Psychedelic Treatments for Psychiatric Disorders: A Systematic Review and Thematic Synthesis of Patient Experiences in Qualitative Studies

This review (2020) identified 15 studies (n=178) that used a variety of psychedelics to have overlapping therapeutic processes, were compared favorably over conventional treatments, and often elicited other positive changes beyond the specific diagnosis.

Abstract

“Introduction Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. Processes that may affect therapeutic change are not yet fully understood. Qualitative research methods are increasingly used to examine patient accounts; however, currently, no systematic review exists that synthesizes these findings in relation to the use of psychedelics for the treatment of mental disorders.

Objective To provide an overview of salient themes in patient experiences of psychedelic treatments for mental disorders, presenting both common and diverging elements in patients’ accounts, and elucidating how these affect the treatment process.

Methods We systematically searched the PubMed, MEDLINE, PsycINFO, and Embase databases for English-language qualitative literature without time limitations. Inclusion criteria were qualitative research design; peer-reviewed studies; based on verbalized patient utterances; and a level of abstraction or analysis of the results. Thematic synthesis was used to analyze and synthesize results across studies. A critical appraisal of study quality and methodological rigor was conducted using the Critical Appraisal Skills Programme (CASP).

Results Fifteen research articles, comprising 178 patient experiences, were included. Studies exhibited a broad heterogeneity in terms of substance, mental disorder, treatment context, and qualitative methodology. Substances included psilocybin, lysergic acid diethylamide (LSD), ibogaine, ayahuasca, ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Disorders included anxiety, depression, eating disorders, post-traumatic stress disorder, and substance use disorders. While the included compounds were heterogeneous in pharmacology and treatment contexts, patients reported largely comparable experiences across disorders, which included phenomenological analogous effects, perspectives on the intervention, therapeutic processes and treatment outcomes. Comparable therapeutic processes included insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum, which patients reported contributed to clinically and personally relevant responses.

Conclusions This review demonstrates how qualitative research of psychedelic treatments can contribute to distinguishing specific features of specific substances, and carry otherwise undiscovered implications for the treatment of specific psychiatric disorders.”

Authors: Joost J. Breeksema, Alistair R. Niemeijer, Erwin Krediet, Eric Vermetten & Robert A. Schoevers

Notes

This paper is included in our ‘Top 10 Articles on Psychedelics in the Treatment of Depression‘

• The 15 studies selected described the experiences of patients that took psychedelics for the purpose of treating a mental health disorder
• Patients reported high rates or report with the caregivers and compared the treatments favorably to conventional (previously tried) treatments
• Common (between the different drugs and settings) where the following themes: insight, altered self-perception, feelings of connectedness, transcendental experiences, expanded emotional spectrum, and (long-lasting) positive changes in quality of life
• This paper is the first to bring this qualitative analysis to psychedelics for mental disorders

“Our review revealed several connected therapeutic processes—seen across substances and for different disorders—that contributed to clinically signifcant and personally meaningful outcomes. Exploring patient experiences can increase our understanding of underlying therapeutic mechanisms and processes, the role of (extra) pharmacological factors in these treatment modalities, which may contribute to optimizing treatment context, and lead to improved clinical responses and personal benefts. Despite the heterogeneity of substance, setting, and population, these studies also suggest that, in addition to a shared phenomenology, psychedelic treatments exhibit similar therapeutic processes and result in comparable outcomes.”

Summary

Abstract

Interest in the use of psychedelic substances for the treatment of mental disorders is increasing. However, no systematic review exists that summarizes these findings.

We searched for patient experiences of psychedelic treatments for mental disorders in databases and used thematic synthesis to analyze and synthesize results across studies.

Fifteen research articles were included, comprising 178 patient experiences. Patients reported largely comparable experiences across disorders, including insights, altered self-perception, increased connectedness, transcendental experiences, and an expanded emotional spectrum.

1 Introduction

Psychedelic drugs have been investigated as potentially effective treatments for several mental disorders, including substance use disorders, post-traumatic stress disorder, anxiety, and depression secondary to a life-threatening illness, and suicidal ideation.

Patients compare psychedelic treatments favorably with conventional treatments, emphasizing non-pharmacological factors such as trust, safety, interpersonal rapport, attention, the role of music, and the length of treatment sessions. Pharmacologically distinct psychedelics exhibit overlap-ping therapeutic processes for different mental disorders.

The influence of extrap-harmacological variables contributes significantly to the pharmacological qualities of psychedelics, as evidenced by the high variability of individual experiences. Several potential psychological mediators have been postulated in treatments with psychedelics.

A close examination of patients’ experiential accounts could increase our understanding of psychedelic-induced patient experiences and help inform future research. Qualitative inquiry can also complement quantitative research by generating hypotheses that can be tested using quantitative instruments.

This article presents an overview of the available qualitative research on the role of the subjective psychedelic experience in the treatment of mental disorders. It identifies salient themes across studies and presents how these relate to patients’ disorders, therapeutic processes, and personally and clinically significant outcomes.

The safety, clinical benefits and therapeutic outcomes of psychedelic interventions are thought to be fundamentally reliant on a supportive environment, and the use of psychedelics in different settings is often accompanied by the use of music to facilitate an introspective experience.

2.1 Selection Criteria

For this systematic review we selected papers that described patient experiences after taking psychedelics for the purpose of treating a mental disorder.

2.2 Search Strategy and Study Selection

We conducted a systematic search of the PubMed, MEDline, PsycINFO, and EMBASE databases between 5 and 12 March 2019, using index terms and freetext terms in two categories. The search was complemented by hand searching of reference lists of identified articles and relevant, non-indexed journals.

2.3 Data Analysis and Synthesis

Qualitative research seeks to develop a contextual understanding of behavior in the natural environment it observes. It uses thematic synthesis and a post-synthesis sensitivity analysis to assess the methodological rigor of the studies.

Thematic synthesis took place in three stages: first, all included articles were read and re-read carefully several times by the first author, who then assigned primary codes, noted down comments, observations and reflections, and finally reanalyzed and grouped together by all authors into major themes.

3.1 Study Selection

After removing duplicates, 1472 publications were screened, and 97 full-text articles were obtained and read. Seventy-nine additional articles were excluded for not meeting the criteria, and 15 studies with a total of 178 patients were included in the systematic review.

3.2 Study Characteristics

All articles were published between 2014 and 2019. They were heterogeneous in terms of substances, population/mental disorders, contexts, and qualitative research methodologies.

All studies on psilocybin, LSD, ketamine, and MDMA took place in clinical research centers in the US, Switzerland, and the UK.

3.3 Critical Appraisal of Study Quality

The quality of the included studies varied, but the validity, ethical considerations, and value of the studies were all high. The rigor of the data analysis varied most, but was not reflected in the overall quality assessment. We conducted a post hoc sensitivity analysis to determine the extent to which quality variations may have influenced the thematic synthesis. We found that studies with divergent research aims contributed comparatively less to the synthesis.

3.4 Nature of Patient Experiences

We assessed descriptions and narratives of patient experiences, and found that all authors discussed one or more of the following themes: phenomenology of the experience, perspectives on the intervention, therapeutic processes, and outcomes of the intervention.

3.4.1 Phenomenology of the Psychedelic Experience

Several studies explicitly addressed the phenomenology of the acute, inner experience induced by different psychedelic substances. Phenomenological experiences included altered sensory perception, visions and visuals, and somatic effects, and were frequently alluded to the ineffability of the experience.

Ibogaine sent me back to when I was very first born, and I felt like I was inside the womb. I fought the devil, and I felt my grandma all around the whole time.

Participants who had taken ibogaine reported physically unpleasant sensations, neurological effects and perceptual alterations that were not described in other studies, although unusual and strange bodily sensations were also reported for ketamine.

Ayahuasca helped me see myself as a full-bodied, loving woman with long hair. I wanted to be that woman, but I felt like I needed to gain weight.

Several respondents, especially in studies with psilocybin, remarked on the ineffable nature of the experience, and mentioned that it was easier to describe the emotional impact of the experience than the specific content.

3.4.2 Perspectives on the Intervention

Patients reported that trust and a good connection with study guides were important therapeutic aspects.

Many respondents noted the importance of the preparatory sessions and integration sessions in smoking cessation, as well as the added value of the psilocybin experiences.

Besides the ayahuasca itself, trust in the medicine men and follow-up psychotherapy are the most important therapeutic elements in an ayahuasca ceremony.

All studies with psilocybin, MDMA, and LSD, as well as in ayahuasca ceremonies used music. Only patients in various psilocybin studies reflected on the role and function of music, stating that it served as a conduit, enabling them to experience and surrender to painful emotions or memories.

In contrast with many other classes of psychoactive substances, psychedelics do not lead to addiction or dependence. In fact, some patients actively seek out extramedical psilocybin sessions.

Respondents often compared different elements of psychedelic treatments with previously experienced conventional treatments, and also reflected on previous strategies in coping with their disorder.

Standard approaches to eating disorders are top-down and suppress symptoms. Ayahuasca is a bottom-up approach that gets to the root cause and resolves the disorder on a deep level.

Respondents from across the spectrum of disorders and substances compared their psychedelic treatments favorably to previously undergone conventional treatments, highlighting its focus on inner processes as opposed to talk therapy, and providing healing beyond what they found in conventional treatments.

The MDMA allowed me to feel safe in my space, and to fight the issues I had before. I felt I had the ability and tools to tackle them, and I had backup.

3.4.3 Therapeutic Processes

Potential psychological or therapeutic processes or mechanisms of action were a major theme in all studies included in this review. These include insights, altered self-perception, feelings of connectedness, transcendental experiences, and expanded emotional spectrum.

Insights were frequently mentioned as an outcome of the intervention, particularly into one’s self. This included improved self-awareness or self-understanding of one’s disorder, its root causes, and related behaviors.

Psilocybin-induced insights resulted in improved understanding of the underlying disorders, the root psychological causes of addiction, and somatic insights. Patients also gained crucial insights into their behavior towards others.

In many studies, participants experienced increased self-efficacy, decreased self-criticism, and increased self-awareness, as well as increased self-love, self-care, self-confidence, self-acceptance, self-awareness, self-worth, self-control, self-esteem, self-compassion, and self-forgiveness.

Ayahuasca helped me to understand myself better, and I learned a lot about myself. This helped me to stop self-criticism and start loving myself, which is the antidote for an eating disorder.

Psilocybin, ibogaine and ayahuasca increase connection on different levels, including internally with emotions, senses, parts of self and identity, and externally with nature and the world at large.

Psilocybin helps people accept death because they don’t feel alone.

Patients in psilocybin studies described experiences of interconnectedness, including being everybody, one life with 6 billion faces, and swimming in the sea.

Patients’ healing experiences with ayahuasca, ibogaine, and psilocybin were reported to include transcendental experiences, feelings of awe and connection to greater forces, and an interconnectedness with all life.

Respondents report being able to experience a wide range of emotions, including bliss, joy, peace, and love, as well as anger, anxiety, terror, dysphoria, and paranoia.

The first time I took LSD it was very brutal, painful, at least emotionally very painful, but the second time I took LSD it was sublime, like love, expansion, holding, and I knew that this sometimes happens, that participants talk about spiritual experiences.

Participants described accessing previously inaccessible emotions and an improved ability to process unresolved emotions. These experiences were often considered therapeutically useful, especially when participants managed to transform negative into positive emotions.

“I accepted my body for what it is, and I think that acceptance has been liberating” [81] [psilocybin, end-of-life anxiety].

3.4.4 Outcomes of the Intervention

Participants in many studies experienced significant relief from the disorder they were treated for, including reductions in eating disorder-related thoughts and symptoms, PTSD symptoms, anxiety, depression, and substance use.

Participants often considered outcomes beyond the initial diagnosis to be more significant than the smoking cessation.

Patients who experienced therapeutic outcomes described being better able to understand, reflect on, or be aware of themselves, as well as having greater self-confidence and self-esteem.

The sense of connectedness was reported across substances, and respondents alluded to positive changes in friendships and improved relationships with family members.

After the trips, certain changes happened, such as a shift in values and a realization that family comes first.

Across the board, participants reported positive and often lasting changes in quality of life, including an increased sense of peace and mental space in daily life, an increased sense of purpose or meaning in life, and an increased appreciation of beauty in art, music, and nature.

4 Discussion

This paper describes the patient experiences of treatments using psychedelic substances for the treatment of a mental disorder. It includes a broad definition of psychedelics.

Several substances were used to treat several distinct mental disorders, including depression, nicotine dependence, alcohol use disorder and end-of-life distress, including psilocybin, LSD, ayahuasca and ketamine. The therapeutic effect of these substances was likely to be dependent on the subjective experience induced by these compounds.

Despite the oft-reported ineffability of their experiences, participants in several studies did offer detailed descriptions of their experiences, as well as reflections on the intervention. However, it is important to understand when, by whom, and how data collection and analysis were performed.

In some studies, treatment-resistant patients in placebo groups reported enduring, clinically significant improvements. This may illustrate the importance attributed to extrapharmacological factors, such as trust, interpersonal rapport, attention, the length of treatment sessions, and a safe treatment setting.

Participants stressed the importance of preparatory and integration sessions in establishing therapeutic alliance.

This review revealed several therapeutic mechanisms, including gaining insights, altered self-perception, increased feelings of connectedness, transcendental experiences, and expanded emotional spectrum. These mechanisms often overlapped, and it is plausible that multiple mechanisms may act together in producing therapeutically relevant outcomes.

The phenomenology of the subjective experience was closely intertwined with the description of therapeutic processes, and it was often difficult to distinguish between treatment outcomes and acute experiences. Patients reported increased self-love, self-worth, and self-compassion, irrespective of a specific disorder or substance.

Psychedelics may intensify emotions and may be used for this purpose since early psychotherapy research in the 1950s. Patients consider improved access to a greater range of emotions and emotional content important, and explicitly attribute value to overcoming difficult experiences.

Respondents reported both clinically and personally meaningful outcomes, and did not always consider symptom reduction to be the primary benefit. They also reported decreases in craving and withdrawal symptoms, which may explain why psychedelics may be effective for many mental disorders.

This review had several limitations, including the fact that studies included in this review varied in terms of design, qualitative research methodology, analysis methods, timing of the interviews, and overall quality. It also considered mental disorders non-specifically, and did not provide sufficient evidence to establish substance-specific characteristics for the treatment of specific disorders. This review indicates that psychedelics may induce states of consciousness that are considered valuable by patients, suggesting a broad applicability of different psychedelics for mental disorders. It is possible that respondents’ favorable reports of their psychedelic treatments are due to selection or expectation bias, that research in this field overvalues positive aspects of these treatments, and that larger and more heterogeneous patient samples are needed to appraise the real impact and ecological validity of these treatments.

Psychedelic treatments may contribute to a new paradigm for psychiatry, by setting in motion subjective therapeutic processes that address root causes or core elements of a single psychopathology dimension.

5 Conclusions

The therapeutic mediators and mechanisms through which psychedelics contribute to treatment outcomes remain insufficiently understood. Qualitative research of psychedelic treatments can contribute to distinguishing specific features of these compounds, and show potential for elucidating otherwise undiscovered implications for the treatment of distinct mental disorders.