some patients reported increased anxiety about exposure in a group setting. Hearing the traumatic narratives and experiences of their peers appeared to be challenging in itself.93,99 Others discussed the presence and impact of difficult interpersonal dynamics that emerged in the group.93,99

I found some parts a bit triggering when people recounted their personal experiences. I felt quite frozen and couldn’t speak. I found it harder to concentrate and felt myself go into a darker place when discussing suicide.99

Experience of Self

Patients described a range of positive and negative responses to PTSD treatment that affected their sense of trust and confidence in self.70,85,89,90,95,101 In turn, this seemed, at times, to impact their belief in their ability to endure and benefit from the treatment. Patients described a gradual process characterised by noticing moderate positive changes or differences in their self-narratives, beliefs, and emotional responses.

I noticed changes, I noticed differences. I thought, it is helping. So, let me just come back.89

Correspondingly, patients also described how adverse responses to treatment negatively impacted their perception of self and capacity to utilise the treatment.

I became depressed, withdrawn, I started to have some nightmares again, and I tried it for about a week, and it kept getting worse and worse and I said this is not worth it. I did not feel physically and mentally able to continue because of those reasons.70

Psychedelic Therapy

Although the studies varied in their methodology, patient populations, and psychedelic compounds, there were themes relating to the patient experience of PT in clinical trials that were consistently reported. We present a snapshot of our findings relating to trauma-informed PT below.

Themes identified in this review:

Indirect Trauma Processing Reorganisation of self-narratives via processes of relatedness and identification Key Treatment CharacteristicsIndirect Trauma Processing

Studies referred to traumatic stress as being a main contributing factor to psychopathology.55,107–117 In most studies, processing traumatic incidents appeared to be an integral part of the narrative surrounding patients’ experience of the therapeutic process. Researchers reported patients confronting adverse childhood events and present-day stressors such as life-threatening diagnoses. Although not the explicit focus of the PT intervention, trauma-related material appeared in the form of visualisations, disturbing conscious and previously repressed memories, somatic trauma responses, and emotional states such as grief and fear. Some patients reported how the treatment supported integrating traumatic incidents into their lives or unburdening themselves from its weight as part of the change process.

Mostly from my childhood, related to my parents quarrelling. I saw a lot of bad things. I saw my father bribing my mother with jewelry, flattering her with leisure activities, with superfluous things. I saw him drinking, falling down where he stored his drinks.115

Reorganisation of Self-Narratives via Processes of Relatedness and Identification

All studies reported themes concerning patients’ perceived changes in self-narratives after PT. Reported changes in self-narratives may be catalysed or accompanied by the previously highlighted mechanisms of change in PT.56,71,118,119 Further, increases in caring emotional responses towards self,57 connectedness towards others,55 experience of positive affect120 and health behavior change121 have been reported.

This synthesis found patients reported changes in self-narratives after describing meaningful PT experiences characterised by processes of relatedness and identification across the following domains:

1a. With psychedelic compound

1b. With condition

1c. With the known biographical self, including body

1d. With significant others

1e. With spiritual or transcendental states

1f. With clinical team

Psychedelic Compound

Patients reported perceiving the compound itself as possessing intentions and wisdom, attributing personifying meaning to the elicited subjective effects, and experiencing a helpful intrapersonal form of communication between self and the compound. Patients discussed how the compound seemingly “gave” or “showed” them something of importance, highlighting areas that required their attention and encouraging engagement with previously avoided challenging experiences.38,55,110,111 Infused with this knowledge or newfound sense of direction, patients reportedly felt reassured and had a perceived sense of empowerment. It is possible that these occurrences may have in turn supported better treatment engagement.

During the session the thoughts were … “Do I travel the right path”? That was my question. Not dealing with death during the session but if I am on the right path. LSD gave me the feeling intensively that I am on the right path. That was nice.111

Condition

Patients reported the presence of a helping relationship between the compound and their condition. Potentially promoting cognitive flexibility,122 patients appeared to have gained a sense of internal space or distance between self and the condition via the interaction between the compound and the condition.55,110,112,116,117,123 Correspondingly, these processes were often accompanied by positive cognitive reconstructions related to the nature of the condition, increased positive affect and reduction in adverse psychological symptoms.

I would say [I have] less anxiety about my body and my sickness coming back, my cancer coming back…I saw this body for what it’s worth, I picked it, it’s mine… I think that acceptance has been liberating.112

Known Biographical Self, Including Body

Patients described how PT appeared to facilitate a reexamination of past as well as present and at times, imagined future oriented, life experiences.38,55,107,112–116 Patients reported perceiving important life experiences during their treatment via imagery, cognitions, emotions, physical sensations, and memories. These biographical remembrances, directly linked with patients’ self-narratives, were reportedly imbued with meaning and affect, which in turn promoted a more open and reflective stance towards their challenging experience and self-representation.

I don’t know if I really learned – it was more like letting back in stuff that I had blocked out?… I don’t think I changed my values, just remembered more of them. Or just remembered to honor them more, or…allow them more.114

Significant Others

Patients described exploring past and present relationships with loved ones and friends.55,107,109,111,113,117,123 Patients described perceiving with more clarity and appropriate affect relational ruptures and experiencing resolution. Some patients reported feeling supported by their loved ones during the psychedelic treatment session, enhancing feelings of connectedness and the significance of others in their own self-narratives.117,123 Notably, some patients reported perceiving the presence of an internal “guide” or a “being” which appeared to have their best interests at heart; at times appearing as a loved one.109,112

I was thinking about relationships I had with other people and thinking I could see them clearly almost as if for the first time. I had fresh insight into things. It was almost as if suddenly the scales dropped from my eyes, I could see things as they really are.55

Transcendental / Spiritual States

Across the included studies, patients reported various transcendental or spiritual states.55,107–117 Patients reported feelings of unity, ego dissolution, profound connection to others, the natural world and the universe. These states, potentially leading to perspective change and feelings of greater contentedness, were often accompanied by a range of intense affects and a visceral sense of knowing. Within these states, some patients reported grappling with existential themes concerning birth and dying. Overall, patients reported dramatically changed perspectives concerning everyday reality, at times accompanied by a greater appreciation towards self, others, and life itself. These experiences were also characterised by an overarching sense of persuasiveness and purposefulness.

I see myself as part of something bigger. I felt myself connected into what had to be the collective mind yesterday, realizing it’s like “Oh, this exists, and we’re all just facets of this. It’s me connected to a wider sense of life or consciousness. And it’s, like, I know that rationally, but it was a time to feel it in a very real sense and experience it as real”.107

Clinical Team

Patients described the significance of therapists’ presence across most studies to positive outcomes. The degree of rapport and interpersonal safety with therapists was associated with feelings of trust towards the often challenging and unfamiliar treatment process. Some, but not all, patients discussed their therapists as an integral component of the treatment, supporting engagement by conveying a sense of confidence in the patient’s capacity to leverage their experience towards improvement.38,55,107–109,113,114 Notably, only one study55 highlighted instances of negative perceptions of therapists and its potential adverse influence on outcomes. These incidents included a brief discussion of a “problematic transference”, in which the patient linked their negative responses towards a therapist with previous experiences of care.

It’s not just the psilocybin sessions [but] it’s that human connection, and the support that comes with that human connection, that ultimately leads to success at the end of the day.114

Key Treatment Characteristics Ineffability and Awe

Some patients found it difficult to describe or find the “right words” to convey their experience of the psychedelic session.55,107,109–111,113,114,117,123 The richness of the reported experiences and its corresponding therapeutic impact can be inferred by observing treatment responders’ language, often laden with metaphors, symbols, affect and a sense of meaningfulness. When describing their experience, patients appeared to be struck by the multifaceted nature and novelty of PT. Acknowledging the limits of intellectual understanding, most patients in the reviewed studies appeared to be curious about their experience, or positively affected by this sense of awe173 as opposed to being disturbed by it. Of note, the MDMA-AT study112 did not report similar themes. This may be due to the mechanism of action and subjective effects of MDMA, an entactogen, as opposed to classical psychedelics.

It was a feeling beyond an intellectual feeling—it was a feeling to the bottom of my core. that’s one reason that it’s hard to talk about. it’s beyond words.117

Immersive Experiential Immediacy and Intensity

Patients across most studies reported vivid descriptions of intense experiential processes characterised by immersive and dramatic physiological and psychological responses to the compound’s subjective effects and treatment process.38,55,109–116,123 The immediacy effect of the treatment was reported in the context of having direct and unavoidable encounters with the unfolding phenomena observed during their psychedelic treatment session. Of note, the immersive and intense nature of the treatment appeared to empower patients to confront rather than avoid both negative and positive cognitions, emotions, and somatic reactions to the treatment.

I feel like what happened was that in a very short period of intense time I dealt with some really powerful things and put it behind me.109

Arc of Struggle and Distress Towards Resolution

Patients reported being compelled to engage with challenging experiences in the service of promoting healing and change.38,55,107–111,114–117,123 Patients reported a sense of working through burdensome aspects of their experience catalysed by the compound (eg, intense emotional states, somatic reactions, ego-dissolution, and complex imagery) to eventually perceive a sense of resolution. These experiences were characterised by a sense of movement between previously avoided internal states, and a sense of momentum, which appeared to support patients to engage with the unfolding experience. Terms such as “rollercoaster”111 or “turbulence”114 were identified. Acceptance of the struggle and possessing a willingness to engage in experiential excursions into challenging states, appeared supportive in achieving a meaningful perception of resolution.

It was an intense, intense struggle, and that’s where it became medicinal because it allowed that struggle to happen. It didn’t coat it, it wasn’t an antidepressant. it brought it all out.117

Change Beyond Symptom Reduction

Across all studies patients reported responses to treatment that appeared beyond the scope of symptomatic reduction. Patients’ post-treatment made references to possessing a changed perspective regarding self, others, and the world. These shifts were accompanied by a sense of clarity about what matters most (eg, values) and a determination to make meaningful changes aligned with these values. At times philosophical, these changes appeared to be a consequence of and catalyst for increased positive affect post-treatment. Frequently reported values pertained to the importance of meaningful relationships, possessing a more curious stance towards self and others, and a sense of connection to spiritual aspects in everyday life, including the natural world. Of note, patients often reported changes in behavior that appeared to support these shifts, including initiating meditation practices, engaging in new hobbies, and repairing relationships.

I’ve been involved with the local literacy council all the time now … And then the other thing is I’ve become very involved with this environmental group as well … instead of sitting around and just watching television and smoking and doing nothing.114

Difference from Other Treatments

Some studies described patients’ reports of how PT differed from standard treatment.55,110,111,115,117 These accounts were in support of PT over first-line treatments. This is unsurprising given that PT trials are for patients who have not been helped by standard treatments. PT appeared to accelerate therapeutic processes (eg, promoting insights, enhancing access to a wider range of affects, and facilitating a more immediate connection to self during and after treatment). Patients reported confronting, as opposed to avoiding, challenging and yet necessary therapeutic processes. In the context of addressing psychophysical ailments including addiction and cancer-related distress, patients referred to the need for a holistic and integrated approach to care.

In usual psychotherapy it is mainly about talking, about words. In LSD-assisted psychotherapy it is mainly about inner processes, inner change, inner experience, it gets enriched by it.111

Importance of Non-Pharmacological Factors

Studies highlighted patients’ accounts concerning the central importance of the treatment’s non-pharmacological factors.38,55,107,109,111,112,114,116,121,123 Factors often referred to include the impact of therapist presence and interventions, the significance of music and the focus of the non-psychedelic sessions (eg, preparation / integration). Patients made references to the therapeutic utility of the actual physical environment of the psychedelic session, including the lights and sonic ambience inside the treatment room. In a group-based intervention, patients made references to other patients undergoing the treatment. Positive reactions to these factors appeared to enhance feelings of safety and in turn encourage greater immersion in the psychedelic state.

I started not just hearing, but playing the music. My entire body was the musical instrument for every sound which was coming through my head.112

Discussion

This synthesis explores salient themes in patient experience of EBPI in PTSD and PT for mental-health indications in authorised, medically supervised, clinical trials. This study identified a total of 7 key themes from the thematic analysis of the included papers. In EBPI: Patient Burden, Psychological Safety and Trust, Readiness and Key Mechanisms of Change. In PT: Reorganisation of Self-Narratives via Processes of Relatedness and Identification, Indirect Trauma Processing and Key Treatment Characteristics (Figure 3).

Figure 3 Core Themes diagram demonstrating the 7 key themes from Psychedelic Therapy (PT) and Evidence-based Psychotherapy Interventions (EBPI) in PTSD which may contribute to Trauma Informed Care (TIC) in PT.

Overall, the included studies demonstrated that EBPI in PTSD and PT across indications compel the patient to contend with a range of arduous processes in the service of recovery. In both treatment paradigms, patients highlighted the intense biopsychosocial nature and heavy demands of treatment. Applying insights from this review, below we expand on 5 areas relevant to positive safety outcomes in future PT research and practice.

Traumatic Stress in PT

An integral finding of this study pertains to the overarching presence of trauma-related psychopathology across indications in PT research. This may be due to higher prevalence of trauma exposure in treatment-resistant patient populations.124,125 Correspondingly, researchers have discussed the potential utility of PT to treat PTSD,72 citing psychedelics’ mechanisms of action58,126 and its hypothesised transdiagnostic utility.59,127

Given the prevalence of trauma-related psychopathology across mental-health conditions, the results of this study indicate it is crucial that PT research protocols consider the impact of trauma exposure on patients and the potential value of trauma-informed care (TIC)14,128,129 in mitigating adverse events. Adding to DSM-based conceptualisations of mental ill health,130 TIC considers the unique predispositions patients who have been exposed to traumatic events present with;73 treating the person, rather than the condition, within the context of their psychosocial and cultural lived-experience. Further, comparative research studies investigating the safety and effectiveness of adjunct psychotherapeutic interventions in PT are absent. In this context, some have advocated for CBT to be considered the “default” model in PT,131 while others have highlighted the utility of the common factors theory of psychotherapy,74 psychoanalytic psychology132 and non-specific psychological support.22 It is important that data is gathered to support or refute these hypotheses. However, until an evidence base is developed, implementing trauma-informed approaches, that carefully consider the biopsychosocial effects of psychedelics, may promote positive safety outcomes in PT research by personalising care.

As traumatic experiences may have elements of interpersonal or institutional betrayal, secrecy, or persecution,133,134 TIC highlights interpersonal and intrapersonal dimensions that require careful clinical consideration.135,136 Here we discuss factors relating to psychological safety and trust, which may help inform clinical practice in PT research.

Interpersonal Factors

Adverse interpersonal dynamics, also influenced by patients’ and therapists’ attachment styles contribute to the quality of the therapeutic alliance (TA).137–139 Higher TA scores are associated with greater symptom reduction in PTSD psychotherapy.60 In PT, one study found a correlation between TA and positive outcomes140 while another, larger and multi-centre study, did not find TA to moderate outcomes.141 Nevertheless, given the importance of non-pharmacological factors in PT and healthcare,142 the quality of interpersonal care is considered important to positive outcomes.143

This synthesis suggests that traumatised patients may be acutely sensitive to adverse relational and attachment dynamics that may emerge during and in response to treatment. These may include instances of empathic failures and therapist mis-attunement and power imbalances and ruptures.61,144,145 For example, in this synthesis EBPI patients highlighted the adverse impact of therapists prioritising rigid adherence to the treatment protocol over meaningful interpersonal contact.80,92

Further, excessive shame, past experiences of betrayal, and moral injury might make it difficult for traumatised patients to request support during intense PT sessions, potentially leading to feelings of isolation and withdrawal.75,133 Slipping into traumatic awareness,76 some patients may experience these occurrences as traumatic reenactments, reminiscent of past experiences of neglect and abandonment.146 Taken together, clinicians should be mindful of patients’ experiences of interpersonal trauma, associated impact on personality147 and subsequent capacity to engage in PT, an intervention that may elicit profound regressive states.148

Intrapersonal Factors

Traumatised patients may be bur