Anxiety DisordersHealthy VolunteersPsilocybin

Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees

In a naturalistic observational study of retreat attendees, ingestion of psilocybin-containing truffles in a supportive group setting produced rapid and sustained reductions in both state and trait anxiety up to one week post-ceremony. Reductions were predicted by the intensity of ego dissolution and accompanied by decreased neuroticism and increased mindful non-judging, supporting the feasibility and potential anxiolytic efficacy of group psychedelic sessions.

Authors

  • Kiraga, M. K.
  • Kuypers, K. P. C.
  • Mason, N. L.

Published

Frontiers in Psychiatry
individual Study

Abstract

Anxiety disorders are the most common type of psychiatric disorders among Western countries. Evidence-based treatment modalities including pharmacological and cognitive-behavioral therapy result in deficient treatment responses. Historical and recent research suggests psychedelic drugs may be efficacious in alleviating anxiety-related symptoms among healthy and clinical populations. The main aim of the present study was investigation of the effects of psilocybin-containing truffles, when taken in a supportive group setting, on ratings of state and trait anxiety across self-reported healthy volunteers. Attendees of psilocybin ceremonies were asked to complete a test battery at three separate occasions: before the ceremony (baseline), the morning after, and 1 week after the ceremony. The test battery included questionnaires assessing state and trait anxiety (State-Trait Anxiety Inventory), mindfulness capacities (Five Facet Mindfulness Questionnaire), and personality (Big Five Inventory). Additionally, the psychedelic experience was quantified with the Persisting Effects Questionnaire and the Ego Dissolution Inventory. The total amount of psilocybin-containing truffles consumed by each participant was recorded, and a sample of the truffles was analyzed to determine psilocin concentrations. Fifty-two attendees (males = 25; females = 25; others = 2) completed parts of the baseline assessment, 46 (males = 21; females = 24; others = 1) completed assessments the morning after the ceremony, and 23 (males = 10; females = 13) completed assessments at the 1-week follow-up. Average psilocin consumption across individuals was 27.1 mg. The morning after the ceremony, we observed medium reductions in anxiety measures (both state and trait) compared to baseline ( d ¯ = 6.4; p < 0.001 and d ¯ = 6; p = 0.014, respectively), which persisted over a 1-week period post-ceremony ( d ¯ = 6.7; p = 0.001 and d ¯ = 8.6; p = 0.004, respectively). At 1 week post-ceremony, the non-judging facet of the mindfulness scale was increased ( d ¯ = 1.5; p = 0.03), while the personality trait neuroticism decreased ( d ¯ = 5.2; p = 0.005), when compared to baseline. Additionally, we found ratings of ego dissolution (mean: 59.7, SD: 28.3) and changes in neuroticism to be the strongest predictors of reductions in state and trait anxiety, respectively. In sum, results suggest rapid and persisting (up to 1 week) anxiolytic effects in individuals with sub-clinical anxiety symptoms, which are related to the acute experience of ego dissolution, as well as lasting changes in trait neuroticism. Results also add support to the feasibility and potential efficacy of group sessions with psychedelics. To understand whether these effects extend to wider populations suffering from heightened anxiety, and the mechanisms involved, further experimental research is needed.

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Research Summary of 'Decreases in State and Trait Anxiety Post-psilocybin: A Naturalistic, Observational Study Among Retreat Attendees'

Introduction

Anxiety disorders are highly prevalent and burdensome worldwide, yet existing treatments yield only partial response rates (typically around 50–58% for pharmacological or cognitive-behavioural approaches). Historical and contemporary research has suggested that psychedelic substances—including psilocybin—can reduce anxiety symptoms in clinical and naturalistic samples, sometimes producing durable effects after a single administration. Two psychological candidates for mediating such effects are reductions in the personality trait neuroticism and enhancements in mindfulness capacities; additionally, the intensity or quality of the acute psychedelic experience (for example, ego dissolution) has been linked to longer‑term outcomes in prior work. Kiraga and colleagues designed a naturalistic observational study to examine whether ingestion of psilocybin-containing truffles in a supportive retreat context produces sub-acute and one‑week reductions in state and trait anxiety among volunteer attendees. The investigators also set out to test whether post‑retreat changes in mindfulness and neuroticism occur, and whether these psychological changes—or acute ratings of ego dissolution—predict reductions in state and trait anxiety. The study therefore aimed to characterise short-term anxiolytic effects and potential psychological mechanisms in a real‑world group setting.

Methods

Participants were adult volunteers attending legal psilocybin retreats in the Netherlands organised by the Psychedelic Society UK. Inclusion required being at least 18 years old and proficient in English; facilitators conducted pre-retreat intakes that screened out individuals with psychiatric disorders or on psychiatric medications and other medical risk factors. Ethics approval was obtained from Maastricht University's Ethics Review Committee (ERCPN-175_03_2017_A5), participation was voluntary, and the research team did not take part in retreat organisation or facilitation. Assessments occurred at three time points: baseline (the evening before ingestion), sub-acute (within 24 hours after ingestion; the morning after), and follow-up (7 days post-ingestion, completed online). Retreat participants consumed psilocybin‑containing truffles prepared as tea in a consistent retreat setting with facilitators, music and group support. The total truffle mass consumed per participant was recorded and a truffle sample was analysed by HPLC to determine psilocybin and psilocin content; the authors report an average psilocin consumption of 27.1 mg per participant after accounting for metabolic conversion. Measures included the State‑Trait Anxiety Inventory (STAI; state and trait scales), the Five Facet Mindfulness Questionnaire (FFMQ; five facets), and the Big Five Inventory (BFI; administered at baseline and follow-up). The Ego Dissolution Inventory (EDI) was completed at the sub‑acute session to quantify the acute experience, and a shortened Persisting Effects Questionnaire (PEQ) was administered at day 7 to assess lasting subjective effects. All instruments were in English. For statistical analysis the investigators fitted separate ordinary least squares multi‑linear regression models for each outcome with Session (baseline, sub‑acute, follow-up) as a categorical predictor and performed contrasts comparing baseline to sub‑acute and baseline to follow‑up. Descriptive statistics were computed for EDI and PEQ items. To examine multivariate associations among psychological predictors and anxiety outcomes, canonical correlation analyses were conducted using follow‑up non‑judge FFMQ scores, follow‑up neuroticism scores, and EDI scores as predictors and sub‑acute and follow‑up state and trait anxiety as criterion variables. The alpha significance threshold was p ≤ 0.05 and reported Cohen's d effect sizes for significant effects.

Results

Sample and dose: Fifty‑five volunteers provided informed consent (mean age 34.8, SD 8.9; 47% male, 47% female, 5% other). Most were European (80%) and many had prior psychedelic experience. Participants ingested a mean 34.2 g (SD 8.9) of truffles, and analysis of a 15 g sample (Psilocybe Hollandia) detected 1.9 mg psilocybin and 10.5 mg psilocin; using a conversion factor the authors report an average psilocin consumption of 27.1 mg. Attrition across assessments was notable: depending on the measure, completion counts were lower at the sub‑acute and follow‑up time points (for example, STAI completed by 46 at baseline, 42 at sub‑acute, and 22 at one week). Primary anxiety outcomes (STAI): Ordinary least squares regression revealed a significant main effect of Session on state anxiety (F2,107 = 14.10; p < 0.001). Compared with baseline, state anxiety was reduced by 6.4 points the morning after ingestion (p < 0.001; d = 0.77) and by 6.7 points at one week (p = 0.001; d = 0.87). Trait anxiety also showed a significant Session effect (F2,107 = 10.13; p = 0.002): trait anxiety was about 6.0 points lower the morning after (p = 0.014; d = 0.52) and 8.6 points lower at one week (p = 0.004; d = 0.77) on the 20–80 STAI scale. Mindfulness (FFMQ) and personality (BFI): FFMQ completion counts were 52 at baseline, 46 at sub‑acute and 23 at follow‑up. A significant Session effect emerged for the Non‑judge facet (F2,118 = 4.37; p = 0.04). The contrast versus baseline showed a non‑significant 0.5 increase the morning after (p = 0.39; d = 0.17) and a significant 1.5 point increase at one week (p = 0.03; d = 0.51). No significant Session effects were detected for the other FFMQ facets. BFI data (48 at baseline, 23 at follow‑up) showed significant Session effects for Neuroticism (F1,69 = 8.46; p = 0.005) and Agreeableness (F1,69 = 8.87; p = 0.004). At one week participants scored 5.2 points lower on neuroticism compared with baseline (d = 0.76) and 3.8 points higher on agreeableness (d = 0.78). No significant changes were reported for the remaining three traits. Acute and persisting subjective effects: The EDI was completed by 47 participants at sub‑acute; mean EDI = 59.7 (SD 28.3), range 3–100. The PEQ was completed by 20 participants at day 7. On the PEQ items assessing personal meaningfulness and spiritual significance, a substantial proportion rated the experience among the most meaningful or spiritually significant of their lives (for example, 10% rated it the single most meaningful experience, 50% among the 5 most meaningful). Psychological challenge and insight were also variably reported: 35% rated the experience as the single most psychologically insightful experience of their life. Hypothesis‑driven multivariate associations: Canonical correlation analysis used three predictor variables (follow‑up Non‑judge FFMQ, follow‑up neuroticism, and EDI) and four anxiety outcome variables (sub‑acute and follow‑up state and trait anxiety). Three canonical functions had squared canonical correlations (Rc2) of 0.891, 0.324 and 0.096. The full model was significant (F[12,18.81] = 2.81; p = 0.022), and the authors treated the first two functions as noteworthy. Function 1 suggested that reductions in neuroticism were the dominant predictor of changes in trait anxiety, explaining the largest share of covariance. Function 2 implicated higher EDI scores (stronger ego dissolution) as the dominant predictor of reductions in state anxiety.

Discussion

Kiraga and colleagues interpret the findings as evidence that a single administration of psilocybin in a supportive retreat context was associated with medium to large reductions in both state and trait anxiety that persisted for at least one week. The investigators also observed increases in the Non‑judge facet of mindfulness and decreases in trait neuroticism, and consider reductions in neuroticism and the intensity of ego dissolution to be the strongest correlates of reduced trait and state anxiety, respectively. The authors situate these results alongside historical and modern studies showing anxiolytic effects of psychedelics in clinical populations (including patients with life‑threatening illness and treatment‑resistant depression) while noting mixed outcomes in laboratory studies of healthy volunteers. They highlight that the present naturalistic findings are consistent with reports that psychedelic experiences can induce relatively rapid and durable changes in personality (notably neuroticism) and that ego dissolution or other intense acute experiences often correlate with longer‑term positive outcomes. Several limitations and uncertainties are acknowledged. Most importantly, the naturalistic observational design lacks experimental control—there was no placebo or comparator condition and retreat variables (setting, facilitator support, exact dosing and timing) were not controlled. Attrition reduced sample sizes at later time points and could introduce bias; the authors note that attrition predictors in web‑based psychedelic studies have paralleled those in other fields and that prior work did not find attrition to be driven by advocacy or negative experiences. The investigators also caution that it remains unclear whether intense subjective experiences such as ego dissolution are necessary causal mechanisms for longer‑term benefits or whether they are epiphenomena of underlying neurobiological actions, and that other psychological processes (for example, insight, catharsis or suggestibility) may be relevant. In terms of implications, the authors call for controlled experimental studies to disentangle pharmacological and extra‑pharmacological contributors (set and setting) to treatment outcomes, and propose that group‑based psychedelic interventions merit further study as a potentially more scalable and cost‑effective modality, subject to rigorous evaluation of feasibility, safety and efficacy.

Conclusion

The study concludes that ingestion of psilocybin in a supportive group retreat was associated with persisting reductions in state and trait anxiety and in trait neuroticism, together with increases in a mindfulness facet (non‑judgement) up to one week after the experience. The authors recommend systematic investigation of the role of set and setting and further research into group formats for psychedelic‑assisted interventions to inform optimisation and potential cost‑effectiveness of therapeutic programmes.

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RESULTS

Data analyses and visualizations were performed using the Seaborn (version 0.11.2), Statsmodels (version 0.12.2), Scipy (version 1.7.1), and Patsy (version 0.5.1) packages for Python 3.8. A separate multi-linear regression model using the ordinary least square method (OLS) was fit for each outcome variable. The model included Session encoded as a dummy independent variable of three levels: baseline, the sub-acute and follow-up sessions. Subsequently, separate contrasts were performed between baseline and sub-acute as well as baseline and follow-up sessions. Quantification of the acute experience was done by analyzing the results of EDI. Descriptive statistics (mean, standard deviation, range of scores) were calculated for the ratings of ego dissolution, together with a visual representation of kernel density estimation. To quantify the persisting functional outcomes of the experience, main outcome measures and additional questions of the PEQ were aggregated and reported in a tabular form. Additionally, we sought to examine previously reported associations between anxiety and personalityas well as between anxiety and mindfulness capacities. Given that ratings of ego dissolution have been shown to correlate with persisting effects after a psychedelic experience in both clinical and naturalistic studies), we tested for the possible associations between EDI scores and changes in anxiety. Canonical correlationswere conducted to evaluate the association between psilocybin-induced changes in (i) self-rated mindfulness capacities and neuroticism, (ii) ratings of ego dissolution, and (iii) state and trait anxiety. Variables were separated into two sets; set 1 included the psychological processes (i) and acute ratings of ego dissolution (ii) as predictors, and set 2 included the anxiety variables as criterion (iii). Canonical correlations were chosen as this approach assesses the relationship between two multivariate data sets, allowing investigation of variables that may have multiple causes and effects, while also reducing the potential of type 1 error. For all statistical analyses, the alpha criterion level of statistical significance was set at p ≤ 0.05 and Cohen`s effect (d) size was reported in case of significant results to demonstrate the effect's magnitude with 0.2-0.5 considered as small, 0.5-0.8 as a medium, and > 0.8 as large effect size.

CONCLUSION

The impact of anxiety disorders on people's lives and the treatment challenges are well-known within the field of mental health. The current study investigated the effects of a single administration of psilocybin on ratings of state and trait anxiety across retreat attendees, when taken in a supportive naturalistic setting. We further explored hypothesized psychological processes which may predict reductions in anxiety. Compared to baseline measures, we observed medium to large reductions in state anxiety ratings, and medium decreases in trait anxiety ratings, which persisted over a one week period post the ingestion of psilocybin. Additionally, we found enhancements in self-rated mindfulness capacities and alterations in personality traits at one week post ceremony. Regarding the post-retreat changes in anxiety, analyses showed that ratings of neuroticism and ego dissolution were the most strongly correlated with reductions in trait and state anxiety, respectively. The present study's findings are in line with results from historical (clinical) studies, which suggest reductions of anxiety symptoms after a combination of psychedelic drug administration and psychological therapy. From this work, four paradigms (and success rates) emerged in which psychedelic psychotherapy was used: 1. a single LSD session, provided after an intensive psychoanalytic session (56%); 2. repeated LSD sessions used in combination with individual psychotherapy (56%); 3. combination of repeated LSD sessions with individual psychotherapy completed by additional group therapy (62.5%); 4. sessions with psychotomimetics only applied in the course of group therapy (40%)). Similarly, recent clinical studies have found reductions of anxiety in patients with life-threatening illness) and comorbid treatment-resistant depression. Trials with healthy volunteers in the laboratory, however, have shown mixed results. Whereas one study showed reductions in state anxiety one week post administration, and reductions in trait anxiety one month post-administration, of a high dose of psilocybin (25 mg/70 kg), another study found no changes in trait anxiety one and 12 months after a high dose of LSD (200 ug). Finally, previous naturalistic work with individuals reporting heterogenous mental health status also found reductions in anxiety after participation in a 5-MeO-DMT ceremony. That said, a more recent placebo-controlled naturalistic study found that state anxiety ratings decreased 24 hours after volunteers ingested both the placebo and the psychedelic substance, ayahuasca. Taken together, the majority of modern studies present some evidence for psychedelic-induced reductions in anxiety symptoms across diverse populations and study designs. Studies suggest that not only the momentary anxiety estimates (state anxiety), but also the more stable personality-inherent features of anxiety proneness (trait anxiety) showed significant decreases. However, given some of the confounding findings), future research is needed to further explore the role of extra pharmacological factors (e.g., setting, dose, design) on the psilocybin-anxiety interaction. In line with previous studies, we detected long-term decreases in trait neuroticism, which has been shown to be strongly associated with the acuity and comorbidity levels of a range of mental disorders. Interestingly, levels of neuroticism have been found to correlate positively with frontolimbic serotonin 5-HT2A receptor binding, the latter being the main target of psychedelic drugs, suggesting direct 5-HT2A agonism may be the biological basis by which these substances alter neuroticism. Findings from the current and previous studies suggest that a psychedelic-assisted intervention can reduce levels of neuroticism, which are related to reductions in anxiety ratings in our study, and could be related to reductions of symptoms of comorbid conditions such as depression or post-traumatic stress disorder as seen in other studies. We also found post-retreat increases in trait agreeableness, which is in line with a previous naturalistic work done by. Other studies have shown either no changes in agreeableness post-psilocybin experience in depressed patientsor higher agreeableness scores among psychedelics users when compared to the general population. While the psychedelics' effects on neuroticism are more robust and more frequently reported, the emerging effects on agreeableness are novel and their relevance to therapeutic outcomes in patient populations has yet to be determined. Lastly, the present study aimed to further explore hypothesis-driven correlational relationships between changes in mindfulness and neuroticism and changes in anxiety. Although there was an increase in mindfulness capacities following intake of psilocybin, there were no strong associations between changes in mindfulness capacities and anxiety ratings. In regards to neuroticism, in line with theoretical conceptualizations of neuroticism and trait anxiety as stable, personality-dependent dispositions, we found that sub-acute and long-term reductions in trait anxiety were most strongly correlated with reductions in neuroticism. Namely, change scores in neuroticism and trait anxiety shared about 89% of the variance variability, pointing out a strong interdependency between the two variables. Additionally, we also found that the strongest correlator of sub-acute and long-term changes in state anxiety were ratings of ego dissolution, sharing about 32% of the variance. Specifically, the higher the rating of ego dissolution during the acute experience, the larger the decrease in state anxiety scores both 24 hours and one week after the experience. A recent review of twenty studies assessing the clinical response to psychedelics in patients with a range of psychological disorders concluded that the main predictive factor of a response to a psychedelic is the intensity of the acute psychedelic experience. That said, it has yet to be systematically assessed whether such a "peak" experience is necessary for long-term outcomes, or whether the subjective experiences elicited by psychedelic substances are merely epiphenomena of the underlying neurobiological mechanisms, the latter which are conveying any beneficial effects. Additionally, it is possible that other psychological components play important roles in mediating long-term outcomes of psychedelic experience, for instance insight/breakthrough or catharsis, suggestibility, and reliving of trauma have been suggested as important factors determining the psychedelic experience. Therefore, we should remain cautious when developing and interpreting specific theoretical frameworks of psychedelics' (psychological) mechanisms of action and focus future efforts on testing these frameworks in the context of experimental studies. The objectives were tested using a naturalistic, observational design, with attendees of psilocybin ceremonies. Although, this sort of setting has high rates of ecological validity, as it closely resembles a typical environment associated with psychedelic usage, it also comes with a range of confounding variables. In a naturalistic setting there is no control over the ceremonial setting and substance administration. To have some indication of the amount of truffles individuals took, we asked for a sample that was analyzed afterward and we asked how much truffles participants consumed. This allows comparisons between findings of our study and that of controlled studies. Another point is that longitudinal studies traditionally come with high dropout rates); our study was not different in that sense. The concern of such dropouts is that they could create problematic biases in the data, with for example only those individuals experiencing benefits from the experience being motivated to continue responding to the questions. A recent study investigating potential determinants of study attrition in web-based prospective studies on psychedelic use identified that baseline predictors of attrition (i.e., age, educational levels, and personality traits) were consistent with those reported in longitudinal studies in other scientific disciplines, suggesting their transdisciplinary relevance. Moreover, they did not find an association between attrition and psychedelic advocacy or negative drug experiences, advocating against the concerns about problematic biases in these and related data.

Study Details

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