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

This naturalistic study (n=52) assessed the effects psilocybin has on measures of state and trait anxiety among retreat participants with subclinical levels of anxiety. Average psilocin consumption across individuals was 27.1 mg. The morning after the ceremony, medium reductions in both state and trait anxiety were observed and these reductions persisted for 1-week. Higher ratings of ego dissolution and changes in neuroticism were the strongest predictors of these reductions.

Abstract

“Anxiety disorders are the most common type of psychiatric disorders among Western countries. Evidence-based treatment modalities including pharmacological and cognitive-behavioural 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 an 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¯d¯ = 6.4; p < 0.001 and d¯d¯ = 6; p = 0.014, respectively), which persisted over a 1-week period post-ceremony (d¯d¯ = 6.7; p = 0.001 and d¯d¯ = 8.6; p = 0.004, respectively). At 1 week post-ceremony, the non-judging facet of the mindfulness scale was increased (d¯d¯ = 1.5; p = 0.03), while the personality trait neuroticism decreased (d¯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.”

Authors: Maggie K. Kiraga, Kim P. C. Kuypers, Malin V. Uthaug, Johannes G. Ramaekers & Natasha L. Mason

Summary

Manuscript details

Psychedelic drugs may be efficacious in alleviating anxiety-related symptoms among healthy and clinical populations. In the present study, 52 participants consumed 27.1 mg of psilocybin-containing truffles and completed three separate assessments: baseline, morning after ceremony, and one week after ceremony. We observed medium to large reductions in anxiety measures in psilocybin retreat attendees, which persisted over a one-week period post-ceremony. The strongest predictors of reductions in trait and state anxiety were neuroticism and ratings of ego dissolution.

Anxiety disorders are the most common psychiatric disorders, and current treatments only provide partial success rates. Additionally, the exact rate of treatment response also varies per anxiety disorder, and patients with comorbid anxiety and depression tend to prematurely terminate treatment more frequently than patients with a single diagnosis. Studies combining administration of a psychedelic drug and psychological therapy have found significant improvements in anxiety-related symptomatology. Recently, there has been a resurgence of interest regarding the therapeutic potential of these substances in treating an array of different mental health disorders.

Psychedelics have been shown to reduce anxiety symptoms in trials and in naturalistic samples with heterogeneous mental health status. The persisting effect of psychedelics on feelings of anxiety has been mixed, with some studies reporting reductions and others not. The questionable rigidity of the earlier studies warrants further investigation. If psychedelic substances do reduce anxiety, it is of interest to understand what psychological processes may be at play. The personality trait neuroticism has been found to be a core vulnerability factor common to anxiety and mood disorders. Ingestion of psychedelic drugs can induce rapid and persisting changes in personality traits, including reductions in neuroticism, which could explain the persistent changes in anxiety levels observed after ingestion.

Psychedelics have been repeatedly found to enhance mindfulness capacities, which include being able to notice internal feelings, thoughts, and external simulation, label feelings, thoughts and experience with words, attend to what is happening in the present moment, and take a non-evaluative stance toward internal thoughts and feelings. Individuals suffering from anxiety disorders typically lack or have lower levels of mindfulness capacities. Mindfulness-based stress reduction training can be an effective form of treatment for people with anxiety disorders. When taking conventional anxiolytics, the treatment duration varies, but might extend over months. However, psychedelics can have lasting effects up to 12 months after a single dose administration.

Studies have found that psychedelic-induced mystical-type experiences and ego dissolution correlate with long-term (positive) outcomes. Thus, we assessed whether we could predict persisting changes in anxiety based on acute ratings of ego dissolution. In sum, anxiety disorders evoke a notable impact on people’s lives, yet the existing treatment options are of limited success. The present study aimed to assess the sub-acute effects of psilocybin on state and trait anxiety in retreat attendees. We hypothesized that psilocybin would induce reductions in anxiety and neuroticism, whereas mindfulness capacities would be enhanced. We further hypothesized that positive correlations between psychedelic-induced changes in anxiety and ego dissolution would be observed.

Participants were volunteers attending legal psilocybin retreats in the Netherlands, who were assessed 3 times: at baseline, within 24 hours after psilocybin ingestion, and 7 days after psilocybin ingestion. A sample of the truffles taken by each participant was taken to determine the concentrations of alkaloids afterwards.

Psilocybin retreats were held in a large house set in nature, hosted by at least two or more experienced psilocybin 9 facilitators. Participants received psilocybin-containing truffles around noon, in a tea form, and had a closing group meeting the next morning. Participants ingested psilocybin truffles in a tea form, guided by the facilitators. The subjective alterations began 20 – 40 minutes following administration, peaked around 60 – 90 minutes, and subside by six hours post-intake.

The amount of psilocybin truffles taken by each participant was recorded, and a sample of the truffles was taken to determine concentrations of psilocybin and its metabolite, psilocin. Six questionnaires were administered, including the State-Trait Anxiety Inventory, the Five Facet Mindfulness Questionnaire, the Big Five Inventory, and the Ego Dissolution Inventory. The State-Trait Anxiety Inventory (STAI) is a 40-item rating scale with a 4-point response format that is scored into two sub-scales (state anxiety and trait anxiety). It has an internal consistency coefficient of .86 to .95 and test-retest reliability coefficients of .65 to .75. The Five Facet Mindfulness Questionnaire measures five different factors: observing external and internal experiences, describing the experiences, acting with awareness, non-judging the experiences, and nonreacting to the experiences. It has shown adequate psychometric properties in both non-clinical and clinical samples.

The Big Five Inventory (BFI) is a 44-item scale that measures extraversion, agreeableness, conscientiousness, neuroticism and openness. The Persisting Effects Questionnaire (PEQ) is a 90-item scale that measures attitudes, moods, behavior, and spiritual experience.

26 participants completed a questionnaire that included questions about attitudes toward self, mood changes, relationships, and behavioral changes. The scores were calculated and a mean (SE) was calculated for each category. The Ego Dissolution Inventory (EDI) is an eight-item self-report scale that assesses the participant’s experience of ego dissolution during the psilocybin ceremony. A higher total score indicates a stronger experience of ego dissolution. Data analyses were performed using the Seaborn, Statsmodels, Scipy, and Patsy packages for Python 3.8. A separate multi-linear regression model using the ordinary least square method was fit for each outcome variable.

Quantification of the acute experience was done by analyzing the results of EDI, and persisting functional outcomes were measured using the PEQ. We also tested for associations between EDI scores and changes in anxiety. Canonical correlations were used to evaluate the relationship between psilocybin-induced changes in self-rated mindfulness capacities and neuroticism, ratings of ego dissolution, and state and trait anxiety. For all statistical analyses, the alpha criterion level was set at p 0.05, and Cohen’s effect size was reported.

Fifty-five volunteers agreed to participate in the study, of whom 47% identified themselves as males, 47% as females, and 5% reported identification with other gender categories. The mean age of the entire group was 34.8 years, and the majority had experience with cannabis. Psilocybin was ingested by participants in a ceremony, and the STAI was completed by 46 participants at baseline, 42 participants at the morning after the ceremony, and 22 participants at one week after the ceremony.

15 regression revealed that participants’ state anxiety was significantly lower the morning after the psilocybin ceremony, and their trait anxiety was significantly lower one week after the ceremony. The Five Facet Mindfulness Questionnaire (FFMQ), the Big Five Inventory (BFI), and the Persisting Effects Questionnaire (PEQ) were completed by 52, 46, and 23 participants, respectively. The OLS multi-linear regression revealed a significant main effect of Session on the Non-judge dimension of the FFMQ.

Two participants rated the experience as the single most meaningful experience of their lives, 10 rated it as among the 5 most meaningful experiences of their lives, and one rated it as once a month. Three participants rated their experience as the most spiritually significant of their lives, whereas eight participants rated it as among the 5 and 10 most spiritual experiences of their lives. 7 out of 10 people said the experience was the single most psychologically challenging and insightful experience of their life, 6 out of 10 people said it was among the 5 most psychologically challenging and insightful experiences of their life, and 1 out of 10 people said it was no different from every psychologically insightful experience.

47 participants completed the Ego Dissolution Inventory the morning after the ceremony, with ratings varying between 3 and 100. A canonical correlation analysis was conducted using three psychological variables to predict four anxiety outcome measures. The results indicated that the dominant contributors were sub-acute and long-term changes in trait anxiety, whereas the dominant predictor was the change in neuroticism, and the secondary predictor was changes in non-judgement.

A single administration of psilocybin in a supportive naturalistic setting reduced anxiety ratings in retreat attendees. Additionally, mindfulness capacities and personality traits were enhanced, and neuroticism and ego dissolution were most strongly correlated with reduced anxiety. Results from historical studies suggest that psychedelic drug administration and psychological therapy reduce anxiety symptoms. Four paradigms were identified, including single LSD session, repeated LSD sessions, individual psychotherapy, and group therapy. Recent clinical studies have found that psilocybin and LSD can reduce anxiety in patients with life-threatening illness and comorbid treatment-resistant depression. However, trials with healthy volunteers have shown mixed results.

A majority of modern studies have found some evidence for psychedelic-induced reductions in anxiety symptoms across diverse populations and study designs. However, future research is needed to further explore the role of extra pharmacological factors on the psilocybin-anxiety interaction. In line with previous studies, we detected long-term decreases in trait neuroticism, which was associated with reductions in anxiety ratings and could be related to reductions of symptoms of comorbid conditions such as depression or post-traumatic stress disorder. We found that post-retreat increases in trait agreeableness were also associated with decreased anxiety. However, the relationship between changes in mindfulness and neuroticism and changes in anxiety has yet to be determined.

We found that mindfulness capacities increased following intake of psilocybin, but that there were no strong associations between mindfulness capacities and anxiety ratings. Additionally, we found that ratings of ego dissolution were the strongest correlators of state anxiety. A recent review of twenty studies on the clinical response to psychedelics concluded that the intensity of the acute psychedelic experience is the most important predictive factor of a response to a psychedelic. However, it has yet to be systematically assessed whether such a “peak” experience is necessary for long-term outcomes. The objectives were tested using a naturalistic, observational design, with attendees of psilocybin ceremonies. However, this sort of setting comes with a range of confounding variables.

A longitudinal study on psychedelic use has traditionally had high dropout rates, but a recent study found that baseline predictors of attrition were consistent with those reported in longitudinal studies in other scientific disciplines, suggesting their transdisciplinary relevance.

Ingestion of psilocybin in a supportive group setting can reduce anxiety symptoms and trait neuroticism, and increase mindfulness capacities. Additionally, group therapy may be a more financially accessible treatment option.

Acknowledgements

The authors would like to thank Stefana Bosse, Hannes Kettner and Beatrice Da Rios for their help with data collection.

Figures and Tables

Figure 2 shows that there were significant differences in state anxiety scores between baseline and the other two time points, as indicated by the violin plots.

Figure 3 shows that there were significant differences in trait anxiety between baseline and the other two time points, as indicated by the violin plots.