Enhanced meaning in life following psychedelic use: converging evidence from controlled and naturalistic studies

Introduction: Psychedelics, such as psilocybin, are increasingly recognized for their propensity to elicit powerful subjective experiences that carry personal meaning. While research has demonstrated the capacity for these compounds to promote psychological wellbeing, it has yet to be shown to what extent they modulate "meaning in life", a specific contributor to mental and physical health.

Methods: Using the Meaning in Life Questionnaire (MLQ), we examined changes in meaning in life occurring across three different contexts of psychedelic use, including a randomized clinical trial of psilocybin for depression, controlled administration of psilocybin in a single-arm healthy volunteer study, and a naturalistic observational study following participants in psychedelic retreats. Meaning in life changes were analyzed with linear mixed models, and relationships to other predictors and outcomes were examined via Pearson correlations.

Results: Across all contexts, the sub-factor “presence of meaning” was strongly increased after a psychedelic experience, while the sub-factor “search for meaning” was only weakly reduced. Enhancements of meaning in life were also moderately correlated with changes in measures of mental health, including mental wellbeing and depression severity. In line with previous research, we found that mystical, ego dissolution and emotional breakthrough experiences were correlated with an increase of meaning in life, with context-dependent differences in the strength of the association.

Discussion: The convergence of evidence from multiple studies shows that psychedelic use has a robust and long-lasting positive effect on meaning in life. We explore potential mechanisms of psychedelic-induced meaning enhancement and highlight the possible influences of psychosocial context on outcomes.

1 Introduction

Since their initial emergence into Western culture in the 1950s, classical psychedelics like psilocybin and LSD have been recognized for their ability to produce profound subjective experiences (Pahnke and Richards, 1966; Pahnke, 1969; Griffiths et al., 2018). Recent research has shown that psychedelic experiences have a reliable capacity for inducing long-term improvements in mental wellbeing (Haijen et al., 2018; Mans et al., 2021) and for the treatment of mood (Carhart-Harris et al., 2016a; Griffiths et al., 2016; Carhart-Harris et al., 2021) and addictive disorders (Zafar et al., 2023). Several lines of research have demonstrated that the intensity of acute subjective effects experienced following psychedelic intake are associated with beneficial psychological outcomes, with the greatest amount of evidence related to so-called mystical-type experiences characterized by a perception of blissful oneness (Haijen et al., 2018; Roseman et al., 2018; Weiss et al., 2024). The subjective profundity of the psychedelic mystical experience is such that it is often rated among the most meaningful and spiritually significant of an individual's life (Griffiths et al., 2006, 2008; Gukasyan et al., 2022). These reports have led to suggestions that psychedelics act to enhance the perception of meaning (Hartogsohn, 2018), and that this may be a core component of their therapeutic mechanism, particularly when combined with psychological support (Nayak and Johnson, 2021). However, the recently renewed period of psychedelic research has yet to properly assess the impact of psychedelics on meaning in life.

The definition of “meaning in life” has been subject to debate (Park, 2010; Martela and Steger, 2016; King and Hicks, 2021), but it has most frequently been linked to the concept of eudaimonia: a sense of fulfillment arising the actualisation of long-term goals (Steger and Frazier, 2005). Perhaps the best-known discussion on meaning is found in Viktor Frankl's seminal 1946 work Man's Search For Meaning, in which he detailed his own experience as a Holocaust survivor. Frankl posited that creating meaning was the primary drive behind human behavior, and that being able to hold meaning—even in extremely brutal and dehumanizing circumstances—served as a protective factor for mental and physical health. More contemporary evaluations of meaning in life have produced a three-dimensional model comprising (1) coherence, the degree to which individuals feel they can make sense of the world, (2) purpose, the commitment to long-term goals, and (3) significance, the extent to which people regard their lives as valuable (Martela and Steger, 2016; King and Hicks, 2021). Various conditions and events also serve to create and alter meaning over time. Ample research suggests that meaning is made when pre-existing beliefs are challenged, particularly through adverse life events (Park, 2010), while some research has specifically suggested that individuals create meaning to counteract anxiety surrounding death (Simon et al., 1998; Steger and Frazier, 2005). Regardless of its role, meaning in life—and closely related constructs like Purpose and the Japanese concept of Ikigai—have been repeatedly linked with both mental and physical health (King and Hicks, 2021; Wilkes et al., 2022). Higher ratings of meaning in life have been associated with increased subjective wellbeing (Zika and Chamberlain, 1987) and reduced levels of anxiety and depression (Debats, 1996), while a 2017 meta-analysis found small but significant positive correlations between meaning in life and objective measures of health (Czekierda et al., 2017). Conversely, over-commitment to searching for meaning in life has overall been associated with negative affect, including increased ratings of anxiety and depression (Steger et al., 2006). Altogether, meaning in life presents a target for long-term overall health that is yet distinct from other measures of psychological wellbeing (Steger et al., 2006); a target that could be particularly enhanced by psychedelics as compared to other pharmacological interventions (Hartogsohn, 2018).

The contemporary hypothesis that psychedelics enhance personal meaning follows an integration of recent psychological and neuroscientific inquiries. From a psychological perspective, the psychedelic state can present a challenging element, often associated with the perceived loss of one's sense of self, termed ego-dissolution (Barrett et al., 2016; Nour et al., 2016). However, many who undergo this type of experience still report it as beneficial, if they are able to integrate it into a life narrative (Carbonaro et al., 2016). This process parallels the research on meaning-making in response to adverse life situations (Park, 2010). Furthermore, the sheer intensity of the mystical-type experience compared to everyday consciousness could serve as a prominent memory around which meaning is created, as suggested by studies showing associations between mystical experience and lasting personality change (Nour et al., 2017; Kettner et al., 2019). The process of meaning-making may also be expedited by the emotional cartharsis of the psychedelic state, which can allow movement through difficult and previously unprocessed emotional states (Roseman et al., 2019), long-considered a key aspect of psychological healing (Greenberg, 2012). The rapid belief change provoked by psychedelics is explicated by a variety of neuroimaging studies, which point to a model of acutely enhanced neuronal flexibility. For example, fMRI studies on acute psychedelic effects have indicated increased global integration of the brain (Tagliazucchi et al., 2016), alongside specific disintegration of the default mode network (DMN), a brain network related to rumination and sense of self (Carhart-Harris et al., 2017; Gattuso et al., 2023). Both of these effects have been observed to correlate with the subjective experience of mystical experience and ego-dissolution (Carhart-Harris et al., 2017; Tagliazucchi et al., 2016). Meanwhile, EEG studies have reported increases in brain entropy in the psychedelic state (Timmermann et al., 2019; Mediano et al., 2024). These findings have led to unifying theories of psychedelic action where increased brain entropy relaxes high-level beliefs, providing an opportunity for reframing entrenched perspectives (Carhart-Harris et al., 2014; Carhart-Harris and Friston, 2019; Zeifman et al., 2025). While neuroimaging studies on meaning in life are limited, there is some evidence that changes in DMN functional connectivity are also involved (Waytz et al., 2015; Mwilambwe-Tshilobo et al., 2019). Thus, the acute state of psychedelic-induced neuronal and cognitive flexibility (Daws et al., 2022; Lyons et al., 2024) could be particularly beneficial for re-evaluation of meaning in life.

The aim of the present study was to investigate changes in meaning in life after a psychedelic experience. While some previous studies have indicated potential increases in ratings of meaning in life following psychedelic use (Mans et al., 2021; Timmermann et al., 2024; Erritzoe et al., 2024), as well as related changes including greater meaning in the world (Nayak et al., 2023), and purpose in life (Griffiths et al., 2016), these have lacked investigation of contextual factors that are especially influential to psychedelic outcomes (Carhart-Harris et al., 2018; Nayak et al., 2023). Therefore, we compiled and compared data from several studies that included naturalistic and controlled settings, as well as populations of healthy psychedelic-naive individuals, patients with clinical depression, and a large group of ceremony attendees. Meaning in life was measured using the Meaning in Life Questionnaire (MLQ), which comprises “presence” (MLQ-P) and “search” (MLQ-S) subscales (Steger et al., 2006). In line with the other positive effects of psychedelics, we formulated three hypotheses. H1: the presence of meaning in life will be increased following a psychedelic experience, while search for meaning will be attenuated; H2: changes in meaning in life will be correlated with changes in depression severity and overall wellbeing; and H3: positive changes in meaning in life will be correlated with acute qualities of the psychedelic experience including mystical-type experiences.

2 Methods

2.1 Psychometrics

To assess changes in outcome measures including meaning in life, we employed validated rating scales designed to measure underlying psychological traits. We also took this approach to assess qualities of the acute psychedelic state, using scales that probe experience states. Although the individual studies employed a range of measures, we mention below only those pertinent to the present analysis.

2.1.1 Meaning in life questionnaire

The MLQ was developed by Steger and colleagues in 2006 to assess perceived meaning in life (Steger et al., 2006). It comprises 10 items rated on a 7-point Likert scale, where 1 is “Absolutely Untrue” and 7 is “Absolutely True.” The 10-item form was validated across three studies, and contains a two factor structure to measure the presence of (MLQ-P) and search for (MLQ-S) meaning in life. The two factors are typically somewhat inversely correlated (r = −0.19), and each overlap with other wellbeing-related measures such as Life Satisfaction, Neuroticism, and Depression, where Presence is associated with positive wellbeing and Search with negative wellbeing. However, in comparison to previous measures of meaning in life such as the Purpose in Life Index and the Life Regard Index, the MLQ shows a reduced level of shared variance with these other well-being measures, as well as evidence of increased discriminant validity (Steger et al., 2006). Thus, the MLQ presents the current best rating scale to distinctly assess meaning in life as separate from similar, but related wellbeing constructs. The full questionnaire can be found at Supplementary Material Table S1.

2.1.2 Warwick-Edinburgh mental wellbeing scale

The WEMWBS was developed and validated by Tennant and colleagues in 2007 to assess general mental wellbeing (Tennant et al., 2007). It contains 14 items rated on a 5-point Likert scale where 1 is “none of the time” and 5 is “all of the time.” The items are directed at several aspects of mental wellbeing such as stress, clarity and social connection, but ultimately converge on a single unified factor of mental well-being. It has been used previously to assess changes in psychological health following psychedelic use (Haijen et al., 2018; Peill et al., 2022), including in major depression (Carhart-Harris et al., 2021) and in the case of negative responders to psychedelics (Marrocu et al., 2024). Here, this scale was employed to investigate the association between general mental wellbeing and meaning in life following psychedelic intake.

2.1.3 Beck depression inventory

The BDI was first published in 1961 by Beck and colleagues with the aim of standardizing the measurement of depressive symptomatology (Beck et al., 1961). Subsequent revisions (IA and II) have been developed to increase reliability and better align with diagnostic criteria (Beck et al., 1996). The scale, in the IA form, was employed as a secondary outcome measure in a trial of escitalopram against psilocybin for depression, although this measure showed greater differences between the treatment groups compared to the primary outcome measure (Carhart-Harris et al., 2021). The BDI-IA contains 21 items, each rated from 0 to 3 based on the severity of symptoms over the past two weeks; total scores range from 0 to 63, with higher scores indicating more severe depression (Beck et al., 1996).

2.1.4 Mystical experience questionnaire

Originally developed by Pahnke in the 1960s to measure the occurrence of acute mystical experiences occasioned by psilocybin, the MEQ has been more recently revised by Maclean and colleagues to include 30 items that separate into five distinct factors: Mystical, which assess feelings of unity and insight; Positive mood, which measures feelings of joy and euphoria; Transcendence of time/space, which assess feelings of dimensional distortions; and Ineffability, which captures the extent to which the experience cannot be described (Maclean et al., 2012). The scale has been subsequently validated in experimental studies with psilocybin (Barrett et al., 2015). Total summed scores range from 0 to 150, while scores for the sub-factors total 15 (Ineffability), 30 (Positive mood, Transcendence of time/space), and 75 (Mystical).

2.1.5 Ego-dissolution inventory

The EDI was developed and validated by Nour et al. (2016) to measure the perceived loss of ego during psychedelic experiences. It comprises 8 items rated on a visual analog scale from 0–100, where 0 is “No, not more than usually,” and 100 defined as “Yes, entirely or completely.” The items were found to target one single factor, which correlates strongly with the unitive mystical experience as measured via the MEQ. However, the scale also presents discriminant validity for perceptions of ego-inflation, which can occur during some types of mystical experience (Nour et al., 2016). Summed scores range from 0 to 800.

2.1.6 Emotional breakthrough inventory

The EBI was developed and validated by Roseman et al. in 2019 to measure the extent of emotional catharsis during psychedelic experiences (Roseman et al., 2019). It contains 6 items rated on a visual analog scale from 0–100, where 0 is “No, not more than usual” and 100 is “Yes, entirely or completely.” The 6 items converge on a single factor, which is related to but distinct from mystical experiences as assessed with the MEQ (Roseman et al., 2019). Subsequent use of the scale in survey and laboratory studies have demonstrated its value for predicting wellbeing outcomes (Peill et al., 2022), as well as a positive association with preparedness for a psychedelic experience (McAlpine et al., 2024). Total summed scores range from 0 to 600.

2.2 Data acquisition

To assess meaning in life across various contexts, data was acquired from three previous studies that differed in their sample characteristics, drug of use, and the setting of the psychedelic experience. Each of these samples are described in more detail below, and are summarized in Table 1.

Table 1

Table 1. Study design for the three samples analyzed in this study.

2.2.1 Ceremony study

The Ceremony Study was an online prospective study in which participants planning to attend a naturalistic ceremonial retreat completed questionnaires prior to and following the retreat, which involved one to three psychedelic ceremonies. Responses were collected two weeks prior to the retreat (baseline), and at one day, 2 weeks, 4 weeks, and 6 months post-ceremony. Outcome measures, the MLQ and WEMWBS, were collected at baseline, 4 weeks and 6 months. Acute experience measures including the MEQ, EDI, and EBI, were collected at one day post-experience(s); the maximum value of these measures was taken for analysis since the strongest subjective experience was predicted to have the greatest impact on outcome measures. The survey attracted 886 participants in total. Depending on the ceremony, participants either consumed psilocybin or the traditional South American brew ayahuasca, which contains the classic psychedelic dimethyltryptamine (DMT). Ceremonies were conducted in a group setting with a guide and a generally supportive environment. Primary results from this study with a smaller sample were published in Kettner et al. (2021), while the current sample was later published in Peill et al. (2022).

2.2.2 Insight

The Insight study was a laboratory study of the long-term effects of psilocybin on psychology and neurophysiology in healthy, psychedelic-naive participants. The participants completed two psilocybin dosing sessions separated by one month, with follow-ups at 2 weeks following each session. In the first session, participants received an inactive 1 mg placebo dose, while in the second session they received an active 25 mg dose; the subjects were blind to what dose they received. 28 participants completed the study in total, although MLQ scores were not acquired for all participants at all time points. The setting during the dosing sessions was therapeutic and psychologically supported by experienced guides. In the present study, we compared outcomes for the 1 mg and 25 mg doses: for the 1 mg inactive condition, we compared baseline scores to scores at 2 weeks after the first dose, while for the 25 mg active condition we compared scores at 4 weeks — just before the second dose—to scores at 6 weeks—2 weeks after the second dose. Primary results from this study been published in Lyons et al. (2024).

2.2.3 Psilodep

Psilodep was a comparative trial of the established SSRI drug escitalopram and psilocybin for the treatment of treatment-resistant major depressive disorder. The trial was a two-arm randomized controlled design, with 30 patients in the psilocybin group and 29 in the escitalopram group. Both groups participated in “daily dosing” as well as two “acute” treatment sessions separated by 3 weeks. The escitalopram group received a daily dose of 10 mg escitalopram that was doubled to 20 mg in the latter 3 weeks, while their acute doses of psilocybin were an inactive 1 mg placebo dose. The psilocybin group received a daily placebo capsule, while their acute doses of psilocybin were active 25 mg doses. Baseline outcome measures were acquired one day prior to the first acute session while follow-up responses were collected at 6 weeks. Acute experience measures were collected on the days of the acute sessions, with the maximum value from the two sessions being taken for analysis. Both groups received additional psychological support including an initial preparatory therapy session, supervision during and after the dosing, an integration session the day after the dosing, and a debriefing at the end of the study. The primary results of this study were published in Carhart-Harris et al. (2021), where it was found that psilocybin was at least as effective as escitalopram at reducing depressive symptoms.

2.3 Statistical analysis

All statistical analysis was carried out in R version 4.3.3 (R Core Team, 2024). The threshold for statistical significance was set at P < 0.05. For each sample, outcome measures were modeled with linear mixed effects models, which included fixed effects of time and drug condition, and random intercepts for participants. In the case of the Ceremony sample, only time was included as a fixed effect. Time was set with treatment contrasts, where baseline was the reference level, while drug condition was set with treatment contrasts in the case of a placebo condition (Insight) and effects contrasts in the case of an active comparison (Psilodep). Missing data was omitted pairwise during model fitting, such that participant data was only dropped for those groups from which it was missing. Quality of model fit was initially assessed through visual examination of residual and random effects distributions, and normality was tested using the Shapiro-Wilk test. All models conformed to assumptions. Model significance was assessed with F-tests for marginal analysis of deviance. Post-hoc contrasts were conducted via pairwise comparison of estimated marginal means, with Tukey's method for P-value adjustment. Effect sizes were calculated using Cohen's d for both the unadjusted empirical data as well as for the estimated marginal means; the latter is reported in tables. Associations between different outcome measures, as well as between acute experience measures and outcome measures, were assessed with Pearson correlations. Correlations were visualized with scatterplots fit with an OLS linear regression line. Comparison of correlations was performed using the Fisher z-test.

3 Results

3.1 Demographics

In the Ceremony study, 886 participants submitted data to the survey. Eight hundred and forty three completed the MLQ at baseline, although this number dropped to 399 at 4 weeks and 141 at the 6 month follow-up. Due to non-completion of the baseline assessment, demographic information was unavailable for 67 (7.6%) of the participants, so these are not included in the following statistics. 359 of the participants (40.5%) were female, 455 (51.4%) were male, and 5 (0.6%) reported other. The mean age was 44.4 +/– 12.6. Most participants were highly educated, with 693 (78.2%) having received a higher education. 743 (83.9%) of the participants were White, 12 (1.4%) were Black, 48 (5.4%) were Asian, 3 (0.3%) were American Indian or Alaska native, and 33 (3.7%) reported unknown or preferred not to say. While 330 (37.2%) participants had never used psychedelics previously, 489 (55.2%) had used them at least once in their life. Mental health status was mixed; while a majority of participants were clinically mentally healthy with 539 (60.8%) having no lifetime psychiatric diagnoses, 280 (30.6%) had at least one lifetime psychiatric diagnosis. Full demographic information can be found in Peill et al. (2022).

In the Insight study, 28 participants completed the MLQ following both 1 mg and 25 mg doses. Of these, 12 (42.9%) were female and 16 (57.1%) were male. Ages ranged from 28 to 59 years, with a mean of 40.6 +/– 8.7. The participants were mostly highly educated, with 16 (57.1%) having received a higher education. 24 (85.7%) were Caucasian, 1 (3.6%) was Black and 3 (10.7%) did not disclose their ethnicity. All participants had never previously used psychedelics. All participants were screened for good mental and physical health. Full demographic information can be found in Lyons et al. (2024).

In the Psilodep study, all 59 participants completed the MLQ after both dosing days. Of these, 20 (33.9%) were female and 39 (66.1%) were male. Ages ranged from 21 to 64 with a mean of 41.2 +/– 11.7. The majority of participants were highly educated with 45 (76.2%) having received a higher education. 52 (88.1%) were White. 43 (76.2%) had not used psilocybin previously, but no participants had previously used escitalopram. All patients had been diagosed with major depression prior to the study, and were also screened for moderate-to-severe depressive symptoms. For full demographic information, see Carhart-Harris et al. (2021). Tabulated demographic information for all samples can be retrieved in Supplementary Table S2.

3.2 Effects of psychedelics on the presence and search for meaning in life

To investigate the effects of psychedelics on the presence of and search for meaning in life, we compared scores on the MLQ-P and -S, assessed before and after a psychedelic experience, via linear mixed models across each of the three included studies: an online survey of attendees in naturalistic ceremonies (Ceremony), a laboratory study of psilocybin in healthy, psychedelic-naive participants (Insight), and a randomized clinical trial comparing psilocybin and escitalopram for depression (Psilodep).

3.2.1 Presence of meaning

In the Ceremony sample, mixed effects modeling indicated a highly significant effect of time on the presence of meaning in life (F_{2, 514} = 79.85, B_4weeks = 3.54 [2.96 − 4.11 95% CI], B_6months = 3.14 [2.25 − 4.03 95% CI], P < 0.001, n = 843), suggesting substantial differences from before to after the psychedelic experience. Tukey contrasts of estimated marginal means confirmed that MLQ-P scores were significantly increased from baseline (20.4 [±7.8SD]) to 4 weeks after the ceremomy experience (24.3 [±7.3SD], P < 0.001, Cohen's d = 0.51), with no subsequent decrease even at the 6 months endpoint (24.3 [±7.4SD], P < 0.001, Cohen's d = 0.51 vs baseline, Figure 1A). In the Insight study, mixed modeling revealed a significant interaction of time*condition (F_{1, 76} = 9.72, B_2weeks:25mg = 4.03 [1.46 − 6.06 95% CI], P = 0.003, n = 28). Contrasts of estimated marginal means confirmed significant effects from baseline MLQ-P scores (21.1 [+/−6.3 SD]) to 2 weeks (24.5 [±4.9SD]) for the 25 mg condition, which were similar in magnitude to that observed in the Ceremony study (P = 0.0012, Cohen's d = 0.61, Figure 1A). Opposingly, no significant change over time was observed for the control 1 mg condition (P = 0.966), and there was also a significant difference between the 1 mg and 25 mg conditions at the 2 week endpoint (P = 0.0037, Figure 1A). Compared to the Ceremony and Insight studies, MLQ-P scores in the Psilodep study were 39.7% and 41.7% lower, respectively, at baseline in the psilocybin group (12.3 [±5.4SD]). Similarly low scores were also seen in the escitalopram group (12.7 [5.6±SD]). A mixed model indicated a trend level interaction effect of time*condition (F_{1, 57} = 2.92, B_{6weeks:psilocybin} = 2.99 [−0.52 − 6.50 95% CI], P = 0.093, n = 59), reflective of marginally greater increases in MLQ-P scores at 6 weeks following psilocybin (19.6 [±8.7SD]), compared to escitalopram (16.9 [±6.9SD]). Contrasts of estimated marginal means found significant increases in MLQ-P scores from baseline to 6 weeks in both the escitalopram (P = 0.007, Cohen's d = 0.69) and the psilocybin groups (P < 0.001, Cohen's d = 1.02, Figure 1A). All pairwise contrasts of estimated marginal means for MLQ-P can be found in Table 2. These results indicate that psychedelic use reliably enhances presence of meaning in life across contexts with varying levels of psychological support, but also that non-psychedelic treatments like escitalopram therapy can be associated with similar enhancements in the context of moderate-to-severe depression.

Figure 1

Figure 1. Scores on the MLQ before and after psychedelic use in three different studies: Ceremony study (left), Insight (center), and Psilodep (right). In all plots, bar height indicates the group mean and error bars indicate standard error. The group mean is also indicated by the value directly above each bar. Lines between bars indicate statistically significant group differences, as found from Tukey contrasts of mixed model marginal means, with the P-values indicated above the lines. (A) MLQ-P scores before and after psychedelic use in each study. (B) MLQ-S scores before and after psychedelic use in each study.

Table 2

Table 2. Tukey contrasts of estimated marginal means (EMMs) from mixed effects models for MLQ-P scores.

3.2.2 Search for meaning

In the Ceremony sample, a mixed model revealed a significant effect of time on MLQ-S scores (F_{2, 514} = 12.54, B_4weeks = −0.94 [−1.39–0.49 95% CI], B_6months = −1.37 [−2.07–0.68 95% CI], P < 0.001, n = 843). This was reflected by a small yet significant decrease in MLQ-S scores from baseline (21.2 [± 5.3 SD]) to 4 weeks (20.3 [± 5.3 SD], P < 0.001, Cohen's d = −0.18), that was enhanced by 6 months (19.5 [± 5.63 SD], P < 0.001, Cohen's d = −0.33 vs. baseline, Figure 1B). See Table 3 for pairwise contrasts of MLQ-S estimated marginal means. In both the Insight and Psilodep samples, mixed models showed no significant interaction effects of time*condition on MLQ-S scores (Insight: F_{1, 76} = 0.16, B_2weeks:25mg = −0.44 [−2.67–1.78 95% CI], P = 0.692, n = 28; Psilodep: F_{1, 57} = 0.66, B_{6weeks:escitalopram} = 0.48 [−0.7–1.66 95% CI], P = 0.419, n = 59). There was also no significant main effect of time in either case (Insight: F_{1, 76} = 0.16, B_2weeks:25mg = −0.44 [−2.67–1.78 95% CI], P = 0.692, n = 28; Psilodep: F_{1, 57} = 0.66, B_{6weeks:psilocybin} = −0.48 [−0.70–1.66 95% CI], P = 0.419, n = 59). This result was reflective of very small decreases in MLQ-S scores over time in both studies. In Insight, the decrease in MLQ-S in the 25 mg condition from baseline (25.1 [± 5.5 SD]) to 2 weeks (25.0 [± 5.9 SD]) was very small (Cohen's d = −0.026, Figure 1B); similarly, in Psilodep, the decrease in the psilocybin group from baseline (26.8 [± 6.3 SD]) to 6 weeks (25.1 [± 7.5 SD]) was larger albeit still very small (Cohen's d = −0.18, Figure 1B). These results largely indicate that contrary to the effects on presence of meaning in life, psychedelic use may only produce very small decreases in the search for meaning in life, and the robustness of this effect varies with context. However, treatment with esCItalopram also did not decrease search for meaning in life in the context of moderate-to-severe depression, suggesting that this trait may be less amenable to pharmacological perturbation.

Table 3

Table 3. Tukey contrasts of estimated marginal means (EMMs) from a mixed effects model for MLQ-S scores in the Ceremony study.

3.3 Association of post-psychedelic changes in meaning in life with changes in wellbeing and depression severity

To investigate the relationship between psychedelic-induced changes in meaning in life and mental wellbeing, we examined the correlations between changes in MLQ scores and scores on the WEMWBS in the Ceremony and Insight studies. In previous results from both studies, psychedelic use was significantly associated with increased WEMWBS scores at the follow-ups compared to baseline (Kettner et al., 2021; Lyons et al., 2024). In the Ceremony sample, changes in MLQ-P scores were strongly positively correlated with changes in wellbeing at 4 weeks (r = 0.61, P < 0.001, n = 378,) and 6 months (r = 0.57, P < 0.001, n = 135, Figure 2). Conversely, there was a weak negative correlation between WEMWBS and MLQ-S score changes at 4 weeks (r = −0.27, P < 0.001, n = 378) and no correlation at 6 months (r = −0.06, n = 135, P = 0.485). A similar pattern was observed in the Insight study for the 25 mg condition, where changes in WEMWBS and MLQ-P scores at the 2 week endpoint were moderately positively correlated (r = 0.50, P = 0.012, n = 24, Figure 2), while a weak and non-significant negative correlation was observed for the MLQ-S subscale (r = −0.33, P = 0.112, n = 24). Conversely, in the 1 mg condition, no significant correlations were observed for MLQ-P changes (r = 0.33, P = 0.104, n = 25, Figure 2) or MLQ-S changes (r = 0.37, P = 0.067, n = 25) with changes in WEMWBS scores. These correlations suggest that while psychedelic-related increases in presence of meaning are clearly associated with improvements in wellbeing, decreases in the search for meaning are only slightly related to wellbeing enhancements, and this relationship may further weaken over time.

Figure 2

Figure 2. Correlations between changes in MLQ-P scores and changes in WEMWBS and BDI scores. Correlations with WEMWBS changes are reported for the Ceremony (left) and Insight samples (center), while correlations with BDI changes are shown for the Psilodep sample (right). In the Ceremony study, the correlations are shown for both the 4 week (top) and 6 month follow-ups (bottom). In Insight study, correlations are shown for the 25 mg (top) and 1 mg conditions (bottom). In the Psilodep trial, correlations are shown for the psilocybin (top) and escitalopram groups (bottom). In each plot, points represent individual bivariate measurements, while the red lines show an OLS linear regression with the standard error indicated by the shaded region. Pearson's r and the corresponding P-value are also shown.

To examine whether changes in meaning in life were also related to depression severity, we calculated correlations for changes in MLQ scores and changes in BDI scores at the 6 week endpoint of the Psilodep study. In the original trial results, both escitalopram and psilocybin produced reductions in BDI scores, although this was slightly larger in the psilocybin group (Carhart-Harris et al., 2021). We observed a strong negative correlation between changes in MLQ-P and BDI scores in the psilocybin group (r = −0.64, P < 0.001, n = 28), which was only moderate and trending in significance for the escitalopram group (r = −0.37, P = 0.051, n = 28, Figure 2). However, fischer's z-test to compare the two correlation coefficients found no significant difference (z = −1.31, P = 0.191, n = 28). For the MLQ-S, we found only very weak and non-significant correlations with changes in BDI scores for both the psilocybin (r = 0.09, P = 0.633, n = 28) and the escitalopram group (r = 0.05, P = 0.802, n = 28). As with wellbeing, these correlations suggest that while increases in the presence of meaning in life following psychedelic use is associated with reduced depression severity, decreases in search for meaning do not relate to improvements in depression symptoms. Furthermore, we cannot soundly conclude that enhancements of meaning occurring after psilocybin-assisted therapy are more strongly related to depression improvements over and above meaning enhancement occuring from escitalopram treatment.

3.4 Acute psychedelic effects predicting post-psychedelic changes in meaning in life

To determine if specific qualities of the psychedelic experience, including mystical-type experience, predicted subsequent changes in meaning in life, we examined correlations between acute experience measures and changes in MLQ scores. In the Ceremony sample, weak positive correlations were found between MLQ-P changes and EDI scores (r = 0.23, P < 0.001, n = 324), as well as more strongly with EBI scores (r = 0.31, P < 0.001, n = 324). Only weak positive correlations were observed between MLQ-P changes from baseline to 4 weeks and all subscales of the MEQ (Mystical: r = 0.24, P < 0.001; Positive mood: r = 0.26, P < 0.001; Time/space: r = 0.19, P < 0.001; Ineffability: r = 0.22, P < 0.001; n = 324 for all sub-scales, Figure 3B). Inverse relationships were observed for MLQ-S changes, which were negatively predicted most strongly by the EBI (r = −0.20, P < 0.001, n = 324), followed by the MEQ (Mystical: r = −0.16, P = 0.003; Positive mood: r = −0.16, P = 0.004; Time/space: r = −0.08, P = 0.153; Ineffability: r = −0.13, P = 0.023;n = 324 for all subscales) and EDI (r = −0.13, P = 0.017, Figure 3A). In the Insight sample, no statistically significant correlations between acute experience measures and changes in MLQ scores were found for the active 25 mg condition. All the correlations with MLQ-P scores were negatively signed, with the MEQ showing the strongest effect (Mystical: r = −0.31, P = 0.134; Positive mood: r = −0.24, P = 0.255; Time/space: r = −0.14, P = 0.507; Ineffability: r = −0.28, P = 0.171;n = 25 for all subscales, Figure 3B), followed by the EDI (r = −0.29, P = 0.161, n = 25) and the EBI (r = 0.02, P = 0.932, n = 25). For changes in MLQ-S scores, correlation coefficients were again negative, where the EDI showed the greatest effect (r = −0.29, P = 0.161, n = 25), followed by the EBI (r = −0.16, P = 0.439, n = 25, Figure 3A), and the MEQ (Mystical: r = −0.05, P = 0.811; Positive mood: r = −0.01, P = 0.975; Time/space: r = −0.23, P = 0.261; Ineffability: r = 0.00, P = 0.990; n = 25 for all subscales, Figure 3B). In the Psilodep sample, several weak-moderate positive correlations trending toward statistical significance were observed for changes in MLQ-P scores in the psilocybin group. The MEQ showed the strongest effect (Mystical: r = 0.37, P = 0.052; Positive mood: r = 0.14, P = 0.466; Time/space: r = 0.27, P = 0.170; Ineffability: r = 0.22, P = 0.265;n = 28 for all subscales, Figure 3B), followed closely by the EDI (r = 0.34, P = 0.075, n = 28), while the EBI showed only a small and non-significant effect (r = 0.13, P = 0.520, n = 28). A similar pattern of effect sizes was observed for correlations with the MLQ-S, however the signs were negative and showed no statistical significance. Of these, the MEQ showed the strongest effect (Mystical: r = −0.19, P = 0.338; Positive mood: r = −0.03, P = 0.898; Time/space: r = −0.12, P = 0.539; Ineffability: r = −0.01, P = 0.977; n = 28 for all subscales), followed by the EDI (r = −0.19, P = 0.338, n = 28) and then the EBI (r = −0.12, P = 0.557, n = 28, Figure 3A). These results provide some support for the hypothesis that mystical-type experiences positively predict greater enhancements of meaning in life. However, ego-dissolution and emotional breakthrough experiences may also provide similar benefits, and these effects may vary according to contextual factors.

Figure 3

Figure 3. Correlations between acute experience measures and changes in MLQ scores. (A) Correlation matrices for changes in MLQ-P and MLQ-S scores and 7 acute experience measures: EBI, EDI, the 4 subscales of the MEQ and total MEQ scores. One matrix is shown for each study: Ceremony (left), Insight (center) and Psilodep (right). In each matrix, red values indicate positive correlations and blue values indicate negative correlations. The statistical significance is indicated by stars above each correlation coefficient, where “.” = P <0.1 and “***” = P <0.001. (B) Linear correlations between total MEQ scores and changes in MLQ-P scores before and 4 weeks after psychedelic use in the Ceremony study (left), 2 weeks after psychedelic use in the 25 mg condition of Insight study (center) and 6 weeks after psilocybin use in the Psilodep trial (right). Points represent individual bivariate measurements, while the red lines show an OLS linear regression with the standard error indicated by the shaded region. Pearson's r and the corresponding P-value are also shown in each case.

4 Discussion

Meaning in life, although relatively under-researched (King and Hicks, 2021), presents a target for improving both mental and physical health that are independent from those conferred by other traits such as life satisfaction and wellbeing (Steger et al., 2006; McKnight and Kashdan, 2009; Hill and Turiano, 2014; Waytz et al., 2015). Due to their ability to produce rapidly transformative (Haijen et al., 2018; Mans et al., 2021) and spiritually-meaningful experiences (Griffiths et al., 2006, 2008; Gukasyan et al., 2022), psychedelic drugs like psilocybin have shown promise as potential enhancers of meaning (Hartogsohn, 2018; Griffiths et al., 2016; Nayak et al., 2023). The present study provided confirmatory evidence for this hypothesis, demonstrating that reported meaning in life increased from before to after psychedelic use across three distinct study samples, including naturalistic ceremonial psychedelic use (Ceremony), a laboratory study of healthy participants (Insight) and a clinical trial of psilocybin against escitalopram for patients with depression (Psilodep). Additionally, we found correlations between enhanced meaning in life and improvements in other outcomes, including wellbeing and depressive symptoms, as well as correlations with acute subjective psychedelic effects.

Significant increases in MLQ-P scores were observed following psychedelic use in all three samples, demonstrating that psychedelics can enhance meaning in life across a variety of environmental and psychological contexts. This is line with prior studies indicating increased MLQ-P ratings following psychedelic use (Mans et al., 2021; Timmermann et al., 2024), as well as with studies showing increased purpose in life (Griffiths et al., 2016) and reduced loss of meaning (Ross et al., 2021) in cancer patients, and increased meaning in the world (Nayak et al., 2023) after psychedelic use. The enhancement of meaning in life also parallels previous results involving changes in other constructs across similar contexts, including general wellbeing (Haijen et al., 2018; Kettner et al., 2021), connectedness (Watts et al., 2022), psychological insight (Peill et al., 2022) and depression severity (Carhart-Harris and Goodwin, 2017; Zeifman et al., 2020; Carhart-Harris et al., 2021). The magnitude of meaning in life enhancement was greatest in the Psilodep study, where presence of meaning at baseline was also lowest, thus potentially providing greater scope for improvements. This highlights psychedelics as potentially more effective for those with low levels of meaning in life and reiterates previous calls to tailour psychedelic therapy to those expressing certain psychological phenotypes (Zeifman et al., 2023). We also found that meaning in life was similarly enhanced for patients taking escitalopram, with no statistical significance between the groups. It is possible that psychosocial factors played a larger role in meaning enhancement than the type of drug, since both drug conditions saw a similar increase in meaning in life. However, a previous study specifically comparing these two groups found significantly greater MLQ score increases in the psilocybin group at 6 weeks, 3 months, and 6 months compared to the escitalopram group (Erritzoe et al., 2024). Therefore, given the numerically larger increase in the psilocybin group, it appears likely that the present analysis lacked the statistical power to reveal a group difference. It is worth noting that across studies, MLQ-P scores were lower than prior sample averages found in various populations including undergraduate students (Steger et al., 2006), US adults (Kobau et al., 2010), and even patients with life-threatening illness (Naghiyaee et al., 2020). This suggests that those who seek out a psychedelic experience—whether naturalistically, in research, or clinical trial settings—may have an attenuated sense of meaning at baseline. Therefore, the increases in presence of meaning observed here may be greater than those expected for the general population.

In regards to the search for meaning, we observed little impact of psychedelic intake on MLQ-S scores. Given the proposed relationship between heightened search for meaning and lower wellbeing (Steger et al., 2006, 2008; King and Hicks, 2021), we expected that MLQ-S scores would be decreased following psychedelic intake. However, statistically significant decreases were observed only in the Ceremony sample. While this may indicate that ceremonial settings can be a superior context for attenuating the desire to search for meaning, the observed effect sizes were still small and this result was more likely explained by the large sample size. Overall, it appears that psychedelics bear only a slight influence on the search for meaning. One explanation for this finding is that although psychedelics can increase the presence of meaning, this pharmacologically-assisted enhancement does not necessarily correlate to a reduced search for meaning as might occur with meaning-making through other life events. However, this result can also be reconciled with the generally positive effects of psychedelics (Haijen et al., 2018; Mans et al., 2021) by considering the complex nature of searching for meaning (King and Hicks, 2021). Provided it is not overly obsessive or inflexible, it appears reasonable that seeking out meaning could reflect an open and exploratory mindset with opportunities for learning and self-improvement. Indeed, while MLQ-S scores have been associated with anxiety and unhappiness, they have also been found to be related to curiosity, openness and absorption (Steger et al., 2008). Furthermore, some evidence suggests that day-to-day searches for meaning can predict its later acquisition within individuals (Newman et al., 2018). Considering the complex nature of the psychedelic experience, these findings could also be interpreted as indicating that psychedelic experiences can open as many existential questions as they answer. Although the extent of searching for meaning showed little change overall, it is possible that the context or methods of this search may be rendered more productive or fruitful by psychedelics. This hypothesis is supported by the observation of secondary decreases in MLQ-S scores at 6 months compared to 4 weeks in the Ceremony sample. Additional measures probing differences in individual approaches to the search for meaning in life and their relation to wellbeing would be needed to confirm this speculation (King and Hicks, 2021).

4.1 The impact of psychedelic-assisted meaning enhancement on mental health

Although the positive relationship between meaning in life and mental health has been detailed (King and Hicks, 2021), it was unknown if this would hold for meaning made following psychedelic use. Meaning made through pharmacological routes, which can acutely be disorganized and even delusional in nature (Carhart-Harris et al., 2016b), may be too illusory and fleeting to establish long-term associations with wellbeing (Hartogsohn, 2018). Therefore, we compared changes in MLQ scores to changes in other wellbeing measures, including general wellbeing via the WEMWBS and depression severity via the BDI. We found that in the Ceremony and Insight samples, changes in MLQ-P scores were robustly correlated with changes in WEMWBS scores, while in the Psilodep trial there was a strong negative relationship between meaning in life and depression severity. This shows that psychedelic-assisted changes in meaning are still strongly associated with other aspects of mental health across various contexts, and supports a mechanism for co-occurring enhancements of multiple facets of wellbeing following psychedelic use. It is worth noting that the correlations in each case were not very strong (0.5 < r < 0.64), indicating that meaning in life increases can occur in the absence of similarly sized increases in other wellbeing measures, which supports its status as a separate construct (Steger et al., 2006; King and Hicks, 2021).

A related observation from the longer timescale of the Ceremony study was that while MLQ-P scores remained at the same level from 4 weeks to 6 months post-ceremony, general wellbeing decayed over this same period. Accordingly, the strength of the correlation between MLQ-P and WEMWBS scores also slightly decayed over this period. On one hand, this could suggest that while meaning made through psychedelics is robust, its contribution to wellbeing is lessened over time. Alternatively, it might mean that psychedelic use enhances multiple facets of well-being, some of which decay over time, but some of which—including meaning in life—remain strengthened for longer. The latter hypothesis is supported by reports of the psychedelic experience as one of, or the, most meaningful of one's life, even after very long time periods (Griffiths et al., 2008; Johnson et al., 2017). This consistency reinforces the hypothesis that the psychedelic experience is embedded as a core memory in one's life narrative, from which meaning is consistently derived even if other aspects of mental health decline (Stoliker et al., 2022). In this way, psychedelic experiences could serve similar roles to meaningful religious experiences (Steger and Frazier, 2005), particularly in modern society where both religious commitment and sense of meaning are dwindling (Hartogsohn, 2018).

In the Psilodep sample, we saw some evidence for a stronger relationship between psychedelic-assisted meaning enhancement and mental health than for SSRI-assisted meaning enhancement. Although we did not observe a significant difference between the correlation strengths for the given sample size, the relationship for MLQ-P and BDI score changes in the escitalopram group was on the verge of statistical significance (P = 0.051) while for the psilocybin group it was highly significant (P < 0.001). It is important to note that all participants received substantial psychotherapy alongside both treatments, which likely contributed to the meaning enhancement observed in both groups (see below for a further discussion of context). Intriguingly however, this result points toward meaning enhancement from psychedelic therapy being more closely linked to mental health improvements than that from SSRI therapy. This could be related to the proposed differences in the mechanisms of psychedelic and SSRI therapies, namely that the former permits acutely intensive yet often beneficial emotional processing while the latter dampens emotions to improve resilience (Carhart-Harris and Goodwin, 2017; Hartogsohn, 2018). This mechanistic difference is likely related to differential outcomes for psychedelic use, such as a higher probablity of negative outcomes for those with emotional instability (Marrocu et al., 2024), as well as suggestions that psychedelic-assisted therapy works by reducing experiential avoidance (Zeifman et al., 2023). Under this mechanistic model, psychedelic therapy may produce more optimal wellbeing outcomes for those who lack a sense of meaning due to overly constrained patterns of cognition. However, due to the correlational nature of our analysis, we cannot conclude that meaning-making precedes wellbeing enhancement (or vice versa), nor can we rule out that the particular psychotherapeutic support received was key to any observed differences between treatment groups.

4.2 The role of context in psychedelic-assisted changes in meaning in life

A key strength of the present study was our integration of data from a selection of studies with a variety of environmental and psychological contexts, which was lacking in previous investigations of psychedelic-induced meaning change (Nayak et al., 2023), despite being key to the outcomes of psychedelic use (Carhart-Harris et al., 2018; Kettner et al., 2019; Marrocu et al., 2024). We can conclude that psychedelic use is associated with enhancements of meaning in life across these contexts, including naturalistic and controlled settings, and healthy or depressed psychological states.

Ample research has indicated that specific aspects of the acute psychedelic experience can shape subsequent outcomes. The most prominent of these acute states include the mystical-type experience (Haijen et al., 2018; Roseman et al., 2018; Weiss et al., 2024), the ego-dissolution experience (Barrett et al., 2016; Nour et al., 2016) and emotional breakthrough (Roseman et al., 2019; Watts et al., 2022; Weiss et al., 2024), which each predict more positive long-term outcomes and are also shaped by context (Carhart-Harris et al., 2018). To see if these were also related to psychedelic-assisted changes in meaning in life, we examined correlations between MEQ, EDI, and EBI acute experience scores with changes of MLQ-P and MLQ-S scores. Interestingly, while we observed some relationships between MEQ, EBI, and EDI scores and meaning in life, the results were not consistent across samples. In the Ceremony study, we observed the expected trends, whereby greater MEQ, EDI, and in particular EBI scores were associated with larger increases in MLQ-P scores and larger decreases in MLQ-S scores, which were similar in effect size to previous studies examining wellbeing (Haijen et al., 2018; Roseman et al., 2018). In the Psilodep study, the relationships were similar in magnitude but not quite statistically significant, possibly due to the reduced sample size. These results are in agreement with the prior studies and show that the quality of the acute psychedelic experience plays an important role in changes in meaning in life. However in the Insight study, no significant correlations were found, and the direction of the association was reversed for the MLQ-P. While the lack of significance could simply be due to the smaller sample size in this study, this disparity could also reflect contextual differences. For example, psychedelic therapy for depression is thought to benefit from a larger dose of 25 mg or more (Goodwin et al., 2022; Perez et al., 2023), which is concurrently more likely to induce mystical experiences (Ko et al., 2023). In contrast, healthy, psychedelic-naive participants may not benefit as strongly from a more intense experience, as they may be more likely to experience adverse effects such as anxiety due to their lack of experience. It is worth noting that across all the samples, the MEQ, EDI, and EBI scores were strongly positively correlated, suggesting that the scales were equally valid and properly interpreted in all contexts.

Individual differences in long-term responses to acute psychedelic effects may be related to their proposed mechanism of action. Recent neuropsychological models of psychedelic action suggest that psychedelics act to increase cognitive and neuronal flexibility (Daws et al., 2022; Singleton et al., 2022) to permit reframing of beliefs (Carhart-Harris and Friston, 2019; Zeifman et al., 2025), which can involve the discovery of new meaning (Fischman, 2019). It has been suggested that mystical experience is a subjective read-out of commonly observed acute psychedelic-related brain changes including DMN disintegration (Carhart-Harris et al., 2017; Gattuso et al., 2023), global integration (Tagliazucchi et al., 2016) and increased entropy (Carhart-Harris, 2018). Contrary to these acute effects, some evidence has shown greater within-DMN connectivity and DMN-limbic connectivity in the post-psychedelic phase (Carhart-Harris et al., 2017). Interestingly, the limited neuroimaging studies related to meaning in life bear some connection to these results. For example, increased resting state FC within the medial temporal lobe subsystem of the DMN has been found to predict a greater presence of meaning in life, but not scores on other related scales assessing life satisfaction (Waytz et al., 2015). A later study comparing meaning in life with loneliness further implicated the DMN, where higher scores on the Meaning and Purpose survey were associated with greater resting state FC within the DMN, stronger connectivity between default and limbic networks, as well as greater modularity within these two networks (Mwilambwe-Tshilobo et al., 2019). Following a model of psychedelic-induced belief change, a greater degree of mystical experience could therefore be more therapeutic for those with entrenched negative perspectives—particularly those regarding the self—that block the generation of meaning in life. Conversely, for healthy participants, a strong mystical experience may not be particularly helpful if they already have a positive sense of meaning in life and a good degree of cognitive flexibility. Nonetheless, the lack of an association between mystical experience and meaning in life observed here for the Insight sample does not undermine the overall enhancement in meaning in life still observed in this sample, nor the association of mystical experience with meaning enhancement observed in the other two samples.

In addition to the acute experience qualities, the environmental context in each study could play a role in enhancements of meaning in life. Importantly, we note that all the studies examined had some level of psychological support, which is a major factor for positive outcomes (Carhart-Harris et al., 2018), although this did vary between studies. In the Ceremony study, psychedelic experiences took place in groups and were led by a guide, allowing participants and the guide to support each other emotionally and foster a sense of community (Kettner et al., 2021). In the Psilodep trial, participants received substantial psychological therapy in addition to psilocybin treatment, and were also provided an emotionally supportive atmosphere during the experience itself (Carhart-Harris et al., 2021). Participants in the Insight study likely received the lowest level of support, although the experiences still took place in a therapeutic environment alongside supportive guides (Lyons, 2020; Spriggs et al., 2023). Therefore, from these results it is not possible to predict if similar enhancements of meaning in life would occur in other contexts lacking psychological support, such as naturalistic use in isolation. Furthermore, other aspects of the environmental context may have contributed to stronger increases in meaning in life. For example, the ritualistic and perhaps mystical setting of a psychedelic ceremony could have contributed to the further strengthening of the psychedelic experience as a powerful memory, while the clinical setting of the Psilodep trial could have pushed patients receiving psilocybin to further trust and believe the treatment would work. These contextual considerations are related to the suggestion that psychedelics may act as “placebo-enhancers,” whereby the profound subjective effects could produce an amplified placebo response, offering an explanation for their capacity to treat a wide variety of conditions (Hartogsohn, 2018).

Relatedly, participant characteristics and expectations in the different samples may have influenced subsequent changes in meaning in life. As previously mentioned, the Psilodep sample showed substantially lower MLQ-P scores at baseline compared to the other two studies. This may mean they had greater room for improvement, thus accounting for the large effect of psychedelic (and SSRI) therapy on MLQ scores. Additionally, their expectations about the outcome of the trial may have contributed to the improvement, particularly for the psilocybin group where patients could have been biased (Carhart-Harris et al., 2021; Szigeti and Heifets, 2024). However, a follow-up study found that while participants with higher suggestibility were more susceptible to psilocybin therapeutic response, levels of expectancy did not predict psilocybin response, despite it being greater for psilocybin than escitalopram (Szigeti et al., 2024). Likewise in the Ceremony study, participants seeking out a potentially life-changing experience could be more biased toward believing it would be positive; more specifically, participants seeking out a psychedelic ceremony of their own accord could have been more biased toward reporting favorable outcomes of psychedelic use. In both of these studies, a substantial proportion of the sample had previously used psychedelics, meaning they also had some prior expectations about how the drugs would affect them. However, the robust finding of enhanced meaning in life in the psychedelic-naive Insight sample improves confidence that psychedelics can improve meaning in life even when participants are unfamiliar with the subjective and long-term effects.

4.3 Limitations and future research

The nature of the samples used in this study presents several limitations. In addition to the potential confirmation bias and expectancy effects described in the section above, there may also be an effect of demand characteristics. Individuals signing up for a survey, study or clinical trial may be aware of the research surrounding psychedelics and the generally positive findings on wellbeing, and so are more likely to report positive effects. There was also a high level of attrition in the Ceremony study. In comparison to the 843 participants that completed the MLQ at baseline, only 141 (16.7%) completed it at the 6 month follow-up. It is possible that these remaining participants were more likely to report enhancements of meaning in life, while those who dropped out of the study may have had more difficult experiences. Although this cannot be ruled out in this study, previous investigations of attrition in observational studies of psychedelic use have found that baseline attitudes to psychedelics nor the intensity of acute challenging experiences predict participant dropout (Mans et al., 2021; Hübner et al., 2021); however, one study did find that younger age, low educational level and high conscientiousness were associated with increased attrition (Hübner et al., 2021), which is not ideal for study generalizability. Nonetheless, our finding of enhanced meaning in life across three separate samples increases the confidence in this result.

In addition to sample characteristics, our study is limited by use of strictly correlational analysis. While we observed some strong associations between meaning in life and other measures, we cannot infer the causal relationship between them. While it is tempting to say that enhanced meaning in life promotes wellbeing, it may well be that enhanced wellbeing facilitates the creation of meaning. Concurrently, while it is probably accurate to assume that mystical experiences promote meaning-making, we cannot rule out the possibility that individuals prone to make meaning are also prone to having mystical experiences when administered with psychedelics. Future studies should employ more structured experimental designs and mediation analysis to examine the directionality of the relationship between psychedelic-enhanced meaning in life and wellbeing, as has recently been done for psychological insight (Peill et al., 2022). A deeper understanding of the correlates and mechanism of psychedelic-enhanced meaning could also be bolstered with experience sampling and neuroimaging. Furthermore, our relative lack of analysis of both the psychological support and integration process (Bathje et al., 2022) of psychedelic-assisted therapy preclude a full understanding of how these drugs influence the meaning-making process. Future research should additionally focus on tightly controlling extra-pharmacological factors to delineate the contribution of the psychedelic experience itself to the perception of meaning (Hartogsohn, 2018).

4.4 Conclusions

Analysis of data from three studies has demonstrated that psychedelic use produces lasting enhancements in the perception of meaning in life. These enhancements were associated with positive changes in mental health, revealing meaning in life as another factor by which psychedelics can promote wellbeing. As with other psychological changes, contextual factors appeared to play an important role, with greater enhancement of meaning observed in psychedelic-assisted therapy for major depression. The extent of mystical experience, ego-dissolution, and emotional breakthrough were positively associated with meaning enhancement in two of the three studies, with the strength of the effects varying between contexts. Future studies should examine potential underlying mechanisms for the increased attribution of meaning, including the role of psychological support and the direction of causality between psychedelic-assisted meaning-making and general mental health.

Data availability statement

The data analyzed in this study is subject to the following licenses/restrictions: datasets can be made available for research purposes on request to the corresponding author of the primary studies. Requests to access these datasets should be directed to Hannes Kettner, aGFubmVzLmtldHRuZXJAdWNzZi5lZHU=.

Ethics statement

The studies involving humans were approved by the Imperial College London Joint Research Compliance and General Data Protection Regulation Offices, the Imperial College Research Ethics Committee, the Brent Research Ethics Committee, the U.K. Medicines and Healthcare Products Regulatory Agency, and the Health Research Authority. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants' legal guardians/next of kin in accordance with the national legislation and institutional requirements.

Author contributions

WR: Writing – original draft, Writing – review & editing, Data curation, Formal analysis, Methodology, Visualization. HK: Writing – review & editing, Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Supervision. LR: Writing – review & editing, Conceptualization, Data curation, Investigation, Project administration, Resources. MS: Writing – review & editing, Conceptualization, Data curation, Investigation, Project administration, Resources. TL: Writing – review & editing, Data curation, Investigation, Project administration, Resources. JP: Writing – review & editing, Data curation, Project administration. BG: Writing – review & editing, Data curation, Project administration, Resources. DE: Writing – review & editing, Data curation, Project administration, Resources. DN: Writing – review & editing, Project administration. RC-H: Writing – review & editing, Conceptualization, Project administration, Supervision.

Funding

The author(s) declare that financial support was received for the research and/or publication of this article. The Ceremony study was funded by the Ad Astra Chandaria Foundation and the funders of the Center for Psychedelic Research. The Insight study was funded by philanthropic donations to the Centre for Psychedelic Research, Imperial College London, founded in April 2019. The Psilodep psilocybin vs. escitalopram clinical trial was supported by a private donation from the Alexander Mosley Charitable Trust and by the founding partners of Imperial College London's Centre for Psychedelic Research.

Acknowledgments

We would like to acknowledge the other members of the Center for Psychedelic Research at Imperial College London, for their feedback and advice on the study analysis.

Conflict of interest

RC-H is a scientific advisor to Tryp Therapeutics, Osmind, Entheos Labs, Otsuka, and Mindstate and has received fees or shares from these companies. HK is a scientific advisor for Maya Health and Veterans Exploring Treatment Solutions (VETS). DE is a paid advisor for Aya Biosciences, Clerkenwell Health, Lophora Aps, and Mindstate. DN is Chief Research Officer for Awakn Life Sciences and, within the past 2 years, has been a scientific advisor to COMPASS Pathways, Neural therapeutics, Algernon pharmaceuticals and Alvarius.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declare that no Gen AI was used in the creation of this manuscript.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpsyg.2025.1580663/full#supplementary-material

References

Barrett, F. S., Bradstreet, M. P., Leoutsakos, J.-M. S., Johnson, M. W., and Griffiths, R. R. (2016). The challenging experience questionnaire: characterization of challenging experiences with psilocybin mushrooms. J. Psychopharmacol. 30, 1279–1295. doi: 10.1177/0269881116678781

PubMed Abstract | Crossref Full Text | Google Scholar

Barrett, F. S., Johnson, M. W., and Griffiths, R. R. (2015). Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. J. Psychopharmacol. 29, 1182–1190. doi: 10.1177/0269881115609019

PubMed Abstract | Crossref Full Text | Google Scholar

Bathje, G. J., Majeski, E., and Kudowor, M. (2022). Psychedelic integration: an analysis of the concept and its practice. Front. Psychol. 13:824077. doi: 10.3389/fpsyg.2022.824077

PubMed Abstract | Crossref Full Text | Google Scholar

Beck, A. T., Steer, R. A., Ball, R., and Ranieri, W. F. (1996). Comparison of beck depression inventories-IA and-II in psychiatric outpatients. J. Pers. Assess. 67, 588–597. doi: 10.1207/s15327752jpa6703_13

PubMed Abstract | Crossref Full Text | Google Scholar

Beck, A. T., Ward, C. H., Mendelson, M., Mock, J., and Erbaugh, J. (1961). An inventory for measuring depression. Arch. Gen. Psychiatry 4, 561–571. doi: 10.1001/archpsyc.1961.01710120031004

PubMed Abstract | Crossref Full Text | Google Scholar

Carbonaro, T. M., Bradstreet, M. P., Barrett, F. S., MacLean, K. A., Jesse, R., Johnson, M. W., et al. (2016). Survey study of challenging experiences after ingesting psilocybin mushrooms: acute and enduring positive and negative consequences. J. Psychopharmacol. 30, 1268–1278. doi: 10.1177/0269881116662634

PubMed Abstract | Crossref Full Text | Google Scholar

Carhart-Harris, R., Giribaldi, B., Watts, R., Baker-Jones, M., Murphy-Beiner, A., Murphy, R., et al. (2021). Trial of psilocybin versus escitalopram for depression. N. Engl. J. Med. 384, 1402–1411. doi: 10.1056/NEJMoa2032994

PubMed Abstract | Crossref Full Text | Google Scholar

Carhart-Harris, R. L. (2018). The entropic brain - revisited. Neuropharmacology 142, 167–178. doi: 10.1016/j.neuropharm.2018.03.010

PubMed Abstract | Crossref Full Text | Google Scholar

Carhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M. J., Erritzoe, D., Kaelen, M., et al. (2016a). Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiat. 3, 619–627. doi: 10.1016/S2215–0366(16)30065-7

Crossref Full Text | Google Scholar

Carhart-Harris, R. L., and Friston, K. J. (2019). REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacol. Rev. 71, 316–344. doi: 10.1124/pr.118.017160

PubMed Abstract | Crossref Full Text | Google Scholar

Carhart-Harris, R. L., and Goodwin, G. M. (2017). The therapeutic potential of psychedelic drugs: past, present, and future. Neuropsychopharmacology 42, 2105–2113. doi: 10.1038/npp.2017.84

PubMed Abstract | Crossref Full Text | Google Scholar

Carhart-Harris, R. L., Kaelen, M., Bolstridge, M., Williams, T. M., Williams, L. T., Underwood, R., et al. (2016b). The paradoxical psychological effects of lysergic acid diethylamide (LSD). Psychol. Med. 46, 1379–1390. doi: 10.1017/S0033291715002901

PubMed Abstract | Crossref Full Text | Google Scholar

Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., et al. (2014). The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Front. Hum. Neurosci. 8:20. doi: 10.3389/fnhum.2014.00020

PubMed Abstract | Crossref Full Text | Google Scholar

Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., et al. (2017). Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci. Rep. 7:13187. doi: 10.1038/s41598–017-13282-7

PubMed Abstract | Crossref Full Text | Google Scholar

Carhart-Harris, R. L., Roseman, L., Haijen, E., Erritzoe, D., Watts, R., Branchi, I., et al. (2018). Psychedelics and the essential importance of context. J. Psychopharmacol. 32, 725–731. doi: 10.1177/0269881118754710

PubMed Abstract | Crossref Full Text | Google Scholar

Czekierda, K., Banik, A., Park, C. L., and Luszczynska, A. (2017). Meaning in life and physical health: systematic review and meta-analysis. Health Psychol. Rev. 11, 387–418. doi: 10.1080/17437199.2017.1327325

PubMed Abstract | Crossref Full Text | Google Scholar

Daws, R. E., Timmermann, C., Giribaldi, B., Sexton, J. D., Wall, M. B., Erritzoe, D., et al. (2022). Increased global integration in the brain after psilocybin therapy for depression. Nat. Med. 28, 844–851. doi: 10.1038/s41591–022–01744-z

PubMed Abstract | Crossref Full Text | Google Scholar

Debats, D. L. (1996). Meaning in life: clinical relevance and predictive power. Br. J. Clin. Psychol. 35, 503–516. doi: 10.1111/j.2044-8260.1996.tb01207.x

PubMed Abstract | Crossref Full Text | Google Scholar

Erritzoe, D., Barba, T., Greenway, K. T., Murphy, R., Martell, J., Giribaldi, B., et al. (2024). Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial. eClinicalMedicine 76:102799. doi: 10.1016/j.eclinm.2024.102799

PubMed Abstract | Crossref Full Text | Google Scholar

Fischman, L. G. (2019). Seeing without self: discovering new meaning with psychedelic-assisted psychotherapy. Neuropsychoanalysis 21, 53–78. doi: 10.1080/15294145.2019.1689528

Crossref Full Text | Google Scholar

Gattuso, J. J., Perkins, D., Ruffell, S., Lawrence, A. J., Hoyer, D., Jacobson, L. H., et al. (2023). Default mode network modulation by psychedelics: a systematic review. Int. J. Neuropsychopharmacol. 26, 155–188. doi: 10.1093/ijnp/pyac074

PubMed Abstract | Crossref Full Text | Google Scholar

Goodwin, G. M., Aaronson, S. T., Alvarez, O., Arden, P. C., Baker, A., Bennett, J. C., et al. (2022). Single-dose psilocybin for a treatment-resistant episode of major depression. New Engl. J. Med. 387, 1637–1648. doi: 10.1056/NEJMoa2206443

PubMed Abstract | Crossref Full Text | Google Scholar

Greenberg, L. S. (2012). Emotions, the great captains of our lives: their role in the process of change in psychotherapy. Am. Psychol. 67, 697–707. doi: 10.1037/a0029858

PubMed Abstract | Crossref Full Text | Google Scholar

Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., et al. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J. Psychopharmacol. 30, 1181–1197. doi: 10.1177/0269881116675513

PubMed Abstract | Crossref Full Text | Google Scholar

Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., Jesse, R., MacLean, K. A., et al. (2018). Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors. J. Psychopharmacol. 32, 49–69. doi: 10.1177/0269881117731279

PubMed Abstract | Crossref Full Text | Google Scholar

Griffiths, R. R., Richards, W. A., Johnson, M. W., McCann, U. D., and Jesse, R. (2008). Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J. Psychopharmacol. 22, 621–632. doi: 10.1177/0269881108094300

PubMed Abstract | Crossref Full Text | Google Scholar

Griffiths, R. R., Richards, W. A., McCann, U., and Jesse, R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology 187, 268–283. doi: 10.1007/s00213–006–0457-5

PubMed Abstract | Crossref Full Text | Google Scholar

Gukasyan, N., Davis, A. K., Barrett, F. S., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., et al. (2022). Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: prospective 12-month follow-up. J. Psychopharmacol. 36, 151–158. doi: 10.1177/02698811211073759

PubMed Abstract | Crossref Full Text | Google Scholar

Haijen, E. C. H. M., Kaelen, M., Roseman, L., Timmermann, C., Kettner, H., Russ, S., et al. (2018). Predicting responses to psychedelics: a prospective study. Front. Pharmacol. 9:897. doi: 10.3389/fphar.2018.00897

PubMed Abstract | Crossref Full Text | Google Scholar

Hartogsohn, I. (2018). The meaning-enhancing properties of psychedelics and their mediator role in psychedelic therapy, spirituality, and creativity. Front. Neurosci. 12:129. doi: 10.3389/fnins.2018.00129

PubMed Abstract | Crossref Full Text | Google Scholar

Hill, P. L., and Turiano, N. A. (2014). Purpose in life as a predictor of mortality across adulthood. Psychol. Sci. 25, 1482–1486. doi: 10.1177/0956797614531799

PubMed Abstract | Crossref Full Text | Google Scholar

Hübner, S., Haijen, E., Kaelen, M., Carhart-Harris, R. L., and Kettner, H. (2021). Turn on, tune in, and drop out: predictors of attrition in a prospective observational cohort study on psychedelic use. J. Med. Internet Res. 23:e25973. doi: 10.2196/25973

PubMed Abstract | Crossref Full Text | Google Scholar

Johnson, M. W., Garcia-Romeu, A., and Griffiths, R. R. (2017). Long-term follow-up of psilocybin-facilitated smoking cessation. Am. J. Drug Alcohol Abuse 43, 55–60. doi: 10.3109/00952990.2016.1170135

PubMed Abstract | Crossref Full Text | Google Scholar

Kettner, H., Gandy, S., Haijen, E. C. H. M., and Carhart-Harris, R. L. (2019). From egoism to ecoism: psychedelics increase nature relatedness in a state-mediated and context-dependent manner. Int. J. Environ. Res. Public Health 16:5147. doi: 10.3390/ijerph16245147

PubMed Abstract | Crossref Full Text | Google Scholar

Kettner, H., Rosas, F. E., Timmermann, C., Kärtner, L., Carhart-Harris, R. L., and Roseman, L. (2021). Psychedelic communitas: intersubjective experience during psychedelic group sessions predicts enduring changes in psychological wellbeing and social connectedness. Front. Pharmacol. 12:623985. doi: 10.3389/fphar.2021.623985

PubMed Abstract | Crossref Full Text | Google Scholar

King, L. A., and Hicks, J. A. (2021). The science of meaning in life. Ann. Rev. Psychol. 72, 561–584. doi: 10.1146/annurev-psych–072420-122921

Crossref Full Text | Google Scholar

Ko, K., Carter, B., Cleare, A. J., and Rucker, J. J. (2023). Predicting the intensity of psychedelic-induced mystical and challenging experience in a healthy population: an exploratory post-hoc analysis. Neuropsychiatr. Dis. Treat. 19, 2105–2113. doi: 10.2147/NDT.S426193

PubMed Abstract | Crossref Full Text | Google Scholar

Kobau, R., Sniezek, J., Zack, M. M., Lucas, R. E., and Burns, A. (2010). Well-being assessment: an evaluation of well-being scales for public health and population estimates of well-being among US adults. Appl. Psychol. 2, 272–297. doi: 10.1111/j.1758–0854.2010.01035.x

Crossref Full Text | Google Scholar

Lyons, T. (2020). The acute and long-term effects of psilocybin in healthy volunteers. Presented at the Interdisciplinary Conference on Psychedelic Research, Amsterdam, Netherlands.

Google Scholar

Lyons, T., Spriggs, M., Kerkelä, L., Rosas, F. E., Roseman, L., Mediano, P., et al. (2024). Human brain changes after first psilocybin use. bioRxiv 2024.10.11.617955. doi: 10.1101/2024.10.11.617955

Crossref Full Text | Google Scholar

Maclean, K. A., Leoutsakos, J.-M. S., Johnson, M. W., and Griffiths, R. R. (2012). Factor analysis of the mystical experience questionnaire: a study of experiences occasioned by the hallucinogen psilocybin. J. Sci. Study Relig. 51, 721–737. doi: 10.1111/j.1468-5906.2012.01685.x

PubMed Abstract | Crossref Full Text | Google Scholar

Mans, K., Kettner, H., Erritzoe, D., Haijen, E. C. H. M., Kaelen, M., and Carhart-Harris, R. L. (2021). Sustained, multifaceted improvements in mental well-being following psychedelic experiences in a prospective opportunity sample. Front. Psychiatry 12:647909. doi: 10.3389/fpsyt.2021.647909

PubMed Abstract | Crossref Full Text | Google Scholar

Marrocu, A., Kettner, H., Weiss, B., Zeifman, R. J., Erritzoe, D., and Carhart-Harris, R. L. (2024). Psychiatric risks for worsened mental health after psychedelic use. J. Psychopharmacol. 38, 225–235. doi: 10.1177/02698811241232548

PubMed Abstract | Crossref Full Text | Google Scholar

Martela, F., and Steger, M. F. (2016). The three meanings of meaning in life: distinguishing coherence, purpose, and significance. J. Posit. Psychol. 11, 531–545. doi: 10.1080/17439760.2015.1137623

Crossref Full Text | Google Scholar

McAlpine, R. G., Blackburne, G., and Kamboj, S. K. (2024). Development and psychometric validation of a novel scale for measuring “psychedelic preparedness'. Sci. Rep. 14:3280. doi: 10.1038/s41598–024-53829-z

PubMed Abstract | Crossref Full Text | Google Scholar

McKnight, P. E., and Kashdan, T. B. (2009). Purpose in life as a system that creates and sustains health and well-being: an integrative, testable theory. Rev. General Psychol. 13, 242–251. doi: 10.1037/a0017152

Crossref Full Text | Google Scholar

Mediano, P. A. M., Rosas, F. E., Timmermann, C., Roseman, L., Nutt, D. J., Feilding, A., et al. (2024). Effects of external stimulation on psychedelic state neurodynamics. ACS Chem. Neurosci. 15, 462–471. doi: 10.1021/acschemneuro.3c00289

PubMed Abstract | Crossref Full Text | Google Scholar

Mwilambwe-Tshilobo, L., Ge, T., Chong, M., Ferguson, M. A., Misic, B., Burrow, A. L., et al. (2019). Loneliness and meaning in life are reflected in the intrinsic network architecture of the brain. Soc. Cogn. Affect. Neurosci. 14, 423–433. doi: 10.1093/scan/nsz021

PubMed Abstract | Crossref Full Text | Google Scholar

Naghiyaee, M., Bahmani, B., and Asgari, A. (2020). The psychometric properties of the meaning in life questionnaire (MLQ) in patients with life-threatening illnesses. Sci. World J. 2020:8361602. doi: 10.1155/2020/8361602

PubMed Abstract | Crossref Full Text | Google Scholar

Nayak, S., and Johnson, M. W. (2021). Psychedelics and psychotherapy. Pharmacopsychiatry 54, 167–175. doi: 10.1055/a-1312-7297

PubMed Abstract | Crossref Full Text | Google Scholar

Nayak, S. M., Singh, M., Yaden, D. B., and Griffiths, R. R. (2023). Belief changes associated with psychedelic use. J. Psychopharmacol. 37, 80–92. doi: 10.1177/02698811221131989

PubMed Abstract | Crossref Full Text | Google Scholar

Newman, D. B., Nezlek, J. B., and Thrash, T. M. (2018). The dynamics of searching for meaning and presence of meaning in daily life. J. Pers. 86, 368–379. doi: 10.1111/jopy.12321

PubMed Abstract | Crossref Full Text | Google Scholar

Nour, M. M., Evans, L., and Carhart-Harris, R. L. (2017). Psychedelics, personality and political perspectives. J. Psychoact. Drugs 49, 182–191. doi: 10.1080/02791072.2017.1312643

PubMed Abstract | Crossref Full Text | Google Scholar

Nour, M. M., Evans, L., Nutt, D., and Carhart-Harris, R. L. (2016). Ego-dissolution and psychedelics: validation of the ego-dissolution inventory (EDI). Front. Hum. Neurosci. 10:269. doi: 10.3389/fnhum.2016.00269

PubMed Abstract | Crossref Full Text | Google Scholar

Pahnke, W. N. (1969). Psychedelic drugs and mystical experience. Int. Psychiatry Clin. 5, 149–162.

Google Scholar

Pahnke, W. N., and Richards, W. A. (1966). Implications of LSD and experimental mysticism. J. Relig. Health 5, 175–208. doi: 10.1007/BF01532646

PubMed Abstract | Crossref Full Text | Google Scholar

Park, C. L. (2010). Making sense of the meaning literature: an integrative review of meaning making and its effects on adjustment to stressful life events. Psychol. Bull. 136, 257–301. doi: 10.1037/a0018301

PubMed Abstract | Crossref Full Text | Google Scholar

Peill, J. M., Trinci, K. E., Kettner, H., Mertens, L. J., Roseman, L., Timmermann, C., et al. (2022). Validation of the Psychological Insight Scale: a new scale to assess psychological insight following a psychedelic experience. J. Psychopharmacol. 36, 31–45. doi: 10.1177/02698811211066709

PubMed Abstract | Crossref Full Text | Google Scholar

Perez, N., Langlest, F., Mallet, L., De Pieri, M., Sentissi, O., Thorens, G., et al. (2023). Psilocybin-assisted therapy for depression: a systematic review and dose-response meta-analysis of human studies. Eur. Neuropsychopharmacol. 76, 61–76. doi: 10.1016/j.euroneuro.2023.07.011

PubMed Abstract | Crossref Full Text | Google Scholar

R Core Team (2024). R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing.

Google Scholar

Roseman, L., Haijen, E., Idialu-Ikato, K., Kaelen, M., Watts, R., and Carhart-Harris, R. (2019). Emotional breakthrough and psychedelics: validation of the Emotional Breakthrough Inventory. J. Psychopharmacol. 33, 1076–1087. doi: 10.1177/0269881119855974

PubMed Abstract | Crossref Full Text | Google Scholar

Roseman, L., Nutt, D. J., and Carhart-Harris, R. L. (2018). Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression. Front. Pharmacol. 8:974. doi: 10.3389/fphar.2017.00974

PubMed Abstract | Crossref Full Text | Google Scholar

Ross, S., Agin-Liebes, G., Lo, S., Zeifman, R. J., Ghazal, L., Benville, J., et al. (2021). Acute and sustained reductions in loss of meaning and suicidal ideation following psilocybin-assisted psychotherapy for psychiatric and existential distress in life-threatening cancer. ACS Pharmacol. Transl. Sci. 4, 553–562. doi: 10.1021/acsptsci.1c00020

PubMed Abstract | Crossref Full Text | Google Scholar

Simon, L., Arndt, J., Greenberg, J., Pyszczynski, T., and Solomon, S. (1998). Terror management and meaning: evidence that the opportunity to defend the worldview in response to mortality salience increases the meaningfulness of life in the mildly depressed. J. Pers. 66, 359–382. doi: 10.1111/1467-6494.00016

PubMed Abstract | Crossref Full Text | Google Scholar

Singleton, S. P., Luppi, A. I., Carhart-Harris, R. L., Cruzat, J., Roseman, L., Nutt, D. J., et al. (2022). Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape. Nat. Commun. 13:5812. doi: 10.1038/s41467–022-33578-1

Crossref Full Text | Google Scholar

Spriggs, M. J., Giribaldi, B., Lyons, T., Rosas, F. E., Kärtner, L. S., Buchborn, T., et al. (2023). Body mass index (BMI) does not predict responses to psilocybin. J. Psychopharmacol. 37, 107–116. doi: 10.1177/02698811221131994

PubMed Abstract | Crossref Full Text | Google Scholar

Steger, M. F., and Frazier, P. (2005). Meaning in life: one link in the chain from religiousness to well-being. J. Couns. Psychol. 52, 574–582. doi: 10.1037/0022–0167.52.4.574

Crossref Full Text | Google Scholar

Steger, M. F., Frazier, P., Oishi, S., and Kaler, M. (2006). The meaning in life questionnaire: assessing the presence of and search for meaning in life. J. Couns. Psychol. 53, 80–93. doi: 10.1037/0022–0167.53.1.80

Crossref Full Text | Google Scholar

Steger, M. F., Kashdan, T. B., Sullivan, B. A., and Lorentz, D. (2008). Understanding the search for meaning in life: personality, cognitive style, and the dynamic between seeking and experiencing meaning. J. Pers. 76, 199–228. doi: 10.1111/j.1467-6494.2007.00484.x

PubMed Abstract | Crossref Full Text | Google Scholar

Stoliker, D., Egan, G. F., Friston, K. J., and Razi, A. (2022). Neural mechanisms and psychology of psychedelic ego dissolution. Pharmacol. Rev. 74, 876–917. doi: 10.1124/pharmrev.121.000508

PubMed Abstract | Crossref Full Text | Google Scholar

Szigeti, B., and Heifets, B. D. (2024). Expectancy effects in psychedelic trials. Biol. Psychiat. 9, 512–521. doi: 10.1016/j.bpsc.2024.02.004

PubMed Abstract | Crossref Full Text | Google Scholar

Szigeti, B., Weiss, B., Rosas, F. E., Erritzoe, D., Nutt, D., and Carhart-Harris, R. (2024). Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression. Psychol. Med. 54, 1717–1724. doi: 10.1017/S0033291723003653

PubMed Abstract | Crossref Full Text | Google Scholar

Tagliazucchi, E., Roseman, L., Kaelen, M., Orban, C., Muthukumaraswamy, S. D., Murphy, K., et al. (2016). Increased global functional connectivity correlates with LSD-induced ego dissolution. Curr. Biol. 26, 1043–1050. doi: 10.1016/j.cub.2016.02.010

PubMed Abstract | Crossref Full Text | Google Scholar

Tennant, R., Hiller, L., Fishwick, R., Platt, S., Joseph, S., Weich, S., et al. (2007). The warwick-edinburgh mental well-being scale (WEMWBS): development and UK validation. Health Qual. Life Outc. 5:63. doi: 10.1186/1477-7525-5-63

PubMed Abstract | Crossref Full Text | Google Scholar

Timmermann, C., Roseman, L., Schartner, M., Milliere, R., Williams, L. T. J., Erritzoe, D., et al. (2019). Neural correlates of the DMT experience assessed with multivariate EEG. Sci. Rep. 9:16324. doi: 10.1038/s41598–019-51974-4

PubMed Abstract | Crossref Full Text | Google Scholar

Timmermann, C., Zeifman, R. J., Erritzoe, D., Nutt, D. J., and Carhart-Harris, R. L. (2024). Effects of DMT on mental health outcomes in healthy volunteers. Sci. Rep. 14:3097. doi: 10.1038/s41598–024-53363-y

Crossref Full Text | Google Scholar

Watts, R., Kettner, H., Geerts, D., Gandy, S., Kartner, L., Mertens, L., et al. (2022). The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world. Psychopharmacology 239, 3461–3483. doi: 10.1007/s00213–022–06187-5

PubMed Abstract | Crossref Full Text | Google Scholar

Waytz, A., Hershfield, H. E., and Tamir, D. I. (2015). Mental simulation and meaning in life. J. Pers. Soc. Psychol. 108, 336–355. doi: 10.1037/a0038322

PubMed Abstract | Crossref Full Text | Google Scholar

Weiss, B., Roseman, L., Giribaldi, B., Nutt, D. J., Carhart-Harris, R. L., and Erritzoe, D. (2024). Unique psychological mechanisms underlying psilocybin therapy versus escitalopram treatment in the treatment of major depressive disorder. Int. J. Mental Health Addict. 22, 806–841. doi: 10.1007/s11469–024–01253-9

Crossref Full Text | Google Scholar

Wilkes, J., Garip, G., Kotera, Y., and Fido, D. (2022). Can ikigai predict anxiety, depression, and well-being? Int. J. Mental Health Addict. 1, 1–13. doi: 10.1007/s11469–022–00764-7

PubMed Abstract | Crossref Full Text | Google Scholar

Zafar, R., Siegel, M., Harding, R., Barba, T., Agnorelli, C., Suseelan, S., et al. (2023). Psychedelic therapy in the treatment of addiction: the past, present and future. Front. Psychiatry 14:1183740. doi: 10.3389/fpsyt.2023.1183740

PubMed Abstract | Crossref Full Text | Google Scholar

Zeifman, R. J., Spriggs, M. J., Kettner, H., Lyons, T., Rosas, F. E., Mediano, P. A. M., et al. (2025). From relaxed beliefs under psychedelics (REBUS) to revised beliefs after psychedelics (REBAS). Sci. Rep. 15:3651. doi: 10.1038/s41598–023-28111-3

PubMed Abstract | Crossref Full Text | Google Scholar

Zeifman, R. J., Wagner, A. C., Monson, C. M., and Carhart-Harris, R. L. (2023). How does psilocybin therapy work? An exploration of experiential avoidance as a putative mechanism of change. J. Affect. Disord. 334, 100–112. doi: 10.1016/j.jad.2023.04.105

PubMed Abstract | Crossref Full Text | Google Scholar

Zeifman, R. J., Wagner, A. C., Watts, R., Kettner, H., Mertens, L. J., and Carhart-Harris, R. L. (2020). Post-psychedelic reductions in experiential avoidance are associated with decreases in depression severity and suicidal ideation. Front. Psychiatry 11:782. doi: 10.3389/fpsyt.2020.00782

PubMed Abstract | Crossref Full Text | Google Scholar

Zika, S., and Chamberlain, K. (1987). Relation of hassles and personality to subjective well-being. J. Pers. Soc. Psychol. 53, 155–162. doi: 10.1037/0022-3514.53.1.155

Crossref Full Text | Google Scholar