Association between mystical-type experiences under psychedelics and improvements in well-being or mental health - A comprehensive review of the evidence

This review (2023, s=44) synthesizes the evidence for the association between mystical-type experiences and improvements in well-being and mental health. It finds the strongest evidence in cross-sectional studies and healthy people. Some studies suggest that psychological insight and emotional breakthroughs may be similarly or more closely associated with positive changes than mystical-type experiences.

Authors

Kangaslampi, S.

Published

March 3, 2023

Journal of Psychedelic Studies

meta Study

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Abstract

Background and aims Ingestion or administration of classic psychedelics is sometimes associated with improvements in well-being or mental health. Acute mystical-type experiences that psychedelics occasion have been suggested to be related to such improvements. Meanwhile, other features of the psychedelic experience, such as psychological insights and emotional breakthroughs, are also increasingly being studied. This review aimed to collect and assess the available evidence for mystical-type experiences under psychedelics associating with medium-to-long term improvements in well-being or mental health, on their own and as compared with other features of the acute experience.Methods I conducted a pre-registered, comprehensive review of existing empirical studies on the topic, based on a systematic search of the literature.Results Forty-four eligible studies were found, with most reporting positive associations between mystical-type experiences and improvements in well-being or mental health. The current level of evidence appeared stronger among healthy people, in cross-sectional studies, and for links with positive changes in general well-being and life satisfaction, attitudes and behavior, and anxiety, than for depression or other aspects of well-being and mental health. A few studies suggested that psychological insights and emotional breakthroughs may be as or more closely associated with positive changes than mystical-type experiences.Conclusions Despite their significant limitations, the identified studies suggest that mystical-type experiences under psychedelics are associated with improvements in some areas of well-being. However, psychological insights and emotional breakthroughs might be at least as important and should also be measured in future studies.

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Research Summary of 'Association between mystical-type experiences under psychedelics and improvements in well-being or mental health - A comprehensive review of the evidence'

Introduction

Psychedelics such as psilocybin and LSD have been increasingly associated with improvements in well-being and mental health in both clinical and non-clinical populations. Explanations for these benefits often focus on subjective, acute effects of the drugs; among these, mystical-type experiences—characterised by feelings of unity, noetic quality, transcendence of space and time, sacredness, strong positive mood and ineffability—have been proposed as important contributors. Other acute phenomena (for example, ego dissolution, oceanic boundlessness, psychological insight, and emotional breakthrough) are also discussed in the literature, and instruments such as the Mystical Experiences Questionnaire (MEQ) and subscales of the Altered States of Consciousness (ASC) or the Ego Dissolution Inventory (EDI) are commonly used to quantify these states. Kangaslampi set out to comprehensively collect and synthesise quantitative empirical evidence testing whether mystical-type experiences occasioned by classic psychedelics are associated with medium-to-long term improvements in well-being or mental health. The review also aimed to compare the strength of any such associations with those of other acute experiential features (notably psychological insights and emotional breakthroughs), with the intent of clarifying which aspects of the acute psychedelic experience most closely track subsequent positive changes.

Methods

This work is a comprehensive review based on a pre-registered systematic literature search, but it was conducted by a single researcher and does not include a formal, systematic assessment of study quality or risk of bias. Kangaslampi followed PRISMA recommendations where applicable and registered the review on the Open Science Framework prior to searching databases. Eligibility criteria required peer-reviewed empirical, quantitative studies in English, Spanish, Finnish or Swedish that measured the intensity of mystical-type experience under a psychoactive dose of a classic psychedelic and measured change in some aspect of well-being or mental health from before to at least one week after the experience, and that reported the association between those two measurements. Excluded were qualitative-only reports, studies of non-classic-psychedelic substances (for example ketamine or MDMA), microdosing studies, studies with only acute or very short-term outcomes (<1 week), and studies that measured mystical experience but did not report associations with change. Searches covered PubMed and Academic Search Ultimate (EBSCO) using a broad search string for terms related to mysticism, ego dissolution and altered states linked to psychedelics; no additional filters were applied. The author supplemented database searches by hand-searching references of included papers, recent reviews, and all issues of a field-relevant journal not indexed in those databases. After duplicate removal, titles and abstracts were screened, followed by full-text assessment of potentially eligible papers. A predefined data extraction form captured bibliographic details, design features (including sample size, sampling method, randomisation and blinding where applicable), substance and dose/context, measures of mystical-type experience and of outcomes, main findings on associations, other acute features measured, and whether comparisons between features were reported. The synthesis was narrative rather than quantitative; no meta-analysis was performed. Descriptive statistics of study characteristics were computed using R and Excel.

Results

Study selection yielded 942 records from the databases and nine from other sources. After duplicates were removed, 749 titles/abstracts were screened, 148 full texts were assessed, and 44 studies met the inclusion criteria. The 44 included studies (published 2009–2022) were heterogeneous in design and sample size. Sample sizes ranged from 10 to 6,877 (median 58). Average mean age across studies was 38.5 years and the proportion of women ranged from 15% to 72% (mean 39%). Geographically, 13 studies sampled US populations exclusively, four sampled UK populations, three each sampled German and Brazilian participants, while others drew multilingual or multinational samples. Nineteen studies were laboratory-based, 18 were surveys and seven were field studies; for synthesis purposes survey and field studies were treated together because dosing and setting were typically uncontrolled in those designs. Thirty-one studies used prospective designs (pre- to post-experience), while 13 were cross-sectional/retrospective. Substances studied included psilocybin (20 studies), ayahuasca (7), LSD (1), 5‑MeO‑DMT (5), mescaline (5) and various or any psychedelics (14). Fourteen studies sampled clinical or broadly “ill” populations, while 30 sampled healthy or non-clinical populations. Across the literature the author identified 75 reported associations between mystical-type experience and change in some aspect of well-being or mental health; 57 of these associations were reported as statistically significantly positive, with no studies reporting overall negative associations. Outcomes assessed spanned 22 categories. For depression (13 studies) eight reported a positive association between mystical-type experiences and reductions in depressive symptoms, while five reported null findings; notably, all five null findings were from prospective studies (including several clinical samples). Anxiety was assessed in seven studies: six reported positive associations and one reported a null result. Overall well-being and life satisfaction were examined in 13 studies, of which 12 reported positive associations; most of these positive findings came from healthy samples and many relied on single retrospective items from the Persisting Effects Questionnaire. Attitudes and behaviour were assessed in nine studies; seven found positive associations and two were null. Substance-related outcomes were mixed: four studies examined smoking cessation/reduction with mixed evidence (some positive associations in small clinical trials and ritual ayahuasca users, but not replicated across all surveys), while three studies addressing problematic alcohol use/AUD reported positive associations. Personality changes (decreased neuroticism, increased openness, increased extraversion) were assessed in four studies with mixed results: some studies reported increases in openness following mystical-type experiences, whereas others found no consistent links. Three medium-sized surveys linked mystical-type experiences to increased connectedness with nature. Thirty of the 44 studies also analysed other acute experiential features. Challenging experiences and sensory/visual effects were generally not associated with positive longer-term changes. In contrast, psychological insights (measured in 10 studies) and emotional breakthroughs (measured in four studies) were frequently associated with positive outcomes: psychological insights featured as associated with improvement in nine studies and emotional breakthroughs in four studies. Few studies directly compared mystical-type experiences and these other features within the same statistical models; among the four that did, results varied. For example, one survey on mescaline experiences found psychological insights to uniquely predict improvements in depression, anxiety and substance outcomes while mystical-type experiences uniquely predicted PTSD improvement. In other large survey datasets, psychological insights were more strongly associated than mystical-type experiences with reductions in depression and anxiety and with increases in psychological flexibility and well-being; yet some large surveys found both sets of features to be similar predictors. Three studies directly compared emotional breakthrough and mystical-type experiences; in two clinical/prospective contexts emotional breakthrough was a stronger predictor of decreased depression, while in a survey both predicted improved well-being similarly.

Discussion

Kangaslampi concludes that a sizeable number of quantitative studies report positive associations between mystical-type experiences under classic psychedelics and medium-to-long term improvements in some aspects of well-being or mental health. The pattern of evidence was not uniform across outcomes: the clearest and most consistent associations were observed for general well-being and life satisfaction, positive changes in attitudes and behaviour, and reductions in anxiety. Findings were more mixed for depression, where prospective studies in particular sometimes failed to find an association. Smaller literatures suggested links with reductions in substance misuse and increases in nature connectedness, while evidence regarding personality change was inconsistent. The review highlights several important modifiers of the observed pattern. Positive associations were more frequently reported in studies of healthy participants and in cross-sectional/retrospective designs than in clinical or prospective studies. The author emphasises that retrospective surveys are susceptible to recall bias and selection bias (notably the over-representation of psychedelic enthusiasts), whereas prospective pre-post designs, while preferable for symptom-based outcomes, have their own limitations such as scale recalibration. Consequently, prospective designs are generally preferable for outcome domains like depression and anxiety, but for constructs like life satisfaction it may be valuable to include both prospective and retrospective measures. Kangaslampi notes multiple limitations that constrain confidence in current conclusions: the review relied only on published analyses (raising the prospect of publication/reporting bias), it did not include a systematic risk-of-bias assessment, and included studies varied widely in sample size and outcome measurement. Many studies used single-item retrospective measures of change (for example items from the Persisting Effects Questionnaire), and most outcomes were self-reported, introducing risks of demand characteristics. The geographic and linguistic scope of the literature is narrow, and the degree to which standard instruments (for example the MEQ) uniquely and adequately capture a ‘‘mystical’’ construct remains contested. Finally, heterogeneity among outcomes and designs precluded meta-analysis. Given these caveats, the author recommends that future research preregister hypotheses about associations between acute experiential features and later change, include observer-rated and multi-source outcome measures, enrol larger and more diverse samples, and systematically measure multiple acute features (mystical-type experiences, psychological insights, emotional breakthrough, challenging experiences) so that their relative contributions can be directly compared. Kangaslampi emphasises that preliminary evidence points toward psychological insights and emotional breakthroughs being at least as important as mystical-type experiences for some outcomes, particularly depressive symptoms, and argues these non-mystical features deserve greater attention in future trials and applied settings.

Conclusion

Taken together, the studies reviewed suggest that when people report mystical-type experiences after taking classic psychedelics they tend to also report greater positive changes across a range of well-being and mental health measures than when they do not report such experiences. This tendency appears stronger in healthy populations and for outcomes such as general well-being and life satisfaction, attitudes and behaviour, and anxiety than for depression or other specific domains. The evidence is preliminary: methodological limitations, heterogeneous designs and measures, and potential reporting biases temper confidence. A small number of studies indicate that psychological insights and emotional breakthroughs may be as important, or more important, than mystical-type experiences for predicting medium-to-long term positive change, and the author urges future research and therapeutic practice to measure and compare both mystical and non-mystical acute features systematically.

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INTRODUCTION

Increasing evidence suggests that ingestion or administration of classic psychedelics such as psilocybin or LSD is sometimes associated with improvements in well-being or mental health in both clinical populationsand healthy people. Explanations for why and in which cases such improvements occur often focus on the subjective effects of psychedelics, that is, on features or aspects of the acute experience psychedelics cause. In particular, many authorshave emphasized the importance of mystical or mystical-type experiences in determining whether positive changes result from using psychedelics. This comprehensive review based on a systematic search attempts to present all available evidence from empirical studies for the specific claim that mystical-type experiences under psychedelics are associated with (positive) changes in well-being or mental health after the experience. Asalready noted, "no person is ever justified in speaking of the psychedelic experience, as there is great variation among individual experiences". The acute subjective experiences occasioned by (psychoactive "macro" doses of) classic psychedelics with their substantial alterations in state of consciousness, thinking, feeling, and perceiving, may be divided into a wide range of different features, types, or stages. Based on concepts and definitions established by Williamand William, some particular kinds of acute experiences occasioned by psychedelics have been termed mystical or mystical-type experiences. The core hallmarks of such mystical states are claimed to include experiences of internal and external unity, noetic quality, transcendence of space and time, sense of sacredness, deep positive mood, and ineffability and paradoxicalityexperiences otherwise reported during intense meditational states, religious revelries or rituals, or near-death experiences. As measured by psychometric instruments such as the Mystical Experiences Questionnaire (MEQ;and the Mysticism Scale (M-scale;, such mystical-type experiences are quite commonly occasioned by psychedelic use. For example, in laboratory settings, 60% of psychedelic-naïve volunteersand 54% of depressed patientsexperienced what has been termed a "complete mystical experience" after receiving a mediumto-high dose of psilocybin. In this review, I employ a relatively broad definition of mystical-type experience, also including within the concept the particular experiences of oceanic boundlessness (measured by, e.g., a subscale of the Altered States of Consciousness (ASC) rating scale;and ego dissolution (measured by, e.g., the Ego Dissolution Inventory (EDI);. From the earliest stages of research into the therapeutic potential of psychedelics, researchers have suggested that mystical-type experiences contribute to improved well-being or mental health after psychedelic use (e.g.,, possibly by giving the person new perspectives on their life, enhancing meaning and purpose. Many recent studies have explored this association, but to my knowledge, the evidence on this question has not been comprehensively synthesized. Recently,did specifically and systematically review the evidence for mystical experiences under psychedelics associating with reduction in symptoms of mental health disorders in clinical studies of psychedelic-assisted therapy. Including, besides classic psychedelics, studies on ketamine, they found twelve such studies and noted that ten out of them provide evidence for such an association. My review here differs from that ofin that all types of quantitative studies in all kinds of populations are included and in that it is limited to classic psychedelics only. Mystical-type, boundless, and dissolutive experiences are not the only acute features of the effects of psychedelics that have been proposed to be important for their therapeutic effects. Increasingly, researchers have begun to study elements such as emotional breakthroughsand psychological insightsand their importance for later changes in wellbeing or mental health. Again, however, synthesis of the available evidence on whether such features are more associated with positive changes in well-being or mental health than mystical-type experiences, is lacking. More precise understanding of the "active ingredients" of beneficial psychedelic experiences would benefit both potential development and refining of psychedelic-assisted therapy and support and integration offered to people ingesting psychedelics in other contexts.

REGISTRATION

This review was registered on the Open Science Framework () before database searches were carried out.

ELIGIBILITY CRITERIA

Included in this review are 1) articles published in scientific journals, 2) in English, Spanish, Finnish, or Swedish, 3) reporting on empirical, quantitative research that 4) measured the level or intensity of mystical-type experience 5) under the influence of a psychoactive dose of a classic psychedelic and 6) changes in some aspect in well-being or mental health, 7) from before to at least one week after the experience, and 7) reported/studied the association between the level of mystical-type experience and the change in well-being or mental health. Accordingly, the following types of research were excluded: reviews or other non-empirical work, purely qualitative studies, studies on other psychoactive substances such as ketamine, cannabis or MDMA, studies on microdosing, studies that only report acute or post-acute changes up to less than a week after the experience, as well as studies that did not measure both mystical-type experience and change in well-being or mental health or that did not explicitly report the association between the two in some way. Notably, several studies reporting association between mystical-type experience and level, but not change in some aspect of mental health or well-being were excluded.

IDENTIFICATION AND SELECTION OF STUDIES

This is not a systematic review as it was conducted by one person and does not include systematic assessment of quality or risk of bias of the included studies. However, the review is intended to be comprehensive and is based on a systematic search for relevant studies. It also follows the recommendations of the PRISMA statement and guidelines for systematic reviews where applicable. Figurepresents a PRISMA flowchart of study selection. I conducted a comprehensive search of the PubMed and Academic Search Ultimate (EBSCO) databases using the search string (myst p OR ego p OR oceanic p OR transcende p OR spirit p OR MEQ p OR HMS p OR HRS p OR SOCQ p OR 5D-ASC p OR 11D-ASC p ) AND (psyched p OR LSD p OR lysergic p OR psiloc p OR ayahuasc p OR DMT p OR dimethyltrypt p OR mescal p OR peyot p ) for titles and abstracts. To maximize sensitivity, additional filters were not used. I further examined lists of references from included studies as well as recent reviews and other major studies in the field by hand to locate additional studies. I also searched through all issues of the Journal of Psychedelic Studies for additional studies, as this journal is not indexed in these databases, but is directly relevant to the field. After removing duplicate entries, titles and abstracts were first screened to exclude obviously non-eligible studies, and the full texts of potentially eligible articles were then examined to confirm which articles fulfilled all the inclusion criteria.

DATA EXTRACTION

I used a data extraction form prepared beforehand to extract the following information from the included studies: authors, year of publication, title, journal, DOI, study design, sample size, sample characteristics, sampling method, randomization, blinding, substance, dose, context of use, mystical experience measure(s), level of mystical experiences, well-being and mental health measure(s), main findings on association between mystical experience and change in well-being or mental health, other acute features measured and their measures, findings on comparisons between mystical experience and other acute features, positive vs. null findings. The findings were then narratively synthesized, mainly according to which area or aspect of mental health or wellbeing each study assessed and its findings. No meta-analyses were performed. I also calculated descriptive statistics on the included studies and their characteristics. All data processing and analyses were carried out using R 3.4.3 (R Core Team, 2017) and Microsoft Excel Version 2202.

STUDY SELECTION

The search strategy identified 942 articles from the databases and another 9 articles from other sources. After removing duplicates, the titles and abstracts of 749 studies were screened in detail, and 601 were excluded with main reason for exclusion noted. The full texts of 148 articles were retrieved and screened, and another 104 studies were excluded based on assessment of the full text, with main reason for exclusion again noted. Finally, 44 studies met the inclusion criteria and were included in the review.

STUDY CHARACTERISTICS AND RESULTS

Supplementary Tableprovides an overview of the characteristics and findings of all 44 studies included in the review, published between 2009 and 2022. Sample sizes of the studies ranged widely from 10 to 6,877 (Md 5 58, SD 5 1,050). Gender distribution also varied widely, with share of women in the samples of the studies ranging from 15 to 72%, with an average of 39%. Mean ages of the samples ranged from 23 to 56, with average mean age of the samples 38.5. As for geographical distribution, 13 studies relied on samples from the US exclusively, four on samples from the UK, three on German and Brazilian samples each. Meanwhile, sixteen studies had samples of English speakers from several countries, four studies had samples of speakers of other languages (Danish, Finnish, French, multilingual), and one study did not report the nationality or language of the participants. Of the 44 studies, 19 were based on laboratory research, 18 on surveys, and 7 on field studies. For purposes of comparison in Table, survey and field studies are considered together, as in those studies, the dosing/doses and setting were not under the control of the study authors. 31 studies were prospective, meaning that they followed participants from before the psychedelic use to after it, while 13 were fully cross-sectional and retrospective. Notably, even in some prospective studies, changes in well-being or mental health were only assessed with retrospective questions (most commonly using items from the Persisting Effects Questionnaire;. Regarding the substance, 20 studies were on psilocybin, 7 on ayahuasca, one study on LSD, 5-MeO-DMT and mescaline each, while 14 included experiences with other or any psychedelic. Fourteen studies reported on research with broadly clinical or "ill" populations, while 30 were conducted among "healthy" populations or populations with no confirmed diagnosis. The studies reported on 75 associations between mysticaltype experience and changes in some aspect of well-being or mental health. In total, 57 of these associations were reported to be mainly positive to a statistically significant degree. Associations not found to be positive to a statistically significant are later described as "null findings", but it should be noted that no studies reported analyses explicitly aiming to confirm no association or the association being equivalent to zero. Likewise, no study reported overall negative associations between mystical-type experience and change in well-being or mental health, although a few studies did find some measures or subscales of mystical experience to associate negatively with change in some measures or subscales of well-being or mental health.

ASPECTS OF WELL-BEING AND MENTAL HEALTH

The studies analyzed changes in a wide variety of different aspects of well-being and mental health, which could be roughly divided into 22 categories: Depression (13 studies), anxiety (7), overall well-being and life satisfaction (13), attitudes and behavior (9), smoking cessation/cigarette consumption (4), AUD/problematic alcohol use (3), connectedness with nature (3), decreased neuroticism (3), increased openness (3), increased extraversion (2), psychological flexibility (2), DUD/problematic drug use (2), life meaningfulness and purpose (2), PTSD (1), alcohol craving (1), alcohol abstinence selfefficacy (1), cigarette abstinence self-efficacy (1), smoking urge (1), quality of life and optimism (1), spiritual well-being (1), connectedness (1), mindfulness (1). Tablepresents the numbers of positive (mainly statistically significant positive associations were reported) and null (no statistically significant association was found) findings for all aspects of well-being or mental health that at least three included studies analyzed, first for all studies in aggregate and then separated in different ways. A similar table including all 22 categories is presented as Supplementary Table. Findings of the included studies are summarized below for changes in major aspects of well-being or mental health, with special focus on the type and size of studies that provide evidence for associations and notable studies with null findings. Depression. Eight studies reported a positive association between acute mystical-type experiences and reduction in depression, while five studies did not find such an association. Notably, all the five null findings came from the ten prospective studies on the topic, where symptoms of depression were in fact assessed before and after the ingestion/administration of a psychedelic. These included a field study of 63 healthy ayahuasca retreat participants, a survey study of 155 depressed participantsand smaller clinical trials with psilocybin; both longer-term follow-up studies) and ayahuasca. Four of the five studies with null findings were among clinical populations. On the other hand, large cross-sectional surveys involving 452, 149, and 985 participants respectively did find positive associations between mystical-type experiences and reductions in depression retrospectively evaluated. A positive association with medium-term reductions in depression was also reported in several clinical trials that used standard validated measures of symptoms of depression in a prospective design. Anxiety. Six studies found a positive association between acute mystical-type experiences and reduction in anxiety, while a single study reported no significant association. Most positive findings were from cross-sectional survey/field studies, largest among them a survey bywith 985 participants having had a moderate to strong psychedelic experience with elements of psychological insights, another by Agin-Liebes et al. () with 452 participants reporting on mescaline experiences, and a third byon 173 individuals who had taken 5-MeO-DMT in a group setting. Notably, two of these surveys used very simple, single retrospective questions to assess whether anxiety (and depression) had worsened, changed the same, or improved after the experience. Two clinical trials of psilocybin-assisted treatment for individuals with life-threatening illness also reported mysticaltype experiences to associate with improvements in anxiety five to six weeks after end of treatment. The single reported null finding was from a six-month follow-up of thestudy, with just 14 individuals (Agin-Liebes et al., 2020). Overall well-being and life satisfaction. A total of 13 studies assessed the association between mystical-type experiences and changes in well-being and life satisfaction broadly defined, with 12 finding evidence for a positive link. Most notable about these studies is that 11 were carried out among healthy participants and just two with clinical/ill populations. Otherwise, positive links were reported by studies in a wide variety of contexts. These included surveys among 320 French-speaking, 288 Finnish-speaking, and 1,661 Englishspeaking users of any psychedelicand among 6,877 ayahuasca users from several countries, a prospective study of 315 individuals planning to take a psychedelic, as well as several laboratory studies among mainly healthy populations, largest among them the psilocybin trials byand. The only null finding was reported in the open-label psilocybin trial for tobacco cessation by Garcia-Romeu,with just 15 participants, where high, statistically non-significant correlation estimates suggest low statistical power to detect associations. Notably, seven out of these thirteen studies used a single question from the Persisting Effects Questionnaireto retrospectively assess whether the experience had resulted in positive changes in well-being or life satisfaction, and a further two used other very simple questions. These minimal, retrospective measures reduce the strength of the evidence these studies can provide on this association. However, the few studies that used more comprehensive scale-type measures of well-being and life satisfaction did also report a positive link between mysticaltype experiences and changes in them, whether assessed retrospectivelyor prospectively.

ATTITUDES AND BEHAVIOR.

Seven studies reported a positive association between mystical-type experiences and positive changes in attitudes or behavior, while two studies did not find evidence for such an association. Again, with one exception, all studies assessing this link were conducted among healthy populations. Further and most remarkably, although most studies that included a measure of changes in attitudes and/or behavior were prospective in basic study design, every one of them used retrospective measures to assess such changes, in nearly all studies items or subscales or the Persisting Effects Questionnaire. Thus, all these studies are effectively retrospective when examining this particular association, potentially limiting the level of evidence they are able to provide (although, see below for Discussion). This limitation notwithstanding, the largest studies with positive findings were a survey on 183 individuals who had ingested psilocybin in the last year, a study bycombining data from five laboratory experiments with psilocybin with a total sample size of 184, and the laboratory study of psilocybin combined with spiritual practice in 75 participants by. The only study in a purely clinical population, a follow-up of 24 depressed patients after psilocybin-assisted treatment also found mystical-type experience to associate with positive changes in attitudes and behavior at all timepoints up to 12 months after treatment. This contrasted with depression, where no such associations were found in the same study. The only null findings were reported by two laboratory studies with just 12 and 16 healthy participants, respectively. Substance abuse. Four studies examined associations between mystical-type experiences and smoking cessation or reduction. Two studies on the same small open-label clinical trial found positive associations with some though not all measures of smoking cessation at 6 and 16 months. Among 441 ritualistic ayahuasca users in Brazil, mystical-type experiences also had slight predictive power for cessation vs. relapse or reduction (Daldegan-Bueno, Maia, Massarentti, & Tófoli, 2022). Differences in mystical-type experiences between those who had quit vs. just reduced smoking after a psychedelic experience were not found in another survey study of 358 English speakers, however. Three studies assessed the association between mysticaltype experiences and improvements in alcohol use disorder or problematic alcohol use, all with positive findings. This included two large cross-sectional surveys of 452 and 343 participantsand one very small open-label clinical trial of psilocybinassisted treatment of alcoholism. The study by Agin-Liebes et al. () also found mystical-type experiences to associate with improvements in drug use disorder or problematic illegal drug use, while another survey of 444 participants did not find evidence for such a link. A few individual studies further examined associations between mystical-type experiences and other aspects of addiction such as smoking urge and alcohol craving, and alcohol and cigarette abstinence self-efficacy, with mixed findings. Personality. Four studies assessed associations between mystical-type experiences and changes in personality that might typically be considered positive, namely decreased neuroticism, increased openness, and increased extraversion, with mixed findings. In a small open-label trial of psilocybin-assisted therapy for treatment-resistant depression, mystical-type experiences did not overall associate with changes in any of the three areas of personality, although a spiritual experience subscale did correlate with increases in extraversion. Combining two samples of healthy volunteers in laboratories, MacLean,found psilocybin-induced mystical-type experiences to associate with increases in openness at 1-2 months after administration that persisted up to one year. In a prospective field study of 256 ayahuasca retreat participants,found mystical-type experiences to associate with greater self-reported decrease in neuroticism, but not with increases in openness or extraversion. Further, no associations were detected with informant-reported changes in personality.also reported a significant association with reduction in neuroticism in another similar, smaller field study. Connectedness with nature. Three medium-sized survey studies reported a positive association between mystical-type experiences and increased connectedness with nature. Two of these were cross-sectional studies where nature connectedness was assessed with a single, simple question. The prospective survey study byusing a brief scale measure found that degree of experienced ego dissolution was in particular associated with increased nature connectedness.

OTHER ACUTE FEATURES OF THE PSYCHEDELIC EXPERIENCE

Out of the 44 studies, 30 also analyzed the association between some other features of the acute experience and changes in well-being or mental health. The other acute features included challenging experience/discomfort (association with change in well-being or mental health analyzed by 14 studies), psychological insights/insightfulness (10), overall intensity (7), visual/auditory effects (6), emotional breakthrough (4), dread of ego dissolution (3), overall/other features of alteration of consciousness (3), as well as other features (4). Challenging experiences and most specific aspects of alteration of consciousness such as visual or auditory effects were generally not found to associate with positive changes in well-being or mental health (see Supplementary Tablefor details). However, psychological insights and emotional breakthroughs were found to be associated with positive changes in aspects of well-being and mental health in nine studies and four studies, respectively. Few studies directly compared the degree of association or predictive power of mystical-type experiences and insights or emotional breakthroughs with changes in wellbeing or mental health, in terms of, e.g., including them in the same model or explicitly analyzing differences in correlations or coefficients. Four studies directly compared mystical-type experiences and psychological insights in this way. In the survey study on mescaline experiences by Agin-Liebes et al. (), psychological insights were uniquely found to associate with improvements in depression, anxiety, alcohol use disorder and drug use disorder, while mystical-type experiences were uniquely associated with improvements in PTSD. In a large survey data set that two studies used, psychological insights associated more strongly with decrease in depression and anxietyand increases in psychological flexibility and well-being and life satisfaction. Finally, both psychological insights and mystical-type experiences were similar predictors of improved well-being and life satisfaction in the largest survey study of 6,877 participants. All these studies were among healthy participants. Two additional studies including measures of psychological insights and mystical experiences also suggested that insights might be more strongly associated with positive changes in well-being or mental health than mystical-type experiences, but did not directly compare them. Just three studies directly compared emotional breakthroughs and mystical-type experiences. Emotional breakthrough was reported to be a better or the sole predictor of decreased depression in one clinical laboratory study of psilocybinand one prospective survey studyamong depressed individuals. However, both similarly predicted improved well-being and life satisfaction in one survey study among healthy participants.

DISCUSSION

My first aim here was to provide a comprehensive review of the currently available evidence on mystical-type experiences under psychedelics associating with positive changes in aspects of well-being or mental health. The review did find several dozen studies that have assessed this association, with most reporting positive associations between mysticaltype experience and medium-to-long term improvement in well-being or mental health. This concurs with the findings oflimited to clinical studies and changes in symptoms of psychiatric disorders. However, the current level of evidence for such positive links appeared different for changes in different aspects of well-being or mental health. In terms of number of studies, most evidence was available for associations with improvements in overall wellbeing and life satisfaction, positive changes in attitudes and behavior, and anxiety. While a number of studies also found mystical-type experiences to associate with improvements in depressive symptoms, several studies on this association also failed to find a positive association, especially in the longer term. A few studies further demonstrated positive associations with improvements in substance abuse and increases in nature connectedness. Findings from a few studies were mixed on associations with positive changes in personality, and very limited on other aspects of improved well-being or mental health. The mere number of studies reporting evidence for an association is at best a very rough metric for level of evidence, however, so we must also consider the designs, size, and samples of the studies identified. In this regard, it is important to note that most of the identified studies were conducted among healthy participants, and studies in healthy populations also had higher ratios of positive to null findings. In particular, nearly all positive findings this review found on mystical-type experiences associating with improved wellbeing and life satisfaction and attitudes and behavior were from healthy populations. While most of the clinical studies also reported positive associations, their findings were more mixed. Smaller sample sizes and the resulting lack of statistical power partly explain these mixed findings. Still, the relevance of mystical-type experiences for improved wellbeing and mental health after psychedelic administration in clinical populations appears far less settled at the moment. Further, cross-sectional studies also had higher ratios of positive to null findings compared with prospective studies. For relief from depression, prospective studies failing to find an association with mystical-type experiences equaled in number those that did find one. Differences in the findings of retrospective and prospective studies were not as pronounced for change in other aspects of well-being or mental health. Retrospective, cross-sectional study designs are generally considered inferior in reliably capturing change due to recall bias, potentially even more pronounced when thinking back to a time before a significant event such as a mystical experience. Accordingly, we typically put more trust in the evidence provided by prospective studies. However, prospective pre-post approaches to measuring change do suffer from their own biases, especially scale recalibration or adaptation bias, and may not always result in more accurate results when dealing with complex subjective phenomena such as quality of life. Thus, although prospective measurements may be clearly preferable for outcomes such as depressive or anxiety symptoms, for outcomes like life satisfaction or quality of life, it is not obvious which type of measurements provide more reliable data. In future studies, including both might be preferable. In any case, the reliance on retrospective surveys (typically with volunteers enthusiastic about psychedelics) remains a challenge and potential source of bias evident in the current body of research on psychedelics. This review also aimed to identify studies where the association of mystical-type experiences with changes in wellbeing or mental health would be compared with those of other acute features of the subjective state induced by psychedelics. Few studies included direct comparisons of this nature. However, they did provide some initial suggestions that acute psychological insights and emotional breakthroughs may be as much or even more associated with improvements in well-being or mental health. This may be especially the case for depressive symptoms. Meanwhile, features of the experience such as challenging or discomforting nature and aesthetic effects were generally not found to associate with positive changes. These very preliminary findings call for including measures of both mystical-type experiences and other acute features of the psychedelic experience in future studies and comparing their contributions directly to determine their relative importance for positive changes with more certainty.

LIMITATIONS AND QUALITY OF EVIDENCE

This review is limited by only considering evidence from explicit analyses presented in published studies. Accordingly, publication bias is likely to affect its findings. A number of studies considered for inclusion that did include both measures of mystical-type experience and change in aspects of well-being or mental health did not report the association between some or all of them. The same is true for other acute features of the experience. It is possible that many null findings regarding potential associations have not been reported in the extant literature. Preregistration of (typically secondary) hypotheses regarding associations between acute features of the psychedelic experience and later changes in well-being or mental health and following open science practicesare strongly suggested for future studies to reduce this risk. While I was not able to systematically evaluate the quality and risk of bias of the included studies, clearly they are highly varied in the level of evidence they are able to provide. The two main issues are sample sizes and the measures (of change) used. Sample sizes varied widely, and the smaller, often clinical or laboratory, studies may not have been adequately powered to detect potentially meaningful associations. Most measures of well-being and mental health were based on self-report, introducing concerns of demand effects and socially desirable responding, especially considering the preponderance of psychedelic enthusiasts among participants. Indeed, two included studies found mystical-type experiences to associate with self-reported positive changes in well-being or mental health, but not with observer-rated changes. Including other sources of information in future studies would increase our confidence in findings about changes in well-being or mental health. Further, for changes in general well-being and life satisfaction, many studies relied on single retrospective questions, and for changes in attitudes and behavior, all included studies used retrospective measures, mainly the Persisting Effects Questionnaire. Many studies were also fully crosssectional and conducted months or even years after the target psychedelic experiencethe quality of evidence these studies provide is clearly lower, as both the mystical experience and changes in well-being or mental health are being simultaneously measured so long after the fact. The review is overall also limited by only considering quantitative evidence. Qualitative research can and has already contributed to our understanding of what aspects of the acute psychedelic experience are relevant for therapeutic change (see, e.g.,. It is also limited by the fact that the highly varied outcomes and outcome measures together with dissimilar study designs of the included studies did not allow for meaningful meta-analyses. In terms of generalizability, this review, too, makes it clear that psychedelic research is still very much centered on English speakers, and the US, Europe, and to some extent South America as geographical regions. While mysticism itself has been studied all over the world, whether people living in, e.g., East Asia, the Middle East, or Sub-Saharan Africa are likely to report similar mystical-type experiences after taking psychedelics, and whether such experiences might contribute to their well-being or mental health, remains unexplored in current research. Finally, this review relies on information about mysticaltype experiences captured by certain questionnaire measures, most commonly the MEQ. The question of whether such instruments truly and uniquely capture the level or degree of a phenomenon appropriately called a "mystical experience" is mostly beyond my scope here, but is an important point of active discussion. For instance, van Elk and Yaden (2022) note that the mystical experience is a multi-dimensional construct, and may be more appropriately viewed as an umbrella construct than a specific, singular experience or state. Here, I included more specific features such as ego dissolution and oceanic boundlessness on their own as simply exemplifying mystical-type experiences, but more careful distinctions may often be warranted. Even within measures like the MEQ, some of the included studies found associations with changes in well-being or mental health to differ for different aspects of mystical-type experiences (e.g.,. Meanwhile, Taves (2020), among others, has criticizedquest to identify a common core of mystical experiences and the measures that follow him in basically operationalizing mysticism too narrowly as a positive experience of unity. She proposes studying a wider range of alterations in sense of self with more fine-grained measures.has also emphasized changes in perceptions and sense of self rather than in metaphysical beliefs as explaining the possible link between mystical-type experiences and positive changes in well-being or mental health. He points out that even when a subject's experience under psychedelics fulfils the typical criteria for a (complete) mystical experience on the MEQ, for example, it may not have involved apprehension of supernatural realities, convincing encounters with a supreme being or other non-naturalist metaphysical ideations.

CONCLUSIONS

Despite the methodological limitations and highly varied nature of the studies included in this review, in toto they do suggest that people tend to report more positive changes in different areas of well-being and mental health when they also report having had mystical-type experiences after ingestion of classic psychedelics than when they do not report such experiences. The present review found more, and more unequivocal, evidence for this among healthy people than in clinical populations, and for positive changes in general well-being and life satisfaction, attitudes and behavior, and anxiety, than for depression or other aspects of well-being and mental health. However, at this stage, such findings should be considered preliminary, providing inspiration for future research rather than answers. Few studies have directly compared other features of the acute experience such as psychological insights and emotional breakthroughs with mystical-type experiences in how they associate with or predict later positive changes. But these few studies do suggest that insights or breakthroughs might be as important or even more important for medium-to long-term positive changes in well-being or mental health. Accordingly, future research and potential therapeutic use of psychedelics should also increasingly focus on such non-mystical aspects of the psychedelic experience.