This survey study (n=985) finds that psychological flexibility fully mediated the effects of mystical/peak experiences on depression/anxiety.
Prior research has shown that acute subjective psychedelic effects are associated with both spontaneous and intended changes in depression and anxiety. Psychedelics are also theorized to produce increases in psychological flexibility, which could explain decreases in depression and anxiety following a psychedelic experience. Therefore, the present cross-sectional survey study sought to examine whether psychological flexibility mediated the relationship between acute psychedelic experiences and spontaneous or intended changes in depression and anxiety among a large international sample of people who reported having used a psychedelic (n = 985; male = 71.6%; Caucasian/white = 84.1%; Mage = 32.2, SD = 12.6). Regression analysis showed that acute effects (i.e., mystical and insightful effects) were significantly associated with decreases in depression/anxiety following a psychedelic experience. A path analysis revealed that, while controlling for age and sex, increases in psychological flexibility fully mediated the effect of mystical and insightful experiences on decreases in depression and anxiety following a psychedelic experience. This suggests that psychological flexibility may be an important mediator of the therapeutic effects of psychedelic drugs. Future prospective experimental studies should examine the effect of psychedelic drug administration on psychological flexibility in order to gain a better understanding of the psychological processes that predict therapeutic effects of psychedelics.
Depression and anxiety are highly prevalent and burdensome mental health conditions for which many existing treatments are inaccessible or insufficiently effective for a sizable subset of people. Interest has grown in the therapeutic potential of classic serotonergic psychedelics (for example psilocybin, LSD, ayahuasca, 5‑MeO‑DMT), which produce profound alterations in perception, mood and cognition and have shown preliminary efficacy for reducing symptoms of depression and anxiety in both clinical trials and naturalistic contexts. Prior work suggests that the intensity of certain acute subjective effects during a psychedelic session—notably mystical-type phenomena and psychological insight—relates to subsequent reductions in depressive and anxious symptoms, but the psychological mechanisms that might explain these associations remain incompletely specified. Davis and colleagues set out to test whether increases in psychological flexibility could account for the relationship between acute psychedelic effects and self-reported decreases in depression and anxiety. Psychological flexibility is a transdiagnostic construct central to Acceptance and Commitment Therapy (ACT), encompassing processes such as acceptance, cognitive defusion, present-moment contact, values-based action and self-as-context; reductions in psychological flexibility (i.e., inflexibility) are theorised to underlie many forms of psychopathology. The study hypothesised that (H1) greater acute mystical and insight effects would predict larger decreases in depression/anxiety, and in a path model that (H2) acute effects would predict increases in psychological flexibility, (H3) increases in psychological flexibility would predict decreases in depression/anxiety, and (H4) psychological flexibility would mediate the relationship between acute effects and symptom change.
Papers cited by this study that are also in Blossom
Araújo, A. M., Carvalho, F. M., Carvalho, M. et al. · Archives of Toxicology (2015)
Barrett, F. S., Bradstreet, M. P., Leoutsakos, J. M. S. et al. · Journal of Psychopharmacology (2016)
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)
Carhart-Harris, R. L., Bolstridge, M., Rucker, J. et al. · Lancet Psychiatry (2016)
The investigators conducted a large anonymous cross-sectional internet survey targeting adults who reported a moderate-to-strong single-substance psychedelic experience that produced psychological insight. Recruitment occurred between June 2018 and January 2019 via online forums, email announcements and a popular-press article; respondents accessed a Qualtrics survey, provided consent and completed questionnaires. Inclusion criteria required being at least 18 years old, fluent in English, having used only a single psychedelic during the focal experience, and reporting that the experience contributed to psychological insight. Of 14,911 people who clicked the study link, 3,080 consented and completed the survey; after excluding those who reported multi-substance use and respondents who did not indicate a change in depression or anxiety, the analysed sample comprised 985 individuals. Participants reported demographic information and characteristics of the psychedelic session (substance used, subjective dose level, route of administration, and time since the experience). Acute mystical-type phenomena were measured with the 30-item Mystical Experiences Questionnaire (MEQ; items rated 0–5; total mean score used; alpha = .94). Acute psychological insight was measured with the 28-item Psychological Insight Questionnaire (PIQ; 0–5 scale; total mean score used; alpha = .93); the PIQ was under development and its psychometrics would be reported elsewhere. Depression and anxiety before and after the experience were assessed using the Depression, Anxiety, and Stress Scale (DASS-21); the authors combined the DASS depression and anxiety subscales to create a single change score by subtracting post-experience from pre-experience totals (negative values represent symptom decreases). Psychological flexibility was assessed with the Acceptance and Action Questionnaire-II (AAQ‑II); because lower AAQ‑II scores indicate greater flexibility, the team calculated an after-minus-before change score so a positive value indicates an increase in psychological flexibility. Internal consistencies for the pre/post measures were acceptable to good. Data quality checks examined completion time distributions to identify careless responding. Analyses began with descriptive statistics and Pearson/point-biserial correlations among age, sex, MEQ, PIQ, depression/anxiety change, and psychological flexibility change; given the large sample, a correlation coefficient threshold of 0.20 and a significance level of p < .001 were used to denote meaningful and statistically significant associations. Hypothesis testing used multiple linear regression to examine H1 and structural path analysis to test H2–H4, controlling for age and sex. Path models were estimated in MPlus v7.0 using weighted least square mean and variance estimators; other analyses used SPSS v25. Supplementary subgroup analyses split respondents by whether symptom change was intended or spontaneous and examined depression and anxiety subscales separately.
The final sample (N = 985) was predominantly male (72%), white/Caucasian (84%), with mean age 32.2 years (SD = 12.6). Most respondents lived in the United States (65%) and around three-quarters reported that their focal experience had occurred at least one year prior to the survey. The most commonly reported substances were LSD (42%) and psilocybin/mushrooms (38%); 36% reported a moderately-high dose and 21% a high dose. Mean change scores indicated an overall decrease in combined depression/anxiety from before to after the psychedelic experience (M = -6.80, SD = 5.61; range -21 to +9) and an increase in psychological flexibility (mean change M = 2.01, SD = 1.44; range -4.14 to +6). Mean acute-effect scores were MEQ M = 3.81 (SD = 0.89) and PIQ M = 3.38 (SD = 0.91). Bivariate analyses showed that mystical and insight intensities were moderately correlated with each other; insight intensity showed a moderate correlation with decreases in depression/anxiety, and both acute effects correlated with increases in psychological flexibility to varying degrees. Drug type (psilocybin, LSD, other) was not meaningfully correlated with the primary variables. A multiple linear regression testing H1 (mystical and insight predicting depression/anxiety change) yielded a significant overall model (p < .001) that accounted for 10% of variance in symptom change. Both mystical and insight intensities were associated with greater decreases in depression/anxiety, though the model explained a relatively small portion of variance. Path analysis controlling for age and sex supported H2–H4. Greater acute mystical and insight intensities were directly associated with increases in psychological flexibility (Mystical: β = 0.09, p < .01; Insight: β = 0.46, p < .001). In turn, increases in psychological flexibility were strongly associated with decreases in depression/anxiety (β = -0.62, p < .001). Indirect (mediated) effects were observed: psychological flexibility mediated the relation between mystical intensity and symptom change (indirect β = 0.06, SE = 0.02, p < .01) and between insight intensity and symptom change (indirect β = 0.29, SE = 0.02, p < .001). Model fit indices indicated good fit (RMSEA = 0.055, 95% CI 0.01–0.12; CFI = 0.995; WRMR = 0.394). Supplementary subgroup analyses replicated the main findings across groups defined by whether symptom change was intended or spontaneous and when examining depression and anxiety separately, with two exceptions: among participants who intended to change their anxiety, mystical intensity was not significantly associated with decreases in anxiety and was not significantly related to increases in psychological flexibility in that subsample.
Davis and colleagues interpret their findings as consistent with the idea that acute psychedelic experiences—both mystical-type phenomena and psychological insight—are associated with subsequent reductions in depressive and anxious symptoms, and that increases in psychological flexibility provide a plausible mediating pathway. The path coefficients indicated that psychological insight had a substantially larger direct association with increases in psychological flexibility than mystical experiences did, and correspondingly larger indirect effects on symptom change; the authors highlight psychological insight as a particularly robust predictor in their models. These results align with earlier research linking acute psychedelic phenomenology to therapeutic benefit and with preliminary evidence that psychedelics can alter psychological flexibility. The investigators situate their findings within broader mechanistic discussions of psychedelic action, noting that psychological flexibility is one among several proposed mediators (others include changes in brain network dynamics and experiences of awe or ego dissolution). They further suggest clinical implications: if psychological flexibility proves to be a consistent mediator in prospective trials, combining psychedelic administration with contextual behavioural therapies such as Acceptance and Commitment Therapy (ACT), which expressly target psychological flexibility processes, might enhance therapeutic outcomes. The discussion also notes qualitative parallels between acute psychedelic effects and ACT processes (for example, self-as-context, defusion, values clarification and contact with the present moment) and points to prior trial data showing behavioural change following psychedelic-assisted interventions. Several limitations are emphasised. The anonymous internet-based, retrospective survey design introduces potential selection bias and recall bias, and the parent study’s recruitment focus on insight experiences may have accentuated associations involving insight. The sample lacked demographic diversity (predominantly young, white, and male), limiting generalisability. Because the data are cross-sectional and retrospective, causal inferences cannot be drawn. The authors therefore call for prospective, controlled laboratory trials that assess psychological flexibility and the core ACT processes longitudinally to test causality and to determine whether targeting these processes in psychotherapy augments psychedelic treatment effects.
The study concludes that increases in psychological flexibility appear to mediate the association between acute psychedelic effects and self-reported decreases in depression and anxiety. Davis and colleagues recommend future controlled trials that measure psychological flexibility and core ACT processes before and after psychedelic administration to establish causal pathways and to evaluate whether integrating psychedelic dosing with therapies that explicitly target psychological flexibility can enhance durable therapeutic outcomes.
Depression and anxiety disorders are common mental health problems. Global lifetime prevalence of depression and anxiety are approximately 10% and 13%, respectively. The public health burden of depression and anxiety includes occupational impairment, and increases the risk for chronic physical conditions such as cardiovascular disease. Given high prevalence rates and the substantial public health and personal burden of these mental health conditions, numerous interventions have been developed, which include combinations of psychotherapy and pharmacotherapy. Despite evidence supporting the use of these interventions, many people do not have access to these treatments, and many people who have access will not experience symptom relief despite intervention, highlighting the need for more treatment options. One emerging area of research has examined the psychotherapeutic action of psychedelic compounds (e.g., psilocybin, LSD, ayahuasca, 5-MeO-DMT) administered in clinical trialsand used in naturalistic settings. These substances act primarily as agonists of serotonin (e.g., 5-HT1A/2A/C) receptors and often produce profound changes in sensory perceptions, mood, cognitions, and behavior. For example, recent studies examining psychedelics administered as an adjunct to psychotherapy have demonstrated efficacy in decreasing symptoms of anxiety and depression. Published reports also show that decreases in depression and anxiety occur following naturalistic psychedelic use in ceremonial and recreational contexts. Although more work is needed to fully understand the mechanisms of therapeutic action, the beneficial effects of these substances appear to be associated with the intensity of certain types of acute psychedelic effects (e.g., mystical-type phenomena, psychological insight) during these experiences in both healthyand clinicalpopulations. Potential mediators of psychedelic effects on therapeutic outcomes have been suggested, including changes in the entropy of brain network connectivity, the importance of awe/ego dissolution; and the possible role of changes in psychological flexibility following a psychedelic experience. Psychological flexibility is described as an essential set of processes that help people manage stressors and engage in adaptive behaviors that promote values-driven action. Psychological flexibility is a transdiagnostic construct wherein people are thought to have the capacity to develop skills recognizing and adapting to various contextual demands, shift their mindset or behaviors during individual and social experiences, maintain balance across important life domains, and learn to be open to, aware of, and committed to behaviors that are congruent with their values. According to this model, well-being is supported by fully contacting the present moment as a conscious human being and changing or persisting in a values-driven behavior regardless of what is present in each moment. Conversely, dysfunctions in mental health, including depression and anxiety disorders, are theorized to be the result of reduced psychological flexibility (or psychological inflexibility). Psychological interventions have been developed using this theoretical framework (e.g., Acceptance and Commitment Therapy (ACT);, which attempt to increase psychological flexibility via six interconnected processes (i.e., acceptance, defusion, being present, self-as-context, determining direction for behavior change, and using techniques to facilitate change;. Metaanalyses have shown moderate to strong effects in favor of ACT interventions (compared to control conditions: waitlist, psychological placebo, and treatment as usual) in decreasing anxiety and depression symptoms, and evidence shows that the positive outcomes of this intervention are mediated by increases in psychological flexibility. If psychedelic experiences promote increases in psychological flexibility, then such increases could be mediating the antidepressive and anxiolytic effects observed in clinical trialsand the associations found in naturalistic psychedelic use. This relationship could also justify a psychotherapeutic approach to psychedelic-assisted therapy that focuses on processes of change with the psychological flexibility model. The present cross-sectional survey study sought to examine psychological flexibility as a potential mediator of acute psychedelic experiences on changes in anxiety/depression. Prior research has shown that acute psychedelic effects are associated with reductions in depression and anxiety, that psychedelic effects are associated with changes in psychological flexibility, and that increases in psychological flexibility are associated with positive depression and anxiety outcomes. Therefore, in a regression model we expect to find (Hypothesis 1: H1) acute psychedelic effects (mystical and insight effects) will predict changes in depression and anxiety following a psychedelic experience, and in a path model we expect to find that H2) acute psychedelic effects will be directly related to increases in psychological flexibility, H3) increases in psychological flexibility will be directly related to decreases in depression/anxiety, and H4) psychological flexibility will mediate the relationships between acute psychedelic effects and decreases in depression and anxiety symptoms.
The current study data were collected as part of a large anonymous internet-based cross-sectional survey of individuals who reported having a moderate to strong psychedelic experience in the past. Specifically, people were recruited as part of a larger study examining acute insight (e.g., an awareness into emotions, behaviors, beliefs, memories, relationships, etc.) gained as a result of a psychedelic experience. Recruitment from the parent study is ongoing and results will be published in a forthcoming article. Respondents were recruited by using electronic message postings and advertisements on several internet websites, electronic mail announcements, and via an article published by Motherboard/VICE). Advertisements directed potential respondents to a secure web-based survey (hosted by: www.qualtrics. com), and those who clicked a study link were presented with a consent document detailing the inclusion criteria. Eligible volunteers had to endorse being at least 18 years old, able to read, write and speak English fluently, have taken a dose of a single psychedelic (e.g., psilocybin mushrooms, psilocybin, LSD, ayahuasca, mescaline, N,N-DMT, 5-MeO-DMT, peyote, 4-Acetoxy-DMT, Salvia, Ibogaine, etc.) that produced moderate to strong psychoactive effects, and after taking the substance they must have had an experience that contributed to gaining psychological insight. Following consent, respondents completed each study questionnaire (described below). The study was approved by the Johns Hopkins School of Medicine Institutional Review Board and the full survey is available from the corresponding author. No incentives were offered in this study.
Respondents were recruited from June 2018 through January 2019. Of all individuals who clicked the advertisement link (n = 14,911), 3080 consented and completed the survey. However, 960 of these respondents were excluded because they reported using more than one substance in their psychedelic experience. Of the remaining 2120, a total of 985 were included in the final sample because they indicated experiencing a change in anxiety or depression as a result of a psychedelic experience.
We asked respondents to report which psychedelic substance they had used (e.g., psilocybin, LSD, N,N-DMT, Ayahuasca, 5-MeO-DMT, Mescaline, Salvia/Salvinorin A, peyote cactus, Iboga/ibogaine, or "Other"), the subjective level of dose (i.e., Low, Moderate, Moderately high, High), route of administration (i.e., Oral, Sublingual, Smoked or Vaporized, Buccal, Intravenous, Intranasal), and length of time since the experience (e.g., 3-6 months ago, 7-11 months ago, 1-2 years ago, etc.).
The Mystical Experiences Questionnaire (MEQ) was used to assess subjective mystical-type phenomena that may have occurred after taking the psychedelic. Respondents were asked to think back on their experience with a psychedelic and then to rate the extent to which each of 30 descriptors applied at any point during their session on a 6-point scale from 0 = "None; not at all" to 5 = "Extreme (more than ever before in my life)." Similar to prior research, we calculated a total mean score of all items on the questionnaire. Internal consistency reliability of the total scale was excellent (alpha = .94).
The Psychological Insight Questionnaire (PIQ) was created to assess the degree to which respondents experienced acute insight (e.g., gained an awareness into your emotions, behaviors, beliefs, memories, or relationships) that sometimes occurs after taking a psychedelic. Respondents were asked to think back on their experience with a psychedelic and then to rate the intensity with which they experienced each of 28 insight experiences at any point during their session, and similar to the MEQ they rated each item on a 6-point scale from 0 = "No; not at all" to 5 = "Extremely (more than ever before in my life)." A total score was calculated as the mean of the responses to each item, and the internal reliability of this total score was excellent (alpha = .93). The PIQ is under development and the psychometric properties of this questionnaire will be reported in a forthcoming manuscript. See Tablefor items, item means (and standard deviations), and percent endorsement of each item ('No, not at all' = 0 and all other response options = 1).
The Depression, Anxiety, and Stress Scale (DASS-21) was used to assess for anxiety and depression symptoms during the 3 months before and 3 months after the psychedelic experience. This 21-item scaleexamines the core negative emotional experiences of depression and anxiety that respondents reported experiencing. The DASS-21 is comprised of three subscales: depression, anxiety, and stress, of which we used a subscale consisting of the combined depression and anxiety subscales in the current study. There are seven items in each subscale and respondents are asked to respond to each item on a scale from 0 = "Never" to 3 = "Almost always." Internal consistency reliability was good for the before measures (depression subscale alpha = .91; anxiety subscale alpha = .80) and adequate-to-good for the after measures (depression subscale alpha = .84; anxiety subscale alpha = .69). In the present study, we examined subjective changes in depression and anxiety following a psychedelic experience by calculating a mean total change score by subtracting the total depression and anxiety after scores from the total depression and anxiety before scores for each respondent (e.g., negative scores represent a decrease in depression/anxiety). A single measure combining depression and anxiety subscales (depression/anxiety) was analyzed as the dependent measure in analyses reported in this report. Separate analyses for depression and anxiety subscales are reported in supplementary material.
The Acceptance and Action Questionnaire II (AAQII;was developed as a measure of psychological inflexibility, and in the present survey it was used to assess the degree of psychological flexibility respondents experienced before and after the psychedelic experience. The AAQII is comprised of 7 items and respondents were asked to respond to each item on a scale from 1 = "Never true" to Note. Range of scores of all items was 0-5. a Response options were on a scale from 0 = "No, Not at all" to 5 = "Extremely (more than ever before in my life)". Data in this column show the proportion of respondents who endorsed any option other than "No, Not at all.". 7 = "Always true." Lower scores on this measure indicate greater psychological flexibility. Internal consistency reliability was good for the psychological flexibility before measure (alpha = .88) and the psychological flexibility after measure (alpha = .88). We examined changes in psychological flexibility by calculating a mean change score. This calculation involved subtracting the mean psychological flexibility before score from the mean psychological flexibility after score for each respondent in order to ease interpretation (i.e., we calculated a positive change score to denote increases in psychological flexibility). This change score was used in all analyses.
We included items inquiring about the age, sex, gender, race, ethnicity, country/region of residence, income, level of education, and relationship status of each respondent.
Data Quality. Study completion time was examined in order to identify cases of rushed and possibly careless responding. Overall, respondents completed the survey in approximately 47 min. Only 3 respondents took less than 15 min to complete the survey; 25% of the sample completed the survey in less than approximately 33 min; and 75% of the sample completed the survey in less than approximately 67 min. Although 3 respondents completed the survey in less than 15 min, a review of their responses did not provide any indication of careless responding. This pattern of response time suggests that careless responding was not a concern. Analytic Plan. First, descriptive statistics for demographic and background characteristics for all study variables were calculated. Pearson and point biserial correlation coefficients were calculated to examine the relationships among all primary study variables (age, sex, acute insight and mystical effects, depression/anxiety change score, and psychological flexibility change score). Given the large number of respondents in the sample, we used a coefficient cutoff of 0.20, and used an alpha cutoff of p < .001, to determine whether a correlation was both meaningful and statistically significant, respectively. Next, a regression analysis was used to test (H1): acute mystical and insight experiences will be negatively associated with depression/anxiety change score. A path analysis was then used to test hypothesized direct effects (H2-H3: Intensity of psychological insight and mystical effects have a direct effect on changes in psychological flexibility, and changes in psychological flexibility have a direct effect on changes in depression/ anxiety) and mediation effects (H4): Intensity of psychological insight and mystical effects are indirectly related to changes in depression/ anxiety via and the path analyses. Analyses were conducted in SPSS v 25and MPlus version 7.0 using weighted least square mean and variance estimators.
Most of the sample reported they were male (72%), Caucasian/ white (84%), never married (51%), currently live in the United States (65%) and earned $35,000 or more in income (60%). Average age in the sample was 32.2 (SD = 12.6). Over three-quarters of the sample reported that their psychedelic experience was occasioned by LSD (42%) or psilocybin/mushrooms (38%) as the psychedelic substance used to occasion their experience. Furthermore, about one-half of the sample reported that the dose was moderately-high (36%) or high (21%). The psychedelic experience had occurred at least 1 year prior to the survey in 75% of the sample. Overall, there was a mean decrease in depression/anxiety (M = -6.80; SD = 5.61; Range: -21 to +9), and a mean increase in psychological flexibility (M = 2.01; SD = 1.44; Range: -4.14 to +6), from before to after the psychedelic experience. Additional details about respondent characteristics are shown in Supplemental Table. Associations between acute psychedelic effects and psychological flexibility and depression/anxiety change scores. A series of point-biserial correlations revealed that the type of psychedelic drug used by respondents (Psilocybin: No = 0, Yes = 1; LSD: No = 0, Yes = 1; Other Psychedelic: No = 0, Yes = 1) was unrelated (range: -0.19 to 0.14) to all other variables (age, sex, acute insight and mystical effects, depression/anxiety change score, and psychological flexibility change score). Additionally, as Tableshows, the intensity of mystical effects was moderately correlated with insight effects and to a lesser degree with decreases in depression/anxiety and increases in psychological flexibility. Intensity of psychological insight was moderately correlated with decreases in depression/anxiety; and the intensity of psychological insight and decreases in depression/anxiety were correlated with increases in psychological flexibility.
Tableshows data from the multiple linear regression including acute mystical (M = 3.81; SD = 0.89) and insight effects (M = 3.38; SD = 0.91) as predictors of decreases in depression/anxiety (M = -6.80; SD = 5.61). The overall model was significant (p < .001), accounting for 10% of the variance in depression/anxiety change scores (H1). Although accounting for a relatively small amount of variance in this model, the intensities of both mystical and insight effects were associated with decreases in depression/anxiety (see Table). b The AAQII was originally developed as a measure of psychological inflexibility. Reduction in AAQ scores indicates an increase in psychological flexibility. However, to ease interpretation, we have calculated a positive change score to denote increases in psychological flexibility.
As shown in Fig., the path analysis controlling for age and sex revealed that greater mean intensity of acute mystical and psychological insight effects were directly related (Mystical: β = 0.09, p < .01; Insight: β = 0.46, p < .001) to mean increases in psychological flexibility (M increase = 2.09; SD = 1.44; supporting H2), mean increases in psychological flexibility were directly related (β = -0.62, p < .001) to mean decreases in depression/anxiety (supporting H3), and indirect effects were found wherein psychological flexibility mediated the relationships between the intensity of acute mystical (β = 0.06, SE = 0.02, p < .01) and insight (β = 0.29, SE = 0.02, p < .001) effects and mean decreases in depression/anxiety (supporting H4). Model fit was good: root mean square error of approximation = .055 (95% CI: 0.01, 0.12); comparative fit index = 0.995; weighted root-mean-square residual = 0.394.
The sample used for our primary analyses (described above) was a group of individuals who reported a spontaneous or intended change in anxiety (intended N = 142; spontaneous N = 197) or depression (intended N = 366; spontaneous N = 280) following a psychedelic experience. In the path analysis shown in Fig., we collapsed these groups into one sample (N = 985), and averaged measures of depression and anxiety into a single measure, in order to examine our primary study hypotheses in a more concise manner. However, we also analyzed all study hypotheses (H1-H4) within each of these subgroups using the same analytic approach described above, and these tables and figures are available in supplementary files (Suppl. Tables; Suppl. Figures). In short, all hypotheses were replicated in each subsample, with two notable exceptions. Among those who intended to change their anxiety after a psychedelic experience, the regression analyses (Suppl. Table) showed that intensity of mystical effects was not significantly associated with decreases in anxiety (contrary to H1). Furthermore, in the path analysis (Suppl. Figure), intensity of mystical effects was not significantly associated with increases in psychological flexibility (contrary to H2), nor were there indirect relationships between acute mystical effects and decreases in anxiety via increases in psychological flexibility. However, all other findings showed that our models were identical regardless of whether one had a spontaneous or intended change in these their anxiety/depression.
The present retrospective cross-sectional survey study examined whether psychedelic occasioned mystical-type or psychological insight experiences predicted decreases in depression and anxiety following a psychedelic experience (H1), acute psychedelic effects predicted increases in psychological flexibility (H2), increases in psychological flexibility predicted decreases in depression/anxiety, (H3) and whether increases in psychological flexibility mediated the relationships between acute psychedelic effects and decreases in depression and anxiety symptoms (H4). Findings from our regression and path analysis models supported each of these hypotheses. Consistent with prior studies, in the present study mystical experiences were associated with decreases in depression and anxiety. Importantly, these observations were extended by showing that experiences of psychological insight during a psychedelic experience are also associated with decreases in depression and anxiety. Further, when mystical and psychological insight effects were included simultaneously as predictors of changes in our models, results showed that psychological insight stands out as a more robust predictor of change, as evidenced by the larger direct (Insight: β = 0.46 versus Mystical: β = 0.09) and indirect (Insight: β = 0.29 versus Mystical: β = 0.06) coefficients in the path analysis. That psychological insight is strongly related to decreases in depression and anxiety is perhaps not surprising given the history of insight-oriented therapies (Connolly, but it has also been questioned whether gaining insight is sufficient in and of itself to produce lasting changes in behavior or mental health functioning. To this point, our models also showed that psychological insight was predictive of change when accounting for the correlation between insight and mystical experiences. Insightful as well as mystical-type experiences have been identified as subtypes of the phenomenon of quantum change, which refers to a sudden, distinctive, benevolent, and enduring experience resulting in personal transformations that affect a broad range of personal emotions, cognitions and behaviors. Such experiences after taking a psychedelic have also been implicated in decreases in alcohol use among individuals with alcohol use disorder. Furthermore, findings from the present study underscore a potential explanation for how acute psychedelic experiences, including gaining psychological insight and mystical experiences, may exert such changes. Specifically, we demonstrated the importance of increases in psychological flexibility as a mediator of the positive therapeutic effects. Although several other mechanisms have been proposed at various levels of functioning, from changes in the entropy of brain network connectivityto the importance of awe/ego dissolution, findings from this study are consistent with evidence demonstrating that psychedelic effects are associated with changes in psychological flexibility among a small sample of subjects who use the psychedelic ayahuasca, and research showing that increases in psychological flexibility is associated with positive depression and anxiety outcomes. Although the exploration of potential mediators of psychedelic effects on therapeutic outcomes is in its early stages, if psychological flexibility emerges as a consistent and robust mediator of effects in prospective clinical trials, then the field of psychedelic-assisted psychotherapy should consider integrating psychedelic administration with contextual behavioral therapies (e.g., ACT;or other therapies designed to target psychological flexibility. Such therapies are designed to enhance processes of change by supporting increases in psychological flexibility which could be enhanced through the administration of a psychedelic. Moreover, it is possible that some acute psychedelic effects overlap with the core processes of the ACT model of psychopathology. For example, consistent with the core processes of ACT, qualitative analysis of first-hand accounts of tobacco smokers in a clinical trial examining the effect of psilocybin-assisted therapy, suggested that their psychedelic experiences helped them see themselves in the context of their addiction (i.e., self as context), realize that they are not the labels (e.g., smoker) which they previously identified as (i.e., defusion), understood their values more clearly than before (i.e., values), and connected with the fullness of the present moment and their experience of it (i.e., contact with the present moment). Although not highlighted in the qualitative reports per se, another component of the ACT model, committed action, was demonstrated in the clinical trial by the high rates (80%) of biologically verified abstinence at 6 months post-treatment. These data suggest that psychedelics appear to occasion both mindfulness/acceptance processes as well as commitment and behavior change processes. However, more research is needed to systematically investigate these processes in rigorous longitudinal trials among individuals with depression or anxiety in order to replicate these findings in this population. This study has several limitations. Internet-based recruitment and data collection procedures were anonymous. Although this likely increased participation from individuals from a variety of geographical locations, it would have excluded people who are unable or prefer not to participate in research conducted on the internet. Further, a limitation of survey methods is that all reports are retrospective, increasing the likelihood that current affect and personality bias could influence recollection of subjective psychedelic experiences as well as depression and anxiety symptoms that were experienced many years ago. However, this potential confound is not expected to be more or less than similar confounds in other retrospective survey research. Additionally, the parent study from which the data were drawn, was designed to investigate the acute effect of gaining insight during a psychedelic experience. Although the mean score of the intensity of mystical experiences in this sample was similar to prior studies, suggesting comparably strong mystical effects in addition to insight effects, we cannot rule out the possibility that recruiting people who specifically reported gaining insight as part of a psychedelic experience accounts for some of the differential strength in the association between acute insight and other study variables. Another limitation to this study is that, despite our efforts to recruit individuals with diverse backgrounds by placement of notices on a variety of internet forums, respondents were primarily young, white, and male. Although our sample is consistent with prior studies of psychedelic users using similar recruitment procedures, similar towe strongly encourage future researchers to continue efforts in recruiting a diverse sample. There are several possible explanations for the lack of diverse representation in psychedelic survey studies. For example, it could be that the topic of these studies are not interesting to some potential respondents, that there is a perceived risk involved with reporting an illegal behavior, or that the internet computer format excluded individuals from differing socio-economic backgrounds. Efforts to overcome these factors could include a community-based participatory research methodology, wherein the study is designed through engagement with leaders from a variety of diverse backgrounds, with the intention of better understanding the ways in which the study can be designed to connect with individuals from these communities.
The findings from the present study highlight the role of psychological flexibility as a mediator of acute psychedelic effects and decreases in depression/anxiety. Future studies should examine the effect of psychedelic drug administration on psychological flexibility in a laboratory setting using a controlled trial design in order to ascertain the causal influences of psychological processes that predict therapeutic effects of hallucinogens. Such work should include measurement of the core processes of ACT (e.g., defusion, values, self as context, etc.) in order to examine whether changes in these core processes occur and predict enduring effects of psychedelic substances on therapeutic outcomes. If psychological flexibility continues to be shown to mediate positive therapeutic outcomes, future research should explore whether such therapeutic effects can be further enhanced by using a psychotherapeutic approach to psychedelic-assisted therapy that specifically targets processes of change within a transdiagnostic psychological flexibility model.
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