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


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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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fpsyt-13-883869 July 1, 2022 Time: 15:37 # 1
published: 07 July 2022
doi: 10.3389/fpsyt.2022.883869
Edited by:
Felix Mayer,
Florida Atlantic University,
United States
Reviewed by:
Nicky Mehtani,
University of California,
San Francisco, United States
Christopher Nicholas,
University of Wisconsin-Madison,
United States
Natasha Leigh Mason
Specialty section:
This article was submitted to
a section of the journal
Frontiers in Psychiatry
Received: 25 February 2022
Accepted: 01 June 2022
Published: 07 July 2022
Kiraga MK, Kuypers KPC,
Uthaug MV, Ramaekers JG and
Mason NL (2022) Decreases in State
and Trait Anxiety Post-psilocybin:
A Naturalistic, Observational Study
Among Retreat Attendees.
Front. Psychiatry 13:883869.
doi: 10.3389/fpsyt.2022.883869
Decreases in State and Trait Anxiety
Post-psilocybin: A Naturalistic,
Observational Study Among Retreat
Maggie Kamila Kiraga, Kim P. C. Kuypers, Malin Vedoy Uthaug, Johannes G. Ramaekers
and Natasha Leigh Mason*
Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University,
Maastricht, Netherlands
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
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Kiraga et al. Decreases in Anxiety Following Psilocybin
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.
Keywords: psilocybin, anxiety, mindfulness, personality, neuroticism
Anxiety disorders (e.g., generalized anxiety disorder, panic
disorder, social phobia) are the most common psychiatric
disorders, with a current worldwide prevalence of 7.3% (1,2).
They were also found to be burdensome and costly to individuals
and wider society (3). Despite such a widespread presence,
current treatments only provide partial success rates, with
pharmacological therapies (benzodiazepine and antidepressant
medications) resulting in response rates (typically defined as
>50% decrease in symptoms relative to baseline) of 50.8–
58.3% (4,5), and cognitive behavioral therapies (CBT) resulting
in response rates of 51.7–53.6% (5,6) in adults with anxiety
disorders. Additionally, the combination of the two approaches
has not been found to result in more promising outcomes, with
a response rate of 54.2% (5). Further studies have concluded
that the exact rate of treatment response also varies per anxiety
disorder. For instance, in patients with a lifetime panic disorder,
the response rates drop drastically to about 13% for each of the
aforementioned therapeutic modalities (7), whereas patients with
comorbid anxiety and depression tend to prematurely terminate
treatment more frequently than patients with a single diagnosis
(8). The above findings illustrate a rising urgency within the field
of mental health for efficient fast-acting treatment options that
prove efficacious for the large heterogeneous cluster that makes
up anxiety disorders, and that persist after treatment.
Before criminalization of psychedelic drugs in the 1970s,
studies combining administration of a psychedelic drug and
psychological therapy found significant improvements in
anxiety-related symptomatology (9). Recently, there has been
a resurgence of interest regarding the therapeutic potential of
these substances, including psilocybin, ayahuasca, and LSD, in
treating an array of different mental health disorders (1014).
More modern trials have assessed the efficacy of psychedelics to
reduce anxiety symptoms among patients with a life-threatening
illness, and have demonstrated large significant reductions in
ratings of anxiety, with a response rate of 60–80% (defined
as >50% decrease in measure relative to baseline), sustained
over the course of 6–12 months post treatment (1517),
and in a smaller cohort up to 4.5 years post treatment (18).
Similar reductions in ratings of anxiety symptoms have been
demonstrated in trials assessing the efficacy of a psychedelic
to alleviate symptoms of treatment-resistant depression (12,
19,20), and in naturalistic samples with heterogeneous mental
health status (2123). In healthy volunteers, the persisting effect
of psychedelics on feelings of anxiety have been mixed, with one
study reporting persisting reductions in acute (state)anxiety
1 week, and reductions in personality-related (trait)anxiety
1 month after psilocybin ingestion (24), and another study
reporting no changes in trait anxiety 1 and 12 months after
LSD (25). The questionable rigidity in the research design of the
earlier studies, including lack of statistical analysis and validated
outcome measures (9), and the promising findings of modern
trials, warrant further investigation of the persisting effects of
ingestion of a psychedelic drug on acute and personality-related
anxiety, independent of life-threatening illness or comorbid
depression. Furthermore, if psychedelic substances do reduce
anxiety, it is of interest to understand what psychological
processes may be at play.
The personality trait neuroticism, reflecting an individual’s
tendency to experience negative emotions, sensitivity to aversive
cues, and insufficient ability to cope with stress, has been found
to be the personality trait that is the most strongly associated
with many forms of psychopathology (2631), and a core
vulnerability factor common to anxiety and mood disorders
(32). Although it has been argued that personality traits are
relatively stable throughout adulthood, an array of clinical work
has shown that personality is amenable to changes across the
lifespan (33), with neuroticism being found to fluctuate to one
standard deviation across the lifespan (34). As such, it has been
suggested that reducing neuroticism should be the primary focus
of therapeutic interventions when treating psychopathologies
such as anxiety (33). It has been repeatedly found that ingestion
of a psychedelic drug can induce rapid and persisting changes
in personality traits, and particularly reductions in neuroticism,
in both healthy and clinical populations (24,3541). Thus, given
the reduction in self-rated neuroticism found after ingestion of a
psychedelic, it could be suggested that one mechanism by which
psychedelic substances induce persisting changes in anxiety
levels could be by altering maladaptive personality structures
which exacerbate anxiety. However, the relationship between
psychedelic-induced changes in anxiety and psychedelic-induced
changes in neuroticism has yet to be assessed.
A further psychological process which may be of particular
salience when discussing therapeutic efficacy for anxiety, and
which psychedelics have been repeatedly found to enhance,
are mindfulness capacities (10,22,23,4246). Mindfulness has
been described as “paying attention in a particular way: on
purpose, in the present moment, and non-judgmentally” (47).
It is generally considered multifaceted, including capacities such
as being able to: notice or attend to internal feelings, thoughts,
and external simulation (“observing”), label feelings, thoughts
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Kiraga et al. Decreases in Anxiety Following Psilocybin
and experience with words (“describing”), attending to what is
happening in the present moment (“acting with awareness”), take
a non-evaluative stance toward internal thoughts and feelings
(“non-judgment of inner experience”), and being able to allow
emotions and thoughts to come and go, without being interfered
by them (“non-reactivity to inner experience”). Given that one
of the core components of anxiety disorders is the practice of
excessive rumination on non-present fears, leading to a vicious
circle of higher levels of physical arousal and more worrying
(48), individuals suffering from anxiety disorders typically lack
or have lower levels of mindfulness capacities (49). Accordingly,
it has been shown that interventions which enhance mindfulness
capacities, such as mindfulness-based stress reduction training
(MBSR), can be an effective form of treatment for people
with anxiety disorders (50), resulting in higher efficiency and
improvement rates than cognitive-behavioral group therapy (51).
That said, the relationship between psychedelic-induced changes
in mindfulness capacities, and psychedelic-induced changes in
anxiety, has yet to be assessed.
Finally, another important factor when thinking about
therapeutic applications is the longevity of effects. Usually when
taking conventional anxiolytics the treatment duration will vary
but might extend over months (5,6). For psychedelics, persisting
effects on personality or wellbeing can be found up to 12
months after a single dose administration (25), whereas increased
mindfulness capacities have been found to persist up to 3
months (43). It has been suggested by some studies that the
intensity or quality of the psychedelic experience determines the
treatment outcome (5254). Specifically, it has been repeatedly
found that psychedelic-induced mystical-type experiences and
ego dissolution, the latter a phenomenon characterized by
the reduction in self-referential awareness, disruption self-
world boundaries, and increased feelings of unity with one’s
surroundings (55), correlates with long-term (positive) outcomes
(23,5254,5658). Thus, in the present study we also assessed
whether we could predict sub-acutechanges in anxiety based on
acute ratings of ego dissolution.
In sum, anxiety symptoms and disorders evoke a notable
impact on people’s lives, yet the existing treatment options
are of limited success. Based on this and previous findings of
psychedelic-induced alleviation of anxiety in clinical populations,
the present study was designed to assess the sub-acute effects
of psilocybin in self-reported healthy retreat attendees on state
and trait anxiety, when taken in a supportive group setting.
The population is informative to investigate as sub-clinical,
“healthy” samples often report meaningful anxiety symptoms
that impact one’s well-being and quality of life (5963), however,
due to the lack of clinically established severity of symptoms,
it is unlikely that this population is recruited into randomized
clinical trials. Thus, this sample of retreat attendees presents an
opportunity to explore psychedelic-induced effects in a clinically
under-represented, but highlighly salient sample. Additionally,
the retreat setting presents an opportunity to assess the feasibility
and efficacy of group sessions with psychedelic substances, a
likely increasingly popular context upon regulatory rescheduling
of psychedelic compounds, as well as a potentially more cost-
and time-efficient clinical therapeutic approach. In this context,
we also aimed to replicate the previously reported findings on
the substance’s ability to increase mindfulness capacities and
decrease neuroticism (10,22,23,3739,43,44,46). As previously
rationalized, that such changes may be related to reductions
in anxiety, we further aimed to assess whether changes in
mindfulness capacities and neuroticism correlated with changes
in anxiety. Lastly, we wanted to assess the relationship between
psychedelic-induced changes in state and trait anxiety and
ego dissolution.
We hypothesized that, compared to baseline, reductions in
state and trait anxiety and neuroticism would be observed 24 h
and 7 days after ingestion of psilocybin, whereas mindfulness
capacities would be enhanced. Furthermore, we hypothesized
that reductions in ratings on both aspects of anxiety would
be negatively correlated with enhancements in mindfulness
capacities and positively correlated with reductions in the
personality trait, neuroticism. Finally, we hypothesized that
positive changes in ratings of anxiety would be correlated with
higher subjective ratings of ego dissolution, the latter measured
with the Ego Dissolution Inventory (55).
Participants and Study Procedure
Participants were volunteers attending legal psilocybin retreats
in the Netherlands, organized by the Psychedelic Society
UK. Attendees of those ceremonies were either invited to
participate in the study on site, or contacted the researchers
by email after hearing about the study through the retreat
organizers. To participate in the study, volunteers had to
be a minimum of 18 years old and proficient in English.
Participants were assessed 3 times: at baseline (the evening
before psilocybin ingestion), within 24 h after psilocybin
ingestion (hereafter referred to as: sub-acute) and 7 days after
psilocybin ingestion (hereafter referred to as: follow-up). Seven-
days later, participants received the final follow-up measurement
online (through Qualtrics). The total amount of truffles (g)
taken by each participant was recorded, and a sample of
the truffles was taken to determine the concentrations of
alkaloids afterwards.
The study was conducted in accordance with the Declaration
of Helsinki and subsequent amendments concerning research
in humans and was approved by the Ethics Review Committee
of Psychology and Neuroscience and Maastricht University
(ERCPN-175_03_2017_A5). Participation was voluntary and no
incentives to participate were provided. All volunteers gave
their written informed consent prior to participation. The
research team was not involved in the screening, preparation,
organization, administration, and supervision of the psilocybin
ceremonies that were visited.
Psilocybin Retreats
Prior to participation in the retreat, personal intakes were done
by the facilitators, which included screening for (and excluding)
individuals with psychiatric disorders or taking psychiatric
medications, and medical factors like high blood pressure.
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The setting in which psilocybin was taken was the same
throughout all of the retreats. Participants stayed in a large
house set in nature, hosted by at least two or more experienced
psilocybin facilitators. They arrived the evening before psilocybin
administration, and were able to get acquainted with each other,
the facilitators, and the schedule of the retreat. Participants were
able to discuss their intentions in the group, and participated in
group activities to get to know each other. The next day, after a
group breakfast, participants received the psilocybin-containing
truffles around noon, in a tea form. Facilitators provided music,
tools to draw and/or write, food, and overall support. Support
was not a guiding of the experience, but more so making sure
participants were safe, comfortable, and holding space when
necessary. In the evening, all participants and facilitators came
back together as a group. The next morning, all participants
had breakfast together, had time for integration experiences
(including drawing, journaling, walking) and had a closing group
meeting. To note: the retreat attendees were individuals who
wanted to have a safe psychedelic experience. No therapy was
given during the retreat, but rather the role of the facilitators
was to provide a safe space for this experience, and to encourage
reflection on the experience in the following days.
Participants ingested the truffles in a tea form, guided by the
facilitators. To do this, the truffles were crushed, and boiling
hot ginger tea was added. After infusing for a few minutes,
the participants drank the tea, and were subsequently free to
add more water and repeat the process 2–3 times. Afterwards
participants could eat the remaining truffle contents in the cup.
Previous experimental studies have demonstrated that subjective
alterations after psilocybin intake begin 20–40 min following
administration, peak around 60–90 min, and subside by 6 h
post-intake (64). However, anecdotal reports suggest that when
ingested in tea form, subjective alterations are felt more quickly,
and for a shorter amount of time (65).
The total 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. The German Central Customs Authority determined the
contents of psilocin and psilocybin after freeze-drying the truffles
using a previously described HPLC method (66).
The assessments included a basic demographic section and six
questionnaires: the State-Trait Anxiety Inventory (STAI), the
Five Facet Mindfulness Questionnaire (FFMQ), the Big Five
Inventory (BFI), the Persisting Effects Questionnaire (PEQ),
and the Ego Dissolution Inventory (EDI). All materials were
provided in English. The STAI and FFMQ were filled out three
times, i.e., at baseline, sub-acute session, and follow-up. The
BFI was administered twice, during the baseline and the follow-
up session. Whereas the remaining 2 questionnaires were only
completed once; the EDI during the sub-acute session, to assess
the magnitude of the psychedelic experience in retrospect, and
the PEQ at the 7 day follow-up, to assess persisting effects and the
significance of the experience.
State-Trait Anxiety Inventory
The State-Trait Anxiety Inventory [STAI; (67)] is a 40-item rating
scale with a 4-point response format, ranging from 1 (almost
never) to 4 (almost always) that is scored into two sub-scales
(state anxiety and trait anxiety). For “state” anxiety questions,
participants were asked to select the response for each item that
best describes how they feel “right now, that is, at this moment.”
For “trait” anxiety questions, participants were asked to select
the response that best describes how they “generally feel, that is,
most of the time.” The reverse-scored and (e.g., “I feel pleasant”)
and direct-scored (e.g., “I feel nervous and restless”) items are
summed per each subscale to create a total score which ranges
between 20 and 80, with higher scores indicating greater anxiety.
Internal consistency coefficients for the scale have been shown to
range from 0.86 to 0.95 and test-retest reliability coefficients from
0.65 to 0.75 over a 2-month interval (68). Considerable evidence
attests to the construct and concurrent validity of the scale (68).
When evaluating clinical anxiety according to the STAI, a cutoff
score of 40 for state anxiety is commonly used to define probable
clinical levels of anxiety, whereas a cut-off score of 44 for trait
anxiety is used (69).
Five Facet Mindfulness Questionnaire
The Five Facet Mindfulness Questionnaire, 39 items, [FFMQ;
(70)] measures five different factors: (1) Observe: noticing
external and internal experiences, e.g., body sensations, thoughts,
or emotions; (2) Describe: putting words to, or labeling the
internal experience; (3) Acting with awareness: focusing on
the present activity instead of behaving mechanically; (4) Non-
judging the inner experience: taking a non-evaluative stance
toward the present experience, thoughts, or emotions; and (5)
Non-reacting to the inner experience: allowing thoughts and
feelings to come, without getting caught up in, or carried away,
by them. Sample item of the Observe dimension is: “When I
take a shower or bath, I stay alert to the sensations of water
on my body.” Participants were asked to rate the degree of
concordance with each statement on a 5-point Likert scale that
ranges from 1 (never or very true) to 5 (very often or always true),
for 39 statements. The FFMQ has shown adequate psychometric
properties in both non-clinical and clinical samples. Cronbach’s
αfor each individual sub-scale range from 0.75 to 0.91 (70), and
the internal consistency of the scale in our sample was of 0.83 and
0.86 (pre- and post-intake, respectively).
Big Five Inventory
The Big Five Inventory [BFI-44; (71)] was used to measure the
Big Five personality dimensions, specifically: (1) Extraversion
(8 items); (2) Agreeableness (9 items); (3) Conscientiousness
(9 items); (4) Neuroticism (8 items) and Openness (10 items),
total of 44 items. Those prototypical traits defining each of
the Big Five dimensions are assessed by short and easy-to-
understand phrases, for example: “I see myself as someone who
is talkative.” The items are rated on a 5-point Likert scale
ranging from 1 (disagree strongly) to 5 (agree strongly). The
direct and reverse-scored items for each dimension are summed
together to create a total score, which, given the variability in
terms of number of items, ranges between 8 and 40, 9 and 45,
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Kiraga et al. Decreases in Anxiety Following Psilocybin
or 10 and 50. The BFI scales have shown substantial internal
consistency, retest reliability, and clear factor structure, as well
as considerable convergent and discriminant validity with longer
Big Five measures (72,73).
Persisting Effects Questionnaire
The Persisting Effects Questionnaire (PEQ) is a 143-item long
scale aiming to assess changes in attitudes, moods, behavior,
and spiritual experience (74). Prior research found that PEQ is
sensitive to the prolonged effects of psychedelics, occurring even
a 1 year after the ingestion (25). Due to time constraints, the
current study used a shortened version of the scale (90 items),
including five out of six main categories: attitudes about life
(Number of items (N) =26); attitudes about self (N =22); mood
changes (N =18); relationships (N =18); and behavioral changes
(N =2). The 86 items of these five categories were rated on a 6-
point scale (ranging from 0 =none to 5 =extreme). The scores
of the resulting 10 scales (positive and negative scales for each of
5 categories) were assessed by calculating mean (SE) separately
for each category.
The questionnaire also included four questions rated on an
eight-point scale (1 =no more than routine, and 8 =the single
most meaningful experience of my life): (1) “How personally
meaningful was the experience?”; (2) “Indicate the degree to
which the experience was spiritually significant to you?”; (3)
“How psychologically challenging were the most psychologically
challenging portions of the experiences?”; (4) “How personally
psychologically insightful to you were the experiences?” (57,75).
Ego Dissolution Inventory
The Ego Dissolution Inventory (EDI) is an eight-item self-report
scale that assesses the participant’s experience of ego dissolution
(76). In the present study, the original, English version was
used to acquire a better understanding of the experiences the
participants had about ego dissolution during the psilocybin
ceremony. For example “I experienced a dissolution of my “self
or ego” and “I felt at one with the universe.” The participants
answered the scale with endpoints of either 0% (No, not more
than usual) or 100% (Yes, I experienced this completely/entirely).
The EDI was scored by calculating the mean of all items, with
a higher total score indicating a stronger experience of ego
dissolution. The scale has been shown to have excellent internal
consistency (76). The investigation of convergent validity of the
scale has shown strong positive correlations between EDI and the
mystical-type (or “peak”) of experience (76).
Statistical Analyses
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 personality (77,78) as well
as between anxiety and mindfulness capacities (49,50). Given
that ratings of ego dissolution have been shown to correlate
with persisting effects after a psychedelic experience in both
clinical and naturalistic studies (23,5254,56,57), we tested
for the possible associations between EDI scores and changes in
anxiety. Canonical correlations (79) were 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 (79).
Finally, we ran an exploratory analysis (independent sample
t-tests and chi-square tests) with a twofold purpose: (1) to
examine if there are differences between psilocybin-naïve and
experienced participants on the anxiety measures (both state and
trait anxiety); (2) to assess attrition factors for variables that
have previously found to be significant in similar studies [i.e.,
demographic variables and personality traits; (80)], as well as
study-specific factors of interest [i.e., baseline anxiety levels (state
and trait) and acute drug effects (EDI scores)].
For all statistical analyses, the alpha criterion level of statistical
significance was set at p0.05 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 (81).
Participants and Dose
Demographic information and concentrations of the psilocybin
sample are all previously published elsewhere, and briefly
summarized here (82).
Fifty-five volunteers agreed to participate in the present study
and signed the informed consent. Of those 55 participants, 47%
(N= 26) identified themselves as males, 47% (N= 26) as
females, and 5% (N= 3) reported identification with other gender
categories. The exact numbers of participants’ enrollment and
questionnaire completion are shown in Figure 1. Incomplete or
missing test batteries were due to time constraints, as attendees
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FIGURE 1 | Flow-chart of participants’ enrollment and survey completion.
must carry on with the semi-fixed retreat schedule, or participant
The mean age of the entire group was 34.8 (SD =8.9),
ranging from 20 to 58 years. The highest completed levels of
education were graduate school (41.8%), undergraduate school
(41.8%), secondary school (7.3%), or undisclosed (9.1%). Most
participants were from Europe (80%), while the rest were
from North America (7.3%), Africa (3.6%), Central America
(1.8%), Asia (1.8%), or undisclosed (5.4%). About half of the
sample had previous experience with classical psychedelics
(psilocybin =52.7%; LSD =40%; ayahuasca =52.7%;
DMT =58%), MDMA (56%), and the majority had experience
with cannabis (78%). For 69.1% of the participants, this was the
first time taking a psychedelic in a retreat setting.
Psilocybin Sample
The truffle sample (15 grams; Psilocybe Hollandia) contained
1.9 mg of psilocybin and 10.5 mg of psilocin. Participants
ingested an average (SD) 34.2 (8.9) grams of truffles. Once
ingested, psilocybin is quickly metabolized to psilocin at a
calculation factor of 0.719, resulting in a final (average) psilocin
consumption of 27.1 mg.
State-Trait Anxiety Inventory
Overall 46 (at baseline), 42 (at the morning after the ceremony),
and 22 (at 1 week after the ceremony) participants completed all
the parts of STAI and were included into analyses. The OLS multi-
linear regression revealed a significant main effect of Session
[F(2,107)=14.10; p<0.001] on scores capturing state anxiety.
Compared to baseline, participants’ state anxiety reports were
6.4 points lower the morning after the psilocybin ceremony
(p<0.001; d=0.77), and 6.7 points lower 1 week after the
ceremony (p=0.001; d=0.87; Figure 2). Session was also found
to have significant effects on estimates of trait anxiety [F(2,107)=
10.13; p=0.002]. Specifically, compared to baseline, self-rated
trait anxiety was about 6 points lower the morning after the
FIGURE 2 | Violin plots displaying scores on measures of state anxiety, which
demonstrated significant differences between baseline and the other two time
points. The plot consists of median (SE) ratings of state anxiety before, 1-day
after and 7-days after psilocybin truffles. The thick line indicates the
interquartile range, whereas the white dot indicates the median. Each gray dot
indicates a data point, whereas the density is scaled to the relative count
across all bins. Wider sections of the violin plot represent a higher probability
of observations of a given value.
ceremony (p=0.014; d=0.52) and 8.6 points lower 1 week after
the ceremony (p=0.004; d=0.77; Figure 3) on a 60- point range.
Five Facet Mindfulness Questionnaire
In total, 52 (at baseline), 46 (at the sub-acute session), and 23
(at the follow-up session) participants completed the FFMQ. The
OLS multi-linear regression revealed a significant main effect of
Session on the Non-judge dimension [F(2,118)=4.37; p=0.04] of
FIGURE 3 | Violin plots displaying scores on measures of trait anxiety, which
demonstrated significant differences between baseline and the other two time
points. The plot consists of median (SE) ratings of trait anxiety before, 1-day
after and 7-days after psilocybin truffles. The thick line indicates the
interquartile range, whereas the white dot indicates the median. Each gray dot
indicates a data point, whereas the density is scaled to the relative count
across all bins. Wider sections of the violin plot represent a higher probability
of observations of a given value.
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Kiraga et al. Decreases in Anxiety Following Psilocybin
the FFMQ. The contrasts analysis showed, in comparison to the
baseline, a 0.5 increase in non-judgmental mindfulness capacities
the morning after the ceremony (p<0.39; d=0.17) and 1.5
increase at the follow-up (p= 0.03; d=0.51). There was no main
effect of Session on the remaining, four facets (Table 1).
Big Five Inventory
The BFI was completed by 48 and 23 participants at baseline
and follow-up, respectively. The OLS multi-linear regression
model revealed a significant main effect of Session on Neuroticism
[F(1,69)=8.46; p= 0.005] and Agreeableness [F(1,69)=8.87;
p=0.004] of the BFI. The two traits showed an opposite
pattern of changes over time. While, in comparison with baseline,
participants scored 5.2 points lower on Neuroticism (d=0.76)
at the follow-up, they scored 3.8 points higher on Agreeableness
(d=0.78). There were no main effects of Session on the
remaining three personality traits (Table 1).
Persisting Effects Questionnaire
In total, 20 participants filled in the PEQ 7 days after the
ceremony. Mean (SE) of the positive and negative ratings
assessing attitudes, mood, social effects, and behavior are
presented in Table 2.
On the question, “how personally meaningful was the
experience, 2 (10%) rated it as the single most meaningful
experience of their lives, whereas 10 (50%) and 2 (10%), rated it
as among the 5 and 10 most meaningful experiences of their lives,
respectively. Two participants (10%) rated it as similar to the
meaningful experiences that occur on average once every 5 years,
three (15%) stated it to be similar to meaningful experiences
that occur once a year, and one (5.0%) stated it was similar to
experiences that occur on average once a month.
On the question, “how spiritually significant was the
experience, 3 (15%) rated it as the most spiritually significant
experience of their lives, whereas 8 (40%) and 3 (15%) rated it
as among the 5 and 10 most spiritual experiences of their lives,
respectively. Three participants (15%) rated it as similar to the
spiritually meaningful experiences that occur on average once
every year, 2 (10%) stated it was similar to spiritually meaningful
experiences that occur once a month, and one (5.0%) stated it was
no more spiritual than a routine, everyday experience.
In regards to how psychologically challenging the experience
was, 1 (5%) rated it as the single most difficult or challenging
TABLE 1 | Summary of regression and contrast analyses of the dependent measures.
Variable F (p) Session Mean SE P d
State Anxiety 14.1 (<0.001) Baseline 34.3 1.17
Sub-acute 27.9 1.7 <0.001 0.77
Follow-up 27.6 2.06 0.001 0.87
Trait Anxiety Baseline 42.6 1.68
Sub-acute 36.55 2.42 0.014 0.52
Follow-up 34.05 2.94 0.004 0.77
Observe (FFMQ) 0.11 (0.74) Baseline 10.27 0.43
Sub-acute 10.28 0.63 0.93 0.003
Follow-up 10.57 0.78 0.7 0.1
Describe (FFMQ) 0.79 (0.38) Baseline 10.36 0.92
Sub-acute 12.24 1.34 0.17 0.25
Follow-up 11.35 1.66 0.56 0.34
Acting with awareness (FFMQ) 2.96 (0.09) Baseline 9.44 0.37
Sub-acute 10.39 0.54 0.08 0.36
Follow-up 10.39 0.66 0.16 0.36
Non-judging (FFMQ) 4.37 (0.04) Baseline 11.36 0.4
Sub-acute 11.83 0.58 0.39 0.16
Follow-up 12.87 0.72 0.03 0.51
Non-reacting (FFMQ) 0.12 (0.73) Baseline 9.63 0.36
Sub-acute 9.59 0.53 0.93 0.02
Follow-up 9.39 0.65 0.71 0.09
Extraversion (BFI) 1.76 (0.19) Baseline 27.0 0.86
Follow-up 29.0 1.5 0.36
Agreeableness (BFI) 8.87 (0.004) Baseline 33.96 0.7
Follow-up 37.74 1.27 0.78
Conscientiousness (BFI) 3.6 (0.06) Baseline 28.8 0.97
Follow-up 32.0 1.7 0.47
Neuroticism (BFI) 8.5 (0.005) Baseline 23.9 1.0
Follow-up 18.7 1.78 0.76
Openness (BFI) 3.59 (0.06) Baseline 37.7 0.7
Follow-up 40.0 1.2 0.5
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TABLE 2 | Mean (SE) scores on outcome measures of the persisting
effects questionnaire.
Questionnaire subscales and single items Mean (SE)
Attitudes about life
Positive 59.30 (2.19)
Negative 15.65 (0.67)
Attitudes about self
Positive 45.30 (2.50)
Negative 14.75 (0.71)
Mood changes
Positive 37.55 (2.06)
Negative 9.95 (0.41)
Social effects
Positive 36.85 (2.38)
Negative 10.30 (0.45)
Behavioral changes
Positive 4.65 (0.28)
Negative 1.15 (0.15)
experience of their lives, 6 (30%) rated it as among the 5 most
challenging experiences of their life, and 1 (5%) rated it as among
the top 10 most challenging experiences of their lives, followed by
3 (15%) stating it was similar to the challenging experiences that
occur every 5 years, 3 (15%) who said occur every once a year, 4
(20%) who said occur once a month, 1 (10%) who said occur once
a week, and 1 (10%) who stated it was no more psychologically
challenging than a routine, everyday experience.
Finally, regarding the psychological insightfulness of the
experience, 7 (35%) stated the experience to be the single most
psychologically insightful experience of their life, 6 (30%) and
2 (10%) stated among the 5 and 10 most insightful experiences,
respectively. Three (15%) stated that the experience was similar to
psychologically insightful experiences that occur on average once
every 5 years, one (5%) stated similar to experiences that occur
on average once a month, and one (5%) stated the experience was
no different from every psychologically insightful experience.
Ego Dissolution Inventory
The EDI was completed by 47 participants the morning after
the ceremony. The mean (SD) of participants who filled in the
Ego Dissolution Inventory was 59.7 (28.3), with ratings varying
between 3 (minimal reported score) and 100 (maximal reported
score). The kernel density estimate of the probability density
function of the individual EDI scores is presented in Figure 4.
Hypothesis-Driven Correlations
A canonical correlation analysis was conducted using the three
psychological variables which demonstrated significant effects as
predictors (follow-up (change) scores on non-judge dimension of
FFMQ, follow-up (change) neuroticism scores, and EDI scores)
of the four anxiety outcome measures: sub-acute and follow-up
(change) scores on state and trait anxiety measures. The analysis
yielded three functions with squared canonical correlations (Rc2)
of 0.891, 0.324, and 0.096 for each successive function. The
full model across all functions was statistically significant [F(12,
FIGURE 4 | Probability distribution plot of the experience of ego dissolution as
assessed by the EDI morning after the psilocybin ceremony. The plot depicted
kernel density estimation (KDE), histogram, and raw data points.
18.81)=2.81, p=0.022], explaining 93.4% of the variance. From
this model, the first two functions were considered noteworthy
in the context of this study, explaining 89.1% and 32.4% of the
variance, respectively.
Table 3 presents the standardized canonical function
coefficients, the structure coefficients (rs), and the squared
structure coefficients (rs2)for each function, as well as the
communalities (h2) across the functions for each variable
[for an in-depth explanation and interpretation of canonical
correlations and associated terminology, the reader is referred
to (79)]. Function 1 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-judgment. Overall, this
function suggests that the strongest predictor of changes in trait
anxiety were changes in neuroticism.
Function 2 indicated that the dominant contributors were sub-
acute and long-term changes in state anxiety, with the dominant
predictor of ratings of EDI. Overall, this function suggests that the
strongest predictor of changes in state anxiety was higher ratings
in ego dissolution.
Exploratory Analysis
The first goal of the exploratory analysis was to evaluate
whether participants with a previous experience with psilocybin
(N=29) differed from the naïve participants (N=21) on
measures of anxiety. None of the six independent sample
t-tests (2 STAI measurements ×3 assessment points) found
significant differences between the groups (see Table 4 for
details), suggesting that the previous experience with psilocybin
had no effect on the anxiety changes observed in the present
study. The second goal of the exploratory analysis was to
investigate the determinants of attrition. Tests (9 independent
sample t-tests: Age, 5 personality traits, 2 STAI measurements,
and EDI score; 2 chi-square tests: Gender, Education) revealed
significant differences for the age (t=2.39; p=0.02), education
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TABLE 3 | Canonical solution for psychological variables predicting state and trait anxiety for Functions 1 and 2.
Function 1 Function 2
Variable Coef rsrs2(%) Coef rsrs2(%) h2(%)
State anxiety (subacute) 0.097 0.494 24.40 0.353 0.528 27.88 52.28
Trait anxiety (subacute) 0.312 0.819 67.08 1.04 0.065 0.42 67.50
State anxiety (followup) 0.331 0.526 27.67 0.997 0.712 50.69 78.36
Trait anxiety (followup) 0.904 0.963 92.74 0.156 0.227 5.15 97.89
Rc289.15 32.43
Non-judging (followup) 0.221 0.547 29.92 0.267 0.303 9.18 39.10
Neuroticism (followup) 1.189 0.974 92.23 0.136 0.157 2.46 94.69
EDI 0.126 0.246 6.05 1.160 0.949 90.06 96.11
rsgreater than | 0.45| and h2greater than 45% are underlined and deemed valuable contributors.
Coef, standardized canonical function coefficients; rs, structure coefficients; rs2, squared structure coefficient; h2, communality coefficient; Rc2, squared canonical
TABLE 4 | Summary results of exploratory analysis.
Variable Session Group Mean (SE) t/χ2 p
State Anxiety Baseline Naïve 36.58 (2.27)
Experienced 32.17 (1.69) 1.56 0.13
Sub-acute Naïve 29.88 (2.08)
Experienced 26.95 (1.41) 1.16 0.25
Follow-up Naïve 29.29 (2.0)
Experienced 26.73 (1.66) 0.98 0.34
Trait Anxiety Baseline Naïve 45.53 (2.73)
Experienced 39.97 (2.5) 1.53 0.14
Sub-acute Naïve 38.65 (2.94)
Experienced 34.72 (2.11) 1.09 0.29
Follow-up Naïve 32.86 (3.1)
Experienced 34.6 (2.84) 0.41 0.69
Demographics Age Dropouts 32.27 (1.28)
Completers 38.17 (2.09) 2.39 0.02
Gender (male/female/other) n Dropouts 16/13/3
Completers 10/13/0 1.74 0.19
school) n
Dropouts 10/15/4
Completers 13/8/0 4.98 0.03
BFI Scores (Baseline) Extraversion Dropouts 26.59 (1.44)
Completers 27.52 (1.19) 0.5 0.62
Agreeableness Dropouts 32.96 (1.07)
Completers 35.24 (1.0) 1.54 0.13
Openness Dropouts 36.74 (1.11)
Completers 38.95 (0.83) 1.59 0.12
Neuroticism Dropouts 25.11 (1.45)
Completers 22.33 (1.46) 1.36 0.18
Conscientiousness Dropouts 28.41 (1.23)
Completers 29.33 (1.47) 0.48 0.63
STAI (Baseline) State Dropouts 37.58 (1.84)
Completers 30.68 (1.62) 2.78 0.01
Trait Dropouts 45.58 (2.77)
Completers 39.41 (2.06) 1.79 0.08
EDI Dropouts 59.18 (5.63)
Completers 60.57 (6.15) 0.17 087
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(χ2=4.98; p=0.03), and baseline state anxiety (t= 2.78;
p=0.01) between those who completed the 1-week follow-
up assessment (N=23) and those who did not (N=32).
Analysis indicated that those who dropped out were younger,
reached a lower level of education, and had higher baseline state
anxiety levels than those who completed the study. There were
no significant differences between the groups in terms of gender,
personality traits, baseline trait anxiety, or ego dissolution (see
Table 4 for details).
Of note, anecdotal statements from the participants who
dropped out also claimed demographic-unrelated reasons for
not completing the study, or for turning in the follow-up
measurement past the 1 week deadline (meaning the follow-up
measurement was not included in our final analysis). Reasons
included travel, as many people attended the retreat from abroad,
and stayed in the Netherlands for some time afterward to travel
around, or work, as some people took time off to attend the
retreat, and thus used the following week to catch up on work.
The impact of anxiety symptoms and disorders on people’s lives
and the treatment challenges are well-known within the field of
mental health (2,5,7,83,84). 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 retreat 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 1 week period post the
ingestion of psilocybin. Additionally, we found enhancements in
self-rated mindfulness capacities and alterations in personality
traits at 1 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 (85). Similarly, recent
clinical studies have found reductions of anxiety in patients
with life-threatening illness and/or comorbid treatment-resistant
depression after administration of psilocybin (16,17,19,20),
LSD (15), and ayahuasca (12). Our findings complement
clinical work by demonstrating sub-acute reductions in both
anxiety estimates in a self-reported healthy population, whom
demonstrate STAI ratings under the clinical threshold (69). This
population is informative because sub-clinical, psychologically
“healthy” samples often report meaningful anxiety symptoms
that impact daily life, including feelings of distress and
impairments in cognitive functioning, work performance, and
sleep quality (5963). Importantly, as these symptoms do not
meet diagnostic criteria for a clinical disorder, such symptoms
often go untreated, and such populations are often under-
represented in clinical trials. Thus, the current findings provide
preliminary evidence that psilocybin-assisted psychotherapy may
also be a treatment option for individuals with sub-clinical
anxiety symptoms, if they choose to seek an intervention
for their symptoms.
That said, two previous experimental studies assessing the
effect of a psychedelic on anxiety symptoms in healthy volunteers
have demonstrated mixed results. Whereas one study showed
reductions in state anxiety 1 week post administration, and
reductions in trait anxiety 1 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 µg) (24,25). Additionally, previous naturalistic
work with individuals reporting heterogenous mental health
status also found reductions in anxiety after participation in a
5-MeO-DMT ceremony (22), however a more recent placebo-
controlled observational study found that state anxiety ratings
decreased 24 h after volunteers ingested either a placebo,
or the psychedelic substance ayahuasca, during the context
of a group retreat (86). Taking these findings together, one
could hypothesize that the significant reduction in anxiety-
related symptoms in our self-reported healthy sample is due
to both pharmacological and extra-pharmacological factors.
A noteworthy extra-pharmacological factor in our study, and
some of the previously mentioned studies (22,86), is the
consumption of a psychedelic drug in a group context.
Psychedelic drugs have been found to modulate social cognition
and interpersonal experiences (87), and individuals whom
have undergone psychedelic therapy with psychological support
have indicated that increased feelings of social connectedness
were an important aspect of the therapeutic process (88).
Thus taking together the aforementioned reports, as well as
reports from historical research with psychedelic-assisted group
therapy [see (89), for a review], it could be hypothesized
that the incorporation of groups into psychedelic-assisted
psychotherapy may enhance therapeutic outcomes (89). Whereas
contemporary psychedelic-assisted group therapy trials are
currently limited to one (90), outside of the clinical setting
psychedelic drugs have been used for centuries in traditional
communal settings. Thus, the retreat setting captured in this
study adds further evidence to the feasibility and efficacy of
group sessions with psychedelic substances. The latter should
also be highlighted, as it will likely be an increasingly popular
context upon regulatory rescheduling of psychedelic compounds,
as well as a potentially more cost- and time-efficient clinical
therapeutic approach.
In line with previous studies (3739), we detected 1-week
decreases in trait neuroticism, which has been shown to be
strongly associated with the acuity and comorbidity levels
of a range of mental disorders (77,78). Interestingly, levels
of neuroticism have been found to correlate positively with
frontolimbic serotonin 5-HT2Areceptor binding, the latter being
the main target of psychedelic drugs (28,91), suggesting direct
5-HT2Aagonism 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
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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 Weiss et al. (41).
Other studies have shown either no changes in agreeableness
post-psilocybin experience in depressed patients (37) or higher
agreeableness scores among psychedelics users when compared
to the general population (38). In contrast with other studies (20,
43), we did not observe meaningful changes in openness. The
changes observed in the present study were marginally significant
and of moderate effect size (p=0.06: d=0.5), which may have
been due to dropout rate and decreased power during the 1-
week assessment. In sum, the effects of psychedelic substances
on neuroticism seem to be more robust and more frequently
reported, compared to changes in other personality traits such as
agreeableness or openness.
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 1-week 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. Although
trait anxiety and neuroticism inherently share overlapping
constructs, it is important to state that they are not identical (92,
93). Neuroticism via the BFI consists of facets much broader than
the construct of trait anxiety via the STAI, including anxiety,
angry hostility, depression, self-consciousness, impulsivity,
and vulnerability. Future studies should assess what facets of
neuroticism correlate with trait anxiety, and what facets overlap
with trait anxiety.
Additionally, we also found that the strongest correlator of
sub-acute and 1-week 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 h and 1 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 (94). That said,
it has yet to be systematically assessed whether such a “peak”
experience is necessary for long-term outcomes (95), 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 (15,88,96100). 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 (101104), it also comes with a range of confounding
variables, including lack of control over participant inclusion
or substance administration The present study was conducted
with a self-selected sample of self-determined healthy individuals.
To have an 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 (105,106); 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 (80).
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. Finally, the absence of a control group or
placebo hampers the ability to draw hard conclusions as to
pharmacological vs. extra-pharmacological effects, as it has been
found that the retreat setting alone also produces changes in
psychological outcomes (86). Future studies should be designed
to further assess the contribution of pharmacological versus
extra-pharmacological factors [see e.g., (107) for a thorough
discussion and recommendations].
Taken together, the present study suggests persisting reductions
in anxiety symptoms and trait neuroticism, and increases
in mindfulness capacities, after ingestion of psilocybin in a
supportive group setting. Given the important role of set and
setting on the outcome of psychedelic experience (102,104),
future studies should systematically evaluate the contribution of
these extra-pharmacological factors to the treatment outcome, in
order to optimize therapeutic strategies. Additionally, naturalistic
retreat studies such as this, as well as modern clinical trials (90),
are beginning to demonstrate feasibility, safety, and efficacy of
group sessions with psychedelics, across different disorders. As it
is likely that psychedelic-assisted psychotherapy will be costly and
time-consuming for both the patient and the practitioners, future
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Kiraga et al. Decreases in Anxiety Following Psilocybin
studies exploring the feasibility of group therapy could potentially
substantially lower treatment costs, resulting in a more financially
accessible treatment option.
The raw data supporting the conclusions of this article will be
made available by the authors, without undue reservation.
The studies involving human participants were reviewed
and approved by Ethics Review Committee of Psychology
and Neuroscience, Maastricht University, Faculty of
Psychology and Neuroscience, Maastricht, Netherlands. The
patients/participants provided their written informed consent
to participate in this study.
NM, KK, and JR conceived of the presented idea. NM and
MU collected the data. MK and NM conducted the statistical
analysis. MK, NM, and KK prepared the first draft of the
manuscript. All authors discussed the results and contributed to
the final manuscript.
We would like to acknowledge and thank Stefana Bosse and
the Psychedelic Society United Kingdom for their collaboration
and permission to collect data at their experience weekends.
We would like to thank Hannes Kettner and Beatrice Da Rios
for helping with data collection. We would like to thank all
participants for their time and effort. We would also like to
thank the reviewers, whose comments and questions improved
the quality of the manuscript.
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Frontiers in Psychiatry | 15 July 2022 | Volume 13 | Article 883869
... In contrast to the growing body of research on psilocybin, there exists a relative paucity of data concerning other "classic" serotonergic psychedelics such as mescaline, ayahuasca, N,N-dimethyltryptamine (DMT), ibogaine, and lysergic acid diethylamide (LSD) . While psilocybin has demonstrated promising results in adults with major depressive disorder, end-of-life distress, and alcohol use disorder, with multiple clinical trials currently underway, there remain barriers to its clinical utility and scalability (Aday, Carhart-Harris, and Woolley 2023;Carhart-Harris et al. 2021;Johnson, Richards, and Griffiths 2008;Kiraga et al. 2022;Ross et al. 2016). Given these challenges, there may be therapeutic opportunities with other classic psychedelics beyond psilocybin. ...
... Historically, it has been used in peyote ceremonies in North America for nearly 6000 years (Bruhn et al. 2002). The activation of 5-HT1A receptors by mescaline has also been implicated in its mood-enhancing and anxiolytic effects (Uthaug et al. 2022). Ibogaine is a naturally occurring alkaloid derived from the Tabernanthe iboga plant (Noller, Frampton, and Yazar-Klosinski 2018). ...
There has been a resurgence of interest in the use of psychedelic therapies for several mental and substance use disorders. Psilocybin, a “classic” serotonergic psychedelic, has emerged as one of the primary compounds of interest in clinical research. While research on psilocybin’s potential mental health benefits has grown, data on the safety and efficacy of other serotonergic psychedelics remain limited. A comprehensive scoping review on the use of mescaline, ibogaine, ayahuasca, N,N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD) in the treatment of mental and substance disorders was conducted. Independent reviewers screened titles, abstracts, and full texts and conducted data extraction. Seventy-seven studies met the inclusion criteria. There were 43 studies of LSD, 24 studies of ayahuasca, 5 studies of DMT, 5 studies of ibogaine, and 5 studies of mescaline. Commonly reported benefits included improved mood and anxiety symptoms, improved insight, reduced substance use, improved relationships, and decreased vegetative symptoms. Commonly reported adverse effects were psychological, neurological, physical, and gastrointestinal in nature. Serious adverse events (homicide and suicide) were reported in published studies of LSD. In conclusion, there is only low-level evidence to support the safety and efficacy of non-psilocybin serotonergic psychedelics in individuals with mental and substance use disorders.
... Interestingly, significant reductions in anxiety and depression were also identified in ayahuasca-naive participants who underwent such a ceremony (29). Using psilocybin truffles in supportive group settings has been linked to a reduction in anxiety (47,48). Those who microdosed psilocybin also report short to medium term improvements in mood and mental health (49). ...
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The large-scale disruption to peoples’ daily lives during the COVID-19 pandemic provides a context for examining whether use of substances such as psychedelics in a naturalistic (outside of a controlled environment) setting, is associated with better mental wellbeing and resilience relative to those who use other drugs, or who do not use drugs at all. We interrogate data from the Great British Intelligence Test and identify that 7.8% out of N = 30,598 unique respondents used recreational drugs inclusive of psychedelics, cannabis, cocaine, and MDMA during the COVID-19 pandemic. Recruitment materials did not mention drug use would be surveyed, thereby enabling us to model the relationship with mood and resilience in people who had not specifically self-selected themselves for a ‘drug’ study. We report that people form clusters, characterized by different real-world patterns of drug use, and the majority of psychedelics users also use cannabis. However, a subset of cannabis users do not use psychedelics, enabling a subtractive comparison. Those who primarily used psychedelics and cannabis during the COVID-19 pandemic had worse mood self-assessment and resilience scores compared to those who never used drugs or primarily used cannabis. This pattern was also evident for other recreational drug use clusters, except for those who primarily used MDMA and cannabis, who had better mood but were of too low incidence to have confidence in this estimate. These findings cast light on the significant differences in mental wellbeing between users of different drugs and the non-user population during a global-crisis and call for future research to explore the pharmacological, contextual and cultural variables associated with these differences, their generalisability and causal links with greater precision.
Background: Psilocybin therapy is receiving attention as a mental health intervention with transdiagnostic potential. In line with psychotherapeutic research, qualitative research has highlighted the role of reductions in experiential avoidance (and increases in connectedness) within psilocybin therapy. However, no quantitative research has examined experiential avoidance as a mechanism underlying psilocybin therapy's therapeutic effects. Method: Data was used from a double-blind randomized controlled trial that compared psilocybin therapy (two 25 mg psilocybin session plus daily placebo for six weeks) with escitalopram (two 1 mg psilocybin sessions plus 10–20 mg daily escitalopram for six weeks) among individuals with major depressive disorder (N = 59). All participants received psychological support. Experiential avoidance, connectedness, and treatment outcomes were measured at pre-treatment and at a 6 week primary endpoint. Acute psilocybin experiences and psychological insight were also measured. Results: With psilocybin therapy, but not escitalopram, improvements in mental health outcomes (i.e., well-being, depression severity, suicidal ideation, and trait anxiety) occurred via reductions in experiential avoidance. Exploratory analyses suggested that improvements in mental health (except for suicidal ideation) via reduction in experiential avoidance were serially mediated through increases in connectedness. Additionally, experiences of ego dissolution and psychological insight predicted reductions in experiential avoidance following psilocybin therapy. Limitations: Difficulties inferring temporal causality, maintaining blindness to condition, and reliance upon self-report. Conclusions: These results provide support for the role of reduced experiential avoidance as a putative mechanism underlying psilocybin therapy's positive therapeutic outcomes. The present findings may help to tailor, refine, and optimize psilocybin therapy and its delivery.
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Rationale Psychedelic research continues to garner significant public and scientific interest with a growing number of clinical studies examining a wide range of conditions and disorders. However, expectancy effects and effective condition masking have been raised as critical limitations to the interpretability of the research. Objective In this article, we review the many methodological challenges of conducting psychedelic clinical trials and provide recommendations for improving the rigor of future research. Results Although some challenges are shared with psychotherapy and pharmacology trials more broadly, psychedelic clinical trials have to contend with several unique sources of potential bias. The subjective effects of a high-dose psychedelic are often so pronounced that it is difficult to mask participants to their treatment condition; the significant hype from positive media coverage on the clinical potential of psychedelics influences participants’ expectations for treatment benefit; and participant unmasking and treatment expectations can interact in such a way that makes psychedelic therapy highly susceptible to large placebo and nocebo effects. Specific recommendations to increase the success of masking procedures and reduce the influence of participant expectancies are discussed in the context of study development, participant recruitment and selection, incomplete disclosure of the study design, choice of active placebo condition, as well as the measurement of participant expectations and masking efficacy. Conclusion Incorporating the recommended design elements is intended to reduce the risk of bias in psychedelic clinical trials and thereby increases the ability to discern treatment-specific effects of psychedelic therapy.
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The present study examines prospective changes in personality traits relevant to social functioning as well as perceived social connectedness in relation to the naturalistic use of psychedelic compounds in an online volunteer sample. The study also examined the degree to which demographic characteristics, social setting, baseline personality, and acute subjective factors (e.g., emotional breakthrough experiences) influenced trajectories of personality and perceived social connectedness. Participants recruited online completed self-report measures of personality and social connectedness at three timepoints (baseline, 2weeks post-experience, 4weeks post-experience). Linear mixed models were used to examine changes in outcomes and the moderation of these outcomes by covariates. The most substantive changes were reductions in the personality domains Neuroticism, and increases in Agreeableness and social connectedness. Notably, reductions in Neuroticism and increases in Agreeableness covaried over time, which may be suggestive of common processes involving emotion regulation. Preliminary evidence was found for a specific effect on a component of Agreeableness involving a critical and quarrelsome interpersonal style. Although moderation by demographic characteristics, social setting, baseline personality, and acute factors generally found limited support, baseline standing on Neuroticism, perspective taking, and social connectedness showed tentative signs of amplifying adaptive effects on each trait, respectively. Our findings hold implications for the potential use of psychedelics for treating interpersonal elements of personality pathology as well as loneliness.
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Background: Naturalistic and placebo-controlled studies have suggested that ayahuasca, a traditional Amazonian beverage, could be helpful in the treatment of psychopathologies like depression and anxiety disorders by changing otherwise disturbed cognitive and emotional processes. To better understand its full therapeutic potential, one way is to study the effects on processes like flexible thinking, empathy, and well-being, which are normally compromised in stress-related psychopathologies. Materials and Methods: Volunteers attending ayahuasca ceremonies were asked to complete a test battery at three separate occasions: baseline, the morning after, and 1 week after the ceremony. We included the constructs of creative thinking (measured by Picture Concept Test), empathy (Multifaceted Empathy Test), satisfaction with life (Satisfaction with Life Scale), decentering (Experiences Questionnaire), and personality (Big Five Inventory) into the test battery. Additionally, the psychedelic experience was quantified with the Persisting Effects Questionnaire, the Ego Dissolution Scale, and Visual Analogue Scales. Results: In total, 43 attendees (males = 22; females = 21) completed parts of the baseline assessment, 20 (males = 12; females = 8) completed assessments in the morning after the ceremony, and 19 (males = 14; females = 5) completed assessments at the 1-week follow-up. At one and 7 days post-ceremony, cognitive empathy, satisfaction with life, and decentering increased, while divergent thinking ( Fluency corrected for Originality ) decreased, when compared to baseline. Implicit emotional empathy increased at 1-week follow-up, whereas ratings of the trait neuroticism decreased. Conclusion: The study suggests that a single ingestion of ayahuasca in a social setting is associated with enhancement of subjective well-being, an enhanced ability to take an objective and non-judging stance towards the self (decentering), and the ability to correctly recognize emotions in others, compared to baseline, lasting up to 1 week post-ceremony. To understand the therapeutic potential related to these effects, further research with clinical populations is needed in which these effects can be assessed, including its link with therapeutic outcomes. Together, this will increase our understanding of the effectiveness and breadth of future therapeutic options.
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Mindfulness-based interventions and psychedelic-assisted therapy have been experimentally utilised in recent years as alternative treatments for various psychopathologies with moderate to great success. Both have also demonstrated significant post-acute and long-term decreases in clinical symptoms and enhancements in well-being in healthy participants. These two therapeutic interventions share various postulated salutogenic mechanisms, such as the ability to alter present-moment awareness and anti-depressive action, via corresponding neuromodulatory effects. Recent preliminary evidence has also demonstrated that psychedelic administration can enhance mindfulness capacities which has already been demonstrated robustly as a result of mindfulness-based interventions. These shared mechanisms between mindfulness-based interventions and psychedelic therapy have led to scientists theorising, and recently demonstrating, synergistic effects when both are used in combination, in the form of potentiated therapeutic benefit. These synergistic results hold great promise but require replication in bigger sample groups and better controlled methodologies, to fully delineate the effect of set and setting, before they can be extended onto clinical populations.
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Background The resurgence of research and public interest in the positive psychological effects of psychedelics, together with advancements in digital data collection techniques, have brought forth a new type of research design, which involves prospectively gathering large-scale naturalistic data from psychedelic users; that is, before and after the use of a psychedelic compound. A methodological limitation of such studies is their high attrition rate, particularly owing to participants who stop responding after initial study enrollment. Importantly, study dropout can introduce systematic biases that may affect the interpretability of results. Objective Based on a previously collected sample (baseline n=654), here we investigated potential determinants of study attrition in web-based prospective studies on psychedelic use. Methods Logistic regression models were used to examine demographic, psychological trait and state, and psychedelic-specific predictors of dropout. Predictors were assessed 1 week before, 1 day after, and 2 weeks after psychedelic use, with attrition being defined as noncompletion of the key endpoint 4 weeks post experience. Results Predictors of attrition were found among demographic variables including age (β=0.024; P=.007) and educational levels, as well as personality traits, specifically conscientiousness (β=–0.079; P=.02) and extraversion (β=0.082; P=.01). Contrary to prior hypotheses, neither baseline attitudes toward psychedelics nor the intensity of acute challenging experiences were predictive of dropout. Conclusions The baseline predictors of attrition identified here are consistent with those reported in longitudinal studies in other scientific disciplines, suggesting their transdisciplinary relevance. Moreover, the lack of an association between attrition and psychedelic advocacy or negative drug experiences in our sample contextualizes concerns about problematic biases in these and related data.
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Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience.
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Background: Psilocybin therapy has shown promise as a rapid-acting treatment for depression, anxiety, and demoralization in patients with serious medical illness (e.g., cancer) when paired with individual psychotherapy. This study assessed the safety and feasibility of psilocybin-assisted group therapy for demoralization in older long-term AIDS survivor (OLTAS) men, a population with a high degree of demoralization and traumatic loss. Methods: Self-identified gay men OLTAS with moderate-to-severe demoralization (Demoralization Scale-II ≥8) were recruited from the community of a major US city for a single-site open-label study of psilocybin-assisted group therapy comprising 8-10 group therapy visits and one psilocybin administration visit (0·3-0·36 mg/kg po). Primary outcomes were rate and severity of adverse events, and participant recruitment and retention. The primary clinical outcome was change in mean demoralization from baseline to end-of-treatment and to 3-month follow-up assessed with a two-way repeated measures ANOVA. Trial registration: (NCT02950467). Findings: From 17 July 2017 to 16 January 2019, 18 participants (mean age 59·2 years (SD 4·4)) were enrolled, administered group therapy and psilocybin, and included in intent-to-treat analyses. We detected zero serious adverse reactions and two unexpected adverse reactions to psilocybin; seven participants experienced self-limited, severe expected adverse reactions. We detected a clinically meaningful change in demoralization from baseline to 3-month follow-up (mean difference -5·78 [SD 6·01], ηp2 = 0·47, 90% CI 0·21-0·60). Interpretation: We demonstrated the feasibility, relative safety, and potential efficacy of psilocybin-assisted group therapy for demoralization in OLTAS. Groups may be an effective and efficient means of delivering psychotherapy pre- and post-psilocybin to patients with complex medical and psychiatric needs. Funding: Carey Turnbull, Heffter Research Institute, NIMH R25 MH060482, NIH UL1 TR001872, River Styx Foundation, Saisei Foundation, Sarlo Foundation, Stupski Foundation, Usona Institute, US Department of Veterans Affairs (Advanced Neurosciences Fellowship and IK2CX001495).
Psychedelic and mindfulness interventions have been shown to improve mental ill-health and wellbeing, with a range of clinical processes and effects in common. However, each appear to contain specific challenges in the context of mental health treatment. In this Perspective, we focus on a set of distinct affordances, “useful differences”, within psychedelic and mindfulness interventions that might address common challenges within the other intervention. Accordingly, we propose a set of applied synergies, indicating specific ways in which these two promising interventions might be combined for greater benefit. Metaphorically, on the journey toward mental health and wellbeing, we propose that psychedelic treatments may serve the role of Compass (initiating, motivating, and steering the course of mindfulness practice), with mindfulness interventions serving the role of Vehicle (integrating, deepening, generalizing, and maintaining the novel perspectives and motivation instigated by psychedelic experience). We outline a set of testable hypotheses and future research associated with the synergistic action of psychedelic and mindfulness interventions toward improved clinical outcomes.